U.S. patent application number 12/557253 was filed with the patent office on 2010-03-18 for novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of lung cancer.
This patent application is currently assigned to Compugen LTD.. Invention is credited to Pinchas Akiva, Michal Ayalon-Soffer, Gad S. Cojocaru, Dvir Dahary, Alexander Diber, Naomi Keren, Zurit Levine, Amit Novik, Sarah Pollock, Shirley Sameah-Greenwald, Osnat Sella-Tavor, Ronen Shemesh, Rotem Sorek, Amir Toporik, Shira Walach.
Application Number | 20100068736 12/557253 |
Document ID | / |
Family ID | 41692165 |
Filed Date | 2010-03-18 |
United States Patent
Application |
20100068736 |
Kind Code |
A1 |
Pollock; Sarah ; et
al. |
March 18, 2010 |
Novel Nucleotide and Amino Acid Sequences, and Assays and Methods
of Use Thereof for Diagnosis of Lung Cancer
Abstract
Novel markers for lung cancer that are both sensitive and
accurate. These markers are overexpressed in lung cancer
specifically, as opposed to normal lung tissue. The measurement of
these markers, alone or in combination, in patient samples provides
information that the diagnostician can correlate with a probable
diagnosis of lung cancer. The markers of the present invention,
alone or in combination, show a high degree of differential
detection between lung cancer and non-cancerous states.
Inventors: |
Pollock; Sarah; (Tel-Aviv,
IL) ; Levine; Zurit; (Herzlia, IL) ; Novik;
Amit; (Beit-HaSharon, IL) ; Dahary; Dvir;
(Tel-Aviv, IL) ; Sorek; Rotem; (Rechovot, IL)
; Toporik; Amir; (Azur, IL) ; Sameah-Greenwald;
Shirley; (Kfar-Saba, IL) ; Sella-Tavor; Osnat;
(Kfar Kish, IL) ; Diber; Alexander;
(Richon-LeZion, IL) ; Cojocaru; Gad S.;
(Ramat-HaSharon, IL) ; Ayalon-Soffer; Michal;
(Ramat-HaSharon, IL) ; Walach; Shira;
(Hod-HaSharon, IL) ; Akiva; Pinchas; (Ramat-Gan,
IL) ; Keren; Naomi; (Givat Shmuel, IL) ;
Shemesh; Ronen; (Modiln, IL) |
Correspondence
Address: |
MINTZ, LEVIN, COHN, FERRIS, GLOVSKY AND POPEO, P.C
ONE FINANCIAL CENTER
BOSTON
MA
02111
US
|
Assignee: |
Compugen LTD.
Tel Aviv
IL
|
Family ID: |
41692165 |
Appl. No.: |
12/557253 |
Filed: |
September 10, 2009 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11978554 |
Oct 30, 2007 |
|
|
|
12557253 |
|
|
|
|
11051720 |
Jan 27, 2005 |
7569662 |
|
|
11978554 |
|
|
|
|
60620916 |
Oct 22, 2004 |
|
|
|
60620874 |
Oct 22, 2004 |
|
|
|
60589815 |
Jul 22, 2004 |
|
|
|
60607307 |
Sep 7, 2004 |
|
|
|
60620853 |
Oct 22, 2004 |
|
|
|
60628112 |
Nov 17, 2004 |
|
|
|
60539129 |
Jan 27, 2004 |
|
|
|
Current U.S.
Class: |
435/7.92 ;
435/7.9; 436/501; 436/64; 530/300; 530/387.9 |
Current CPC
Class: |
C12Q 1/6886 20130101;
C12Q 2600/158 20130101; G01N 33/57423 20130101; C12Q 2600/112
20130101 |
Class at
Publication: |
435/7.92 ;
530/300; 530/387.9; 436/501; 435/7.9; 436/64 |
International
Class: |
G01N 33/53 20060101
G01N033/53; C07K 2/00 20060101 C07K002/00; C07K 16/00 20060101
C07K016/00; G01N 33/574 20060101 G01N033/574 |
Claims
1-23. (canceled)
24. An isolated polypeptide comprising the amino acid sequence set
forth in SEQ ID NO: 1795.
25. The polypeptide of claim 24, wherein said polypeptide consists
of the amino acid sequence set forth in SEQ ID NO: 1795.
26. An isolated polypeptide comprising an amino acid sequence at
least 95% identical to SEQ ID NO:1300.
27. An isolated polypeptide consisting of the amino acid sequence
of SEQ ID NO: 1793.
28. A monoclonal or polyclonal antibody that specifically binds to
an epitope in a polypeptide of claim 24, or an epitope-binding
fragment thereof.
29. The antibody of claim 28 that specifically binds to an epitope
in a polypeptide consisting of the amino acid sequence of any one
of SEQ ID NOs: 1300 or 1795.
30. A kit for detecting lung cancer, comprising the antibody of
claim 28.
31. The kit of claim 30, wherein said kit further comprises at
least one immunoassay reagent.
32. The kit of claim 31, wherein said immunoassay reagent is
selected from the group consisting of an enzyme linked
immunosorbent assay (ELISA), an immunoprecipitation assay, an
immunofluorescence analysis, an enzyme immunoassay (EIA), a
radioimmunoassay (RIA), and a Western blot analysis.
33. A method for detecting lung cancer, comprising detecting
overexpression of the polypeptide comprising the polypeptide
sequence with the amino acid sequence of SEQ ID NOs: 1300 or 1795
in a sample.
34. The method of claim 33, wherein detecting cancer comprises
detecting the presence or severity of the cancer, prognosis,
prediction, screening, early diagnosis, staging, treatment
selection, treatment monitoring.
35. A biomarker for detecting lung cancer comprising a polypeptide
with the amino acid sequence of claim 25 marked with a label.
Description
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is related to Novel Nucleotide and Amino
Acid Sequences, and Assays and Methods of use thereof for Diagnosis
of Lung Cancer, and is a continuation-in-part of U.S.
Non-provisional application Ser. No. 11/051,720 filed on Jan. 27,
2005, which claims the benefit of priority from the below U.S.
Provisional Applications which are: [0002] Application No.
60/620,916 filed Oct. 22, 2004--Differential Expression of Markers
in Colon Cancer [0003] Application No. 60/620,874 filed Oct. 22,
2004--Differential Expression of Markers in Ovarian Cancer [0004]
Application No. 60/589,815 filed Jul. 22, 2004--Differential
Expression of Markers in Lung Cancer [0005] Application No.
60/607,307 filed Sep. 7, 2004--Differential Expression of Markers
in Lung Cancer [0006] Application No. 60/620,853 filed Oct. 22,
2004--Differential Expression of Markers in Lung Cancer [0007]
Application No. 60/628,112 filed Nov. 17, 2004--Differential
Expression of Markers in Lung Cancer II [0008] Application No.
60/539,129 filed Jan. 27, 2004--Methods and Systems for Annotating
Biomolecular Sequences
[0009] Each of the above-identified U.S. Non-provisional and U.S.
Provisional Applications are incorporated herein by reference in
their entirety.
FIELD OF THE INVENTION
[0010] The present invention is related to novel nucleotide and
protein sequences that are diagnostic markers for lung cancer, and
assays and methods of use thereof.
BACKGROUND OF THE INVENTION
[0011] Lung cancer is the primary cause of cancer death among both
men and women in the U.S., with an estimated 172,000 new cases
being reported in 1994. The five-year survival rate among all lung
cancer patients, regardless of the stage of disease at diagnosis,
is only 13%. This contrasts with a five-year survival rate of 46%
among cases detected while the disease is still localized. However,
only 16% of lung cancers are discovered before the disease has
spread. Lung cancers are broadly classified into small cell or
non-small cell lung cancers. Non-small cell lung cancers are
further divided into adenocarcinomas, bronchoalveolar-alveolar,
squamous cell and large cell carcinomas. Approximately, 75-85
percent of lung cancers are non-small cell cancers and 15-25
percent are small cell cancers of the lung.
[0012] Early detection is difficult since clinical symptoms are
often not seen until the disease has reached an advanced stage.
Currently, diagnosis is aided by the use of chest x-rays, analysis
of the type of cells contained in sputum and fiberoptic examination
of the bronchial passages. Treatment regimens are determined by the
type and stage of the cancer, and include surgery, radiation
therapy and/or chemotherapy.
[0013] Early detection of primary, metastatic, and recurrent
disease can significantly impact the prognosis of individuals
suffering from lung cancer. Non-small cell lung cancer diagnosed at
an early stage has a significantly better outcome than that
diagnosed at more advanced stages. Similarly, early diagnosis of
small cell lung cancer potentially has a better prognosis.
[0014] Although current radiotherapeutic agents, chemotherapeutic
agents and biological toxins are potent cytotoxins, they do not
discriminate between normal and malignant cells, producing adverse
effects and dose-limiting toxicities. There remains a need for lung
cancer specific cancer markers. There remains a need for reagents
and kits which can be used to detect the presence of lung cancer
markers in samples from patients. There remains a need for methods
of screening and diagnosing individuals who have lung cancer and
methods of monitoring response to treatment, disease progression
and disease recurrence in patients diagnosed with lung cancer.
There remains a need for reagents, kits and methods for determining
the type of lung cancer that an individual who has lung cancer has.
There remains a need for compositions which can specifically target
lung cancer cells. There remains a need for imaging agents which
can specifically bind to lung cancer cells. There remains a need
for improved methods of imaging lung cancer cells. There remains a
need for therapeutic agents which can specifically bind to lung
cancer cells. There remains a need for improved methods of treating
individuals who are suspected of suffering from lung cancer.
SUMMARY OF THE INVENTION
[0015] The background art does not teach or suggest markers for
lung cancer that are sufficiently sensitive and/or accurate, alone
or in combination.
[0016] The present invention overcomes these deficiencies of the
background art by providing novel markers for lung cancer that are
both sensitive and accurate. Furthermore, these markers are able to
distinguish between different types of lung cancer, such as small
cell or non-small cell lung cancer, and further between non-small
cell lung cancer types, such as adenocarcinomas, squamous cell and
large cell carcinomas. These markers are overexpressed in lung
cancer specifically, as opposed to normal lung tissue. The
measurement of these markers, alone or in combination, in patient
(biological) samples provides information that the diagnostician
can correlate with a probable diagnosis of lung cancer. The markers
of the present invention, alone or in combination, show a high
degree of differential detection between lung cancer and
non-cancerous states.
[0017] According to preferred embodiments of the present invention,
examples of suitable biological samples which may optionally be
used with preferred embodiments of the present invention include
but are not limited to blood, serum, plasma, blood cells, urine,
sputum, saliva, stool, spinal fluid or CSF, lymph fluid, the
external secretions of the skin, respiratory, intestinal, and
genitourinary tracts, tears, milk, neuronal tissue, lung tissue,
any human organ or tissue, including any tumor or normal tissue,
any sample obtained by lavage (for example of the bronchial system
or of the breast ductal system), and also samples of in vivo cell
culture constituents. In a preferred embodiment, the biological
sample comprises lung tissue and/or sputum and/or a serum sample
and/or a urine sample and/or any other tissue or liquid sample. The
sample can optionally be diluted with a suitable eluant before
contacting the sample to an antibody and/or performing any other
diagnostic assay.
[0018] Information given in the text with regard to cellular
localization was determined according to four different software
programs: (i) tmhmm (from Center for Biological Sequence Analysis,
Technical University of Denmark DTU, dpt cbs dot dtu dot
dk/services/TMHMM/TMHMM2 dot 0b dot guide dot php) or (ii) tmpred
(from EMBnet, maintained by the ISREC Bioinformatics group and the
LICR Information Technology Office, Ludwig Institute for Cancer
Research, Swiss Institute of Bioinformatics, dot ch dot embnet dot
org/software/TMPRED_form dot html for transmembrane region
prediction; (iii) signalp_hmm or (iv) signalp_nn (both from Center
for Biological Sequence Analysis, Technical University of Denmark
DTU, dot cbs dot dtu dot dk/services/SignalP/background/prediction
dot php) for signal peptide prediction. The terms "signalp_hmm" and
"signalp_nn" refer to two modes of operation for the program
SignalP: hmm refers to Hidden Markov Model, while nn refers to
neural networks. Localization was also determined through manual
inspection of known protein localization and/or gene structure, and
the use of heuristics by the individual inventor. In some cases for
the manual inspection of cellular localization prediction inventors
used the ProLoc computational platform [Einat Hazkani-Covo, Erez
Levanon, Galit Rotman, Dan Graur and Amit Novik; (2004) "Evolution
of multicellularity in metazoa: comparative analysis of the
subcellular localization of proteins in Saccharomyces, Drosophila
and Caenorhabditis." Cell Biology International 2004; 28(3):171-81,
which predicts protein localization based on various parameters
including, protein domains (e.g., prediction of trans-membranous
regions and localization thereof within the protein), pI, protein
length, amino acid composition, homology to pre-annotated proteins,
recognition of sequence patterns which direct the protein to a
certain organelle (such as, nuclear localization signal, NLS,
mitochondria localization signal), signal peptide and anchor
modeling and using unique domains from Pfam that are specific to a
single compartment.
[0019] Information is given in the text with regard to SNPs (single
nucleotide polymorphisms). A description of the abbreviations is as
follows. "T.fwdarw.C", for example, means that the SNP results in a
change at the position given in the table from T to C. Similarly,
"M.fwdarw.Q", for example, means that the SNP has caused a change
in the corresponding amino acid sequence, from methionine (M) to
glutamine (Q). If, in place of a letter at the right hand side for
the nucleotide sequence SNP, there is a space, it indicates that a
frameshift has occurred. A frameshift may also be indicated with a
hyphen (-). A stop codon is indicated with an asterisk at the right
hand side (*). As part of the description of an SNP, a comment may
be found in parentheses after the above description of the SNP
itself. This comment may include an FTId, which is an identifier to
a SwissProt entry that was created with the indicated SNP. An FTId
is a unique and stable feature identifier, which allows
construction of links directly from position-specific annotation in
the feature table to specialized protein-related databases. The
FTId is always the last component of a feature in the description
field, as follows: FTId=XXX_number, in which XXX is the 3-letter
code for the specific feature key, separated by an underscore from
a 6-digit number. In the table of the amino acid mutations of the
wild type proteins of the selected splice variants of the
invention, the header of the first column is "SNP position(s) on
amino acid sequence", representing a position of a known mutation
on amino acid sequence. SNPs may optionally be used as diagnostic
markers according to the present invention, alone or in combination
with one or more other SNPs and/or any other diagnostic marker.
Preferred embodiments of the present invention comprise such SNPs,
including but not limited to novel SNPs on the known (WT or wild
type) protein sequences given below, as well as novel nucleic acid
and/or amino acid sequences formed through such SNPs, and/or any
SNP on a variant amino acid and/or nucleic acid sequence described
herein.
[0020] Information given in the text with regard to the Homology to
the known proteins was determined by Smith-Waterman version 5.1.2
using special (non default) parameters as follows: [0021]
model=sw.model [0022] GAPEXT=0 [0023] GAPOP=100.0 [0024]
MATRIX=blosum100
[0025] Information is given with regard to overexpression of a
cluster in cancer based on ESTs. A key to the p values with regard
to the analysis of such overexpression is as follows: [0026]
library-based statistics: P-value without including the level of
expression in cell-lines (P1) [0027] library based statistics:
P-value including the level of expression in cell-lines (P2) [0028]
EST clone statistics: P-value without including the level of
expression in cell-lines (SP1) [0029] EST clone statistics:
predicted overexpression ratio without including the level of
expression in cell-lines (R3) [0030] EST clone statistics: P-value
including the level of expression in cell-lines (SP2) [0031] EST
clone statistics: predicted overexpression ratio including the
level of expression in cell-lines (R4)
[0032] Library-based statistics refer to statistics over an entire
library, while EST clone statistics refer to expression only for
ESTs from a particular tissue or cancer.
[0033] Information is given with regard to overexpression of a
cluster in cancer based on microarrays. As a microarray reference,
in the specific segment paragraphs, the unabbreviated tissue name
was used as the reference to the type of chip for which expression
was measured. There are two types of microarray results: those from
microarrays prepared according to a design by the present
inventors, for which the microarray fabrication procedure is
described in detail in Materials and Experimental Procedures
section herein; and those results from microarrays using Affymetrix
technology. As a microarray reference, in the specific segment
paragraphs, the unabbreviated tissue name was used as the reference
to the type of chip for which expression was measured. For
microarrays prepared according to a design by the present
inventors, the probe name begins with the name of the cluster
(gene), followed by an identifying number. Oligonucleotide
microarray results taken from Affymetrix data were from chips
available from Affymetrix Inc, Santa Clara, Calif., USA (see for
example data regarding the Human Genome U133 (HG-U133) Set at dot
affymetrix dot com/products/arrays/specific/hgu133 dot affx;
GeneChip Human Genome U133A 2.0 Array at dot affymetrix dot
com/products/arrays/specific/hgu133av2 dot affx; and Human Genome
U133 Plus 2.0 Array at dot affymetrix dot
com/products/arrays/specific/hgu133plusdot affx). The probe names
follow the Affymetrix naming convention. The data is available from
NCBI Gene Expression Omnibus (see dot ncbi dot nlm dot nih dot
gov/projects/geo/ and Edgar et al, Nucleic Acids Research, 2002,
Vol. 30, No. 1 207-210). The dataset (including results) is
available from dot ncbi dot nlm dot nih dot gov/geo/query/acc dot
cgi?acc=GSE1133 for the Series GSE1133 database (published on March
2004); a reference to these results is as follows: Su et al (Proc
Natl Acad Sci USA. 2004 Apr. 20; 101(16):6062-7. Epub 2004 Apr. 9).
Probes designed by the present inventors are listed below.
TABLE-US-00001 >H61775_0_11_0 (SEQ ID NO: 204)
CCCCAGCTTTTATAGAGCGGCCCAAGGAAGAATATTTCCAAGAAGTAGGG
>M85491_0_0_25999 (SEQ ID NO: 205)
GACATCTTTGCATATCATGTCAGAGCTATAACATCATTGTGGAGAAGCTC
>M85491_0_14_0 (SEQ ID NO: 206)
GTCATGAAAATCAACACCGAGGTGCGGAGCTTCGGACCTGTGTCCCGCAG
>Z21368_0_0_61857 (SEQ ID NO: 207)
AGTTCATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACTCTTGAAG
>HUMGRP5E_0_0_16630 (SEQ ID NO: 208)
GCTGATATGGAAGTTGGGGAATCTGAATTGCCAGAGAATCTTGGGAAGAG
>HUMGRP5E_0_2_0 (SEQ ID NO: 209)
TCTCATAGAAGCAAAGGAGAACAGAAACCACCAGCCACCTCAACCCAAGG >D56406_0_5_0
(SEQ ID NO: 210) TCTGACTTTTACGGACTTGGCTTGTTAGAAGGCTGAAAGATGATGGCAGG
>F05068_0_0_5744 (SEQ ID NO: 211)
ACGGGAGGGAAGGAAGGTGTGCGGGAGGAGTTCTCTGTCTCCACTCCCCT
>F05068_0_0_5754 (SEQ ID NO: 212)
CAAGGGGAACTGACCGTTGGTCCCGAAGGTCTAGAAGTGAATGGGAGCAG >F05068_0_8_0
(SEQ ID NO: 213) CTGGGGTTGGACTTCGGAGTTTTGCCATTGCCAGTGGGACGTCTGAGACT
>F05068_0_1_5751 (SEQ ID NO: 214)
TCTTAGCAGGTAGGTGCCGCAGACCCTGCGGGTTAAGAGGTGGGGTGGGG >H38804_0_3_0
(SEQ ID NO: 215) CGTAATTGCAGTGCATTTAGACAGGCATCTATTTGGACCTGTTTCTATCT
>HSENA78_0_1_0 (SEQ ID NO: 216)
TGAAGAGTGTGAGGAAAACCTATGTTTGCCGCTTAAGCTTTCAGCTCAGC >R00299_0_8_0
(SEQ ID NO: 217) CCAAGGCTCGTCTGCGCACCTTGTGTCTTGTAGGGTATGGTATGTGGGAC
>Z44808_0_8_0 (SEQ ID NO: 218)
AAAAGCATGAGTTTCTGACCAGCGTTCTGGACGCGCTGTCCACGGACATG
>Z44808_0_0_72347 (SEQ ID NO: 219)
ATGTTCTTAGGAGGCAAGCCAGGAGAAGCCGGGTCTGACTTTTCAGCTCA
>Z44808_0_0_72349 (SEQ ID NO: 220)
TCCTCCAGACCCAAAGCCACAACCCATCGCAAGTCAAGAACACTTTCCAG
>AA161187_0_0_433 (SEQ ID NO: 221)
ACCCTGGGTGGGCAAAAACGTGCTTTCCCGGACGGGGTTGAAGGGGAGAA
>AA161187_0_0_430 (SEQ ID NO: 222)
TGGAGACTGTTGCCCCACTCTGCAGATGCAGAAACGGAGGCTTGGCTGCT >R66178_0_7_0
(SEQ ID NO: 223) CCAGTGTGGTATCCTGGGAAACTCGGTTAAAAGGTGAGGCAGAGTACCAG
>HUMPHOSLIP_0_0_18458 (SEQ ID NO: 224)
AAGGAAGCAGGACCAGTGGATGTGAGGCGTGGTCGAAGAACAACAGAAAG
>HUMPHOSLIP_0_0_18487 (SEQ ID NO: 225)
ACAGGGGCCAGATGGTGACCCATGACCCAGCCTAAAAGGCAGCCAGAGGG
>A1076020_0_3_0 (SEQ ID NO: 226)
ATCAGCACTGCCACCTACACCACGGTGCCGCGCGTGGCCTTCTACGCCGG
>T23580_0_0_902 (SEQ ID NO: 227)
GTGAAACCCCATTGGCTTCATTGGCTCCTTGATTTAAACCACGCCCGGCT
>T23580_0_0_901 (SEQ ID NO: 228)
TGAGTCCGTGTTATATCATGTGGTCTCATTGATAGGCGGGATAGGGAGGG >M79217_0_9_0
(SEQ ID NO: 229) TTTGTGGAATAGCAACCCATGGTTATGGCGAGTGACCCGACGTGATCTGG
>M62096_0_0_20588 (SEQ ID NO: 230)
AAGGCTTAGGTGCAAAGCCATTGGATACCATACCTGAGACCACACAGCCA >M62096_0_7_0
(SEQ ID NO: 231) ACCAGAAGCAGCTGTCCAGACTCCGAGACGAAATTGAGGAGAAGCAGAAA
>M78076_0_7_0 (SEQ ID NO: 232)
GAGAAGATGAACCCGCTGGAACAGTATGAGCGAAAGGTGAATGCGTCTGT
>T99080_0_0_58896 (SEQ ID NO: 233)
AACTCACAGCAAGAGCTGTGTTCCAGTTAGCTTTGCTACCAGTTATGCAG >T08446_0_9_0
(SEQ ID NO: 234) CATTTCCACTACGAGAACGTTGACTTTGGCCACATTCAGCTCCTGCTGTC
>HUMCA1XIA_0_0_14909 (SEQ ID NO: 235)
GCTGCAATCTAAGTTTCGGAATACTTATACCACTCCAGAAATAATCCTCG
>HUMCA1XIA_0_18_0 (SEQ ID NO: 236)
TTCAGAACTGTTAACATCGCTGACGGGAAGTGGCATCGGGTAGCAATCAG >T11628_0_9_0
(SEQ ID NO: 237) ACAAGATCCCCGTGAAGTACCTGGAGTTCATCTCGGAATGCATCATCCAG
>T11628_0_0_45174 (SEQ ID NO: 238)
TAAACAATCAAAGAGCATGTTGGCCTGGTCCTTTGCTAGGTACTGTAGAG
>T11628_0_0_45161 (SEQ ID NO: 239)
TGCCTCGCCACAATGGCACCTGCCCTAAAATAGCTTCCCATGTGAGGGCT
>HUMCEA_0_0_96 (SEQ ID NO: 240)
CAAGAGGGGTTTGGCTGAGACTTTAGGATTGTGATTCAGCTTAGAGGGAC
>HUMCEA_0_0_15183 (SEQ ID NO: 241)
CCTGGTGGGAGCCCATGAGAAGCGAGTTCTCTGTGCAACGGACTTAGTAA
>HUMCEA_0_0_15182 (SEQ ID NO: 242)
GCTCCCTGGAGCATCAGCATCATATTCTGGGGTGGAGTCTATCTGGTTCT
>HUMCEA_0_0_15168 (SEQ ID NO: 243)
TCCTGCCTGTCACCTGAAGTTCTAGATCATTCCCTGGACTCCACTCTATC
>HUMCEA_0_0_15180 (SEQ ID NO: 244)
TTTAACACAGGATTGGGACAGGATTCAGAGGGACACTGTGGCCCTTCTAC >R35137_0_5_0
(SEQ ID NO: 245) TATGTGGAGGTGGTGAACATGGACGCTGCAGTGCAGCAGCAGATGCTGAA
>Z25299_0_3_0 (SEQ ID NO: 246)
AACTCTGGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTG
>HSSTROL3_0_0_12518 (SEQ ID NO: 247)
ATGAGAGTAACCTCACCCGTGCACTAGTTTACAGAGCATTCACTGCCCCA
>HSSTROL3_0_0_12517 (SEQ ID NO: 248)
CAGAGATGAGAGCCTGGAGCATTGCAGATGCCAGGGACTTCACAAATGAA
>HSS100PCB_0_0_12280 (SEQ ID NO: 249)
CTCAAAATGAAACTCCCTCTCGCAGAGCACAATTCCAATTCGCTCTAAAA
>R20779_0_0_30670 (SEQ ID NO: 250)
CCGCGTTGCTTCTAGAGGCTGAATGCCTTTCAAATGGAGAAGGCTTCCAT
[0034] The following list of abbreviations for tissues was used in
the TAA histograms. The term "TAA" stands for "Tumor Associated
Antigen", and the TAA histograms, given in the text, represent the
cancerous tissue expression pattern as predicted by the biomarkers
selection engine, as described in detail in examples 1-5 below:
[0035] "BONE" for "bone"; [0036] "COL" for "colon"; [0037] "EPI"
for "epithelial"; [0038] "GEN" for "general"; [0039] "LIVER" for
"liver"; [0040] "LUN" for "lung"; [0041] "LYMPH" for "lymph nodes";
[0042] "MARROW" for "bone marrow"; [0043] "OVA" for "ovary"; [0044]
"PANCREAS" for "pancreas"; [0045] "PRO" for "prostate"; [0046]
"STOMACH" for "stomach"; [0047] "TCELL" for "T cells"; [0048]
"THYROID" for "Thyroid"; [0049] "MAM" for "breast"; [0050] "BRAIN"
for "brain"; [0051] "UTERUS" for "uterus"; [0052] "SKIN" for
"skin"; [0053] "KIDNEY" for "kidney"; [0054] "MUSCLE" for "muscle";
[0055] "ADREN" for "adrenal"; [0056] "HEAD" for "head and neck";
[0057] "BLADDER" for "bladder";
[0058] It should be noted that the terms "segment", "seg" and
"node" are used interchangeably in reference to nucleic acid
sequences of the present invention; they refer to portions of
nucleic acid sequences that were shown to have one or more
properties as described below. They are also the building blocks
that were used to construct complete nucleic acid sequences as
described in greater detail below. Optionally and preferably, they
are examples of oligonucleotides which are embodiments of the
present invention, for example as amplicons, hybridization units
and/or from which primers and/or complementary oligonucleotides may
optionally be derived, and/or for any other use.
[0059] As used herein the phrase "lung cancer" refers to cancers of
the lung including small cell lung cancer and non-small cell lung
cancer, including but not limited to lung adenocarcinoma, squamous
cell carcinoma, and adenocarcinoma.
[0060] The term "marker" in the context of the present invention
refers to a nucleic acid fragment, a peptide, or a polypeptide,
which is differentially present in a sample taken from subjects
(patients) having lung cancer (or one of the above indicative
conditions) as compared to a comparable sample taken from subjects
who do not have lung cancer (or one of the above indicative
conditions).
[0061] The phrase "differentially present" refers to differences in
the quantity of a marker present in a sample taken from patients
having lung cancer (or one of the above indicative conditions) as
compared to a comparable sample taken from patients who do not have
lung cancer (or one of the above indicative conditions). For
example, a nucleic acid fragment may optionally be differentially
present between the two samples if the amount of the nucleic acid
fragment in one sample is significantly different from the amount
of the nucleic acid fragment in the other sample, for example as
measured by hybridization and/or NAT-based assays. A polypeptide is
differentially present between the two samples if the amount of the
polypeptide in one sample is significantly different from the
amount of the polypeptide in the other sample. It should be noted
that if the marker is detectable in one sample and not detectable
in the other, then such a marker can be considered to be
differentially present.
[0062] As used herein the phrase "diagnostic" means identifying the
presence or nature of a pathologic condition. Diagnostic methods
differ in their sensitivity and specificity. The "sensitivity" of a
diagnostic assay is the percentage of diseased individuals who test
positive (percent of "true positives"). Diseased individuals not
detected by the assay are "false negatives." Subjects who are not
diseased and who test negative in the assay are termed "true
negatives." The "specificity" of a diagnostic assay is 1 minus the
false positive rate, where the "false positive" rate is defined as
the proportion of those without the disease who test positive.
While a particular diagnostic method may not provide a definitive
diagnosis of a condition, it suffices if the method provides a
positive indication that aids in diagnosis.
[0063] As used herein the phrase "diagnosing" refers to classifying
a disease or a symptom, determining a severity of the disease,
monitoring disease progression, forecasting an outcome of a disease
and/or prospects of recovery. The term "detecting" may also
optionally encompass any of the above.
[0064] Diagnosis of a disease according to the present invention
can be effected by determining a level of a polynucleotide or a
polypeptide of the present invention in a biological sample
obtained from the subject, wherein the level determined can be
correlated with predisposition to, or presence or absence of the
disease. It should be noted that a "biological sample obtained from
the subject" may also optionally comprise a sample that has not
been physically removed from the subject, as described in greater
detail below.
[0065] As used herein, the term "level" refers to expression levels
of RNA and/or protein or to DNA copy number of a marker of the
present invention.
[0066] Typically the level of the marker in a biological sample
obtained from the subject is different (i.e., increased or
decreased) from the level of the same variant in a similar sample
obtained from a healthy individual (examples of biological samples
are described herein).
[0067] Numerous well known tissue or fluid collection methods can
be utilized to collect the biological sample from the subject in
order to determine the level of DNA, RNA and/or polypeptide of the
variant of interest in the subject.
[0068] Examples include, but are not limited to, fine needle
biopsy, needle biopsy, core needle biopsy and surgical biopsy
(e.g., brain biopsy), and lavage. Regardless of the procedure
employed, once a biopsy/sample is obtained the level of the variant
can be determined and a diagnosis can thus be made.
[0069] Determining the level of the same variant in normal tissues
of the same origin is preferably effected along-side to detect an
elevated expression and/or amplification and/or a decreased
expression, of the variant as opposed to the normal tissues.
[0070] A "test amount" of a marker refers to an amount of a marker
in a subject's sample that is consistent with a diagnosis of lung
cancer (or one of the above indicative conditions). A test amount
can be either in absolute amount (e.g., microgram/ml) or a relative
amount (e.g., relative intensity of signals).
[0071] A "control amount" of a marker can be any amount or a range
of amounts to be compared against a test amount of a marker. For
example, a control amount of a marker can be the amount of a marker
in a patient with lung cancer (or one of the above indicative
conditions) or a person without lung cancer (or one of the above
indicative conditions). A control amount can be either in absolute
amount (e.g., microgram/nil) or a relative amount (e.g., relative
intensity of signals).
[0072] "Detect" refers to identifying the presence, absence or
amount of the object to be detected.
[0073] A "label" includes any moiety or item detectable by
spectroscopic, photo chemical, biochemical, immunochemical, or
chemical means. For example, useful labels include .sup.32P,
.sup.35S, fluorescent dyes, electron-dense reagents, enzymes (e.g.,
as commonly used in an ELISA), biotin-streptavadin, dioxigenin,
haptens and proteins for which antisera or monoclonal antibodies
are available, or nucleic acid molecules with a sequence
complementary to a target. The label often generates a measurable
signal, such as a radioactive, chromogenic, or fluorescent signal,
that can be used to quantify the amount of bound label in a sample.
The label can be incorporated in or attached to a primer or probe
either covalently, or through ionic, van der Waals or hydrogen
bonds, e.g., incorporation of radioactive nucleotides, or
biotinylated nucleotides that are recognized by streptavadin. The
label may be directly or indirectly detectable. Indirect detection
can involve the binding of a second label to the first label,
directly or indirectly. For example, the label can be the ligand of
a binding partner, such as biotin, which is a binding partner for
streptavadin, or a nucleotide sequence, which is the binding
partner for a complementary sequence, to which it can specifically
hybridize. The binding partner may itself be directly detectable,
for example, an antibody may be itself labeled with a fluorescent
molecule. The binding partner also may be indirectly detectable,
for example, a nucleic acid having a complementary nucleotide
sequence can be a part of a branched DNA molecule that is in turn
detectable through hybridization with other labeled nucleic acid
molecules (see, e.g., P. D. Fahrlander and A. Klausner,
Bio/Technology 6:1165 (1988)). Quantitation of the signal is
achieved by, e.g., scintillation counting, densitometry, or flow
cytometry.
[0074] Exemplary detectable labels, optionally and preferably for
use with immunoassays, include but are not limited to magnetic
beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish
peroxide, alkaline phosphatase and others commonly used in an
ELISA), and calorimetric labels such as colloidal gold or colored
glass or plastic beads. Alternatively, the marker in the sample can
be detected using an indirect assay, wherein, for example, a
second, labeled antibody is used to detect bound marker-specific
antibody, and/or in a competition or inhibition assay wherein, for
example, a monoclonal antibody which binds to a distinct epitope of
the marker are incubated simultaneously with the mixture.
[0075] "Immunoassay" is an assay that uses an antibody to
specifically bind an antigen. The immunoassay is characterized by
the use of specific binding properties of a particular antibody to
isolate, target, and/or quantify the antigen.
[0076] The phrase "specifically (or selectively) binds" to an
antibody or "specifically (or selectively) immunoreactive with,"
when referring to a protein or peptide (or other epitope), refers
to a binding reaction that is determinative of the presence of the
protein in a heterogeneous population of proteins and other
biologics. Thus, under designated immunoassay conditions, the
specified antibodies bind to a particular protein at least two
times greater than the background (non-specific signal) and do not
substantially bind in a significant amount to other proteins
present in the sample. Specific binding to an antibody under such
conditions may require an antibody that is selected for its
specificity for a particular protein. For example, polyclonal
antibodies raised to seminal basic protein from specific species
such as rat, mouse, or human can be selected to obtain only those
polyclonal antibodies that are specifically immunoreactive with
seminal basic protein and not with other proteins, except for
polymorphic variants and alleles of seminal basic protein. This
selection may be achieved by subtracting out antibodies that
cross-react with seminal basic protein molecules from other
species. A variety of immunoassay formats may be used to select
antibodies specifically immunoreactive with a particular protein.
For example, solid-phase ELISA immunoassays are routinely used to
select antibodies specifically immunoreactive with a protein (see,
e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988),
for a description of immunoassay formats and conditions that can be
used to determine specific immunoreactivity). Typically a specific
or selective reaction will be at least twice background signal or
noise and more typically more than 10 to 100 times background.
[0077] According to preferred embodiments of the present invention,
preferably any of the above nucleic acid and/or amino acid
sequences further comprises any sequence having at least about 70%,
preferably at least about 80%, more preferably at least about 90%,
most preferably at least about 95% homology thereto.
[0078] Unless otherwise noted, all experimental data relates to
variants of the present invention, named according to the segment
being tested (as expression was tested through RT-PCR as
described).
[0079] All nucleic acid sequences and/or amino acid sequences shown
herein as embodiments of the present invention relate to their
isolated form, as isolated polynucleotides (including for all
transcripts), oligonucleotides (including for all segments,
amplicons and primers), peptides (including for all tails, bridges,
insertions or heads, optionally including other antibody epitopes
as described herein) and/or polypeptides (including for all
proteins). It should be noted that oligonucleotide and
polynucleotide, or peptide and polypeptide, may optionally be used
interchangeably.
[0080] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1 and 2.
[0081] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1022, 1023, 1024, 1025, 1026 and 1027.
[0082] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1281 and 1282.
[0083] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
3 and 4.
[0084] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037 and
1038.
[0085] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1283 and 1284.
[0086] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
5, 6, 7 and 8.
[0087] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049,
1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060,
1061, 1062, 1063, 1064, 1065 and 1066.
[0088] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1285, 1286, 1287 and 1288.
[0089] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
9, 10, 11, 12, 13, 14 and 15.
[0090] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077,
1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086, 1087, 1088,
1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099
and 1100.
[0091] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1289, 1290, 1291, 1292, 1293 and 1294.
[0092] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
20 and 21.
[0093] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1130, 1131, 1132, 1133 and 1134.
[0094] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1299 and 1300.
[0095] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
22, 23 and 24.
[0096] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143 and 1144.
[0097] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1301, 1302 and 1303.
[0098] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
25, 26 and 27.
[0099] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1145, 1146, 1147, 1148, 1149, 1150, 1151, 1152, 1153, 1154, 1155
and 1156.
[0100] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1304 and 1305.
[0101] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
28.
[0102] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1157, 1158, 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167,
1168, 1169, 1170 and 1171.
[0103] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1306.
[0104] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
29 and 30.
[0105] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181, 1182,
1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190 and 1191.
[0106] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1307 and 1308.
[0107] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
31.
[0108] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1192, 1193, 1194, 1195, 1196, 1197 and 1198.
[0109] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1309.
[0110] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
32.
[0111] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1199, 1200, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209,
1210, 1211, 1212, 1213, 1214 and 1215.
[0112] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO.
1310.
[0113] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
33.
[0114] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1216 and 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1226
and 1227.
[0115] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1311.
[0116] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
34.
[0117] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1228, 1229, 1230, 1231, 1232 and 1223.
[0118] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1312.
[0119] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
35.
[0120] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243, 1244,
1245, 1246, 1247, 1248, 1249, 1250, 1251, 1252, 1253 and 1254.
[0121] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1313.
[0122] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
36, 37, 38, 39 and 40.
[0123] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1255, 1256, 1257, 1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265,
1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1274 and 1275.
[0124] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1314, 1315, 1316 and 1317.
[0125] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
125, 126, 127, 128, 129 and 130.
[0126] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899,
900, 901 and 902.
[0127] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1394, 1395, 1396, 1397 and 1398.
[0128] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising a
transcript SEQ ID NOs: 131 and 132.
[0129] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
903, 904, 905, 906, 907, 907, 908 and 909.
[0130] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1399 and 1400.
[0131] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
99, 100, 101 and 102.
[0132] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754,
755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767,
768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780,
781, 782, 783, 784, 785, 786, 787 and 788.
[0133] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1372, 1373, 1374 and 1375.
[0134] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
134.
[0135] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925,
926, 927, 928, 929, 930, 931, 932, 933, 934, 935 and 936.
[0136] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1402.
[0137] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NO:
133.
[0138] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
910, 911 and 912.
[0139] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
141, 142 and 142.
[0140] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973,
974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986,
987, 988, 989 and 990.
[0141] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising:
[0142] Protein Name
[0143] HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627)
[0144] HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628)
[0145] HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629)
[0146] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
51, 52, 53, 54, 55, 56 and 57.
[0147] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530,
531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543,
544, 545, 546, 547,548, 549, 550, 551, 552, 553, 554, 555, 556,
557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569 and
570.
[0148] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1327, 1328, 1329, 1330, 1331, 1332 and 1333.
[0149] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
135, 136, 137, 138, 139 and 140.
[0150] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949,
950, 951, 952, 953, 954, 955, 956, 957, 958, 959 and 960.
[0151] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1403, 1404, 1405, 1406, 1407 and 1408.
[0152] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
41, 42, 43, 44, 45, 46 and 47.
[0153] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
482, 483, 484, 495, 486, 487, 488, 489, 490, 491, 492, 493, 494,
495, 496, 497, 498, 499, 500 and 501.
[0154] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1318, 1319, 1320, 1321, 1322 and 1323.
[0155] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
121, 122, 123 and 124.
[0156] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
876, 877, 878, 879, 880, 881, 882, 883, 884, 885 and 886.
[0157] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1390, 1391, 1392 and 1393.
[0158] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
48, 49 and 50.
[0159] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514,
515, 516 and 517.
[0160] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1324, 1325 and 1326.
[0161] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1464 and 1465.
[0162] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising a SEQ ID
NOs: 1276, 1277, 1278, 1279 and 1280.
[0163] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1415.
[0164] Protein Name Corresponding Transcript(s)
[0165] HSU33147_PEA.sub.--1_P5 HSU33147_PEA.sub.--1_T1 (SEQ ID
NO:1464); HSU33147_PEA.sub.--1_T2 (SEQ ID NO:1465)
[0166] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NO:
58.
[0167] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
571, 572, 573, 574, 575, 576, 577 and 578.
[0168] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1334.
[0169] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
74, 75, 76, 77, 78, 79, 80, 81 and 82.
[0170] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671,
672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684,
685, 686, 687, 688, 689, 690, 691, 692 and 693.
[0171] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1350, 1351, 1352, 1353, 1354, 1355, 1356 and 1357.
[0172] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID
NOs:
[0173] Transcript Name
[0174] T23580_T10 (SEQ ID NO:1626)
[0175] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
579, 580, 581, 582 and 583.
[0176] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1335.
[0177] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
59, 60, 61, 62, 63 and 64.
[0178] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596,
597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609,
610, 611, 612, 613, 614 and 615.
[0179] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1336, 1337, 1338, 1339 and 1340.
[0180] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
65, 66, 67, 68, 69, 70, 71, 72 and 73.
[0181] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628,
629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641,
642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654,
655, 656, 657, 658 and 659.
[0182] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348 and 1349.
[0183] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 and 96.
[0184] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
695, 696, 697, 698, 699, 700, 701, 702, 703, 704 and 705.
[0185] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368
and 1369.
[0186] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
97 and 98.
[0187] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718,
719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731,
732, 733, 734, 735, 736, 737, 738, 739, 740 and 741.
[0188] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1370 and 1371.
[0189] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
103, 104, 105, 106, 107 and 108.
[0190] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801,
802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812 and 813.
[0191] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1376, 1377, 1378 and 1379.
[0192] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
114, 115, 116, 117, 118 and 119.
[0193] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868,
869, 870, 871, 872, 873, 874 and 875.
[0194] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1385, 1386, 1387, 1388 and 1389.
[0195] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
144, 145, 146, 147, 148 and 149.
[0196] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002,
1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013,
1014, 1015 and 1016.
[0197] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs:
1409, 1410, 1411, 1412 and 1413.
[0198] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NO:
150.
[0199] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
1017, 1018, 1019, 1020 and 1021.
[0200] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NO:
1414.
[0201] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
109, 110, 111, 112 and 113.
[0202] According to preferred embodiments of the present invention,
there is provided an isolated polynucleotide comprising SEQ ID NOs:
814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826,
827, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840,
841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853,
854 and 855.
[0203] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide comprising SEQ ID NOs
1380, 1381, 1382, 1383 and 1384.
[0204] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding
for.HSSTROL3_P4 (SEQ ID NO:1394), comprising a first amino acid
sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P4 (SEQ ID NO:1394), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:1394), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLG
PAPLTELGLVRFPVHAALVWGPEKNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDA
DG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 165-445 of
HSSTROL3_P4 (SEQ ID NO:1394), and a third amino acid sequence being
at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:
251) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID
NO:1394), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[0205] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HSSTROL3_P4 (SEQ ID NO:1394), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:
251) in HSSTROL3_P4 (SEQ ID NO:1394).
[0206] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSSTROL3_P5 (SEQ ID NO:1395), comprising a first amino acid
sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P5 (SEQ ID NO:1395), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:1395), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQ corresponding
to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:1455), which also
corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:1395),
and a third amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO: 252)
corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID
NO:1395), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[0207] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HSSTROL3_P5 (SEQ ID NO:1395), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK
(SEQ ID NO: 252) in HSSTROL3_P5 (SEQ ID NO:1395).
[0208] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSSTROL3_P7 (SEQ ID NO:1396), comprising a first amino acid
sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P7 (SEQ ID NO:1396), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:1396), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG
corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 165-359 of
HSSTROL3_P7 (SEQ ID NO:1396), and a third amino acid sequence being
at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID
NO: 253) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ
ID NO:1396), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[0209] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HSSTROL3_P7 (SEQ ID NO:1396), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:
253) in HSSTROL3_P7 (SEQ ID NO:1396).
[0210] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSSTROL3_P8 (SEQ ID NO:1397), comprising a first amino acid
sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P8 (SEQ ID NO:1397), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P8 (SEQ ID NO:1397), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE corresponding
to amino acids 165-286 of MM11_HUMAN (SEQ ID NO:1455), which also
corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID NO:1397),
and a third amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence VRPCLPVPLLLCWPL (SEQ ID NO: 254) corresponding to
amino acids 287-301 of HSSTROL3_P8 (SEQ ID NO:1397), wherein said
first amino acid sequence, bridging amino acid, second amino acid
sequence and third amino acid sequence are contiguous and in a
sequential order.
[0211] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HSSTROL3_P8 (SEQ ID NO:1397), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID
NO: 254) in HSSTROL3_P8 (SEQ ID NO:1397).
[0212] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSSTROL3_P9 (SEQ ID NO:1398), comprising a first amino acid
sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-96 of HSSTROL3_P9 (SEQ ID NO:1398), a second amino acid sequence
being at least 90% homologous to
RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding
to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:1455), which also
corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:1398),
a bridging amino acid H corresponding to amino acid 148 of
HSSTROL3_P9 (SEQ ID NO:1398), a third amino acid sequence being at
least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG
corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 149-343 of
HSSTROL3_P9 (SEQ ID NO:1398), and a fourth amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID
NO: 253) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ
ID NO:1398), wherein said first amino acid sequence, second amino
acid sequence, bridging amino acid, third amino acid sequence and
fourth amino acid sequence are contiguous and in a sequential
order.
[0213] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HSSTROL3_P9 (SEQ ID NO:1398), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KR, having a structure as follows: a
sequence starting from any of amino acid numbers 96-x to 96; and
ending at any of amino acid numbers 97+((n-2)-x), in which x varies
from 0 to n-2.
[0214] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HSSTROL3_P9 (SEQ ID NO:1398), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:
253) in HSSTROL3_P9 (SEQ ID NO:1398).
[0215] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCA1XIA_P14 (SEQ ID NO:1372), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE
DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ
GPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPQGPIGYPGPRGVKGADGVRGLKG
SKGEKGEDGFPGFKGDMGLKGDRGEVGQIGPRGEDGPEGPKGRAGPTGDPGPSGQAGEKGKLGVPGLPG
YPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGP
PGERGPQGPQGPVGFPGPKGPPGPPGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERG
HPGPPGPPGEQGLPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP
V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID
NO:1447), which also corresponds to amino acids 1-1056 of
HUMCA1XIA_P14 (SEQ ID NO:1372), and a second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO: 256) corresponding to amino
acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:1372), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0216] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCA1XIA_P14 (SEQ ID NO:1372), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO: 256) in HUMCA1XIA_P14 (SEQ ID
NO:1372).
[0217] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCA1XIA_P15 (SEQ ID NO:1373), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYICEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE
DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ
GPIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID
NO:1446), which also corresponds to amino acids 1-714 of
HUMCA1XIA_P15 (SEQ ID NO:1373), and a second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence MCCNLSFGILIPLQK
(SEQ ID NO: 257) corresponding to amino acids 715-729 of
HUMCA1XIA_P15 (SEQ ID NO:1373), wherein said first amino acid
sequence and second amino acid sequence are contiguous and in a
sequential order.
[0218] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCA1XIA_P15 (SEQ ID NO:1373), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID
NO: 257) in HUMCA1XIA_P15 (SEQ ID NO:1373).
[0219] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE
DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ
ID NO:1446), which also corresponds to amino acids 1-648 of
HUMCA1XIA_P16 (SEQ ID NO:1374), a second amino acid sequence being
at least 90% homologous to
GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to
amino acids 667-714 of CA1B_HUMAN (SEQ ID NO:1446), which also
corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID
NO:1374), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence
VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO: 258)
corresponding to amino acids 697-738 of HUMCA1XIA_P16 (SEQ ID
NO:1374), wherein said first amino acid sequence, second amino acid
sequence and third amino acid sequence are contiguous and in a
sequential order.
[0220] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise AG, having a structure as follows: a
sequence starting from any of amino acid numbers 648-x to 648; and
ending at any of amino acid numbers 649+((n-2)-x), in which x
varies from 0 to n-2.
[0221] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO: 258) in
HUMCA1XIA_P16 (SEQ ID NO:1374).
[0222] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCA1XIA_P17 (SEQ ID NO:1375), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDE corresponding to
amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:1446), which also
corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:1375),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence VRSTRPEKVFVFQ (SEQ ID NO: 259) corresponding to amino
acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:1375), wherein said first
amino acid sequence and second amino acid sequence are contiguous
and in a sequential order.
[0223] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCA1XIA_P17 (SEQ ID NO:1375), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VRSTRPEKVFVFQ in
HUMCA1XIA_P17 (SEQ ID NO:1375).
[0224] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R20779_P2 (SEQ ID NO:1402), comprising a first amino acid sequence
being at least 90% homologous to
MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLVNAGDVGCGVFE
CFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECY
LKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1-169 of
STC2_HUMAN (SEQ ID NO:1458), which also corresponds to amino acids
1-169 of R20779_P2 (SEQ ID NO:1402), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
CYKIEITMPKRRKVKLRD (SEQ ID NO: 260) corresponding to amino acids
170-187 of R20779_P2 (SEQ ID NO:1402), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0225] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R20779_P2 (SEQ ID NO:1402), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO:
260) in R20779_P2 (SEQ ID NO:1402).
[0226] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ
corresponding to amino acids 1-58 of OSTP_HUMAN (SEQ ID NO:1462),
which also corresponds to amino acids 1-58 of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VFLNFS (SEQ ID NO: 261) corresponding to amino acids 59-64
of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0227] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VFLNFS (SEQ ID NO: 261) in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21
(SEQ ID NO:1627).
[0228] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31
of OSTP_HUMAN (SEQ ID NO:1462), which also corresponds to amino
acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID
NO:1628), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence H corresponding to amino acids
32-32 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0229] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31
of OSTP_HUMAN (SEQ ID NO:1462), which also corresponds to amino
acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID
NO:1629), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VSIFYVFI (SEQ ID NO: 262)
corresponding to amino acids 32-39 of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0230] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VSIFYVFI (SEQ ID NO: 262) in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30
(SEQ ID NO:1629).
[0231] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISE
corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-67 of
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), and a second amino
acid sequence being at least 90% homologous to
KVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMKDPVASTSNLDMD
FRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLDMLL
RATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAK
MALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHE
VVTNHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV corresponding to
amino acids 163-493 of PLTP_HUMAN (SEQ ID NO:1433), which also
corresponds to amino acids 68-398 of HUMPHOSLIP_PEA.sub.--2_P10
(SEQ ID NO:1327), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0232] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327),
comprising a polypeptide having a length "n", wherein n is at least
about 10 amino acids in length, optionally at least about 20 amino
acids in length, preferably at least about 30 amino acids in
length, more preferably at least about 40 amino acids in length and
most preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EK, having a structure as follows: a
sequence starting from any of amino acid numbers 67-x to 67; and
ending at any of amino acid numbers 68+((n-2)-x), in which x varies
from 0 to n-2.
[0233] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVG
IDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAG
ALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPP
DQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLN
corresponding to amino acids 1-427 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-427 of
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GKAGV (SEQ ID NO: 263) corresponding to amino acids
428-432 of HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0234] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
GKAGV (SEQ ID NO: 263) in HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID
NO:1328).
[0235] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISE
corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-67 of
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO: 264)
corresponding to amino acids 68-98 of HUMPHOSLIP_PEA.sub.--2_P31
(SEQ ID NO:1330), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0236] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO: 264) in
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330).
[0237] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQ corresponding to amino
acids 1-183 of PLTP_HUMAN (SEQ ID NO:1433), which also corresponds
to amino acids 1-183 of HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID
NO:1331), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VWAATGRRVARVGMLSL (SEQ ID NO: 265)
corresponding to amino acids 184-200 of HUMPHOSLIP_PEA.sub.--2_P33
(SEQ ID NO:1331), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0238] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VWAATGRRVARVGMLSL (SEQ ID NO: 265) in HUMPHOSLIP_PEA.sub.--2_P33
(SEQ ID NO:1331).
[0239] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPV
corresponding to amino acids 1-205 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-205 of
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence LWTSLLALTIPS (SEQ ID NO: 266) corresponding to amino acids
206-217 of HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0240] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
LWTSLLALTIPS (SEQ ID NO: 266) in HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID
NO:1332).
[0241] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWF corresponding to amino acids
1-109 of PLTP_HUMAN (SEQ ID NO:1433), which also corresponds to
amino acids 1-109 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), a
second amino acid sequence bridging amino acid sequence comprising
of L, a third amino acid sequence being at least 90% homologous to
KVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 163-183 of
PLTP_HUMAN (SEQ ID NO:1433), which also corresponds to amino acids
111-131 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), and a
fourth amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VWAATGRRVARVGMLSL (SEQ ID NO: 265) corresponding to amino
acids 132-148 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333),
wherein said first amino acid sequence, second amino acid sequence,
third amino acid sequence and fourth amino acid sequence are
contiguous and in a sequential order.
[0242] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for an edge
portion of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise FLK having a structure as follows
(numbering according to HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID
NO:1333)): a sequence starting from any of amino acid numbers 109-x
to 109; and ending at any of amino acid numbers 111+((n-2)-x), in
which x varies from 0 to n-2.
[0243] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VWAATGRRVARVGMLSL (SEQ ID NO: 265) in HUMPHOSLIP_PEA.sub.--2_P35
(SEQ ID NO:1333).
[0244] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGG
LPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFAT
corresponding to amino acids 1-412 of CT31_HUMAN (SEQ ID NO:1459),
which also corresponds to amino acids 1-412 of
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV (SEQ ID NO: 268)
corresponding to amino acids 413-449 of R38144_PEA.sub.--2_P6 (SEQ
ID NO:1403), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0245] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV (SEQ ID NO: 268) in
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403).
[0246] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P13 (SEQ ID NO:1404), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQ corresponding to amino
acids 1-323 of CT31_HUMAN (SEQ ID NO:1459), which also corresponds
to amino acids 1-323 of R38144_PEA.sub.--2_P13 (SEQ ID NO:1404),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence NLLKAQCTSTVPRGIPPS (SEQ ID NO: 269) corresponding to
amino acids 324-341 of R38144_PEA.sub.--2_P13 (SEQ ID NO:1404),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0247] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P13 (SEQ ID NO:1404), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
NLLKAQCTSTVPRGIPPS (SEQ ID NO: 269) in R38144_PEA.sub.--2_P13 (SEQ
ID NO:1404).
[0248] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LE corresponding to amino acids 1-282 of CT31_HUMAN (SEQ ID
NO:1459), which also corresponds to amino acids 1-282 of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence PHWRH
(SEQ ID NO: 270) corresponding to amino acids 283-287 of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), wherein said first amino
acid sequence and second amino acids sequence are contiguous and in
a sequential order.
[0249] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence PHWRH (SEQ
ID NO: 270) in R38144_PEA.sub.--2_P15 (SEQ ID NO:1405).
[0250] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGG
LPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFAT
corresponding to amino acids 1-412 of CT31_HUMAN (SEQ ID NO:1459),
which also corresponds to amino acids 1-412 of
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
KRSRSVAQAGVQWCDHDSPQP (SEQ ID NO: 270) corresponding to amino acids
413-433 of R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0251] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
KRSRSVAQAGVQWCDHDSPQP (SEQ ID NO: 270) in R38144_PEA.sub.--2_P19
(SEQ ID NO:1406).
[0252] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIR corresponding
to amino acids 1-121 of CT31_HUMAN (SEQ ID NO:1459), which also
corresponds to amino acids 1-121 of R38144_PEA.sub.--2_P24 (SEQ ID
NO:1407), and a second amino acid sequence being at least 90%
homologous to
EYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGGL
PEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFATIKDLRDHKL
DNRMESFFLAETVKYLYLLFDPTNFIHNNGSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKE
EQWEVEDLMREFYSLKRSRSKFQKNTVSSGPWEPPARPGTLFSPENHDQARERKPAKQKVPLLSCPSQPFT
SKLALLGQVFLDSS corresponding to amino acids 282-578 of CT31_HUMAN
(SEQ ID NO:1459), which also corresponds to amino acids 122-418 of
R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0253] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise RE, having a structure as follows: a
sequence starting from any of amino acid numbers 121-x to 121; and
ending at any of amino acid numbers 122+((n-2)-x), in which x
varies from 0 to n-2.
[0254] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR corresponding to amino acids
1-36 of AAH16184 (SEQ ID NO:1460), which also corresponds to amino
acids 1-36 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) corresponding to
amino acids 37-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0255] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) in R38144_PEA.sub.--2_P36
(SEQ ID NO:1408).
[0256] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHY corresponding to amino acids
1-35 of AAQ88943 (SEQ ID NO:1461), which also corresponds to amino
acids 1-35 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence RFWGMSQNSKEWLKCSRTAWTLILM corresponding to amino acids
36-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0257] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
RFWGMSQNSKEWLKCSRTAWTLILM in R38144_PEA.sub.--2_P36 (SEQ ID
NO:1408).
[0258] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR corresponding to amino acids
1-36 of CT31_HUMAN (SEQ ID NO:1459), which also corresponds to
amino acids 1-36 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) corresponding to
amino acids 37-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0259] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) in R38144_PEA.sub.--2_P36
(SEQ ID NO:1408).
[0260] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
AA161187_P6 (SEQ ID NO:1319), comprising a first amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273)
corresponding to amino acids 1-42 of AA161187_P6 (SEQ ID NO:1319),
and a second amino acid sequence being at least 90% homologous to
GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMVQ
FGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDC
WVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGG
PLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALP
LLGPV corresponding to amino acids 31-314 of TEST_HUMAN (SEQ ID
NO:1431), which also corresponds to amino acids 43-326 of
AA161187_P6 (SEQ ID NO:1319), wherein said first amino acid
sequence and second amino acid sequence are contiguous and in a
sequential order.
[0261] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
AA161187_P6 (SEQ ID NO:1319), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273) of
AA161187_P6 (SEQ ID NO:1319).
[0262] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
AA161187_P13 (SEQ ID NO:1320), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of TEST_HUMAN (SEQ ID NO:1431), which also corresponds
to amino acids 1-183 of AA161187_P13 (SEQ ID NO:1320), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG (SEQ ID NO: 274)
corresponding to amino acids 184-213 of AA161187_P13 (SEQ ID
NO:1320), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[0263] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
AA161187_P13 (SEQ ID NO:1320), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG (SEQ ID NO: 274) in AA161187_P13
(SEQ ID NO:1320).
[0264] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
AA161187_P14 (SEQ ID NO:1321), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of TEST_HUMAN (SEQ ID NO:1431), which also corresponds
to amino acids 1-183 of AA161187_P14 (SEQ ID NO:1321), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
GCCLSPSHYRPHSTAISPHPPGSSGRHHKQLYVQPPLPQVQFPQGHLWRHGLCWQCPRREGCLLRECPCH
HSQPRKASCVPVPYLTLMPTPGGGDCCPTLQMQKRRLGCCQGEEEDVHPVYPAP (SEQ ID NO:
275) corresponding to amino acids 184-307 of AA161187_P14 (SEQ ID
NO:1321), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[0265] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
AA161187_P14 (SEQ ID NO:1321), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
GCCLSPSHYRPHSTAISPHPPGSSGRHHKQLYVQPPLPQVQFPQGHLWRHGLCWQCPRREGCLL-
RECPCH HSQPRKASCVPVPYLTLMPTPGGGDCCPTLQMQKRRLGCCQGEEEDVHPVYPAP (SEQ
ID NO: 275) in AA161187_P14 (SEQ ID NO:1321).
[0266] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
AA161187_P18 (SEQ ID NO:1322), comprising a first amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273)
corresponding to amino acids 1-42 of AA161187_P18 (SEQ ID NO:1322),
a second amino acid sequence being at least 90% homologous to
GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFET
corresponding to amino acids 31-86 of TEST_HUMAN (SEQ ID NO:1431),
which also corresponds to amino acids 43-98 of AA161187_P18 (SEQ ID
NO:1322), a third amino acid sequence being at least 90% homologous
to
DLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQ
ASTFEFENRTDCWVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQG
GKDACF corresponding to amino acids 89-235 of TEST_HUMAN (SEQ ID
NO:1431), which also corresponds to amino acids 99-245 of
AA161187_P18 (SEQ ID NO:1322), and a fourth amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
VSVPATTPSPGKHPVSLCLI (SEQ ID NO: 277) corresponding to amino acids
246-265 of AA161187_P18 (SEQ ID NO:1322), wherein said first amino
acid sequence, second amino acid sequence, third amino acid
sequence and fourth amino acid sequence are contiguous and in a
sequential order.
[0267] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
AA161187_P18 (SEQ ID NO:1322), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273) of
AA161187_P18 (SEQ ID NO:1322).
[0268] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of AA161187_P18 (SEQ ID NO:1322), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise TD, having a structure as follows: a
sequence starting from any of amino acid numbers 98-x to 99; and
ending at any of amino acid numbers 99+((n-2)-x), in which x varies
from 0 to n-2.
[0269] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
AA161187_P18 (SEQ ID NO:1322), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VSVPATTPSPGKHPVSLCLI
(SEQ ID NO: 277) in AA161187_P18(SEQ ID NO:1322).
[0270] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
AA161187_P19 (SEQ ID NO:1323), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of TEST_HUMAN (SEQ ID NO:1431), which also corresponds
to amino acids 1-183 of AA161187_P19 (SEQ ID NO:1323), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence DKRTQ (SEQ ID NO: 278) corresponding to amino acids
184-188 of AA161187_P19 (SEQ ID NO:1323), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0271] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
AA161187_P19 (SEQ ID NO:1323), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence DKRTQ (SEQ ID NO: 278)
in AA161187_P19 (SEQ ID NO:1323).
[0272] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK
corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:1454),
which also corresponds to amino acids 1-131 of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GKQGMRAH
(SEQ ID NO: 279) corresponding to amino acids 132-139 of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0273] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GKQGMRAH
(SEQ ID NO: 279) in Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390).
[0274] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK
corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:1454),
which also corresponds to amino acids 1-131 of
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO: 269) corresponding to amino
acids 132-156 of Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), wherein
said first and second amino acid sequences are contiguous and in a
sequential order.
[0275] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO: 269) in Z25299_PEA.sub.--2_P3
(SEQ ID NO:1391).
[0276] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNP corresponding to amino acids 1-81 of ALK1_HUMAN (SEQ ID
NO:1454), which also corresponds to amino acids 1-81 of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence RGSLGSAQ
(SEQ ID NO: 622) corresponding to amino acids 82-89 of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0277] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence RGSLGSAQ
(SEQ ID NO: 622) in Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392).
[0278] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPT corresponding to amino acids 1-82 of ALK1_HUMAN (SEQ
ID NO:1454), which also corresponds to amino acids 1-82 of
Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393).
[0279] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R66178_P3 (SEQ ID NO:1324), comprising a first amino acid sequence
being at least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVEVNIT
corresponding to amino acids 1-334 of PVR1_HUMAN (SEQ ID NO:1432),
which also corresponds to amino acids 1-334 of R66178_P3 (SEQ ID
NO:1324), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence GEGHSLPISPGVLQTQNCGP (SEQ ID NO:
694) corresponding to amino acids 335-354 of R66178_P3 (SEQ ID
NO:1324), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[0280] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R66178_P3 (SEQ ID NO:1324), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence GEGHSLPISPGVLQTQNCGP (SEQ ID
NO: 694) in R66178_P3 (SEQ ID NO:1324).
[0281] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R66178_P4 (SEQ ID NO:1325), comprising a first amino acid sequence
being at least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVEVNIT
corresponding to amino acids 1-334 of PVR1_HUMAN (SEQ ID NO:1432),
which also corresponds to amino acids 1-334 of R66178_P4 (SEQ ID
NO:1325), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence AFCQLIYPGKGRTRARMF (SEQ ID NO:
1702) corresponding to amino acids 335-352 of R66178_P4 (SEQ ID
NO:1325), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[0282] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R66178_P4 (SEQ ID NO:1325), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence AFCQLIYPGKGRTRARMF (SEQ ID NO:
1702) in R66178_P4 (SEQ ID NO:1325).
[0283] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R66178_P8 (SEQ ID NO:1326), comprising a first amino acid sequence
being at least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVE corresponding
to amino acids 1-330 of PVR1_HUMAN (SEQ ID NO:1432), which also
corresponds to amino acids 1-330 of R66178_P8 (SEQ ID NO:1326), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC (SEQ ID NO: 1717)
corresponding to amino acids 331-363 of R66178_P8 (SEQ ID NO:1326),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0284] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R66178_P8 (SEQ ID NO:1326), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence
NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC (SEQ ID NO: 1717) in R66178_P8
(SEQ ID NO:1326).
[0285] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), comprising a first amino
acid sequence being at least 90% homologous to
MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFIDDNATTNAIDELKECFLNQTD
ETLSNVE corresponding to amino acids 1-78 of MGBA_HUMAN (SEQ ID
NO:1416), which also corresponds to amino acids 1-78 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), and a second amino acid
sequence being at least 90% homologous to QLIYDSSLCDLF
corresponding to amino acids 82-93 of MGBA_HUMAN (SEQ ID NO:1416),
which also corresponds to amino acids 79-90 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0286] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415),
comprising a polypeptide having a length "n", wherein n is at least
about 10 amino acids in length, optionally at least about 20 amino
acids in length, preferably at least about 30 amino acids in
length, more preferably at least about 40 amino acids in length and
most preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EQ, having a structure as follows: a
sequence starting from any of amino acid numbers 78-x to 78; and
ending at any of amino acid numbers 79+((n-2)-x), in which x varies
from 0 to n-2.
[0287] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), comprising a first amino
acid sequence being at least 90% homologous to
MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFIDDNATTNAIDELKECFLNQTD
ETLSNVE corresponding to amino acids 1-78 of MGBA_HUMAN (SEQ ID
NO:1416), which also corresponds to amino acids 1-78 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), and a second amino acid
sequence being at least 90% homologous to QLIYDSSLCDLF
corresponding to amino acids 82-93 of MGBA_HUMAN (SEQ ID NO:1416),
which also corresponds to amino acids 79-90 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0288] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415),
comprising a polypeptide having a length "n", wherein n is at least
about 10 amino acids in length, optionally at least about 20 amino
acids in length, preferably at least about 30 amino acids in
length, more preferably at least about 40 amino acids in length and
most preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EQ, having a structure as follows: a
sequence starting from any of amino acid numbers 78-x to 78; and
ending at any of amino acid numbers 79+((n-2)-x), in which x varies
from 0 to n-2.
[0289] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids 1-517 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-517 of M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GE corresponding to amino acids 518-519 of
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0290] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids
1-526 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 1-526 of M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence ECLTVNPSLQIPLNP (SEQ ID NO: 1718) corresponding to amino
acids 527-541 of M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0291] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ECLTVNPSLQIPLNP (SEQ ID NO: 1718) in M78076_PEA.sub.--1_P4 (SEQ ID
NO:1351).
[0292] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids
1-526 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 1-526 of M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO: 1719) corresponding to
amino acids 527-544 of M78076_PEA.sub.--1_P12 (SEQ ID NO:1352),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0293] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ECVCSKGFPFPLIGDSEG (SEQ ID NO:1719) in M78076_PEA.sub.--1_P12 (SEQ
ID NO:1352).
[0294] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSE
IQRDEL corresponding to amino acids 1-570 of APP1_HUMAN (SEQ ID
NO:1439), which also corresponds to amino acids 1-570 of
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO: 1720)
corresponding to amino acids 571-619 of M78076_PEA.sub.--1_P14 (SEQ
ID NO:1353), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0295] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO: 1720)
in M78076_PEA.sub.--1_P14 (SEQ ID NO:1353).
[0296] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
corresponding to amino acids 1-352 of APP1_HUMAN (SEQ ID NO:1439),
which also corresponds to amino acids 1-352 of
M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), and a second amino acid
sequence being at least 90% homologous to
AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHL
AQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLE
QYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHG
VVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP corresponding to amino acids
406-650 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 353-597 of M78076_PEA.sub.--1_P21 (SEQ ID NO:1354),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0297] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EA, having a structure as follows: a
sequence starting from any of amino acid numbers 352-x to 352; and
ending at any of amino acid numbers 353+((n-2)-x), in which x
varies from 0 to n-2.
[0298] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQI
corresponding to amino acids 1-481 of APP1_HUMAN (SEQ ID NO:1439),
which also corresponds to amino acids 1-481 of
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
RECLLPWLPLQISEGRS (SEQ ID NO: 1721) corresponding to amino acids
482-498 of M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0299] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
RECLLPWLPLQISEGRS (SEQ ID NO: 1721) in M78076 _PEA.sub.--1_P24 (SEQ
ID NO:1355).
[0300] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQV corresponding to amino acids 1-449 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-449 of M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLTCCVFDPCFLALG
FLLPPPSILCSVPWIFTAFPRIVFFFFFFFLRQVLALSPRQESSVRSWLIATSTSWVQAILLPQPLE
(SEQ ID NO: 1722) corresponding to amino acids 450-588 of
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0301] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLTCCVFDPCFLALG
FLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIATSTSWVQAILLPQPLE
(SEQ ID NO: 1722) in M78076_PEA.sub.--1_P2 (SEQ ID NO:1356).
[0302] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQ corresponding to amino acids 1-448 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-448 of M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP
(SEQ ID NO: 1723) corresponding to amino acids 449-505 of
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0303] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID
NO: 1723) in M78076_PEA.sub.--1_P25 (SEQ ID NO:1357).
[0304] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P1 (SEQ ID NO:1336), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPICATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMNFLVSHITRKPPIK
VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTRLPHDKTKCFKFI
corresponding to amino acids 13-931 of BAA25445 (SEQ ID NO:1437),
which also corresponds to amino acids 1-919 of M79217_PEA1_P1 (SEQ
ID NO:1336).
[0305] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHK corresponding to amino acids 1-807 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
1-807 of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), and a second amino
acid sequence being at least 90% homologous to
AIRDMVDEYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYM
PLLYTQFRVDSVLFKTRLPHDKTKCFKFI corresponding to amino acids 820-919
of EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino
acids 808-907 of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0306] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KA, having a structure as follows: a
sequence starting from any of amino acid numbers 807-x to 807; and
ending at any of amino acid numbers 808+((n-2)-x), in which x
varies from 0 to n-2.
[0307] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence PELRQPARLGLPECWDYRHEPRCPAQMGSHFIVQAGLKLLASSKPPKCWDY (SEQ
ID NO: 1724) corresponding to amino acids 1-51 of
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), and a second amino acid
sequence being at least 90% homologous to
RVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVD
EYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFR
VDSVLFKTRLPHDKTKCFKFI corresponding to amino acids 759-919 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
52-212 of M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0308] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PELRQPARLGLPECWDYRHEPRCPAQMGSHFIVQAGLKLLASSKPPKCWDY (SEQ ID NO:
1724) of M79217_PEA.sub.--1_P4 (SEQ ID NO:1338).
[0309] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRHATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHK corresponding to amino acids 1-807 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
1-807 of M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VRKSW (SEQ ID NO: 1725) corresponding to amino acids
808-812 of M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0310] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence VRKSW (SEQ
ID NO: 1725) in M79217_PEA.sub.--1_P8 (SEQ ID NO:1339).
[0311] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MATYIH (SEQ ID NO: 1726) corresponding to amino acids 1-6
of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), and a second amino acid
sequence being at least 90% homologous to
VSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKMTRILQDSLGGNCRTTIVICCSPSV-
FN
EAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPED
EQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLD
QDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQ
KTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISK
MKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQD
SLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKII
DEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLR
KLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRA
TAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVH
AIRGGGGSSSNSTHYQK corresponding to amino acids 239-957 of
KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino acids
7-725 of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), wherein said first
amino acid sequence and second amino acid sequence are contiguous
and in a sequential order.
[0312] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MATYIH
(SEQ ID NO: 1726) of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341).
[0313] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P5 (SEQ ID NO:1342), comprising a first amino
acid sequence being at least 90% homologous to
MTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNK
TLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYR
QLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAV
NYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGT
NDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHE
AKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQ
MESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKR
EQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKV
HKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMAR
RAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK corresponding to amino
acids 284-957 of KF5C_HUMAN (SEQ ID NO:1438), which also
corresponds to amino acids 1-674 of M62096_PEA.sub.--1_P5 (SEQ ID
NO:1342).
[0314] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P3 (SEQ ID NO:1343), comprising a first amino
acid sequence being at least 90% homologous to
MELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEIN
QQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEV
EDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADV
NGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDY
MQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAH
QKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLK
GLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRD
NADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQI
AKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK corresponding to amino acids
365-957 of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to
amino acids 1-593 of M62096_PEA.sub.--1_P3 (SEQ ID NO:1343).
[0315] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) corresponding to
amino acids 1-19 of M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), and a
second amino acid sequence being at least 90% homologous to
LNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQ
DLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERV
KALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGG
GGSSSNSTHYQK corresponding to amino acids 738-957 of KF5C_HUMAN
(SEQ ID NO:1438), which also corresponds to amino acids 20-239 of
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0316] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) of M62096_PEA.sub.--1_P7 (SEQ
ID NO:1344).
[0317] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQ
LDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVN
YDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTN
DVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEA
KIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQ
MESHREAHQKQLSRLRDEIEEKQKIIDEIR corresponding to amino acids 1-736
of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino
acids 1-736 of M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence E corresponding to amino acids 737-737 of
M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0318] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQ
LDDKDDEINQQSQLAEKLKQQMLDQDE corresponding to amino acids 1-454 of
KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino acids
1-454 of M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRCPFTASYKLIITEFRK (SEQ
ID NO: 1728) corresponding to amino acids 455-514 of
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0319] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRCPFTASYKLIITEFRK (SEQ
ID NO: 1728) in M62096_PEA.sub.--1_P9 (SEQ ID NO:1346).
[0320] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) corresponding to
amino acids 1-19 of M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), a
second amino acid sequence being at least 90% homologous to
LNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQ
DLTTRVKK corresponding to amino acids 738-815 of KF5C_HUMAN (SEQ ID
NO:1438), which also corresponds to amino acids 20-97 of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), and a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
VSSLCLNGTEKKIKDGREESFSVEISLA (SEQ ID NO: 1730) corresponding to
amino acids 98-125 of M62096_PEA.sub.--1_P10 (SEQ ID NO:1347),
wherein said first amino acid sequence, second amino acid sequence
and third amino acid sequence are contiguous and in a sequential
order.
[0321] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) of M62096_PEA.sub.--1_P10
(SEQ ID NO:1347).
[0322] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VSSLCLNGTEKKIKDGREESFSVEISLA (SEQ ID NO: 1730) in
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347).
[0323] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGHPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGICANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRN corresponding to amino acids 1-372 of KF5C_HUMAN
(SEQ ID NO:1438), which also corresponds to amino acids 1-372 of
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
DFLAAHVFGKLLE (SEQ ID NO: 1731) corresponding to amino acids
373-385 of M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0324] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DFLAAHVFGKLLE (SEQ ID NO: 1731) in M62096_PEA.sub.--1_P11 (SEQ ID
NO:1348).
[0325] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P12 (SEQ ID NO:1349), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQR corresponding to amino
acids 1-323 of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds
to amino acids 1-323 of M62096_PEA.sub.--1_P12 (SEQ ID NO:1349),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence V corresponding to amino acids 324-324 of
M62096_PEA.sub.--1_P12 (SEQ ID NO:1349), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0326] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MPASARLAGAGLLLAFLRALGCAGRAPGLS (SEQ ID NO: 1732)
corresponding to amino acids 1-30 of T99080_PEA.sub.--4_P5 (SEQ ID
NO:1360), and a second amino acid sequence being at least 90%
homologous to
MAEGNTLISVDYEIFGKVQGVFFRKHTQAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLET
RGSPKSHIDKANFNNEKVILKLDYSDFQIVK corresponding to amino acids 1-99
of ACYO_HUMAN_V1 (SEQ ID NO:1441), which also corresponds to amino
acids 31-129 of T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0327] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MPASARLAGAGLLLAFLRALGCAGRAPGLS (SEQ ID NO: 1732) of
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360).
[0328] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence M corresponding to amino acids 1-1 of
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361), and a second amino acid
sequence being at least 90% homologous to
QAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEKVILKLDYSDFQ
IVK corresponding to amino acids 28-99 of ACYO_HUMAN_V1 (SEQ ID
NO:1441), which also corresponds to amino acids 2-73 of
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0329] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 90% homologous to
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME corresponding to amino
acids 1-185 of SNXQ_HUMAN (SEQ ID NO:1442), which also corresponds
to amino acids 1-185 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFF
PSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQR
VFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHS
VSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSA
NTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGR
CLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFF
ALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPV
GPAPAGSCESLSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFD
PLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAG-
G
APASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGG
APPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAH
PGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVP
TPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPT-
R
SWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLAL
GPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGG
ELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC (SEQ ID NO: 1733)
corresponding to amino acids 186-1305 of T08446_PEA.sub.--1_P18
(SEQ ID NO:1370), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0330] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFF
PSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQR
VFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHS
VSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSA
NTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGR
CLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFF
ALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPV
GPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDF-
D
PLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGA-
GG
APASATPTPALSPGRSLRPHUPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGG
APPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAH
PGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVP
TPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPT-
R
SWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLAL
GPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGG
ELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC (SEQ ID NO: 1733) in
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[0331] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A MSVPGEEERLVRV (SEQ ID NO: 1734) corresponding to amino acids
1-443 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a second amino
acid sequence being at least 90% homologous to
HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRV
QSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPK
APASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSE
ESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSP-
S
HRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRG-
P
TSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEM-
C
SKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQ
SPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQV
SAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRS
SLGPPAPLDRGENLYYEIGASEGSPYSG corresponding to amino acids 1-674 of
Q9NT23 (SEQ ID NO:1443), which also corresponds to amino acids
444-1117 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a bridging
amino acid P corresponding to amino acid 1118 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), and a third amino acid
sequence being at least 90% homologous to
TRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYV-
NL
ALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYG-
R GGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC corresponding to
amino acids 676-862 of Q9NT23 (SEQ ID NO:1443), which also
corresponds to amino acids 1119-1305 of T08446_PEA.sub.--1_P18 (SEQ
ID NO:1370), wherein said first amino acid sequence, second amino
acid sequence, bridging amino acid and third amino acid sequence
are contiguous and in a sequential order.
[0332] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A MSVPGEEERLVRV (SEQ ID NO: 1734) of T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370).
[0333] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A
MSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESV
GMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQART
QGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSG
SRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSS-
ES
SAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASA-
F
PPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLR-
GA
EAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQ
QSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPM
GTSRRG corresponding to amino acids 1-1010 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), and a second amino acid
sequence being at least 90% homologous to
LRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSS
PAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLL
SYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQK-
Q
RAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSE
GQTRSYC corresponding to amino acids 1-295 of Q96CP3 (SEQ ID
NO:1444), which also corresponds to amino acids 1011-1305 of
T08446_PEA1_P18 (SEQ ID NO:1370), wherein said first amino acid
sequence and second amino acid sequence are contiguous and in a
sequential order.
[0334] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T08446PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A
MSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESV
GMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQART
QGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSG
SRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSS-
ES
SAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASA-
F
PPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLR-
GA
EAPLTDACQAEMCSKLRGAQGPLGPDMESPLPPPPSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQ
QSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPM
GTSRRG of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[0335] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQ corresponding to amino acids 1-154 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a second amino acid
sequence being at least 90% homologous to
MLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELS
FEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAV
PRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIY
RLSGVSSNIQRLRHEFDSERMELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERL
VRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFRE
VRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPT
TPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSA
KSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALS-
G
SPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAIS-
P
RGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQ-
Q
EMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPP
ASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGP
A corresponding to amino acids 1-861 of BAC86902 (SEQ ID NO:1445),
which also corresponds to amino acids 155-1015 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
QVSAQLRAGGGGRDAPEAAAQSPCSVPS corresponding to amino acids 1016-1043
of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a fourth amino acid
sequence being at least 90% homologous to
QVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYS
GPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYS
corresponding to amino acids 862-989 of BAC86902 (SEQ ID NO:1445),
which also corresponds to amino acids 1044-1171 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), and a fifth amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
APQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGP
WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC
corresponding to amino acids 1172-1305 of T08446_PEA.sub.--1_P18
(SEQ ID NO:1370), wherein said first amino acid sequence, second
amino acid sequence, third amino acid sequence, fourth amino acid
sequence and fifth amino acid sequence are contiguous and in a
sequential order.
[0336] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQ of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[0337] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for an edge
portion of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising an
amino acid sequence being at least 70%, optionally at least about
80%, preferably at least about 85%, more preferably at least about
90% and most preferably at least about 95% homologous to the
sequence encoding for QVSAQLRAGGGGRDAPEAAAQSPCSVPS, corresponding
to T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[0338] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
APQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGP
WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC in
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[0339] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE
(SEQ ID NO: 1735) corresponding to amino acids 1-55 of
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), and a second amino acid
sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFG-
A DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of
Q8WVH6 (SEQ ID NO:1450), which also corresponds to amino acids
56-154 of T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0340] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:
1735) of T11628_PEA.sub.--1_P2 (SEQ ID NO:1376).
[0341] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P5 (SEQ ID NO:1377), comprising a first amino
acid sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGA
DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56-154 of
MYG_HUMAN_V1 (SEQ ID NO:1449), which also corresponds to amino
acids 1-99 of T11628_PEA.sub.--1_P5 (SEQ ID NO:1377).
[0342] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P7 (SEQ ID NO:1378), comprising a first amino
acid sequence being at least 90% homologous to
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASEDLKKHGATV
LTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK
corresponding to amino acids 1-134 of MYG_HUMAN_V1 (SEQ ID
NO:1449), which also corresponds to amino acids 1-134 of
T11628_PEA.sub.--1_P7 (SEQ ID NO:1378), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence G
corresponding to amino acids 135-135 of T11628 _PEA.sub.--1_P7 (SEQ
ID NO:1378), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0343] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE
(SEQ ID NO: 1735) corresponding to amino acids 1-55 of
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), and a second amino acid
sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFG-
A DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of
Q8WVH6 (SEQ ID NO:1450), which also corresponds to amino acids
56-154 of T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[0344] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:
1735) of T11628_PEA.sub.--1_P10 (SEQ ID NO:1379).
[0345] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEV
corresponding to amino acids 1-274 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-274 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
AYEAGGGSRAMARPSSPDGPPPPPHLTWPCAGAGSAAAMWRW (SEQ ID NO: 1737)
corresponding to amino acids 275-385 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0346] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
AYEAGGGSRAMARPSSPDGPPPPPHLTWPCAGAGSAAAMWRW (SEQ ID NO: 1737) in
R35137_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385).
[0347] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEVYQDNVYAAG
SQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGEC corresponding to amino acids
1-320 of ALAT_HUMAN_V1 (SEQ ID NO:1453), which also corresponds to
amino acids 1-320 of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8
(SEQ ID NO:1386), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence VRTRRVGARGPWPGPPRPMGHPLLRT
(SEQ ID NO: 1738) corresponding to amino acids 321-346 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0348] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence VRTRRVGARGPWPGPPRPMGHPLLRT (SEQ ID NO: 1738) in
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386).
[0349] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVMANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQAR corresponding to amino acids 1-229 of
ALAT_HUMAN_V1 (SEQ ID NO:1453), which also corresponds to amino
acids 1-229 of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ
ID NO:1387), and a second amino acid sequence being at least 90%
homologous to SGFGQREGTYHFRMTILPPLEKLRLLLEKLSRFHAKFTLEYS
corresponding to amino acids 455-496 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 230-271 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0350] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ
ID NO:1387), comprising a polypeptide having a length "n", wherein
n is at least about 10 amino acids in length, optionally at least
about 20 amino acids in length, preferably at least about 30 amino
acids in length, more preferably at least about 40 amino acids in
length and most preferably at least about 50 amino acids in length,
wherein at least two amino acids comprise RS, having a structure as
follows: a sequence starting from any of amino acid numbers 229-x
to 229; and ending at any of amino acid numbers 230+((n-2)-x), in
which x varies from 0 to n-2.
[0351] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQUREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEV
corresponding to amino acids 1-274 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-274 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
VPRRLCGGGEHGRCSAAADAEADECAAVPAGARTGPAGPGGQPARAHRPLLCAVPG (SEQ ID
NO: 1739) corresponding to amino acids 275-399 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0352] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
VPRRLCGGGEHGRCSAAADAEADECAAVPAGARTGPAGPGGQPARAHRPLLCAVPG (SEQ ID
NO: 1739) in R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID
NO:1338).
[0353] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEVYQDNVYAAG
SQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCPP
VPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKAKLTEQVFNEAPGISCNPVQGAMYSFPRVQLP
PRAVERAQELGLAPDMFFCLRLLEETGICVVPGSGFGQREGTYHFRMTILPPLEKLRLLLEKLSRFHAKFTL
E corresponding to amino acids 1-494 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-494 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
SPGRLWSPLYLLLMPGGVGWGGCWAPASLQVPNKAVWQSDSKKEALAAAWPAPTCLPFLQA (SEQ
ID NO: 1740) corresponding to amino acids 495-555 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[0354] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
SPGRLWSPLYLLLMPGGVGWGGCWAPASLQVPNKAVWQSDSKKEALAAAWPAPTCLPFLQA (SEQ
ID NO: 1740) in R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ
ID NO:1389).
[0355] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO: 1741)
corresponding to amino acids 1-110 of R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410), and a second amino acid sequence being at least 90%
homologous to
MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLG
FGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino
acids 1-112 of Q8IXM0 (SEQ ID NO:1707), which also corresponds to
amino acids 111-222 of R11723_PEA.sub.--1_P6 (SEQ ID NO:1410),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0356] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAGSPCRGLAPGREEORALHKAGAVGGGVR (SEQ ID NO: 1741) of
R11723_PEA.sub.--1_p6 (SEQ ID NO:1410).
[0357] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 1-83 of Q96AC2 (SEQ ID
NO:1708), which also corresponds to amino acids 1-83 of R11723
_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0358] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[0359] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 1-83 of Q8N2G4 (SEQ ID
NO:1709), which also corresponds to amino acids 1-83 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0360] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[0361] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 24-106 of BAC85518 (SEQ
ID NO:1710), which also corresponds to amino acids 1-83 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0362] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[0363] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 1-64 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-64 of R11723_PEA.sub.--1_P7 (SEQ
ID NO:1411), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0364] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[0365] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 1-64 of Q8N2G4 (SEQ ID NO:1709), which
also corresponds to amino acids 1-64 of R11723_PEA1_P7 (SEQ ID
NO:1411), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0366] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[0367] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MWVLG (SEQ ID NO: 1744) corresponding to amino acids 1-5
of R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), second amino acid
sequence being at least 90% homologous to
IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 22-80 of BAC85273, which also
corresponds to amino acids 6-64 of R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[0368] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MWVLG (SEQ
ID NO: 1744) of R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[0369] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[0370] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 24-87 of BAC85518 (SEQ ID NO:1710),
which also corresponds to amino acids 1-64 of R11723_PEA.sub.--1_P7
(SEQ ID NO:1411), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT
(SEQ ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0371] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[0372] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P13 (SEQ ID NO:1412), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P13 (SEQ
ID NO:1412), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:
1745) corresponding to amino acids 64-84 of R11723_PEA.sub.--1_P13
(SEQ ID NO:1412), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[0373] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P13 (SEQ ID NO:1412), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO: 1745) in R11723_PEA.sub.--1_P13
(SEQ ID NO:1412).
[0374] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P10 (SEQ
ID NO:1413), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0375] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[0376] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q8N2G4 (SEQ ID NO:1709), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P10 (SEQ
ID NO:1413), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0377] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[0378] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MWVLG (SEQ ID NO: 1744) corresponding to amino acids 1-5
of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), second amino acid
sequence being at least 90% homologous to
IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 22-79 of BAC85273, which also
corresponds to amino acids 6-63 of R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[0379] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MWVLG (SEQ
ID NO: 1744) of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[0380] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723PEA.sub.--1_P10 (SEQ ID NO:1413).
[0381] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 24-86 of BAC85518 (SEQ ID NO:1710),
which also corresponds to amino acids 1-63 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) corresponding to
amino acids 64-90 of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0382] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723PEA.sub.--1_P10 (SEQ ID NO:1413).
[0383] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a first amino
acid sequence being at least 90% homologous to
MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPG corresponding to amino
acids 1-41 of NOV_HUMAN (SEQ ID NO:1463), which also corresponds to
amino acids 1-41 of R16276PEA.sub.--1_P7 (SEQ ID NO:1414), a
bridging amino acid Q corresponding to amino acid 42 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), a second amino acid
sequence being at least 90% homologous to
CPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICT
corresponding to amino acids 43-103 of NOV_HUMAN (SEQ ID NO:1463),
which also corresponds to amino acids 43-103 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), and a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GNPAPSAV
(SEQ ID NO: 1748) corresponding to amino acids 104-111 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), wherein said first amino
acid sequence, bridging amino acid, second amino acid sequence and
third amino acid sequence are contiguous and in a sequential
order.
[0384] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GNPAPSAV
(SEQ ID NO: 1748) in R16276_PEA.sub.--1_P7 (SEQ ID NO:1414).
[0385] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a first amino
acid sequence being at least 90% homologous to
MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPG corresponding to amino
acids 1-41 of NOV_HUMAN (SEQ ID NO:1463), which also corresponds to
amino acids 1-41 of R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), a
bridging amino acid Q corresponding to amino acid 42 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), a second amino acid
sequence being at least 90% homologous to
CPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICT
corresponding to amino acids 43-103 of NOV_HUMAN (SEQ ID NO:1463),
which also corresponds to amino acids 43-103 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), and a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GNPAPSAV
(SEQ ID NO: 1748) corresponding to amino acids 104-111 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), wherein said first amino
acid sequence, bridging amino acid, second amino acid sequence and
third amino acid sequence are contiguous and in a sequential
order.
[0386] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GNPAPSAV
(SEQ ID NO: 1748) in R16276_PEA.sub.--1_P7 (SEQ ID NO:1414).
[0387] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREHYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILNVL corresponding to amino acids 1-234 of
CEA5_HUMAN (SEQ ID NO:1451), which also corresponds to amino acids
1-234 of HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG
SGSTPYDGRNR (SEQ ID NO: 1749) corresponding to amino acids 235-315
of HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0388] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG
SGSTPYDGRNR (SEQ ID NO: 1749) in HUMCEA_PEA_PEA.sub.--1_P4 (SEQ ID
NO:1380).
[0389] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFI
PNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWW
VNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRP
GVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELP
KPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVC
GIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAK-
I TPNNNGTYACFVSNLATGRNNSIVKSITVS corresponding to amino acids 1-675
of CEA5_HUMAN (SEQ ID NO:1451), which also corresponds to amino
acids 1-675 of HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:
1750) corresponding to amino acids 676-719 of HUMCEA_PEA.sub.--1_P5
(SEQ ID NO:1381), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0390] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably atleast about 95% homologous to the sequence
GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO: 1750) in
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381).
[0391] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREHYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILN corresponding to amino acids 1-232 of CEA5_HUMAN
(SEQ ID NO:1451), which also corresponds to amino acids 1-232 of
HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), and a second amino acid
sequence being at least 90% homologous to
VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLA
TGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino
acids 589-702 of CEA5_HUMAN (SEQ ID NO:1451), which also
corresponds to amino acids 233-346 of HUMCEA_PEA.sub.--1_P19 (SEQ
ID NO:1383), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[0392] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise NV, having a structure as follows: a
sequence starting from any of amino acid numbers 232-x to 232; and
ending at any of amino acid numbers 233+((n-2)-x), in which x
varies from 0 to n-2.
[0393] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYP
corresponding to amino acids 1-142 of CEA5_HUMAN (SEQ ID NO:1451),
which also corresponds to amino acids 1-142 of
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), and a second amino acid
sequence being at least 90% homologous to
ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARA
YVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLF
IAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
corresponding to amino acids 499-702 of CEA5_HUMAN (SEQ ID
NO:1451), which also corresponds to amino acids 143-346 of
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[0394] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise PE, having a structure as follows: a
sequence starting from any of amino acid numbers 142-x to 142; and
ending at any of amino acid numbers 143+((n-2)-x), in which x
varies from 0 to n-2.
[0395] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of
SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino acids
1-441 of Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO: 1751) corresponding to
amino acids 442-464 of Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0396] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO: 1751) in Z44808_PEA.sub.--1_P5
(SEQ ID NO:1314).
[0397] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRH corresponding to amino acids 1-428 of SMO2_HUMAN (SEQ ID
NO:1430), which also corresponds to amino acids 1-428 of
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence RSKRNL
(SEQ ID NO: 1752) corresponding to amino acids 429-434 of
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0398] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence RSKRNL
(SEQ ID NO: 1752) in Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315).
[0399] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of
SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino acids
1-441 of Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence LLWLRGKVSFYCF (SEQ ID NO: 1753) corresponding to amino
acids 442-454 of Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), wherein
said first and second amino acid sequences are contiguous and in a
sequential order.
[0400] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LLWLRGKVSFYCF (SEQ ID NO: 1753) in Z44808_PEA.sub.--1_P7 (SEQ ID
NO:1316).
[0401] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKT corresponding to amino acids 1-170
of SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino
acids 1-170 of Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), and a
second amino acid sequence being at least 90% homologous to
DIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGY
CWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVH
AASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCD
VNNDKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG corresponding to
amino acids 188-446 of SMO2_HUMAN (SEQ ID NO:1430), which also
corresponds to amino acids 171-429 of Z44808_PEA.sub.--1_P11 (SEQ
ID NO:1317), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0402] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise TD, having a structure as follows: a
sequence starting from any of amino acid numbers 170-x to -170; and
ending at any of amino acid numbers 171+((n-2)-x), in which x
varies from 0 to n-2.
[0403] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H61775_P16 (SEQ ID NO:1281), comprising a first amino acid sequence
being at least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFG
LYSPRIDPDYVG corresponding to amino acids 11-93 of Q9P2J2 (SEQ ID
NO:1694), which also corresponds to amino acids 1-83 of H61775_P16
(SEQ ID NO:1281), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCSVTLQV
(SEQ ID NO: 1754) corresponding to amino acids 84-152 of H61775_P16
(SEQ ID NO:1281), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[0404] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
H61775_P16 (SEQ ID NO:1281), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCS-
VTLQV (SEQ ID NO: 1754) in H61775_P16 (SEQ ID NO:1281).
[0405] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H61775_P16 (SEQ ID NO:1281), comprising a first amino acid sequence
being at least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFG
LYSPRIDPDYVG corresponding to amino acids 1-83 of AAQ88495 (SEQ ID
NO:1695), which also corresponds to amino acids 1-83 of H61775_P16
(SEQ ID NO:1281), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCSVTLQV
(SEQ ID NO: 1754) corresponding to amino acids 84-152 of H61775_P16
(SEQ ID NO:1281), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[0406] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
H61775_P16 (SEQ ID NO:1281), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCS-
VTLQV (SEQ ID NO: 1754) in H61775_P16 (SEQ ID NO:1281).
[0407] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H61775_P17 (SEQ ID NO:1282), comprising a first amino acid sequence
being at least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFG
LYSPRIDPDYVG corresponding to amino acids 11-93 of Q9P2J2 (SEQ ID
NO:1694), which also corresponds to amino acids 1-83 of H61775_P17
(SEQ ID NO:1282).
[0408] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H61775_P17 (SEQ ID NO:1282), comprising a first amino acid sequence
being at least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFG
LYSPRIDPDYVG corresponding to amino acids 1-83 of AAQ88495 (SEQ ID
NO:1695), which also corresponds to amino acids 1-83 of H61775_P17
(SEQ ID NO:1282).
[0409] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), comprising a first amino
acid sequence being at least 90% homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQ
NNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVD
TIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETL
SGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQ
GDEACTHCPINSRTTSEGATNCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSGG
REDLVYNIICKSCGSGRGACTRCGDNVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAVNGVTDQSPFSPQF
ASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEK corresponding
to amino acids 1-476 of EPB2_HUMAN (SEQ ID NO:1417), which also
corresponds to amino acids 1-476 of M85491_PEA.sub.--1_P13 (SEQ ID
NO:1283), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO:
1755) corresponding to amino acids 477-496 of
M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0410] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VPIGWVLSPSPTSLRAPLPG (SEQ ID NO: 1755) in M85491_PEA.sub.--1_P13
(SEQ ID NO:1283).
[0411] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), comprising a first amino
acid sequence being at least 90% homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQ
NNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVD
TIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETL
SGAESTSLVAARGSCIANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR
corresponding to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:1417),
which also corresponds to amino acids 1-270 of
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO: 1756) corresponding to
amino acids 271-301 of M85491_PEA.sub.--1_P14 (SEQ ID NO:1284),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0412] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO: 1756) in
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284).
[0413] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T39971_P6 (SEQ ID NO:1285), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG
corresponding to amino acids 1-276 of VTNC_HUMAN (SEQ ID NO:1418),
which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID
NO:1285), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence TQGVVGD (SEQ ID NO: 1757)
corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:1285),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0414] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
T39971_P6 (SEQ ID NO:1285), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence TQGVVGD (SEQ ID NO: 1757) in
T39971_P6 (SEQ ID NO:1285).
[0415] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
139971_P9 (SEQ ID NO:1286), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWE
YQFQHQPSQEECEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRT corresponding to amino
acids 1-325 of VTNC_HUMAN (SEQ ID NO:1418), which also corresponds
to amino acids 1-325 of T39971_P9 (SEQ ID NO:1286), and a second
amino acid sequence being at least 90% homologous to
SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGANNYDDYRMDW
LVPATCEPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL
corresponding to amino acids 357-478 of VTNC_HUMAN (SEQ ID
NO:1418), which also corresponds to amino acids 326-447 of
T39971_P9 (SEQ ID NO:1286), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[0416] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of T39971_P9 (SEQ ID NO:1286), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise TS, having a structure as follows: a
sequence starting from any of amino acid numbers 325-x to 325; and
ending at any of amino acid numbers 326+((n-2)-x), in which x
varies from 0 to n-2.
[0417] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T39971_P11 (SEQ ID NO:1287), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFKGSQWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWE
YQFQHQPSQEECEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to
amino acids 1-326 of VTNC_HUMAN (SEQ ID NO:1418), which also
corresponds to amino acids 1-326 of T39971_P11 (SEQ ID NO:1287),
and a second amino acid sequence being at least 90% homologous to
DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids
442-478 of VTNC_HUMAN (SEQ ID NO:1418), which also corresponds to
amino acids 327-363 of T39971_P11 (SEQ ID NO:1287), wherein said
first and second amino acid sequences are contiguous and in a
sequential order.
[0418] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of T39971_P11 (SEQ ID NO:1287), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise SD, having a structure as follows: a
sequence starting from any of amino acid numbers 326-x to 326; and
ending at any of amino acid numbers 327+((n-2)-x), in which x
varies from 0 to n-2.
[0419] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T39971_P11 (SEQ ID NO:1287), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFKGSQYWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWE
YQFQHQPSQEECEGSSLSAVFEHFAMMQRDSWEDIFELLFWGRTS corresponding to
amino acids 1-326 of Q9BSH7, which also corresponds to amino acids
1-326 of T39971_P11 (SEQ ID NO:1287), and a second amino acid
sequence being at least 90% homologous to
DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids
442-478 of Q9BSH7, which also corresponds to amino acids 327-363 of
T39971P11 (SEQ ID NO:1287), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[0420] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of T39971_P11 (SEQ ID NO:1287), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise SD, having a structure as follows: a
sequence starting from any of amino acid numbers 326-x to 326; and
ending at any of amino acid numbers 327+((n-2)-x), in which x
varies from 0 to n-2.
[0421] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
T39971_P12 (SEQ ID NO:1288), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFK corresponding to amino acids 1-223 of VTNC_HUMAN (SEQ
ID NO:1418), which also corresponds to amino acids 1-223 of
T39971_P12 (SEQ ID NO:1288), and a second amino acid sequence being
at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence VPGAVGQGRKHLGRV
(SEQ ID NO: 1758) corresponding to amino acids 224-238 of
T39971_P12 (SEQ ID NO:1288), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[0422] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
T39971_P12 (SEQ ID NO:1288), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID
NO: 1758) in T39971_P12 (SEQ ID NO:1288).
[0423] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
139971_P12 (SEQ ID NO:1288), comprising a first amino acid sequence
being at least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFT
MPEDEYTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRP
ETLHPGRPQPPAEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFT
RINCQGKTYLFK corresponding to amino acids 1-223 of Q9BSH7, which
also corresponds to amino acids 1-223 of T39971_P12 (SEQ ID
NO:1288), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO: 1758)
corresponding to amino acids 224-238 of T39971_P12 (SEQ ID
NO:1288), wherein said first and second amino acid sequences are
contiguous in a sequential order.
[0424] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
T39971_P12 (SEQ ID NO:1288), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID
NO: 1758) in T39971_P12 (SEQ ID NO:1288).
[0425] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFF
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMY
PHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQR
KRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP
GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKE
ESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLY
ARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEE
LQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQS
ARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKE
AAQEVDSKLQLFKENNRRRKICERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWN
corresponding to amino acids 1-761 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-761 of
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO: 1759) corresponding to
amino acids 762-790 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0426] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO: 1759) in
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289).
[0427] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL
corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:1697), which
also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ
ID NO:1290), second bridging amino acid sequence comprising A, and
a third amino acid sequence being at least 90% homologous to
FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKR
MYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNIL
QRKRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSV
EPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRK
KEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN
LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEE
EELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELY
QSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPF
KEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSS
NNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQ
CNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids
139-871 of Q7Z2W2 (SEQ ID NO:1697), which also corresponds to amino
acids 59-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), wherein
said first, second and third amino acid sequences are contiguous
and in a sequential order.
[0428] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for an edge
portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise LAF having a structure as follows
(numbering according to Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290)): a
sequence starting from any of amino acid numbers 57-x to 57; and
ending at any of amino acid numbers 59+((n-2)-x), in which x varies
from 0 to n-2.
[0429] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYI
PPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHA
APHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDS
VERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLA
PTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPK
YERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSC
RESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHD
EGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDK
EIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKE
NNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH
NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME (SEQ ID NO: 1760)
corresponding to amino acids 1-751 of Z21368_PEA.sub.--1_P5 (SEQ ID
NO:1290), and a second amino acid sequence being at least 90%
homologous to LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG
corresponding to amino acids 1-40 of AAH12997 (SEQ ID NO:1698),
which also corresponds to amino acids 752-791 of Z21368
_PEA.sub.--1_P5 (SEQ ID NO:1290), wherein said first and second
amino acid sequences are contiguous and in a sequential order.
[0430] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNILLVLTDDQDVELAFFGKYLNEYNGSYI
PPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHA
APHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRQTLMSVDDS
VERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLA
PTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPK
YERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSC
RESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHD
EGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDK
EIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKE
NNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETH
NFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLME (SEQ ID NO: 1760) of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290).
[0431] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL
corresponding to amino acids 1-57 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-57 of Z21368_PEA1_P5 (SEQ
ID NO:1290), and a second amino acid sequence being at least 90%
homologous to
AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKR
MYPHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNIL
QRKRLQTLMSVDDSVERLYNMLVETGELENTYHYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSV
EPGSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRK
KEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRN
LYARGFHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEE
EELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELY
QSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPF
KEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNNHWQTAPFWNLGSFCACTSS
NNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQLHVQLMELRSCQGYKQ
CNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino acids
138-871 of SUL1_HUMAN (SEQ ID NO:1419), which also corresponds to
amino acids 58-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0432] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise LA, having a structure as follows: a
sequence starting from any of amino acid numbers 57-x to 57; and
ending at any of amino acid numbers 58+((n-2)-x), in which x varies
from 0 to n-2.
[0433] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P15 (SEQ ID NO:1291), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFF
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMY
PHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQR
KRLQTLMSVDDSVERLYNMLVETGELENTYHYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP
GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERG
corresponding to amino acids 1-416 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-416 of
Z21368_PEA.sub.--1_P15 (SEQ ID NO:1291).
[0434] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFF
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMY
PHRPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQR
KRLQTLMSVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEP
GSIVPQIVLNIDLAPTILDIAGLDTPPDVDGKSVLKLLDPEKPGNR corresponding to
amino acids 1-397 of SUL1_HUMAN (SEQ ID NO:1419), which also
corresponds to amino acids 1-397 of Z21368_PEA.sub.--1_P16 (SEQ ID
NO:1292), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence CVIVPPLSQPQIH (SEQ ID NO: 1761)
corresponding to amino acids 398-410 of Z21368_PEA.sub.--1_P16 (SEQ
ID NO:1292), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0435] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
CVIVPPLSQPQIH (SEQ ID NO: 1761) in Z21368_PEA.sub.--1_P16 (SEQ ID
NO:1292).
[0436] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFF
GKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK corresponding to
amino acids 1-188 of SUL1_HUMAN (SEQ ID NO:1419), which also
corresponds to amino acids 1-188 of Z21368 _PEA.sub.--1_P22 (SEQ ID
NO:1293), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO:
1762) corresponding to amino acids 189-210 of Z21368
_PEA.sub.--1_P22 (SEQ ID NO:1293), wherein said first and second
amino acid sequences are contiguous and in a sequential order.
[0437] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO: 1762) in Z21368_PEA.sub.--1_P22
(SEQ ID NO:1293).
[0438] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT
corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:1697),
which also corresponds to amino acids 1-137 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GLLHRLNH
(SEQ ID NO: 1763) corresponding to amino acids 138-145 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0439] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GLLHRLNH
(SEQ ID NO: 1763) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294).
[0440] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIME
HGGATFINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT
corresponding to amino acids 1-137 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-137 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GLLHRLNH
(SEQ ID NO: 1763) corresponding to amino acids 138-145 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0441] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GLLHRLNH
(SEQ ID NO: 1763) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294).
[0442] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMGRP5E_P4 (SEQ ID NO:1299), comprising a first amino acid
sequence being at least 90% homologous to
MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTGESSSVSERGSLKQ
QLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSEDSSNFKDVGSKGK
corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:1421),
which also corresponds to amino acids 1-127 of HUMGRP5E_P4 (SEQ ID
NO:1299), and a second amino acid sequence being at least 90%
homologous to GSQREGRNPQLNQQ corresponding to amino acids 135-148
of GRP_HUMAN (SEQ ID NO:1421), which also corresponds to amino
acids 128-141 of HUMGRP5E_P4 (SEQ ID NO:1299), wherein said first
and second amino acid sequences are contiguous and in a sequential
order.
[0443] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of HUMGRP5E_P4 (SEQ ID NO:1299), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KG, having a structure as follows: a
sequence starting from any of amino acid numbers 127-x to 127; and
ending at any of amino acid numbers 128+((n-2)-x), in which x
varies from 0 to n-2.
[0444] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMGRP5E_P5 (SEQ ID NO:1300), comprising a first amino acid
sequence being at least 90% homologous to
MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTGESSSVSERGSLKQ
QLREYIRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSEDSSNFKDVGSKGK
corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:1421),
which also corresponds to amino acids 1-127 of HUMGRP5E_P5 (SEQ ID
NO:1300), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DSLLQVLNVKEGTPS (SEQ ID NO: 1764)
corresponding to amino acids 128-142 of HUMGRP5E_P5 (SEQ ID
NO:1300), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0445] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
HUMGRP5E_P5 (SEQ ID NO:1300), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence DSLLQVLNVKEGTPS (SEQ ID
NO: 1764) in HUMGRP5E_P5 (SEQ ID NO:1300).
[0446] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAHVPSWKMTLLNVCSLVNNL
NSPAEETGEVHEEELVARRKLPTALDGFSLEAMLTIYQLHKICHSRAFQHWE corresponding
to amino acids 1-120 of NEUT_HUMAN (SEQ ID NO:1422), which also
corresponds to amino acids 1-120 of D56406_PEA.sub.--1_P2 (SEQ ID
NO:1301), second amino acid sequence being at least 70%, optionally
at least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence ARWLTPVIPALWEAETGGSRGQEMETIPANT (SEQ ID NO: 1773)
corresponding to amino acids 121-151 of D56406_PEA.sub.--1_P2 (SEQ
ID NO:1301), and a third amino acid sequence being at least 90%
homologous to LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY
corresponding to amino acids 121-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 152-201 of
D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[0447] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for an edge
portion of D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), comprising an
amino acid sequence being at least 70%, optionally at least about
80%, preferably at least about 85%, more preferably at least about
90% and most preferably at least about 95% homologous to the
sequence encoding for ARWLTPVIPALWEAETGGSRGQEMETIPANT (SEQ ID NO:
1773), corresponding to D56406_PEA.sub.--1_P2 (SEQ ID NO:1301).
[0448] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLC corresponding to amino acids 1-23 of
NEUT_HUMAN (SEQ ID NO:1422), which also corresponds to amino acids
1-23 of D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), and a second amino
acid sequence being at least 90% homologous to
SEEEMKALEADFLTNMHTSKISKAHVPSWKMTLLNVCSLVNNLNSPAEETGEVHEEELVARRKLPTALDG
FSLEAMLTIYQLHKICHSRAFQHWELIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDS
YYY corresponding to amino acids 26-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 24-168 of
D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0449] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise CS, having a structure as follows: a
sequence starting from any of amino acid numbers 23-x to 24; and
ending at any of amino acid numbers+((n-2)-x), in which x varies
from 0 to n-2.
[0450] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLCSDSEEEMKALEADFLTNMHTSK corresponding to
amino acids 1-45 of NEUT_HUMAN (SEQ ID NO:1422), which also
corresponds to amino acids 1-45 of D56406_PEA.sub.--1_P6 (SEQ ID
NO:1303), and a second amino acid sequence being at least 90%
homologous to LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY
corresponding to amino acids 121-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 46-95 of
D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0451] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for an
edge portion of D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KL, having a structure as follows: a
sequence starting from any of amino acid numbers 45-x to 46; and
ending at any of amino acid numbers 46+((n-2)-x), in which x varies
from 0 to n-2.
[0452] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
F05068_PEA.sub.--1_P7 (SEQ ID NO:1304), comprising a first amino
acid sequence being at least 90% homologous to
MKLVSVALMYLGSLAFLGADTARLDVASEFRKK corresponding to amino acids 1-33
of ADML_HUMAN (SEQ ID NO:1423), which also corresponds to amino
acids 1-33 of F05068_PEA.sub.--1_P7 (SEQ ID NO:1304).
[0453] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
F05068_PEA.sub.--1_P8 (SEQ ID NO:1305), comprising a first amino
acid sequence being at least 90% homologous to
MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSSSYPTGLADVKAGPAQTLI
RPQDMKGASRSPED corresponding to amino acids 1-82 of ADML_HUMAN (SEQ
ID NO:1423), which also corresponds to amino acids 1-82 of
F05068_PEA.sub.--1_P8 (SEQ ID NO:1305), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence R
corresponding to amino acids 83-83 of F05068_PEA.sub.--1_P8 (SEQ ID
NO:1305), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0454] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H14624_P15 (SEQ ID NO:1306), comprising a first amino acid sequence
being at least 90% homologous to
MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKE
VLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDML
ECDRFPQDNDLCIPLASSDHLLPATEE corresponding to amino acids 1-167 of
Q9HAP5 (SEQ ID NO:1701), which also corresponds to amino acids
1-167 of H14624_P15 (SEQ ID NO:1306), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
GKPSLLLPHSLLG (SEQ ID NO: 1765) corresponding to amino acids
168-180 of H14624_P15 (SEQ ID NO:1306), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0455] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
H14624_P15 (SEQ ID NO:1306), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence GKPSLLLPHSLLG (SEQ ID
NO: 1765) in H14624_P15 (SEQ ID NO:1306).
[0456] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ
(SEQ ID NO: 1766) corresponding to amino acids 1-57 of
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), and a second amino acid
sequence being at least 90% homologous to
MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMRLKYQHTGAVLDCAFYDPTHA
WSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPE
KVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYL
DPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIA
SLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPK corresponding to amino
acids 1-324 of BUB3_HUMAN (SEQ ID NO:1424), which also corresponds
to amino acids 58-381 of H38804_PEA.sub.--1_P5 (SEQ ID NO:1307),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0457] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ (SEQ ID
NO: 1766) of H38804_PEA.sub.--1_P5 (SEQ ID NO:1307).
[0458] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ
(SEQ ID NO: 1766) corresponding to amino acids 1-57 of
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), and a second amino acid
sequence being at least 90% homologous to
MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMRLKYQHTGAVLDCAFYDPTHA
WSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPE
KVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYL
DPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIA
SLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPKSPCT corresponding to
amino acids 1-328 of BUB3_HUMAN (SEQ ID NO:1424), which also
corresponds to amino acids 58-385 of H38804_PEA.sub.--1_P17 (SEQ ID
NO:1308), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0459] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ (SEQ ID
NO: 1766) of H38804_PEA1_P17 (SEQ ID NO:1308).
[0460] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HSENA78_P2 (SEQ ID NO:1309), comprising a first amino acid sequence
being at least 90% homologous to
MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHPKMISNLQVFAIG
PQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID
NO:1425), which also corresponds to amino acids 1-81 of HSENA78_P2
(SEQ ID NO:1309).
[0461] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMODCA_P9 (SEQ ID NO:1310), comprising a first amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) corresponding to
amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:1310), and a second amino
acid sequence being at least 90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 151-461
of DCOR_HUMAN (SEQ ID NO:1426), which also corresponds to amino
acids 30-340 of HUMODCA_P9 (SEQ ID NO:1310), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0462] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
HUMODCA_P9 (SEQ ID NO:1310), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) of HUMODCA_P9 (SEQ
ID NO:1310).
[0463] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMODCA_P9 (SEQ ID NO:1310), comprising a first amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) corresponding to
amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:1310), and a second amino
acid sequence being at least 90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 40-350
of AAA59968, which also corresponds to amino acids 30-340 of
HUMODCA_P9 (SEQ ID NO:1310), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[0464] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
HUMODCA_P9 (SEQ ID NO:1310), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) of HUMODCA_P9 (SEQ
ID NO:1310).
[0465] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
HUMODCA_P9 (SEQ ID NO:1310), comprising a first amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) corresponding to
amino acids 1-29 of HUMODCA_P9 (SEQ ID NO:1310), and a second amino
acid sequence being at least 90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 86-396
of AAH14562 (SEQ ID NO:1703), which also corresponds to amino acids
30-340 of HUMODCA_P9 (SEQ ID NO:1310), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[0466] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
HUMODCA_P9 (SEQ ID NO:1310), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ ID NO: 1768) of HUMODCA_P9 (SEQ
ID NO:1310).
[0467] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R00299_P3 (SEQ ID NO:1311), comprising a first amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769)
corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:1311),
second amino acid sequence being at least 90% homologous to
SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLTIMS
YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNV corresponding to
amino acids 74-191 of Q9NWT9 (SEQ ID NO:1704), which also
corresponds to amino acids 45-162 of R00299_P3 (SEQ ID NO:1311),
and a third amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNME
TMALCH (SEQ ID NO: 1770) corresponding to amino acids 163-238 of
R00299_P3 (SEQ ID NO:1311), wherein said first, second and third
amino acid sequences are contiguous and in a sequential order.
[0468] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
R00299_P3 (SEQ ID NO:1311), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769) of
R00299_P3 (SEQ ID NO:1311).
[0469] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
R00299_P3 (SEQ ID NO:1311), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence
VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHV-
RFLNME TMALCH (SEQ ID NO: 1770) in R00299_P3 (SEQ ID NO:1311).
[0470] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
R00299_P3 (SEQ ID NO:1311), comprising a first amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769)
corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:1311),
and a second amino acid sequence being at least 90% homologous to
SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLT-
IMS
YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMM-
E AASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH (SEQ ID NO:
1770) corresponding to amino acids 21-214 of TESC_HUMAN (SEQ ID
NO:1427), which also corresponds to amino acids 45-238 of R00299_P3
(SEQ ID NO:1311), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[0471] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a head of
R00299_P3 (SEQ ID NO:1311), comprising a polypeptide being at least
70%, optionally at least about 80%, preferably at least about 85%,
more preferably at least about 90% and most preferably at least
about 95% homologous to the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769) of
R00299_P3 (SEQ ID NO:1311).
[0472] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
W60282_PEA.sub.--1_P14 (SEQ ID NO:1312), comprising a first amino
acid sequence being at least 90% homologous to
MRILQLILLALATGLVGGETRIIKGFECKPHSQPWQAALFEKTRLLCGATLIAPRWLLTAAHCLKP
corresponding to amino acids 1-66 of Q8IXD7 (SEQ ID NO:1705), which
also corresponds to amino acids 1-66 of W60282_PEA.sub.--1_P14 (SEQ
ID NO:1312), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence TPASHLAMRQHHHH (SEQ ID NO: 1771)
corresponding to amino acids 67-80 of W60282_PEA.sub.--1_P14 (SEQ
ID NO:1312), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0473] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
W60282_PEA.sub.--1_P14 (SEQ ID NO:1312), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
TPASHLAMRQHHHH (SEQ ID NO: 1771) in W60282_PEA.sub.--1_P14 (SEQ ID
NO:1312).
[0474] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1-95 of
SZ14_HUMAN (SEQ ID NO:1429), which also corresponds to amino acids
1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772)
corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ
ID NO:1313), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0475] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313).
[0476] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of
Q9NS21 (SEQ ID NO:1706), which also corresponds to amino acids 1-95
of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) corresponding to
amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[0477] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in Z41644_PEA1_P10
(SEQ ID NO:1313).
[0478] According to preferred embodiments of the present invention,
there is provided an isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of
AAQ89265 (SEQ ID NO:781), which also corresponds to amino acids
1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772)
corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ
ID NO:1313), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[0479] According to preferred embodiments of the present invention,
there is provided an isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313).
[0480] According to preferred embodiments of the present invention,
there is provided an antibody capable of specifically binding to an
epitope of an amino acid sequences.
[0481] Optionally the amino acid sequence corresponds to a bridge,
edge portion, tail, head or insertion.
[0482] Optionally the antibody is capable of differentiating
between a splice variant having said epitope and a corresponding
known protein.
[0483] According to preferred embodiments of the present invention,
there is provided a kit for detecting lung cancer, comprising a kit
detecting overexpression of a splice variant according to any of
the above claims.
[0484] Optionally the kit comprises a NAT-based technology.
[0485] Optionally the kit further comprises at least one primer
pair capable of selectively hybridizing to a nucleic acid sequence
according to any of the above claims.
[0486] Optionally the kit further comprises at least one
oligonucleotide capable of selectively hybridizing to a nucleic
acid sequence according to any of the above claims.
[0487] Optionally the kit comprises an antibody according to any of
the above claims.
[0488] Optionally the kit further comprises at least one reagent
for performing an ELISA or a Western blot.
[0489] According to preferred embodiments of the present invention,
there is provided a method for detecting lung cancer, comprising
detecting overexpression of a splice variant according to any of
the above claims.
[0490] Optionally the detecting overexpression is performed with a
NAT-based technology.
[0491] Optionally detecting overexpression is performed with an
immunoassay.
[0492] Optionally the immunoassay comprises an antibody according
to any of the above claims.
[0493] According to preferred embodiments of the present invention,
there is provided a biomarker capable of detecting lung cancer,
comprising any of the above nucleic acid sequences or a fragment
thereof, or any of the above amino acid sequences or a fragment
thereof.
[0494] According to preferred embodiments of the present invention,
there is provided a method for screening for lung cancer,
comprising detecting lung cancer cells with a biomarker or an
antibody or a method or assay according to any of the above
claims.
[0495] According to preferred embodiments of the present invention,
there is provided a method for diagnosing lung cancer, comprising
detecting lung cancer cells with a biomarker or an antibody or a
method or assay according to any of the above claims.
[0496] According to preferred embodiments of the present invention,
there is provided a method for monitoring disease progression
and/or treatment efficacy and/or relapse of lung cancer, comprising
detecting lung cancer cells with a biomarker or an antibody or a
method or assay according to any of the above claims.
[0497] According to preferred embodiments of the present invention,
there is provided a method of selecting a therapy for lung cancer,
comprising detecting lung cancer cells with a biomarker or an
antibody or a method or assay according to any of the above claims
and selecting a therapy according to said detection.
[0498] According to some embodiments of the present invention,
there is provided an isolated polynucleotide comprising the
polynucleotide sequence set forth in a member selected from the
group consisting of SEQ ID NOs: 1-195, 204-250, 306-323, 335-693,
695-1021, 1067-1100, 1276-1280, 1464-1465, 1480, 1512-1514, 1517,
1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625, 1626,
1636, 1639, 1642, 1645, 1648, 1651, 1654, 1657, 1660, 1663, 1666,
1669, 1672, 1675, 1678, 1681, 1684, 1687, 1690, and 1693, or a
sequence at least about 95% identical thereto.
[0499] According to some embodiments of the present invention,
there is provided an isolated polypeptide comprising the
polypeptide sequence set forth in a member selected from the group
consisting of SEQ ID NOs: 251-279, 324-325, 369, 622, 694,
1281-1294, 1299-1415, 1508-1511, 1523, 1569-1571, 1581, 1583, 1585,
1613, 1627-1629, 1702, and 1717-1776, or a sequence at least about
95% identical thereto.
[0500] According to some embodiments of the present invention,
there is provided an expression vector comprising anyone of the
foregoing polynucleotide sequences.
[0501] According to some embodiments of the present invention,
there is provided a host cell comprising the foregoing vector.
[0502] According to some embodiments of the present invention,
there is provided a process for producing a polypeptide
comprising:
[0503] culturing the foregoing host cell under conditions suitable
to produce the polypeptide encoded by said polynucleotide; and
recovering said polypeptide.
[0504] According to some embodiments of the present invention,
there is provided an isolated primer pair, comprising the pair of
nucleic acid sequences selected from the group consisting of SEQ
NOs: 1478-1479, 1515-1516, 1527-1528, 1530-1531, 1556-1557,
1572-1573, 1592-1593, 1598-1599, 1614-1615, 1617-1618, 1620-1621,
1623-1624, 1634-1635, 1637-1638, 1640-1641, 1643-1644, 1646-1547,
1649-1650, 1652-1653, 1655-1656, 1658-1659, 1661-1662, 1664-1665,
1667-1668, 1670-1671, 1673-1674, 1676-1677, 1679-1680, 1682-1683,
1685-1686, 1688-1689, 1691-1692.
[0505] According to some embodiments of the present invention,
there is provided an antibody to specifically bind to anyone of the
foregoing polypeptides.
[0506] According to some embodiments of the present invention,
there is provided a kit for detecting lung cancer, comprising at
least one of the foregoing primer pairs.
[0507] According to some embodiments of the present invention,
there is provided a kit for detecting lung cancer, comprising the
foregoing antibody.
[0508] According to further embodiments of the present invention,
there is provided the foregoing kit, wherein said immunoassay is
selected from the group consisting of an enzyme linked
immunosorbent assay (ELISA), an immunoprecipitation assay, an
immunofluorescence analysis, an enzyme immunoassay (EIA), a
radioimmunoassay (RIA), or a Western blot analysis.
[0509] According to some embodiments of the present invention,
there is provided a method for detecting lung cancer, comprising
detecting overexpression of the polynucleotide sequence set forth
in a member selected from the group consisting of SEQ ID NOs:
1-195, 204-250, 306-323, 335-693, 695-1021, 1067-1100, 1276-1280,
1464-1465, 1480, 1512-1514, 1517, 1529, 1532, 1558, 1574, 1594,
1600, 1616, 1619, 1622, 1625, 1626, 1636, 1639, 1642, 1645, 1648,
1651, 1654, 1657, 1660, 1663, 1666, 1669, 1672, 1675, 1678, 1681,
1684, 1687, 1690, and 1693, or a sequence at least about 95%
identical thereto in a sample from a patient.
[0510] According to further embodiments of the present invention,
there is provided the foregoing method for detecting lung cancer,
wherein said detecting overexpression comprises performing nucleic
acid amplification.
[0511] According to some embodiments of the present invention,
there is provided a method for detecting lung cancer, comprising
detecting overexpression of the polypeptide comprising the
polypeptide sequence set forth in a member selected from the group
consisting of SEQ ID NOs: 251-279, 324-325, 369, 622, 694,
1281-1294, 1299-1415, 1508-1511, 1523, 1569-1571, 1581, 1583, 1585,
1613, 1627-1629, 1702, and 1717-1776 in a sample from a
patient.
[0512] According to further embodiments of the present invention,
there is provided the foregoing method for detecting lung cancer,
wherein said detecting comprises detecting binding of the foregoing
antibody to the polypeptide comprising the polypeptide sequence set
forth in a member selected from the group consisting of SEQ ID NOs:
251-279, 324-325, 369, 622, 694, 1281-1294, 1299-1415, 1508-1511,
1523, 1569-1571, 1581, 1583, 1585, 1613, 1627-1629, 1702, and
1717-1776 in a sample from a patient.
[0513] According to some embodiments of the present invention,
there is provided a biomarker for detecting lung cancer, comprising
an amino acid sequence comprising the polypeptide sequence set
forth in a member selected from the group consisting of SEQ ID NOs:
251-279, 324-325, 369, 622, 694, 1281-1294, 1299-1415, 1508-1511,
1523, 1569-1571, 1581, 1583, 1585, 1613, 1627-1629, 1702, and
1717-1776, or a sequence at least about 95% identical thereto,
marked with a label.
[0514] According to some embodiments of the present invention,
there is provided a method to screen for or to diagnose lung
cancer, comprising detecting the disease with the biomarker
comprising an amino acid sequence comprising the polypeptide
sequence set forth in a member selected from the group consisting
of SEQ ID NOs: 251-279, 324-325, 369, 622, 694, 1281-1294,
1299-1415, 1508-1511, 1523, 1569-1571, 1581, 1583, 1585, 1613,
1627-1629, 1702, and 1717-1776, or a sequence at least about 95%
identical thereto.
[0515] According to some embodiments of the present invention,
there is provided a method for monitoring disease progression,
treatment efficacy or relapse of lung cancer, comprising detecting
the disease with the biomarker comprising an amino acid sequence
comprising the polypeptide sequence set forth in a member selected
from the group consisting of SEQ ID NOs: 251-279, 324-325, 369,
622, 694, 1281-1294, 1299-1415, 1508-1511, 1523, 1569-1571, 1581,
1583, 1585, 1613, 1627-1629, 1702, and 1717-1776, or a sequence at
least about 95% identical thereto.
[0516] According to some embodiments of the present invention,
there is provided a method of selecting a therapy for lung cancer,
comprising detecting the disease with the biomarker comprising an
amino acid sequence comprising the polypeptide sequence set forth
in a member selected from the group consisting of SEQ ID NOs:
251-279, 324-325, 369, 622, 694, 1281-1294, 1299-1415, 1508-1511,
1523, 1569-1571, 1581, 1583, 1585, 1613, 1627-1629, 1702, and
1717-1776, or a sequence at least about 95% identical thereto, and
selecting a therapy according to said detection.
[0517] According to some embodiments of the present invention,
there is provided a biomarker for detecting lung cancer, comprising
a nucleotide acid sequence set forth in a member selected from the
group consisting of SEQ ID NOs: 1-195, 204-250, 306-323, 335-693,
695-1021, 1067-1100, 1276-1280, 1464-1465, 1480, 1512-1514, 1517,
1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625, 1626,
1636, 1639, 1642, 1645, 1648, 1651, 1654, 1657, 1660, 1663, 1666,
1669, 1672, 1675, 1678, 1681, 1684, 1687, 1690, and 1693, or a
sequence at least about 95% identical thereto.
[0518] According to some embodiments of the present invention,
there is provided a method to screen for or to diagnose lung
cancer, comprising detecting the disease with the biomarker
comprising a nucleotide acid sequence set forth in a member
selected from the group consisting of SEQ ID NOs: 1-195, 204-250,
306-323, 335-693, 695-1021, 1067-1100, 1276-1280, 1464-1465, 1480,
1512-1514, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619,
1622, 1625, 1626, 1636, 1639, 1642, 1645, 1648, 1651, 1654, 1657,
1660, 1663, 1666, 1669, 1672, 1675, 1678, 1681, 1684, 1687, 1690,
and 1693, or a sequence at least about 95% identical thereto.
[0519] According to some embodiments of the present invention,
there is provided a method for monitoring disease progression,
treatment efficacy or relapse of lung cancer, comprising detecting
the disease with the biomarker comprising a nucleotide acid
sequence set forth in a member selected from the group consisting
of SEQ ID NOs: 1-195, 204-250, 306-323, 335-693, 695-1021,
1067-1100, 1276-1280, 1464-1465, 1480, 1512-1514, 1517, 1529, 1532,
1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625, 1626, 1636, 1639,
1642, 1645, 1648, 1651, 1654, 1657, 1660, 1663, 1666, 1669, 1672,
1675, 1678, 1681, 1684, 1687, 1690, and 1693, or a sequence at
least about 95% identical thereto.
[0520] According to some embodiments of the present invention,
there is provided a method of selecting a therapy for lung cancer,
comprising detecting the disease with the biomarker comprising a
nucleotide acid sequence set forth in a member selected from the
group consisting of SEQ ID NOs: 1-195, 204-250, 306-323, 335-693,
695-1021, 1067-1100, 1276-1280, 1464-1465, 1480, 1512-1514, 1517,
1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625, 1626,
1636, 1639, 1642, 1645, 1648, 1651, 1654, 1657, 1660, 1663, 1666,
1669, 1672, 1675, 1678, 1681, 1684, 1687, 1690, and 1693, or a
sequence at least about 95% identical thereto and selecting a
therapy according to said detection.
[0521] Unless defined otherwise, all technical and scientific terms
used herein have the meaning commonly understood by a person
skilled in the art to which this invention belongs. The following
references provide one of skill with a general definition of many
of the terms used in this invention: Singleton et al., Dictionary
of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge
Dictionary of Science and Technology (Walker ed., 1988); The
Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer
Verlag (1991); and Hale & Marham, The Harper Collins Dictionary
of Biology (1991). All of these are hereby incorporated by
reference as if fully set forth herein. As used herein, the
following terms have the meanings ascribed to them unless specified
otherwise.
BRIEF DESCRIPTION OF DRAWINGS
[0522] FIG. 1 is schematic summary of cancer biomarkers selection
engine and the wet validation stages.
[0523] FIG. 2. Schematic illustration, depicting grouping of
transcripts of a given contig based on presence or absence of
unique sequence regions.
[0524] FIG. 3 is schematic summary of quantitative real-time PCR
analysis.
[0525] FIG. 4 is schematic presentation of the oligonucleotide
based microarray fabrication.
[0526] FIG. 5 is schematic summary of the oligonucleotide based
microarray experimental flow.
[0527] FIG. 6 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster H61775, demonstrating
overexpression in brain malignant tumors and a mixture of malignant
tumors from different tissues.
[0528] FIG. 7 is a histogram showing expression of transcripts of
variants of the immunoglobulin superfamily, member 9, H61775
transcripts, which are detectable by amplicon as depicted in
sequence name H61775seg8 (SEQ ID NO: 1636), in normal and cancerous
lung tissues.
[0529] FIG. 8 is a histogram showing expression of immunoglobulin
superfamily, member 9, H61775 transcripts, which are detectable by
amplicon as depicted in sequence name H61775seg8 (SEQ ID NO: 1636),
in different normal tissues.
[0530] FIG. 9 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster M85491, demonstrating
overexpression in epithelial malignant tumors and a mixture of
malignant tumors from different tissues.
[0531] FIG. 10 is a histogram showing over expression of the
above-indicated Ephrin type-B receptor 2 precursor M85491
transcripts, which are detectable by amplicon as depicted in
sequence name M85491seg24 (SEQ ID NO: 1639), in cancerous lung
samples relative to the normal samples.
[0532] FIG. 11 is a histogram showing the expression of Ephrin
type-B receptor 2 precursor (Tyrosine-protein kinase receptor
EPH-3) M85491 transcripts which are detectable by amplicon as
depicted in sequence name M85491seg24 (SEQ ID NO: 1639) in
different normal tissues.
[0533] FIG. 12 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster T39971, demonstrating
overexpression in liver cancer, lung malignant tumors and pancreas
carcinoma.
[0534] FIG. 13 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster Z21368, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues and pancreas carcinoma.
[0535] FIG. 14 is a histogram showing over expression of the
Extracellular sulfatase Sulf-1 Z21368 transcripts, which are
detectable by amplicon as depicted in sequence name Z21368junc17-21
(SEQ ID NO: 1642), in cancerous lung samples relative to the normal
samples.
[0536] FIG. 15 is a histogram showing the expression of
Extracellular sulfatase Sulf-1 Z21368 transcripts, which are
detectable by amplicon as depicted in sequence name Z21368
junc17-21 (SEQ ID NO: 1642), in different normal tissues.
[0537] FIG. 16 is a histogram showing over expression of the
SUL1_HUMAN--Extracellular sulfatase Sulf-1, Z21368 transcripts,
which are detectable by amplicon as depicted in sequence name
Z21368seg39 (SEQ ID NO: 1645), in cancerous lung samples relative
to the normal samples.
[0538] FIG. 17 is a histogram showing expression of
SUL1_HUMAN--Extracellular sulfatase Sulf-1, Z21368 transcripts,
which are detectable by amplicon as depicted in sequence name
Z21368seg39 (SEQ ID NO: 1645), in different normal tissues.
[0539] FIG. 18 is a histogram showing the expression of SMO2_HUMAN
SPARC related modular calcium-binding protein 2 precursor (Secreted
modular calcium-binding protein 2) (SMOC-2) (Smooth
muscle-associated protein 2) Z44808 transcripts which are
detectable by amplicon as depicted in sequence name Z44808 junc8-11
(SEQ ID NO: 1651) in different normal tissues.
[0540] FIG. 19 is a histogram showing over expression of the
gastrin-releasing peptide (HUMGRP5E) transcripts, which are
detectable by amplicon as depicted in sequence name HUMGRP5Ejunc3-7
(SEQ ID NO: 1648), in several cancerous lung samples relative to
the normal samples.
[0541] FIG. 20 is a histogram showing the expression of
gastrin-releasing peptide (HUMGRP5E) transcripts, which are
detectable by amplicon as depicted in sequence name HUMGRP5Ejunc3-7
(SEQ ID NO: 1648), in different normal tissues.
[0542] FIG. 21 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster F05068, demonstrating
overexpression in uterine malignancies.
[0543] FIG. 22 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster H14624, demonstrating
overexpression in colorectal cancer, epithelial malignant tumors, a
mixture of malignant tumors from different tissues, lung malignant
tumors and pancreas carcinoma.
[0544] FIG. 23 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster H38804, demonstrating
overexpression in transitional cell carcinoma, brain malignant
tumors, a mixture of malignant tumors from different tissues and
gastric carcinoma.
[0545] FIG. 24 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HSENA78, demonstrating
overexpression in epithelial malignant tumors and lung malignant
tumors.
[0546] FIG. 25 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMODCA, demonstrating
overexpression in: brain malignant tumors, colorectal cancer,
epithelial malignant tumors and a mixture of malignant tumors from
different tissues.
[0547] FIG. 26 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster R00299, demonstrating
overexpression in lung malignant tumors.
[0548] FIG. 27 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster Z41644, demonstrating
overexpression in lung malignant tumors, breast malignant tumors
and pancreas carcinoma.
[0549] FIG. 28 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster Z44808, demonstrating
overexpression in colorectal cancer, lung cancer and pancreas
carcinoma.
[0550] FIG. 29 is a histogram showing over expression of the
SMO2_HUMAN SPARC related modular calcium-binding protein 2 Z44808
transcripts, which are detectable by amplicon as depicted in
sequence name Z44808junc8-11 (SEQ ID NO: 1651), in cancerous lung
samples relative to the normal samples.
[0551] FIG. 30 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster AA161187, demonstrating
overexpression in brain malignant tumors, epithelial malignant
tumors and a mixture of malignant tumors from different
tissues.
[0552] FIG. 31 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster AA161187, demonstrating
overexpression in brain malignant tumors and a mixture of malignant
tumors from different tissues.
[0553] FIG. 32 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMCA1XIA, demonstrating
overexpression in bone malignant tumors, epithelial malignant
tumors, a mixture of malignant tumors from different tissues and
lung malignant tumors.
[0554] FIG. 33 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMCEA, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues and pancreas carcinoma.
[0555] FIG. 34 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster R35137, demonstrating
overexpression in hepatocellular carcinoma.
[0556] FIG. 35 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster Z25299, demonstrating
overexpression in brain malignant tumors, a mixture of malignant
tumors from different tissues and ovarian carcinoma.
[0557] FIG. 36 is a histogram showing down regulation of the
Secretory leukocyte protease inhibitor Acid-stable proteinase
inhibitor Z25299 transcripts, which are detectable by amplicon as
depicted in sequence name Z25299 junc13-14-21 (SEQ ID NO: 1666), in
cancerous lung samples relative to the normal samples.
[0558] FIG. 37 is a histogram showing down regulation of the
Secretory leukocyte protease inhibitor Acid-stable proteinase
inhibitor Z25299 transcripts, which are detectable by amplicon as
depicted in sequence name Z25299 seg20 (SEQ ID NO: 1669), in
cancerous lung samples relative to the normal samples.
[0559] FIG. 38 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HSSTROL3, demonstrating
overexpression in transitional cell carcinoma, epithelial malignant
tumors, a mixture of malignant tumors from different tissues and
pancreas carcinoma.
[0560] FIG. 39 is a histogram showing over expression of the
Stromelysin-3 HSSTROL3 transcripts, which are detectable by
amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:
1675), in cancerous lung samples relative to the normal
samples.
[0561] FIG. 40 is a histogram showing the expression of
Stromelysin-3 HSSTROL3 transcripts, which are detectable by
amplicon as depicted in sequence name HSSTROL3 seg24 (SEQ ID NO:
1675), in different normal tissues.
[0562] FIG. 41 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMTREFAC, demonstrating
overexpression in a mixture of malignant tumors from different
tissues, breast malignant tumors, pancreas carcinoma and prostate
cancer.
[0563] FIG. 42 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HSS100PCB, demonstrating
overexpression in a mixture of malignant tumors from different
tissues.
[0564] FIG. 43 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HSU33147, demonstrating
overexpression in a mixture of malignant tumors from different
tissues.
[0565] FIG. 44 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster R20779, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues and lung malignant
tumors.
[0566] FIG. 45 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster R38144, demonstrating
overexpression in epithelial malignant tumors, lung malignant
tumors, skin malignancies and gastric carcinoma.
[0567] FIG. 46 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMOSTRO, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues, lung malignant tumors,
breast malignant tumors, ovarian carcinoma and skin
malignancies.
[0568] FIG. 47 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster HUMOSTRO, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues and kidney malignant
tumors.
[0569] FIG. 48 is a histogram showing over expression of the R11723
transcripts, which are detectable by amplicon as depicted in
sequence name R11723 seg13 (SEQ ID NO: 1684), in cancerous lung
samples relative to the normal samples.
[0570] FIG. 49 is a histogram showing the expression of R11723
transcripts which are detectable by amplicon as depicted in
sequence name R11723seg13 (SEQ ID NO: 1684) in different normal
tissues.
[0571] FIG. 50 is a histogram showing over expression of the R11723
transcripts, which are detectable by amplicon as depicted in
sequence name R11723 junc11-18 (SEQ ID NO: 1687) in cancerous lung
samples relative to the normal samples.
[0572] FIG. 51 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster R16276, demonstrating
overexpression in: lung malignant tumors.
[0573] FIGS. 52-53 are histograms, showing differential expression
of the 6 sequences H61775seg8 (SEQ ID NO: 1636), HUMGRP5E junc3-7
(SEQ ID NO: 1648), M85491Seg24 (SEQ ID NO: 1639), Z21368 junc17-21
(SEQ ID NO: 1642), HSSTROL3seg24 (SEQ ID NO: 1675) and Z25299seg20
(SEQ ID NO: 1669) in in cancerous lung samples relative to the
normal samples.
[0574] FIG. 54a is a histogram showing the relative expression of
trophinin associated protein (tastin)) [T86235] variants (e.g.,
variant no. 23-26, 31, 32) in normal and tumor derived lung samples
as determined by real time PCR using primers for SEQ ID NO:
1480.
[0575] FIG. 54b is a histogram showing the relative expression of
trophinin associated protein (tastin)) [T86235] variants (e.g.,
variant no. 8-10, 22, 23, 26,27, 29-31, 33) in normal and tumor
derived lung samples as determined micro-array analysis using
oligos detailed in SEQ ID NO: 1512-1514.
[0576] FIG. 55 is a histogram showing the relative expression of
Homeo box C10 (HOXC10) [N31842] variants (e.g., variant no. 3) in
normal and tumor derived lung samples as determined by real time
PCR using primers for SEQ ID NO: 1517.
[0577] FIGS. 56a-b are histograms showing on two different scales
the relative expression of Nucleolar protein 4 (NOL4) [T06014]
variants (e.g., variant no. 3, 11 and 12) in normal and tumor
derived lung samples as determined by real time PCR using primers
for SEQ ID NO: 1529. FIG. 56a shows the results on scale:0-1200.
FIG. 56b shows the results on scale:0-24.
[0578] FIGS. 57a-b is a histogram showing on two different scales
the relative expression of Nucleolar protein 4 (NOL4) [T06014]
variants (e.g., variant no. 3, 11 and 12) in normal and tumor
derived lung samples as determined by real time PCR using primers
for SEQ ID NO: 1532.
[0579] FIG. 57a shows the results on scale:0-2000. FIG. 57b shows
the results on scale:0-42.
[0580] FIG. 58 is a histogram showing the relative expression of
AA281370 variants (e.g., variant no. 0, 1, 4 and 5) in normal and
tumor derived lung samples as determined by real time PCR using
primers for SEQ ID NO: 1558.
[0581] FIG. 59 is a histogram showing the relative expression of
Sulfatase 1 (SULF1)-[Z21368] variants (e.g., variant no. 13 and 14)
in normal and tumor derived lung samples as determined by real time
PCR using primers for SEQ ID NO: 1574.
[0582] FIG. 60 is a histogram showing the relative expression of
SRY (sex determining region Y)-box 2 (SOX2))-[HUMHMGBOX] variants
(e.g., variant no. 0) in normal and tumor derived lung samples as
determined by real time PCR using primers for SEQ ID NO: 1594.
[0583] FIG. 61 is a histogram showing the relative expression of
Plakophilin 1 (ectodermal dysplasia/skin fragility syndrome)
(PKP1)-[HSB6PR] variants (e.g., variant no. 0, 5 and 6) in normal
and tumor derived lung samples as determined by real time PCR using
primers for SEQ ID NO: 1600.
[0584] FIG. 62 is a histogram showing the relative expression of
transcripts detectable by SEQ ID NOs: 1480, 1517, 1529, 1532, 1558,
1574, 1594, 1600, 1616, 1619, 1622, 1625 in normal and tumor
derived lung samples as determined by real time PCR.
[0585] FIG. 63 is an amino acid sequence alignment, using NCBI
BLAST default parameters, demonstrating similarity between the
AA281370 lung cancer biomarker if the present invention to WD40
domains of various proteins involved in MAPK signal trunsduction
pathway. FIG. 63a: amino acids at positions 40-790 of AA281370
polypeptide SEQ ID NO: 99 has 75% homology to mouse Mapkbp1 protein
(gi|47124622). FIG. 63b: amino acids at positions 40-886 of the
AA281370 polypeptide SEQ ID NO: 99 has 70% homology to rat
JNK-binding protein JNKBP1 (gi|34856717).
[0586] FIG. 64 is a histogram showing over expression of the Homo
sapiens protease, serine, 21 (testisin) (PRSS21) AA161187
transcripts, which are detectable by amplicon as depicted in
sequence name AA161187 seg25 (SEQ ID NO:1654), in cancerous lung
samples relative to the normal samples.
[0587] FIG. 65 is a histogram showing over expression of the
protein tyrosine phosphatase, receptor type, S (PTPRS) M62069
transcripts, which are detectable by amplicon as depicted in
sequence name M62069 seg19 (SEQ ID NO: 1657), in cancerous lung
samples relative to the normal samples.
[0588] FIG. 66 is a histogram showing over expression of the
protein tyrosine phosphatase, receptor type, S (PTPRS) M62069
transcripts, which are detectable by amplicon as depicted in
sequence name M62069 seg29 (SEQ ID NO: 1660), in cancerous lung
samples relative to the normal samples.
[0589] FIG. 67 is a histogram showing over expression of the
above-indicated Homo sapiens collagen, type XI, alpha 1 (COL11A1)
transcripts which are detectable by amplicon as depicted in
sequence name HUMCA1X1A seg55 (SEQ ID NO:1663) in cancerous lung
samples relative to the normal samples.
[0590] FIG. 68 is a histogram showing down regulation of the Homo
sapiens secretory leukocyte protease inhibitor
(antileukoproteinase) (SLPI) Z25299 transcripts which are
detectable by amplicon as depicted in sequence name Z25299 seg23
(SEQ ID NO: 1672) in cancerous lung samples relative to the normal
samples.
[0591] FIG. 69 is a histogram showing the expression of Secretory
leukocyte protease inhibitor Acid-stable proteinase inhibitor
Z25299 transcripts which are detectable by amplicon as depicted in
sequence name Z25299seg20 (SEQ ID NO: 1669) in different normal
tissues.
[0592] FIG. 70 is a histogram showing the expression of Secretory
leukocyte protease inhibitor Acid-stable proteinase inhibitor
Z25299 transcripts which are detectable by amplicon as depicted in
sequence name Z25299seg23 (SEQ ID NO: 1672) in different normal
tissues.
[0593] FIG. 71 is a histogram showing over expression of the Homo
sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11)
HSSTROL3 transcripts which are detectable by amplicon as depicted
in sequence name HSSTROL3 seg20-2 (SEQ ID NO: 1678) in cancerous
lung samples relative to the normal samples.
[0594] FIG. 72 is a histogram showing over expression of the Homo
sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11)
HSSTROL3 transcripts which are detectable by amplicon as depicted
in sequence name HSSTROL3 junc21-27 (SEQ ID NO: 1681) in cancerous
lung samples relative to the normal samples.
[0595] FIG. 73 is a histogram showing the expression of R11723
transcripts, which were detected by amplicon as depicted in the
sequence name R11723 junc11-18 (SEQ ID NO: 1687) in different
normal tissues.
[0596] FIG. 74 is a histogram showing over expression of the Homo
sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626
transcripts, which are detectable by amplicon as depicted in
sequence name H53626 junc24-27F1R3 (SEQ ID NO: 1690) in cancerous
lung samples relative to the normal samples.
[0597] FIG. 75 is a histogram showing the expression of the Homo
sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626
transcripts, which are detectable by amplicon as depicted in
sequence name H53626 seg25 (SEQ ID NO: 1693) in cancerous lung
samples relative to the normal samples.
[0598] FIG. 76 is a histogram showing Cancer and cell-line vs.
normal tissue expression for Cluster H53626, demonstrating
overexpression in epithelial malignant tumors, a mixture of
malignant tumors from different tissues and myosarcoma.
[0599] FIG. 77 is a histogram showing the expression of of Homo
sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626
transcripts, which are detectable by amplicon as depicted in
sequence name H53626 seg25 (SEQ ID NO: 1693) in different normal
tissues.
[0600] FIG. 78 is a histogram showing the expression of of Homo
sapiens fibroblast growth factor receptor-like 1 (FGFRL1) H53626
transcripts, which are detectable by amplicon as depicted in
sequence name H53626 junc24-27F1R3 (SEQ ID NO: 1690) in different
normal tissues.
[0601] FIG. 79 shows PSEC R11723_PEA.sub.--1 T5 (SEQ ID NO:148) PCR
product; Lane 1: PCR product; and Lane 2: Low DNA Mass Ladder MW
marker (Invitrogen Cat#10068-013).
[0602] FIG. 80: PSEC R11723_PEA.sub.--1 T5 PCR product sequence; In
Red-PSEC Forward primer; In Blue-PSEC Reverse complementary
sequence; and Highlighted sequence-PSEC variant R11723_PEA.sub.--1
T5 (SEQ ID NO:148) ORF.
[0603] FIG. 81--PRSEC PCR product digested with NheI and HindIII;
Lane 1--PRSET PCR product; Lane 2--Fermentas GeneRuler 1 Kb DNA
Ladder #SM0313.
[0604] FIG. 82 shows a plasmid map of His PSEC T5 pRSETA.
[0605] FIG. 83: Protein sequence of PSEC variant R11723_PEA.sub.--1
T5 (SEQ ID NO:148); In red-6His tag; In blue-PSEC.
[0606] FIG. 84 shows the DNA sequence of His PSEC T5 pRSETA;
bold-HisPSEC T5 open reading frame; Italic-flanking DNA sequence
which was verified by sequence analysis.
[0607] FIG. 85 shows Western blot analysis of recombinant HisPSEC
variant R11723_PEA.sub.--1 T5; lane 1: molecular weight marker
(ProSieve color, Cambrex, Cat #50550); lane 2: HisPSEC T5 pRSETA
T0; lane 3: His HisPSEC T5 pRSETA T3; lane 4: His HisPSEC T5 pRSETA
To.n; lane 5: pRSET empty vector T0 (negative control); lane 6:
pRSET empty vector T3 (negative control); lane 7: pRSET empty
vector To.n (negative control); and lane 8: His positive control
protein (HisTroponinT7 pRSETA T3).
[0608] FIG. 86 shows the DNA sequences of WT MMP11
(MMP11.sub.--488, (SEQ ID NO: 1782)) and HSSTROL3_P9
(MMP11.sub.--354, (SEQ ID NO: 1783)) used for mammalian expression.
NcoI and Not I sites used to subclone MMP11 fragments into
bacterial vectors, without the signal peptide are underlined.
Translation initiation site and stop codons are shown in bold.
[0609] FIG. 87 shows Protein sequences used for mammalian
expression of WT MMP11 (MMP11.sub.--488 (SEQ ID NO: 1784)) and
HSSTROL3_P9 (MMP11.sub.--354 (SEQ ID NO: 1785)). His-tag of 8 His
residues is shown in bold.
[0610] FIG. 88 shows WT MMP11 (MMP11.sub.--488) and HSSTROL3_P9
(MMP11.sub.--354) in pIRESpuro3 plasmid maps. NcoI and NotI sites
that were used to subclone MMP11 variants into bacterial expression
vectors are marked by arrows.
[0611] FIG. 89 shows WT MMP11 (MMP11.sub.--488) and HSSTROL3_P9
(MMP11.sub.--354) in pET28 plasmid maps. NcoI and NotI sites that
were used to subclone MMP11 (WT and variant) into bacterial
expression vectors are marked with arrows.
[0612] FIG. 90 shows protein sequences used for bacterial
expression of WT MMP11 (MMP11.sub.--488) and HSSTROL3_P9
(MMP11.sub.--354). His-tag of 8 His residues is shown in bold.
[0613] FIG. 91 shows a Coomassie staining of whole cell lysates
MMP11.sub.--488 and MMP11.sub.--354 in pET28. Lanes 1 to 4 and Lane
11 are unrelated to this experiment; Lane 5 is MMP11.sub.--488
pET28, before induction; Lane 6 is MMP11.sub.--488 pET28, 3 hrs
after induction; Lane 7 is MMP11.sub.--354 pET28, before induction;
Lane 8 is MMP11.sub.--354 pET28, 3 hrs after induction; Lane 9 is
Empty pET 28, before induction; Lane 10 is Empty pET 28, 3 hrs
after induction; Lane 12 is Rainbow Full Range Molecular Weight
Markers GE Healthcare, RPN800
[0614] FIG. 92 shows a western blot analysis of whole cell lysates
of MMP11.sub.--448 and MMP11.sub.--354 in pET28 with anti-His
antibody (Serotec Cat. #MCA1396). Lane 5 is MMP11.sub.--488 pET28,
before induction; Lane 6 is MMP11.sub.--488 pET28, 3 hrs after
induction; Lane 7 is MMP11.sub.--354 pET28, before induction; Lane
8 is MMP11.sub.--354 pET28, 3 hrs after induction; Lane 9 is Empty
pET 28, before induction; Lane 10 is Empty pET 28, 3 hrs after
induction; Lane 11 is Mark Western Protein Standard: Invitrogen
LC5600.
[0615] FIG. 93 shows an overlay of the immunogen Peptide CGEN6301
(SEQ ID NO: 1781) on the primary sequence of the HSSTROL3_P9
protein (SEQ ID NO: 1398). The Peptide CGEN6301 (SEQ ID NO: 1781)
sequence is shown in bold.
[0616] FIG. 94 shows CGEN6301 Affinity Purified Antibodies--ELISA
results of Lot18976C (Rabbit 8350), and Lot18977C (Rabbit
8351).
[0617] FIG. 95 shows Western Blot Data of Affinity Purified
Antibody; Lot 18976C, Rabbit 8350. HSSTROL3_P9 splice variant
protein (SVr) and WT MMP11 protein (WT) were probed (in duplicates)
with pre-purified serum of RB 8350 (upper left), flow through from
affinity purification, (upper right) and affinity purified antibody
(lower) Lot 18976C.
[0618] FIG. 96 shows Western Blot Data of Affinity Purified
Antibody; Lot 18977C Rabbit 8351. HSSTROL3_P9 splice variant
protein (SVr) and WT MMP11 protein (WT) were probed with
pre-purified serum, RB 8351 (upper left), flow through from
affinity purification (upper right) and affinity purified antibody
Lot 18977C (lower).
[0619] FIG. 97 shows CGEN6301 Monoclonal Purified Antibodies--ELISA
results of Clone 13E1.G1.F3. (lot18944C) and Clone 7G11.F6.E1.
(lot19032C).
[0620] FIG. 98 shows the alignment of HUMGRP5E_P5 ((SEQ ID NO:
1300), indicated in the Figure as CgenGRP)) and Wild Type GRP
isoforms WT GPR 1 (SEQ ID NOs:1421), WT GPR 2 (SEQ ID NOs: 1788),
WT GPR 3 (SEQ ID NOs:1789) protein sequences.
[0621] FIG. 99a shows the GRP 148 DNA optimized ORF sequence (SEQ
ID NO: 1790). EcoRI and NotI restriction sites are underlined. Open
reading frame is shown in bold.
[0622] FIG. 99b shows the GRP 142 DNA optimized ORF sequence (SEQ
ID NO: 1791). EcoRI and NotI restriction sites are underlined. Open
reading frame is shown in bold.
[0623] FIG. 100a shows the protein sequence of recombinant GRP-148
(SEQ ID NO: 1792). IL6 signal peptide is shown in bold. The 8xHis
tag is unerlined.
[0624] FIG. 100b shows the protein sequence of recombinant GRP-142
(SEQ ID NO: 1793). IL6 signal peptide is shown in bold. The 8xHis
tag is underlined.
[0625] FIG. 101a shows the schematic presentation of GRP-148 in
pIRESpuro.
[0626] FIG. 101b shows the schematic presentation of GRP-142 in
pIRESpuro.
[0627] FIG. 102 shows the results of western blot analysis of
mammalian expression of GRP proteins using anti His antibodies.
Lane 1 shows the MW markers; Lanes 2-6 represent irrelevant
proteins; Lane 7 represents GRP 148 (SEQ ID NO: 1792); Lane 8
represents GRP 142 (SEQ ID NO: 1793).
[0628] FIG. 103 shows the results of SDS-PAGE, Coomassie staining,
demonstrating the analysis of purified GRP-148, shown in lane 8.
Lane 1 represents a MW marker; Lanes 2-5 represents BSA 2 mg/ml, 1
mg/ml, 0.5 mg/ml, 0.25 mg/ml, respectively; Lane 6 represents BSA 1
mg/ml no DTT; Lanes 7 and 9 are empty; Lane10 shows irrelevant
protein.
[0629] FIG. 104 shows SDS-PAGE, Coomassie stained gel analysis of
GRP-142 (SEQ ID NO:1793), shown in lane 6. Lanes 1-4 represents BSA
1 mg/ml, 0.5 mg/ml, 0.25 mg/ml, 0.1 mg/ml, respectively; Lane 5
corresponds to MW Marker (Cambrex prosieve).
[0630] FIG. 105 shows an overlay of HUMGRP5E_P5 immunogen (SEQ ID
NO:1795) on HUMGRP5E_P5 ((SEQ ID NO: 1300) protein sequence. The
immunogen sequence is shown in bold.
[0631] FIG. 106 shows ELISA results of CGEN0601 Affinity Purified
Antibodies, Lot18878C, Rabbit 8349.
[0632] FIG. 107 shows ELISA results of CGEN0601 Affinity Purified
Antibodies, Lot 18980C, Rabbit 8348.
[0633] FIG. 108 shows Western Blot Data of Affinity Purified
Antibody, Lot 18878C (Rabbit 8349). HUMGRP5E_P5 (SEQ ID NO: 1300)
splice variant (SVr) and WT GRP precursor (SEQ ID NO:1421) (WT)
were probed with pre-purified serum of the Rb 8349 (lanes 1 and 2),
affinity purified antibody lot 18878C, Rb 8349 (lanes 5 and 6) and
flow through from affinity purification, Rb 8349 (lanes 3 and
4).
[0634] FIG. 109 shows Western Blot Data of Affinity Purified
Antibody, Lot 18980C (Rabbit 8348).
[0635] FIG. 110 shows ELISA Data of Rabbit 8349 Cross-adsorbed
product (Lot 18978C).
[0636] FIG. 111 shows concentration of HUMGRP5E_P5 (SEQ ID NO:
1300) in control and SCLC patients' sera.
[0637] FIG. 112 is a histogram showing the expression of NTS D56406
transcripts which are detectable by amplicon as depicted in
sequence name D56406_seg7-9F2R2 in normal and cancerous Lung
tissues.
[0638] FIG. 113 is a histogram showing the expression of NTS D56406
transcripts which are detectable by amplicon as depicted in
sequence name D56406_seg7-9F2R2 in different normal tissues.
[0639] FIG. 114 is a histogram showing the expression of SULF1
Z21368 transcripts which are detectable by amplicon as depicted in
sequence name Z21368_junc59-64F1R1 (SEQ ID NO: 1801) in normal and
cancerous Lung tissues. FIG. 115 is a histogram showing the
expression of SULF1 Z21368 transcripts which are detectable by
amplicon as depicted in sequence name Z21368_junc59-64F1R1 (SEQ ID
NO: 1801) in different normal tissues.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0640] The present invention is of novel markers for lung cancer
that are both sensitive and accurate. Furthermore, at least certain
of these markers are able to distinguish between various types of
lung cancer, such as small cell carcinoma; large cell carcinoma;
squamous cell carcinoma; and adenocarcinoma, alone or in
combination. These markers are differentially expressed, and
preferably overexpressed, in lung cancer specifically, as opposed
to normal lung tissue. The measurement of these markers, alone or
in combination, in patient samples provides information that the
diagnostician can correlate with a probable diagnosis of lung
cancer. The markers of the present invention, alone or in
combination, show a high degree of differential detection between
lung cancer and non-cancerous states. The markers of the present
invention, alone or in combination, can be used for prognosis,
prediction, screening, early diagnosis, therapy selection and
treatment monitoring of lung cancer. For example, optionally and
preferably, these markers may be used for staging lung cancer
and/or monitoring the progression of the disease. Furthermore, the
markers of the present invention, alone or in combination, can be
used for detection of the source of metastasis found in anatomical
places other than lung. Also, one or more of the markers may
optionally be used in combination with one or more other lung
cancer markers (other than those described herein). According to an
optional embodiment of the present invention, such a combination
may be used to differentiate between various types of lung cancer,
such as small cell carcinoma; large cell carcinoma; squamous cell
carcinoma; and adenocarcinoma. Furthermore, the markers of the
present invention, alone or in combination, can be used for
detection of other types of tumors by elimination (for example, for
such detection of carcinoid tumors, which are 5% of lung
cancers).
[0641] The markers of the present invention, alone or in
combination, can be used for prognosis, prediction, screening,
early diagnosis, staging, therapy selection and treatment
monitoring of lung cancer. For example, optionally and preferably,
these markers may be used for staging lung cancer and/or monitoring
the progression of the disease. Furthermore, the markers of the
present invention, alone or in combination, can be used for
detection of the source of metastasis found in anatomical places
other then lung. Also, one or more of the markers may optionally be
used in combination with one or more other lung cancer markers
(other than those described herein).
[0642] Biomolecular sequences (amino acid and/or nucleic acid
sequences) uncovered using the methodology of the present invention
and described herein can be efficiently utilized as tissue or
pathological markers and/or as drugs or drug targets for treating
or preventing a disease.
[0643] These markers are specifically released to the bloodstream
under conditions of lung cancer, and/or are otherwise expressed at
a much higher level and/or specifically expressed in lung cancer
tissue or cells. The measurement of these markers, alone or in
combination, in patient samples provides information that the
diagnostician can correlate with a probable diagnosis of lung
cancer.
[0644] The present invention therefore also relates to diagnostic
assays for lung cancer and/or an indicative condition, and methods
of use of such markers for detection of lung cancer and/or an
indicative condition, optionally and preferably in a sample taken
from a subject (patient), which is more preferably some type of
blood sample.
[0645] In another embodiment, the present invention relates to
bridges, tails, heads and/or insertions, and/or analogs, homologs
and derivatives of such peptides. Such bridges, tails, heads and/or
insertions are described in greater detail below with regard to the
Examples.
[0646] As used herein a "tail" refers to a peptide sequence at the
end of an amino acid sequence that is unique to a splice variant
according to the present invention. Therefore, a splice variant
having such a tail may optionally be considered as a chimera, in
that at least a first portion of the splice variant is typically
highly homologous (often 100% identical) to a portion of the
corresponding known protein, while at least a second portion of the
variant comprises the tail.
[0647] As used herein a "head" refers to a peptide sequence at the
beginning of an amino acid sequence that is unique to a splice
variant according to the present invention. Therefore, a splice
variant having such a head may optionally be considered as a
chimera, in that at least a first portion of the splice variant
comprises the head, while at least a second portion is typically
highly homologous (often 100% identical) to a portion of the
corresponding known protein.
[0648] As used herein "an edge portion" refers to a connection
between two portions of a splice variant according to the present
invention that were not joined in the wild type or known protein.
An edge may optionally arise due to a join between the above "known
protein" portion of a variant and the tail, for example, and/or may
occur if an internal portion of the wild type sequence is no longer
present, such that two portions of the sequence are now contiguous
in the splice variant that were not contiguous in the known
protein. A "bridge" may optionally be an edge portion as described
above, but may also include a join between a head and a "known
protein" portion of a variant, or a join between a tail and a
"known protein" portion of a variant, or a join between an
insertion and a "known protein" portion of a variant.
[0649] Optionally and preferably, a bridge between a tail or a head
or a unique insertion, and a "known protein" portion of a variant,
comprises at least about 10 amino acids, more preferably at least
about 20 amino acids, most preferably at least about 30 amino
acids, and even more preferably at least about 40 amino acids, in
which at least one amino acid is from the tail/head/insertion and
at least one amino acid is from the "known protein" portion of a
variant. Also optionally, the bridge may comprise any number of
amino acids from about 10 to about 40 amino acids (for example, 10,
11, 12, 13 . . . 37, 38, 39, 40 amino acids in length, or any
number in between).
[0650] It should be noted that a bridge cannot be extended beyond
the length of the sequence in either direction, and it should be
assumed that every bridge description is to be read in such manner
that the bridge length does not extend beyond the sequence
itself.
[0651] Furthermore, bridges are described with regard to a sliding
window in certain contexts below. For example, certain descriptions
of the bridges feature the following format: a bridge between two
edges (in which a portion of the known protein is not present in
the variant) may optionally be described as follows: a bridge
portion of CONTIG-NAME_P1 (representing the name of the protein),
comprising a polypeptide having a length "n", wherein n is at least
about 10 amino acids in length, optionally at least about 20 amino
acids in length, preferably at least about 30 amino acids in
length, more preferably at least about 40 amino acids in length and
most preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise XX (2 amino acids in the center of
the bridge, one from each end of the edge), having a structure as
follows (numbering according to the sequence of CONTIG-NAME_P1): a
sequence starting from any of amino acid numbers 49-x to 49 (for
example); and ending at any of amino acid numbers 50+((n-2)-x) (for
example), in which x varies from 0 to n-2. In this example, it
should also be read as including bridges in which n is any number
of amino acids between 10-50 amino acids in length. Furthermore,
the bridge polypeptide cannot extend beyond the sequence, so it
should be read such that 49-x (for example) is not less than 1, nor
50+((n-2)-x) (for example) greater than the total sequence
length.
[0652] In another embodiment, this invention provides antibodies
specifically recognizing the splice variants and polypeptide
fragments thereof of this invention. Preferably such antibodies
differentially recognize splice variants of the present invention
but do not recognize a corresponding known protein (such known
proteins are discussed with regard to their splice variants in the
Examples below).
[0653] In another embodiment, this invention provides an isolated
nucleic acid molecule encoding for a splice variant according to
the present invention, having a nucleotide sequence as set forth in
any one of the sequences listed herein, or a sequence complementary
thereto. In, another embodiment, this invention provides an
isolated nucleic acid molecule, having a nucleotide sequence as set
forth in any one of the sequences listed herein, or a sequence
complementary thereto. In another embodiment, this invention
provides an oligonucleotide of at least about 12 nucleotides,
specifically hybridizable with the nucleic acid molecules of this
invention. In another embodiment, this invention provides vectors,
cells, liposomes and compositions comprising the isolated nucleic
acids of this invention.
[0654] In another embodiment, this invention provides a method for
detecting a splice variant according to the present invention in a
biological sample, comprising: contacting a biological sample with
an antibody specifically recognizing a splice variant according to
the present invention under conditions whereby the antibody
specifically interacts with the splice variant in the biological
sample but do not recognize known corresponding proteins (wherein
the known protein is discussed with regard to its splice variant(s)
in the Examples below), and detecting said interaction; wherein the
presence of an interaction correlates with the presence of a splice
variant in the biological sample.
[0655] In another embodiment, this invention provides a method for
detecting a splice variant nucleic acid sequences in a biological
sample, comprising: hybridizing the isolated nucleic acid molecules
or oligonucleotide fragments of at least about a minimum length to
a nucleic acid material of a biological sample and detecting a
hybridization complex; wherein the presence of a hybridization
complex correlates with the presence of a splice variant nucleic
acid sequence in the biological sample.
[0656] According to the present invention, the splice variants
described herein are non-limiting examples of markers for
diagnosing lung cancer. Each splice variant marker of the present
invention can be used alone or in combination, for various uses,
including but not limited to, prognosis, prediction, screening,
early diagnosis, determination of progression, therapy selection
and treatment monitoring of lung cancer.
[0657] According to optional but preferred embodiments of the
present invention, any marker according to the present invention
may optionally be used alone or combination. Such a combination may
optionally comprise a plurality of markers described herein,
optionally including any subcombination of markers, and/or a
combination featuring at least one other marker, for example a
known marker. Furthermore, such a combination may optionally and
preferably be used as described above with regard to determining a
ratio between a quantitative or semi-quantitative measurement of
any marker described herein to any other marker described herein,
and/or any other known marker, and/or any other marker. With regard
to such a ratio between any marker described herein (or a
combination thereof) and a known marker, more preferably the known
marker comprises the "known protein" as described in greater detail
below with regard to each cluster or gene.
[0658] According to other preferred embodiments of the present
invention, a splice variant protein or a fragment thereof, or a
splice variant nucleic acid sequence or a fragment thereof, may be
featured as a biomarker for detecting lung cancer, such that a
biomarker may optionally comprise any of the above.
[0659] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to a splice variant protein as described herein. Any
oligopeptide or peptide relating to such an amino acid sequence or
fragment thereof may optionally also (additionally or
alternatively) be used as a biomarker, including but not limited to
the unique amino acid sequences of these proteins that are depicted
as tails, heads, insertions, edges or bridges. The present
invention also optionally encompasses antibodies capable of
recognizing, and/or being elicited by, such oligopeptides or
peptides.
[0660] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to a splice
variant of the present invention as described above, optionally for
any application.
[0661] Non-limiting examples of methods or assays are described
below.
[0662] The present invention also relates to kits based upon such
diagnostic methods or assays.
Nucleic Acid Sequences and Oligonucleotides
[0663] Various embodiments of the present invention encompass
nucleic acid sequences described hereinabove; fragments thereof,
sequences hybridizable therewith, sequences homologous thereto,
sequences encoding similar polypeptides with different codon usage,
altered sequences characterized by mutations, such as deletion,
insertion or substitution of one or more nucleotides, either
naturally occurring or artificially induced, either randomly or in
a targeted fashion.
[0664] The present invention encompasses nucleic acid sequences
described herein; fragments thereof, sequences hybridizable
therewith, sequences homologous thereto [e.g., at least 50%, at
least 55%, at least 60%, at least 65%, at least 70%, at least 75%,
at least 80%, at least 85%, at least 95% or more say 100% identical
to the nucleic acid sequences set forth below], sequences encoding
similar polypeptides with different codon usage, altered sequences
characterized by mutations, such as deletion, insertion or
substitution of one or more nucleotides, either naturally occurring
or man induced, either randomly or in a targeted fashion. The
present invention also encompasses homologous nucleic acid
sequences (i.e., which form a part of a polynucleotide sequence of
the present invention) which include sequence regions unique to the
polynucleotides of the present invention.
[0665] In cases where the polynucleotide sequences of the present
invention encode previously unidentified polypeptides, the present
invention also encompasses novel polypeptides or portions thereof,
which are encoded by the isolated polynucleotide and respective
nucleic acid fragments thereof described hereinabove.
[0666] A "nucleic acid fragment" or an "oligonucleotide" or a
"polynucleotide" are used herein interchangeably to refer to a
polymer of nucleic acids. A polynucleotide sequence of the present
invention refers to a single or double stranded nucleic acid
sequences which is isolated and provided in the form of an RNA
sequence, a complementary polynucleotide sequence (cDNA), a genomic
polynucleotide sequence and/or a composite polynucleotide sequences
(e.g., a combination of the above).
[0667] As used herein the phrase "complementary polynucleotide
sequence" refers to a sequence, which results from reverse
transcription of messenger RNA using a reverse transcriptase or any
other RNA dependent DNA polymerase. Such a sequence can be
subsequently amplified in vivo or in vitro using a DNA dependent
DNA polymerase.
[0668] As used herein the phrase "genomic polynucleotide sequence"
refers to a sequence derived (isolated) from a chromosome and thus
it represents a contiguous portion of a chromosome.
[0669] As used herein the phrase "composite polynucleotide
sequence" refers to a sequence, which is composed of genomic and
cDNA sequences. A composite sequence can include some exonal
sequences required to encode the polypeptide of the present
invention, as well as some intronic sequences interposing
therebetween. The intronic sequences can be of any source,
including of other genes, and typically will include conserved
splicing signal sequences. Such intronic sequences may further
include cis acting expression regulatory elements.
[0670] Preferred embodiments of the present invention encompass
oligonucleotide probes.
[0671] An example of an oligonucleotide probe which can be utilized
by the present invention is a single stranded polynucleotide which
includes a sequence complementary to the unique sequence region of
any variant according to the present invention, including but not
limited to a nucleotide sequence coding for an amino sequence of a
bridge, tail, head and/or insertion according to the present
invention, and/or the equivalent portions of any nucleotide
sequence given herein (including but not limited to a nucleotide
sequence of a node, segment or amplicon described herein).
[0672] Alternatively, an oligonucleotide probe of the present
invention can be designed to hybridize with a nucleic acid sequence
encompassed by any of the above nucleic acid sequences,
particularly the portions specified above, including but not
limited to a nucleotide sequence coding for an amino sequence of a
bridge, tail, head and/or insertion according to the present
invention, and/or the equivalent portions of any nucleotide
sequence given herein (including but not limited to a nucleotide
sequence of a node, segment or amplicon described herein).
[0673] Oligonucleotides designed according to the teachings of the
present invention can be generated according to any oligonucleotide
synthesis method known in the art such as enzymatic synthesis or
solid phase synthesis. Equipment and reagents for executing
solid-phase synthesis are commercially available from, for example,
Applied Biosystems. Any other means for such synthesis may also be
employed; the actual synthesis of the oligonucleotides is well
within the capabilities of one skilled in the art and can be
accomplished via established methodologies as detailed in, for
example, "Molecular Cloning: A laboratory Manual" Sambrook et al.,
(1989); "Current Protocols in Molecular Biology" Volumes I-III
Ausubel, R. M., ed. (1994); Ausubel et al., "Current Protocols in
Molecular Biology", John Wiley and Sons, Baltimore, Md. (1989);
Perbal, "A Practical Guide to Molecular Cloning", John Wiley &
Sons, New York (1988) and "Oligonucleotide Synthesis" Gait, M. J.,
ed. (1984) utilizing solid phase chemistry, e.g. cyanoethyl
phosphoramidite followed by deprotection, desalting and
purification by for example, an automated trityl-on method or
HPLC.
[0674] Oligonucleotides used according to this aspect of the
present invention are those having a length selected from a range
of about 10 to about 200 bases preferably about 15 to about 150
bases, more preferably about 20 to about 100 bases, most preferably
about 20 to about 50 bases. Preferably, the oligonucleotide of the
present invention features at least 17, at least 18, at least 19,
at least 20, at least 22, at least 25, at least 30 or at least 40,
bases specifically hybridizable with the biomarkers of the present
invention.
[0675] The oligonucleotides of the present invention may comprise
heterocylic nucleosides consisting of purines and the pyrimidines
bases, bonded in a 3' to 5' phosphodiester linkage.
[0676] Preferably used oligonucleotides are those modified at one
or more of the backbone, internucleoside linkages or bases, as is
broadly described hereinunder.
[0677] Specific examples of preferred oligonucleotides useful
according to this aspect of the present invention include
oligonucleotides containing modified backbones or non-natural
internucleoside linkages. Oligonucleotides having modified
backbones include those that retain a phosphorus atom in the
backbone, as disclosed in U.S. Pat. Nos. 4,469,863; 4,476,301;
5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302;
5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233;
5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111;
5,563,253; 5,571,799; 5,587,361; and 5,625,050.
[0678] Preferred modified oligonucleotide backbones include, for
example, phosphorothioates, chiral phosphorothioates,
phosphorodithioates, phosphotriesters, aminoalkyl phosphotriesters,
methyl and other alkyl phosphonates including 3'-alkylene
phosphonates and chiral phosphonates, phosphinates,
phosphoramidates including 3'-amino phosphoramidate and
aminoalkylphosphoramidates, thionophosphoramidates,
thionoalkylphosphonates, thionoalkylphosphotriesters, and
boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs
of these, and those having inverted polarity wherein the adjacent
pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to
5'-2'. Various salts, mixed salts and free acid forms can also be
used.
[0679] Alternatively, modified oligonucleotide backbones that do
not include a phosphorus atom therein have backbones that are
formed by short chain alkyl or cycloalkyl internucleoside linkages,
mixed heteroatom and alkyl or cycloalkyl internucleoside linkages,
or one or more short chain heteroatomic or heterocyclic
internucleoside linkages. These include those having morpholino
linkages (formed in part from the sugar portion of a nucleoside);
siloxane backbones; sulfide, sulfoxide and sulfone backbones;
formacetyl and thioformacetyl backbones; methylene formacetyl and
thioformacetyl backbones; alkene containing backbones; sulfamate
backbones; methyleneimino and methylenehydrazino backbones;
sulfonate and sulfonamide backbones; amide backbones; and others
having mixed N, O, S and CH.sub.2 component parts, as disclosed in
U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134;
5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257;
5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086;
5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704;
5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439.
[0680] Other oligonucleotides which can be used according to the
present invention, are those modified in both sugar and the
internucleoside linkage, i.e., the backbone, of the nucleotide
units are replaced with novel groups. The base units are maintained
for complementation with the appropriate polynucleotide target. An
example for such an oligonucleotide mimetic, includes peptide
nucleic acid (PNA). United States patents that teach the
preparation of PNA compounds include, but are not limited to, U.S.
Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is
herein incorporated by reference. Other backbone modifications,
which can be used in the present invention are disclosed in U.S.
Pat. No. 6,303,374.
[0681] Oligonucleotides of the present invention may also include
base modifications or substitutions. As used herein, "unmodified"
or "natural" bases include the purine bases adenine (A) and guanine
(G), and the pyrimidine bases thymine (T), cytosine (C) and uracil
(U). Modified bases include but are not limited to other synthetic
and natural bases such as 5-methylcytosine (5-me-C),
5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine,
6-methyl and other alkyl derivatives of adenine and guanine,
2-propyl and other alkyl derivatives of adenine and guanine,
2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and
cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine
and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo,
8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted
adenines and guanines, 5-halo particularly 5-bromo,
5-trifluoromethyl and other 5-substituted uracils and cytosines,
7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine,
7-deazaguanine and 7-deazaadenine and 3-deazaguanine and
3-deazaadenine. Further bases particularly useful for increasing
the binding affinity of the oligomeric compounds of the invention
include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6
and O-6 substituted purines, including 2-aminopropyladenine,
5-propynyluracil and 5-propynylcytosine. 5-methylcytosine
substitutions have been shown to increase nucleic acid duplex
stability by 0.6-1.2.degree. C. and are presently preferred base
substitutions, even more particularly when combined with
2'-O-methoxyethyl sugar modifications.
[0682] Another modification of the oligonucleotides of the
invention involves chemically linking to the oligonucleotide one or
more moieties or conjugates, which enhance the activity, cellular
distribution or cellular uptake of the oligonucleotide. Such
moieties include but are not limited to lipid moieties such as a
cholesterol moiety, cholic acid, a thioether, e.g.,
hexyl-S-tritylthiol, a thiocholesterol, an aliphatic chain, e.g.,
dodecandiol or undecyl residues, a phospholipid, e.g.,
di-hexadecyl-rac-glycerol or triethylammonium
1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate, a polyamine or a
polyethylene glycol chain, or adamantane acetic acid, a palmityl
moiety, or an octadecylamine or hexylamino-carbonyl-oxycholesterol
moiety, as disclosed in U.S. Pat. No. 6,303,374.
[0683] It is not necessary for all positions in a given
oligonucleotide molecule to be uniformly modified, and in fact more
than one of the aforementioned modifications may be incorporated in
a single compound or even at a single nucleoside within an
oligonucleotide.
[0684] It will be appreciated that oligonucleotides of the present
invention may include further modifications for more efficient use
as diagnostic agents and/or to increase bioavailability,
therapeutic efficacy and reduce cytotoxicity.
[0685] To enable cellular expression of the polynucleotides of the
present invention, a nucleic acid construct according to the
present invention may be used, which includes at least a coding
region of one of the above nucleic acid sequences, and further
includes at least one cis acting regulatory element. As used
herein, the phrase "cis acting regulatory element" refers to a
polynucleotide sequence, preferably a promoter, which binds a trans
acting regulator and regulates the transcription of a coding
sequence located downstream thereto.
[0686] Any suitable promoter sequence can be used by the nucleic
acid construct of the present invention.
[0687] Preferably, the promoter utilized by the nucleic acid
construct of the present invention is active in the specific cell
population transformed. Examples of cell type-specific and/or
tissue-specific promoters include promoters such as albumin that is
liver specific, lymphoid specific promoters [Calame et al., (1988)
Adv. Immunol. 43:235-275]; in particular promoters of T-cell
receptors [Winoto et al., (1989) EMBO J. 8:729-733] and
immunoglobulins; [Banerji et al. (1983) Cell 33729-740],
neuron-specific promoters such as the neurofilament promoter [Byrne
et al. (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477],
pancreas-specific promoters [Edlunch et al. (1985) Science
230:912-916] or mammary gland-specific promoters such as the milk
whey promoter (U.S. Pat. No. 4,873,316 and European Application
Publication No. 264,166). The nucleic acid construct of the present
invention can further include an enhancer, which can be adjacent or
distant to the promoter sequence and can function in up regulating
the transcription therefrom.
[0688] The nucleic acid construct of the present invention
preferably further includes an appropriate selectable marker and/or
an origin of replication. Preferably, the nucleic acid construct
utilized is a shuttle vector, which can propagate both in E. coli
(wherein the construct comprises an appropriate selectable marker
and origin of replication) and be compatible for propagation in
cells, or integration in a gene and a tissue of choice. The
construct according to the present invention can be, for example, a
plasmid, a bacmid, a phagemid, a cosmid, a phage, a virus or an
artificial chromosome.
[0689] Examples of suitable constructs include, but are not limited
to, pcDNA3, pcDNA3.1 (+/-), pGL3, PzeoSV2 (+/-), pDisplay,
pEF/myc/cyto, pCMV/myc/cyto each of which is commercially available
from Invitrogen Co. (dot invitrogen dot com). Examples of
retroviral vector and packaging systems are those sold by Clontech,
San Diego, Calif., including Retro-X vectors pLNCX and pLXSN, which
permit cloning into multiple cloning sites and the trasgene is
transcribed from CMV promoter. Vectors derived from Mo-MuLV are
also included such as pBabe, where the transgene will be
transcribed from the 5'LTR promoter.
[0690] Currently preferred in vivo nucleic acid transfer techniques
include transfection with viral or non-viral constructs, such as
adenovirus, lentivirus, Herpes simplex I virus, or adeno-associated
virus (AAV) and lipid-based systems. Useful lipids for
lipid-mediated transfer of the gene are, for example, DOTMA, DOPE,
and DC-Chol [Tonkinson et al., Cancer Investigation, 14(1): 54-65
(1996)]. The most preferred constructs for use in gene therapy are
viruses, most preferably adenoviruses, AAV, lentiviruses, or
retroviruses. A viral construct such as a retroviral construct
includes at least one transcriptional promoter/enhancer or
locus-defining element(s), or other elements that control gene
expression by other means such as alternate splicing, nuclear RNA
export, or post-translational modification of messenger. Such
vector constructs also include a packaging signal, long terminal
repeats (LTRs) or portions thereof, and positive and negative
strand primer binding sites appropriate to the virus used, unless
it is already present in the viral construct. In addition, such a
construct typically includes a signal sequence for secretion of the
peptide from a host cell in which it is placed. Preferably the
signal sequence for this purpose is a mammalian signal sequence or
the signal sequence of the polypeptide variants of the present
invention. Optionally, the construct may also include a signal that
directs polyadenylation, as well as one or more restriction sites
and a translation termination sequence. By way of example, such
constructs will typically include a 5' LTR, a tRNA binding site, a
packaging signal, an origin of second-strand DNA synthesis, and a
3' LTR or a portion thereof. Other vectors can be used that are
non-viral, such as cationic lipids, polylysine, and dendrimers.
Hybridization Assays
[0691] Detection of a nucleic acid of interest in a biological
sample may optionally be effected by hybridization-based assays
using an oligonucleotide probe (non-limiting examples of probes
according to the present invention were previously described).
[0692] Traditional hybridization assays include PCR, RT-PCR,
Real-time PCR, RNase protection, in-situ hybridization, primer
extension, Southern blots (DNA detection), dot or slot blots (DNA,
RNA), and Northern blots (RNA detection) (NAT type assays are
described in greater detail below). More recently, PNAs have been
described (Nielsen et al. 1999, Current Opin. Biotechnol.
10:71-75). Other detection methods include kits containing probes
on a dipstick setup and the like.
[0693] Hybridization based assays which allow the detection of a
variant of interest (i.e., DNA or RNA) in a biological sample rely
on the use of oligonucleotides which can be 10, 15, 20, or 30 to
100 nucleotides long preferably from 10 to 50, more preferably from
40 to 50 nucleotides long.
[0694] Thus, the isolated polynucleotides (oligonucleotides) of the
present invention are preferably hybridizable with any of the
herein described nucleic acid sequences under moderate to stringent
hybridization conditions.
[0695] Moderate to stringent hybridization conditions are
characterized by a hybridization solution such as containing 10%
dextrane sulfate, 1 M NaCl, 1% SDS and 5.times.10.sup.6 cpm
.sup.32P labeled probe, at 65.degree. C., with a final wash
solution of 0.2.times.SSC and 0.1% SDS and fmal wash at 65.degree.
C. and whereas moderate hybridization is effected using a
hybridization solution containing 10% dextrane sulfate, 1 M NaCl,
1% SDS and 5.times.10.sup.6 cpm .sup.32P labeled probe, at
65.degree. C., with a final wash solution of 1.times.SSC and 0.1%
SDS and final wash at 50.degree. C.
[0696] More generally, hybridization of short nucleic acids (below
200 bp in length, e.g. 17-40 bp in length) can be effected using
the following exemplary hybridization protocols which can be
modified according to the desired stringency; (i) hybridization
solution of 6.times.SSC and 1% SDS or 3 M TMACI, 0.01 M sodium
phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS, 100 .mu.g/ml
denatured salmon sperm DNA and 0.1% nonfat dried milk,
hybridization temperature of 1-1.5.degree. C. below the T.sub.m,
final wash solution of 3 M TMACI, 0.01 M sodium phosphate (pH 6.8),
1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5.degree. C. below the T.sub.m;
(ii) hybridization solution of 6.times.SSC and 0.1% SDS or 3 M
TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH 7.6), 0.5%
SDS, 100 .mu.g/ml denatured salmon sperm DNA and 0.1% nonfat dried
milk, hybridization temperature of 2-2.5.degree. C. below the
T.sub.m, final wash solution of 3 M TMACI, 0.01 M sodium phosphate
(pH 6.8), 1 mM EDTA (pH 7.6), 0.5% SDS at 1-1.5.degree. C. below
the T.sub.m, final wash solution of 6.times.SSC, and final wash at
22.degree. C.; (iii) hybridization solution of 6.times.SSC and 1%
SDS or 3 M TMACI, 0.01 M sodium phosphate (pH 6.8), 1 mM EDTA (pH
7.6), 0.5% SDS, 100 .mu.g/ml denatured salmon sperm DNA and 0.1%
nonfat dried milk, hybridization temperature.
[0697] The detection of hybrid duplexes can be carried out by a
number of methods. Typically, hybridization duplexes are separated
from unhybridized nucleic acids and the labels bound to the
duplexes are then detected. Such labels refer to radioactive,
fluorescent, biological or enzymatic tags or labels of standard use
in the art. A label can be conjugated to either the oligonucleotide
probes or the nucleic acids derived from the biological sample.
[0698] Probes can be labeled according to numerous well known
methods. Non-limiting examples of radioactive labels include 3H,
14C, 32P, and 35S. Non-limiting examples of detectable markers
include ligands, fluorophores, chemiluminescent agents, enzymes,
and antibodies. Other detectable markers for use with probes, which
can enable an increase in sensitivity of the method of the
invention, include biotin and radio-nucleotides. It will become
evident to the person of ordinary skill that the choice of a
particular label dictates the manner in which it is bound to the
probe.
[0699] For example, oligonucleotides of the present invention can
be labeled subsequent to synthesis, by incorporating biotinylated
dNTPs or rNTP, or some similar means (e.g., photo-cross-linking a
psoralen derivative of biotin to RNAs), followed by addition of
labeled streptavidin (e.g., phycoerythrin-conjugated streptavidin)
or the equivalent. Alternatively, when fluorescently-labeled
oligonucleotide probes are used, fluorescein, lissamine,
phycoerythrin, rhodamine (Perkin Elmer Cetus), Cy2, Cy3, Cy3.5,
Cy5, Cy5.5, Cy7, FluorX (Amersham) and others [e.g., Kricka et al.
(1992), Academic Press San Diego, Calif.] can be attached to the
oligonucleotides.
[0700] Those skilled in the art will appreciate that wash steps may
be employed to wash away excess target DNA or probe as well as
unbound conjugate. Further, standard heterogeneous assay formats
are suitable for detecting the hybrids using the labels present on
the oligonucleotide primers and probes.
[0701] It will be appreciated that a variety of controls may be
usefully employed to improve accuracy of hybridization assays. For
instance, samples may be hybridized to an irrelevant probe and
treated with RNAse A prior to hybridization, to assess false
hybridization.
[0702] Although the present invention is not specifically dependent
on the use of a label for the detection of a particular nucleic
acid sequence, such a label might be beneficial, by increasing the
sensitivity of the detection. Furthermore, it enables automation.
Probes can be labeled according to numerous well known methods.
[0703] As commonly known, radioactive nucleotides can be
incorporated into probes of the invention by several methods.
Non-limiting examples of radioactive labels include .sup.3H,
.sup.14C, .sup.32P, and .sup.35S.
[0704] Those skilled in the art will appreciate that wash steps may
be employed to wash away excess target DNA or probe as well as
unbound conjugate. Further, standard heterogeneous assay formats
are suitable for detecting the hybrids using the labels present on
the oligonucleotide primers and probes.
[0705] It will be appreciated that a variety of controls may be
usefully employed to improve accuracy of hybridization assays.
[0706] Probes of the invention can be utilized with naturally
occurring sugar-phosphate backbones as well as modified backbones
including phosphorothioates, dithionates, alkyl phosphonates and
a-nucleotides and the like. Probes of the invention can be
constructed of either ribonucleic acid (RNA) or deoxyribonucleic
acid (DNA), and preferably of DNA.
NAT Assays
[0707] Detection of a nucleic acid of interest in a biological
sample may also optionally be effected by NAT-based assays, which
involve nucleic acid amplification technology, such as PCR for
example (or variations thereof such as real-time PCR for
example).
[0708] As used herein, a "primer" defines an oligonucleotide which
is capable of annealing to (hybridizing with) a target sequence,
thereby creating a double stranded region which can serve as an
initiation point for DNA synthesis under suitable conditions.
[0709] Amplification of a selected, or target, nucleic acid
sequence may be carried out by a number of suitable methods. See
generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous
amplification techniques have been described and can be readily
adapted to suit particular needs of a person of ordinary skill.
Non-limiting examples of amplification techniques include
polymerase chain reaction (PCR), ligase chain reaction (LCR),
strand displacement amplification (SDA), transcription-based
amplification, the q3 replicase system and NASBA (Kwoh et al.,
1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al.,
1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol.
Biol., 28:253-260; and Sambrook et al., 1989, supra).
[0710] The terminology "amplification pair" (or "primer pair")
refers herein to a pair of oligonucleotides (oligos) of the present
invention, which are selected to be used together in amplifying a
selected nucleic acid sequence by one of a number of types of
amplification processes, preferably a polymerase chain reaction.
Other types of amplification processes include ligase chain
reaction, strand displacement amplification, or nucleic acid
sequence-based amplification, as explained in greater detail below.
As commonly known in the art, the oligos are designed to bind to a
complementary sequence under selected conditions.
[0711] In one particular embodiment, amplification of a nucleic
acid sample from a patient is amplified under conditions which
favor the amplification of the most abundant differentially
expressed nucleic acid. In one preferred embodiment, RT-PCR is
carried out on an mRNA sample from a patient under conditions which
favor the amplification of the most abundant mRNA. In another
preferred embodiment, the amplification of the differentially
expressed nucleic acids is carried out simultaneously. It will be
realized by a person skilled in the art that such methods could be
adapted for the detection of differentially expressed proteins
instead of differentially expressed nucleic acid sequences. The
nucleic acid (i.e. DNA or RNA) for practicing the present invention
may be obtained according to well known methods.
[0712] Oligonucleotide primers of the present invention may be of
any suitable length, depending on the particular assay format and
the particular needs and targeted genomes employed. Optionally, the
oligonucleotide primers are at least 12 nucleotides in length,
preferably between 15 and 24 molecules, and they may be adapted to
be especially suited to a chosen nucleic acid amplification system.
As commonly known in the art, the oligonucleotide primers can be
designed by taking into consideration the melting point of
hybridization thereof with its targeted sequence (Sambrook et al.,
1989, Molecular Cloning--A Laboratory Manual, 2nd Edition, CSH
Laboratories; Ausubel et al., 1989, in Current Protocols in
Molecular Biology, John Wiley & Sons Inc., N.Y.).
[0713] It will be appreciated that antisense oligonucleotides may
be employed to quantify expression of a splice isoform of interest.
Such detection is effected at the pre-mRNA level. Essentially the
ability to quantitate transcription from a splice site of interest
can be effected based on splice site accessibility.
Oligonucleotides may compete with splicing factors for the splice
site sequences. Thus, low activity of the antisense oligonucleotide
is indicative of splicing activity.
[0714] The polymerase chain reaction and other nucleic acid
amplification reactions are well known in the art (various
non-limiting examples of these reactions are described in greater
detail below). The pair of oligonucleotides according to this
aspect of the present invention are preferably selected to have
compatible melting temperatures (Tm), e.g., melting temperatures
which differ by less than that 7.degree. C., preferably less than
5.degree. C., more preferably less than 4.degree. C., most
preferably less than 3.degree. C., ideally between 3.degree. C. and
0.degree. C.
[0715] Polymerase Chain Reaction (PCR): The polymerase chain
reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and
4,683,202 to Mullis and Mullis et al., is a method of increasing
the concentration of a segment of target sequence in a mixture of
genomic DNA without cloning or purification. This technology
provides one approach to the problems of low target sequence
concentration. PCR can be used to directly increase the
concentration of the target to an easily detectable level. This
process for amplifying the target sequence involves the
introduction of a molar excess of two oligonucleotide primers which
are complementary to their respective strands of the
double-stranded target sequence to the DNA mixture containing the
desired target sequence. The mixture is denatured and then allowed
to hybridize. Following hybridization, the primers are extended
with polymerase so as to form complementary strands. The steps of
denaturation, hybridization (annealing), and polymerase extension
(elongation) can be repeated as often as needed, in order to obtain
relatively high concentrations of a segment of the desired target
sequence.
[0716] The length of the segment of the desired target sequence is
determined by the relative positions of the primers with respect to
each other, and, therefore, this length is a controllable
parameter. Because the desired segments of the target sequence
become the dominant sequences (in terms of concentration) in the
mixture, they are said to be "PCR-amplified."
[0717] Ligase Chain Reaction (LCR or LAR): The ligase chain
reaction [LCR; sometimes referred to as "Ligase Amplification
Reaction" (LAR)] has developed into a well-recognized alternative
method of amplifying nucleic acids. In LCR, four oligonucleotides,
two adjacent oligonucleotides which uniquely hybridize to one
strand of target DNA, and a complementary set of adjacent
oligonucleotides, which hybridize to the opposite strand are mixed
and DNA ligase is added to the mixture. Provided that there is
complete complementarity at the junction, ligase will covalently
link each set of hybridized molecules. Importantly, in LCR, two
probes are ligated together only when they base-pair with sequences
in the target sample, without gaps or mismatches. Repeated cycles
of denaturation, and ligation amplify a short segment of DNA. LCR
has also been used in combination with PCR to achieve enhanced
detection of single-base changes: see for example Segev, PCT
Publication No. W09001069 A1 (1990). However, because the four
oligonucleotides used in this assay can pair to form two short
ligatable fragments, there is the potential for the generation of
target-independent background signal. The use of LCR for mutant
screening is limited to the examination of specific nucleic acid
positions.
[0718] Self-Sustained Synthetic Reaction (3SR/NASBA): The
self-sustained sequence replication reaction (3SR) is a
transcription-based in vitro amplification system that can
exponentially amplify RNA sequences at a uniform temperature. The
amplified RNA can then be utilized for mutation detection. In this
method, an oligonucleotide primer is used to add a phage RNA
polymerase promoter to the 5' end of the sequence of interest. In a
cocktail of enzymes and substrates that includes a second primer,
reverse transcriptase, RNase H, RNA polymerase and ribo- and
deoxyribonucleoside triphosphates, the target sequence undergoes
repeated rounds of transcription, cDNA synthesis and second-strand
synthesis to amplify the area of interest. The use of 3SR to detect
mutations is kinetically limited to screening small segments of DNA
(e.g., 200-300 base pairs).
[0719] Q-Beta (Q.beta.) Replicase: In this method, a probe which
recognizes the sequence of interest is attached to the replicatable
RNA template for Q.beta. replicase. A previously identified major
problem with false positives resulting from the replication of
unhybridized probes has been addressed through use of a
sequence-specific ligation step. However, available thermostable
DNA ligases are not effective on this RNA substrate, so the
ligation must be performed by T4 DNA ligase at low temperatures (37
degrees C.). This prevents the use of high temperature as a means
of achieving specificity as in the LCR, the ligation event can be
used to detect a mutation at the junction site, but not
elsewhere.
[0720] A successful diagnostic method must be very specific. A
straight-forward method of controlling the specificity of nucleic
acid hybridization is by controlling the temperature of the
reaction. While the 3SR/NASBA, and Q.beta. systems are all able to
generate a large quantity of signal, one or more of the enzymes
involved in each cannot be used at high temperature (i.e., >55
degrees C.). Therefore the reaction temperatures cannot be raised
to prevent non-specific hybridization of the probes. If probes are
shortened in order to make them melt more easily at low
temperatures, the likelihood of having more than one perfect match
in a complex genome increases. For these reasons, PCR and LCR
currently dominate the research field in detection
technologies.
[0721] The basis of the amplification procedure in the PCR and LCR
is the fact that the products of one cycle become usable templates
in all subsequent cycles, consequently doubling the population with
each cycle. The final yield of any such doubling system can be
expressed as: (1+X).sup.n=y, where "X" is the mean efficiency
(percent copied in each cycle), "n" is the number of cycles, and
"y" is the overall efficiency, or yield of the reaction. If every
copy of a target DNA is utilized as a template in every cycle of a
polymerase chain reaction, then the mean efficiency is 100%. If 20
cycles of PCR are performed, then the yield will be 2.sup.20, or
1,048,576 copies of the starting material. If the reaction
conditions reduce the mean efficiency to 85%, then the yield in
those 20 cycles will be only 1.85.sup.20, or 220,513 copies of the
starting material. In other words, a PCR running at 85% efficiency
will yield only 21% as much final product, compared to a reaction
running at 100% efficiency. A reaction that is reduced to 50% mean
efficiency will yield less than 1% of the possible product.
[0722] In practice, routine polymerase chain reactions rarely
achieve the theoretical maximum yield, and PCRs are usually run for
more than 20 cycles to compensate for the lower yield. At 50% mean
efficiency, it would take 34 cycles to achieve the million-fold
amplification theoretically possible in 20, and at lower
efficiencies, the number of cycles required becomes prohibitive. In
addition, any background products that amplify with a better mean
efficiency than the intended target will become the dominant
products.
[0723] Also, many variables can influence the mean efficiency of
PCR, including target DNA length and secondary structure, primer
length and design, primer and dNTP concentrations, and buffer
composition, to name but a few. Contamination of the reaction with
exogenous DNA (e.g., DNA spilled onto lab surfaces) or
cross-contamination is also a major consideration. Reaction
conditions must be carefully optimized for each different primer
pair and target sequence, and the process can take days, even for
an experienced investigator. The laboriousness of this process,
including numerous technical considerations and other factors,
presents a significant drawback to using PCR in the clinical
setting. Indeed, PCR has yet to penetrate the clinical market in a
significant way. The same concerns arise with LCR, as LCR must also
be optimized to use different oligonucleotide sequences for each
target sequence. In addition, both methods require expensive
equipment, capable of precise temperature cycling.
[0724] Many applications of nucleic acid detection technologies,
such as in studies of allelic variation, involve not only detection
of a specific sequence in a complex background, but also the
discrimination between sequences with few, or single, nucleotide
differences. One method of the detection of allele-specific
variants by PCR is based upon the fact that it is difficult for Taq
polymerase to synthesize a DNA strand when there is a mismatch
between the template strand and the 3' end of the primer. An
allele-specific variant may be detected by the use of a primer that
is perfectly matched with only one of the possible alleles; the
mismatch to the other allele acts to prevent the extension of the
primer, thereby preventing the amplification of that sequence. This
method has a substantial limitation in that the base composition of
the mismatch influences the ability to prevent extension across the
mismatch, and certain mismatches do not prevent extension or have
only a minimal effect.
[0725] A similar 3'-mismatch strategy is used with greater effect
to prevent ligation in the LCR. Any mismatch effectively blocks the
action of the thermostable ligase, but LCR still has the drawback
of target-independent background ligation products initiating the
amplification. Moreover, the combination of PCR with subsequent LCR
to identify the nucleotides at individual positions is also a
clearly cumbersome proposition for the clinical laboratory.
[0726] The direct detection method according to various preferred
embodiments of the present invention may be, for example a cycling
probe reaction (CPR) or a branched DNA analysis.
[0727] When a sufficient amount of a nucleic acid to be detected is
available, there are advantages to detecting that sequence
directly, instead of making more copies of that target, (e.g., as
in PCR and LCR). Most notably, a method that does not amplify the
signal exponentially is more amenable to quantitative analysis.
Even if the signal is enhanced by attaching multiple dyes to a
single oligonucleotide, the correlation between the final signal
intensity and amount of target is direct. Such a system has an
additional advantage that the products of the reaction will not
themselves promote further reaction, so contamination of lab
surfaces by the products is not as much of a concern. Recently
devised techniques have sought to eliminate the use of
radioactivity and/or improve the sensitivity in automatable
formats. Two examples are the "Cycling Probe Reaction" (CPR), and
"Branched DNA" (bDNA).
[0728] Cycling probe reaction (CPR): The cycling probe reaction
(CPR), uses a long chimeric oligonucleotide in which a central
portion is made of RNA while the two termini are made of DNA.
Hybridization of the probe to a target DNA and exposure to a
thermostable RNase H causes the RNA portion to be digested. This
destabilizes the remaining DNA portions of the duplex, releasing
the remainder of the probe from the target DNA and allowing another
probe molecule to repeat the process. The signal, in the form of
cleaved probe molecules, accumulates at a linear rate. While the
repeating process increases the signal, the RNA portion of the
oligonucleotide is vulnerable to RNases that may carried through
sample preparation.
[0729] Branched DNA: Branched DNA (bDNA), involves oligonucleotides
with branched structures that allow each individual oligonucleotide
to carry 35 to 40 labels (e.g., alkaline phosphatase enzymes).
While this enhances the signal from a hybridization event, signal
from non-specific binding is similarly increased.
[0730] The detection of at least one sequence change according to
various preferred embodiments of the present invention may be
accomplished by, for example restriction fragment length
polymorphism (RFLP analysis), allele specific oligonucleotide (ASO)
analysis, Denaturing/Temperature Gradient Gel Electrophoresis
(DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP)
analysis or Dideoxy fingerprinting (ddF).
[0731] The demand for tests which allow the detection of specific
nucleic acid sequences and sequence changes is growing rapidly in
clinical diagnostics. As nucleic acid sequence data for genes from
humans and pathogenic organisms accumulates, the demand for fast,
cost-effective, and easy-to-use tests for as yet mutations within
specific sequences is rapidly increasing.
[0732] A handful of methods have been devised to scan nucleic acid
segments for mutations. One option is to determine the entire gene
sequence of each test sample (e.g., a bacterial isolate). For
sequences under approximately 600 nucleotides, this may be
accomplished using amplified material (e.g., PCR reaction
products). This avoids the time and expense associated with cloning
the segment of interest. However, specialized equipment and highly
trained personnel are required, and the method is too labor-intense
and expensive to be practical and effective in the clinical
setting.
[0733] In view of the difficulties associated with sequencing, a
given segment of nucleic acid may be characterized on several other
levels. At the lowest resolution, the size of the molecule can be
determined by electrophoresis by comparison to a known standard run
on the same gel. A more detailed picture of the molecule may be
achieved by cleavage with combinations of restriction enzymes prior
to electrophoresis, to allow construction of an ordered map. The
presence of specific sequences within the fragment can be detected
by hybridization of a labeled probe, or the precise nucleotide
sequence can be determined by partial chemical degradation or by
primer extension in the presence of chain-terminating nucleotide
analogs.
[0734] Restriction fragment length polymorphism (RFLP): For
detection of single-base differences between like sequences, the
requirements of the analysis are often at the highest level of
resolution. For cases in which the position of the nucleotide in
question is known in advance, several methods have been developed
for examining single base changes without direct sequencing. For
example, if a mutation of interest happens to fall within a
restriction recognition sequence, a change in the pattern of
digestion can be used as a diagnostic tool (e.g., restriction
fragment length polymorphism [RFLP] analysis).
[0735] Single point mutations have been also detected by the
creation or destruction of RFLPs. Mutations are detected and
localized by the presence and size of the RNA fragments generated
by cleavage at the mismatches. Single nucleotide mismatches in DNA
heteroduplexes are also recognized and cleaved by some chemicals,
providing an alternative strategy to detect single base
substitutions, generically named the "Mismatch Chemical Cleavage"
(MCC). However, this method requires the use of osmium tetroxide
and piperidine, two highly noxious chemicals which are not suited
for use in a clinical laboratory.
[0736] RFLP analysis suffers from low sensitivity and requires a
large amount of sample. When RFLP analysis is used for the
detection of point mutations, it is, by its nature, limited to the
detection of only those single base changes which fall within a
restriction sequence of a known restriction endonuclease. Moreover,
the majority of the available enzymes have 4 to 6 base-pair
recognition sequences, and cleave too frequently for many
large-scale DNA manipulations. Thus, it is applicable only in a
small fraction of cases, as most mutations do not fall within such
sites.
[0737] A handful of rare-cutting restriction enzymes with 8
base-pair specificities have been isolated and these are widely
used in genetic mapping, but these enzymes are few in number, are
limited to the recognition of G+C-rich sequences, and cleave at
sites that tend to be highly clustered. Recently, endonucleases
encoded by group I introns have been discovered that might have
greater than 12 base-pair specificity, but again, these are few in
number.
[0738] Allele specific oligonucleotide (ASO): If the change is not
in a recognition sequence, then allele-specific oligonucleotides
(ASOs), can be designed to hybridize in proximity to the mutated
nucleotide, such that a primer extension or ligation event can
bused as the indicator of a match or a mis-match. Hybridization
with radioactively labeled allelic specific oligonucleotides (ASO)
also has been applied to the detection of specific point mutations.
The method is based on the differences in the melting temperature
of short DNA fragments differing by a single nucleotide. Stringent
hybridization and washing conditions can differentiate between
mutant and wild-type alleles. The ASO approach applied to PCR
products also has been extensively utilized by various researchers
to detect and characterize point mutations in ras genes and gsp/gip
oncogenes. Because of the presence of various nucleotide changes in
multiple positions, the ASO method requires the use of many
oligonucleotides to cover all possible oncogenic mutations.
[0739] With either of the techniques described above (i.e., RFLP
and ASO), the precise location of the suspected mutation must be
known in advance of the test. That is to say, they are inapplicable
when one needs to detect the presence of a mutation within a gene
or sequence of interest.
[0740] Denaturing/Temperature Gradient Gel Electrophoresis
(DGGE/TGGE): Two other methods rely on detecting changes in
electrophoretic mobility in response to minor sequence changes. One
of these methods, termed "Denaturing Gradient Gel Electrophoresis"
(DGGE) is based on the observation that slightly different
sequences will display different patterns of local melting when
electrophoretically resolved on a gradient gel. In this manner,
variants can be distinguished, as differences in melting properties
of homoduplexes versus heteroduplexes differing in a single
nucleotide can detect the presence of mutations in the target
sequences because of the corresponding changes in their
electrophoretic mobilities. The fragments to be analyzed, usually
PCR products, are "clamped" at one end by a long stretch of G-C
base pairs (30-80) to allow complete denaturation of the sequence
of interest without complete dissociation of the strands. The
attachment of a GC "clamp" to the DNA fragments increases the
fraction of mutations that can be recognized by DGGE. Attaching a
GC clamp to one primer is critical to ensure that the amplified
sequence has a low dissociation temperature. Modifications of the
technique have been developed, using temperature gradients, and the
method can be also applied to RNA:RNA duplexes.
[0741] Limitations on the utility of DGGE include the requirement
that the denaturing conditions must be optimized for each type of
DNA to be tested. Furthermore, the method requires specialized
equipment to prepare the gels and maintain the needed high
temperatures during electrophoresis. The expense associated with
the synthesis of the clamping tail on one oligonucleotide for each
sequence to be tested is also a major consideration. In addition,
long running times are required for DGGE. The long running time of
DGGE was shortened in a modification of DGGE called constant
denaturant gel electrophoresis (CDGE). CDGE requires that gels be
performed under different denaturant conditions in order to reach
high efficiency for the detection of mutations.
[0742] A technique analogous to DGGE, termed temperature gradient
gel electrophoresis (TGGE), uses a thermal gradient rather than a
chemical denaturant gradient. TGGE requires the use of specialized
equipment which can generate a temperature gradient perpendicularly
oriented relative to the electrical field. TGGE can detect
mutations in relatively small fragments of DNA therefore scanning
of large gene segments requires the use of multiple PCR products
prior to running the gel.
[0743] Single-Strand Conformation Polymorphism (SSCP): Another
common method, called "Single-Strand Conformation Polymorphism"
(SSCP) was developed by Hayashi, Sekya and colleagues and is based
on the observation that single strands of nucleic acid can take on
characteristic conformations in non-denaturing conditions, and
these conformations influence electrophoretic mobility. The
complementary strands assume sufficiently different structures that
one strand may be resolved from the other. Changes in sequences
within the fragment will also change the conformation, consequently
altering the mobility and allowing this to be used as an assay for
sequence variations.
[0744] The SSCP process involves denaturing a DNA segment (e.g., a
PCR product) that is labeled on both strands, followed by slow
electrophoretic separation on a non-denaturing polyacrylamide gel,
so that intra-molecular interactions can form and not be disturbed
during the run. This technique is extremely sensitive to variations
in gel composition and temperature. A serious limitation of this
method is the relative difficulty encountered in comparing data
generated in different laboratories, under apparently similar
conditions.
[0745] Dideoxy fingerprinting (ddF): The dideoxy fingerprinting
(ddF) is another technique developed to scan genes for the presence
of mutations. The ddF technique combines components of Sanger
dideoxy sequencing with SSCP. A dideoxy sequencing reaction is
performed using one dideoxy terminator and then the reaction
products are electrophoresed on nondenaturing polyacrylamide gels
to detect alterations in mobility of the termination segments as in
SSCP analysis. While ddF is an improvement over SSCP in terms of
increased sensitivity, ddF requires the use of expensive
dideoxynucleotides and this technique is still limited to the
analysis of fragments of the size suitable for SSCP (i.e.,
fragments of 200-300 bases for optimal detection of mutations).
[0746] In addition to the above limitations, all of these methods
are limited as to the size of the nucleic acid fragment that can be
analyzed. For the direct sequencing approach, sequences of greater
than 600 base pairs require cloning, with the consequent delays and
expense of either deletion sub-cloning or primer walking, in order
to cover the entire fragment. SSCP and DGGE have even more severe
size limitations. Because of reduced sensitivity to sequence
changes, these methods are not considered suitable for larger
fragments. Although SSCP is reportedly able to detect 90% of
single-base substitutions within a 200 base-pair fragment, the
detection drops to less than 50% for 400 base pair fragments.
Similarly, the sensitivity of DGGE decreases as the length of the
fragment reaches 500 base-pairs. The ddF technique, as a
combination of direct sequencing and SSCP, is also limited by the
relatively small size of the DNA that can be screened.
[0747] According to a presently preferred embodiment of the present
invention the step of searching for any of the nucleic acid
sequences described here, in tumor cells or in cells derived from a
cancer patient is effected by any suitable technique, including,
but not limited to, nucleic acid sequencing, polymerase chain
reaction, ligase chain reaction, self-sustained synthetic reaction,
Q.beta.-Replicase, cycling probe reaction, branched DNA,
restriction fragment length polymorphism analysis, mismatch
chemical cleavage, heteroduplex analysis, allele-specific
oligonucleotides, denaturing gradient gel electrophoresis, constant
denaturant gel electrophoresis, temperature gradient gel
electrophoresis and dideoxy fingerprinting.
[0748] Detection may also optionally be performed with a chip or
other such device. The nucleic acid sample which includes the
candidate region to be analyzed is preferably isolated, amplified
and labeled with a reporter group. This reporter group can be a
fluorescent group such as phycoerythrin. The labeled nucleic acid
is then incubated with the probes immobilized on the chip using a
fluidics station. describe the fabrication of fluidics devices and
particularly microcapillary devices, in silicon and glass
substrates.
[0749] Once the reaction is completed, the chip is inserted into a
scanner and patterns of hybridization are detected. The
hybridization data is collected, as a signal emitted from the
reporter groups already incorporated into the nucleic acid, which
is now bound to the probes attached to the chip. Since the sequence
and position of each probe immobilized on the chip is known, the
identity of the nucleic acid hybridized to a given probe can be
determined.
[0750] It will be appreciated that when utilized along with
automated equipment, the above described detection methods can be
used to screen multiple samples for a disease and/or pathological
condition both rapidly and easily.
Amino Acid Sequences and Peptides
[0751] The terms "polypeptide," "peptide" and "protein" are used
interchangeably herein to refer to a polymer of amino acid
residues. The terms apply to amino acid polymers in which one or
more amino acid residue is an analog or mimetic of a corresponding
naturally occurring amino acid, as well as to naturally occurring
amino acid polymers. Polypeptides can be modified, e.g., by the
addition of carbohydrate residues to form glycoproteins. The terms
"polypeptide," "peptide" and "protein" include glycoproteins, as
well as non-glycoproteins.
[0752] Polypeptide products can be biochemically synthesized such
as by employing standard solid phase techniques. Such methods
include but are not limited to exclusive solid phase synthesis,
partial solid phase synthesis methods, fragment condensation,
classical solution synthesis. These methods are preferably used
when the peptide is relatively short (i.e., 10 kDa) and/or when it
cannot be produced by recombinant techniques (i.e., not encoded by
a nucleic acid sequence) and therefore involves different
chemistry.
[0753] Solid phase polypeptide synthesis procedures are well known
in the art and further described by John Morrow Stewart and Janis
Dillaha Young, Solid Phase Peptide Syntheses (2nd Ed., Pierce
Chemical Company, 1984).
[0754] Synthetic polypeptides can optionally be purified by
preparative high performance liquid chromatography [Creighton T.
(1983) Proteins, structures and molecular principles. WH Freeman
and Co. N.Y.], after which their composition can be confirmed via
amino acid sequencing.
[0755] In cases where large amounts of a polypeptide are desired,
it can be generated using recombinant techniques such as described
by Bitter et al., (1987) Methods in Enzymol. 153:516-544, Studier
et al. (1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984)
Nature 310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311,
Coruzzi et al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984)
Science 224:838-843, Gurley et al., (1986) Mol. Cell. Biol.
6:559-565 and Weissbach & Weissbach, 1988, Methods for Plant
Molecular Biology, Academic Press, NY, Section VIII, pp
421-463.
[0756] The present invention also encompasses polypeptides encoded
by the polynucleotide sequences of the present invention, as well
as polypeptides according to the amino acid sequences described
herein. The present invention also encompasses homologues of these
polypeptides, such homologues can be at least 50%, at least 55%, at
least 60%, at least 65%, at least 70%, at least 75%, at least 80%,
at least 85%, at least 95% or more say 100% homologous to the amino
acid sequences set forth below, as can be determined using BlastP
software of the National Center of Biotechnology Information (NCBI)
using default parameters, optionally and preferably including the
following: filtering on (this option filters repetitive or
low-complexity sequences from the query using the Seg (protein)
program), scoring matrix is BLOSUM62 for proteins, word size is 3,
E value is 10, gap costs are 11, 1 (initialization and extension),
and number of alignments shown is 50. Optionally, nucleic acid
sequence identity/homology may be determined by using BlastN
software of the National Center of Biotechnology Information (NCBI)
using default parameters, which preferably include using the DUST
filter program, and also preferably include having an E value of
10, filtering low complexity sequences and a word size of 11.
Finally, the present invention also encompasses fragments of the
above described polypeptides and polypeptides having mutations,
such as deletions, insertions or substitutions of one or more amino
acids, either naturally occurring or artificially induced, either
randomly or in a targeted fashion.
[0757] It will be appreciated that peptides identified according
the present invention may be degradation products, synthetic
peptides or recombinant peptides as well as peptidomimetics,
typically, synthetic peptides and peptoids and semipeptoids which
are peptide analogs, which may have, for example, modifications
rendering the peptides more stable while in a body or more capable
of penetrating into cells. Such modifications include, but are not
limited to N terminus modification, C terminus modification,
peptide bond modification, including, but not limited to, CH2-NH,
CH2-S, CH2-S.dbd.O, O.dbd.C--NH, CH2-O, CH2-CH2, S.dbd.C--NH,
CH.dbd.CH or CF.dbd.CH, backbone modifications, and residue
modification. Methods for preparing peptidomimetic compounds are
well known in the art and are specified. Further details in this
respect are provided hereinunder.
[0758] Peptide bonds (--CO--NH--) within the peptide may be
substituted, for example, by N-methylated bonds (--N(CH3)-CO--),
ester bonds (--C(R)H--C--O--O--C(R)--N--), ketomethylen bonds
(--CO--CH2-), .alpha.-aza bonds (--NH--N(R)--CO--), wherein R is
any alkyl, e.g., methyl, carba bonds (--CH2-NH--), hydroxyethylene
bonds (--CH(OH)--CH2-), thioamide bonds (--CS--NH--), olefinic
double bonds (--CH.dbd.CH--), retro amide bonds (--NH--CO--),
peptide derivatives (--N(R)--CH2-CO--), wherein R is the "normal"
side chain, naturally presented on the carbon atom.
[0759] These modifications can occur at any of the bonds along the
peptide chain and even at several (2-3) at the same time.
[0760] Natural aromatic amino acids, Trp, Tyr and Phe, may be
substituted for synthetic non-natural acid such as Phenylglycine,
TIC, naphthylelanine (Nol), ring-methylated derivatives of Phe,
halogenated derivatives of Phe or o-methyl-Tyr.
[0761] In addition to the above, the peptides of the present
invention may also include one or more modified amino acids or one
or more non-amino acid monomers (e.g. fatty acids, complex
carbohydrates etc).
[0762] As used herein in the specification and in the claims
section below the term "amino acid" or "amino acids" is understood
to include the 20 naturally occurring amino acids; those amino
acids often modified post-translationally in vivo, including, for
example, hydroxyproline, phosphoserine and phosphothreonine; and
other unusual amino acids including, but not limited to,
2-aminoadipic acid, hydroxylysine, isodesmosine, nor-valine,
nor-leucine and ornithine. Furthermore, the term "amino acid"
includes both D- and L-amino acids.
[0763] Table 1 non-conventional or modified amino acids which can
be used with the present invention.
TABLE-US-00002 TABLE 1 Non-conventional amino acid Code
Non-conventional amino acid Code .alpha.-aminobutyric acid Abu
L-N-methylalanine Nmala .alpha.-amino-.alpha.-methylbutyrate Mgabu
L-N-methylarginine Nmarg aminocyclopropane- Cpro
L-N-methylasparagine Nmasn Carboxylate L-N-methylaspartic acid
Nmasp Aminoisobutyric acid Aib L-N-methylcysteine Nmcys
aminonorbornyl- Norb L-N-methylglutamine Nmgin Carboxylate
L-N-methylglutamic acid Nmglu Cyclohexylalanine Chexa
L-N-methylhistidine Nmhis Cyclopentylalanine Cpen
L-N-methylisolleucine Nmile D-alanine Dal L-N-methylleucine Nmleu
D-arginine Darg L-N-methyllysine Nmlys D-aspartic acid Dasp
L-N-methylmethionine Nmmet D-cysteine Dcys L-N-methylnorleucine
Nmnle D-glutamine Dgln L-N-methylnorvaline Nmnva D-glutamic acid
Dglu L-N-methylornithine Nmorn D-histidine Dhis
L-N-methylphenylalanine Nmphe D-isoleucine Dile L-N-methylproline
Nmpro D-leucine Dleu L-N-methylserine Nmser D-lysine Dlys
L-N-methylthreonine Nmthr D-methionine Dmet L-N-methyltryptophan
Nmtrp D-ornithine Dorn L-N-methyltyrosine Nmtyr D-phenylalanine
Dphe L-N-methylvaline Nmval D-proline Dpro L-N-methylethylglycine
Nmetg D-serine Dser L-N-methyl-t-butylglycine Nmtbug D-threonine
Dthr L-norleucine Nle D-tryptophan Dtrp L-norvaline Nva D-tyrosine
Dtyr .alpha.-methyl-aminoisobutyrate Maib D-valine Dval
.alpha.-methyl-.gamma.-aminobutyrate Mgabu D-.alpha.-methylalanine
Dmala .alpha.-methylcyclohexylalanine Mchexa
D-.alpha.-methylarginine Dmarg .alpha.-methylcyclopentylalanine
Mcpen D-.alpha.-methylasparagine Dmasn
.alpha.-methyl-.alpha.-napthylalanine Manap
D-.alpha.-methylaspartate Dmasp .alpha.-methylpenicillamine Mpen
D-.alpha.-methylcysteine Dmcys N-(4-aminobutyl)glycine Nglu
D-.alpha.-methylglutamine Dmgln N-(2-aminoethyl)glycine Naeg
D-.alpha.-methylhistidine Dmhis N-(3-aminopropyl)glycine Norn
D-.alpha.-methylisoleucine Dmile N-amino-.alpha.-methylbutyrate
Nmaabu D-.alpha.-methylleucine Dmleu .alpha.-napthylalanine Anap
D-.alpha.-methyllysine Dmlys N-benzylglycine Nphe
D-.alpha.-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln
D-.alpha.-methylornithine Dmorn N-(carbamylmethyl)glycine Nasn
D-.alpha.-methylphenylalanine Dmphe N-(2-carboxyethyl)glycine Nglu
D-.alpha.-methylproline Dmpro N-(carboxymethyl)glycine Nasp
D-.alpha.-methylserine Dmser N-cyclobutylglycine Ncbut
D-.alpha.-methylthreonine Dmthr N-cycloheptylglycine Nchep
D-.alpha.-methyltryptophan Dmtrp N-cyclohexylglycine Nchex
D-.alpha.-methyltyrosine Dmty N-cyclodecylglycine Ncdec
D-.alpha.-methylvaline Dmval N-cyclododeclglycine Ncdod
D-.alpha.-methylalnine Dnmala N-cyclooctylglycine Ncoct
D-.alpha.-methylarginine Dnmarg N-cyclopropylglycine Ncpro
D-.alpha.-methylasparagine Dnmasn N-cycloundecylglycine Ncund
D-.alpha.-methylasparatate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm
D-.alpha.-methylcysteine Dnmcys N-(3,3-diphenylpropyl)glycine Nbhe
D-N-methylleucine Dnmleu N-(3-indolylyethyl) glycine Nhtrp
D-N-methyllysine Dnmlys N-methyl-.gamma.-aminobutyrate Nmgabu
N-methylcyclohexylalanine Nmchexa D-N-methylmethionine Dnmmet
D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen
N-methylglycine Nala D-N-methylphenylalanine Dnmphe
N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro
N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr
D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nva
D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap
D-N-methylvaline Dnmval N-methylpenicillamine Nmpen
.gamma.-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr
L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg
penicillamine Pen L-homophenylalanine Hphe L-.alpha.-methylalanine
Mala L-.alpha.-methylarginine Marg L-.alpha.-methylasparagine Masn
L-.alpha.-methylaspartate Masp L-.alpha.-methyl-t-butylglycine
Mtbug L-.alpha.-methylcysteine Mcys L-methylethylglycine Metg
L-.alpha.-methylglutamine Mgln L-.alpha.-methylglutamate Mglu
L-.alpha.-methylhistidine Mhis L-.alpha.-methylhomo phenylalanine
Mhphe L-.alpha.-methylisoleucine Mile N-(2-methylthioethyl)glycine
Nmet D-N-methylglutamine Dnmgln N-(3-guanidinopropyl)glycine Narg
D-N-methylglutamate Dnmglu N-(1-hydroxyethyl)glycine Nthr
D-N-methylhistidine Dnmhis N-(hydroxyethyl)glycine Nser
D-N-methylisoleucine Dnmile N-(imidazolylethyl)glycine Nhis
D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtrp
D-N-methyllysine Dnmlys N-methyl-.gamma.-aminobutyrate Nmgabu
N-methylcyclohexylalanine Nmchexa D-N-methylmethionine Dnmmet
D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen
N-methylglycine Nala D-N-methylphenylalanine Dnmphe
N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro
N-(1-methylpropyl)glycine Nile D-N-methylserine Dnmser
N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr
D-N-methyltryptophan Dnmtrp N-(1-methylethyl)glycine Nval
D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap
D-N-methylvaline Dnmval N-methylpenicillamine Nmpen
.gamma.-aminobutyric acid Gabu N-(p-hydroxyphenyl)glycine Nhtyr
L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg
penicillamine Pen L-homophenylalanine Hphe L-.alpha.-methylalanine
Mala L-.alpha.-methylarginine Marg L-.alpha.-methylasparagine Masn
L-.alpha.-methylaspartate Masp L-.alpha.-methyl-t-butylglycine
Mtbug L-.alpha.-methylcysteine Mcys L-methylethylglycine Metg
L-.alpha.-methylglutamine Mgln L-.alpha.-methylglutamate Mglu
L-.alpha.-methylhistidine Mhis L-.alpha.-methylhomophenylalanine
Mhphe L-.alpha.-methylisoleucine Mile N-(2-methylthioethyl)glycine
Nmet L-.alpha.-methylleucine Mleu L-.alpha.-methyllysine Mlys
L-.alpha.-methylmethionine Mmet L-.alpha.-methylnorleucine Mnle
L-.alpha.-methylnorvaline Mnva L-.alpha.-methylornithine Morn
L-.alpha.-methylphenylalanine Mphe L-.alpha.-methylproline Mpro
L-.alpha.-methylserine mser L-.alpha.-methylthreonine Mthr
L-.alpha.-methylvaline Mtrp L-.alpha.-methyltyrosine Mtyr
L-.alpha.-methylleucine Mval Nnbhm L-N-methylhomophenylalanine
Nmhphe N-(N-(2,2-diphenylethyl) N-(N-(3,3-diphenylpropyl)
carbamylmethyl-glycine Nnbhm carbamylmethyl(1)glycine Nnbhe
1-carboxy-1-(2,2-diphenyl Nmbc ethylamino)cyclopropane
[0764] Since the peptides of the present invention are preferably
utilized in diagnostics which require the peptides to be in soluble
form, the peptides of the present invention preferably include one
or more non-natural or natural polar amino acids, including but not
limited to serine and threonine which are capable of increasing
peptide solubility due to their hydroxyl-containing side chain.
[0765] The peptides of the present invention are preferably
utilized in a linear form, although it will be appreciated that in
cases where cyclicization does not severely interfere with peptide
characteristics, cyclic forms of the peptide can also be
utilized.
[0766] The peptides of present invention can be biochemically
synthesized such as by using standard solid phase techniques. These
methods include exclusive solid phase synthesis well known in the
art, partial solid phase synthesis methods, fragment condensation,
classical solution synthesis. These methods are preferably used
when the peptide is relatively short (i.e., 10 kDa) and/or when it
cannot be produced by recombinant techniques (i.e., not encoded by
a nucleic acid sequence) and therefore involves different
chemistry.
[0767] Synthetic peptides can be purified by preparative high
performance liquid chromatography and the composition of which can
be confirmed via amino acid sequencing.
[0768] In cases where large amounts of the peptides of the present
invention are desired, the peptides of the present invention can be
generated using recombinant techniques such as described by Bitter
et al., (1987) Methods in Enzymol. 153:516-544, Studier et al.
(1990) Methods in Enzymol. 185:60-89, Brisson et al. (1984) Nature
310:511-514, Takamatsu et al. (1987) EMBO J. 6:307-311, Coruzzi et
al. (1984) EMBO J. 3:1671-1680 and Brogli et al., (1984) Science
224:838-843, Gurley et al. (1986) Mol. Cell. Biol. 6:559-565 and
Weissbach & Weissbach, 1988, Methods for Plant Molecular
Biology, Academic Press, NY, Section VIII, pp 421-463 and also as
described above.
Antibodies
[0769] "Antibody" refers to a polypeptide ligand that is preferably
substantially encoded by an immunoglobulin gene or immunoglobulin
genes, or fragments thereof, which specifically binds and
recognizes an epitope (e.g., an antigen). The recognized
immunoglobulin genes include the kappa and lambda light chain
constant region genes, the alpha, gamma, delta, epsilon and mu
heavy chain constant region genes, and the myriad-immunoglobulin
variable region genes. Antibodies exist, e.g., as intact
immunoglobulins or as a number of well characterized fragments
produced by digestion with various peptidases. This includes, e.g.,
Fab' and F(ab)'.sub.2 fragments. The term "antibody," as used
herein, also includes antibody fragments either produced by the
modification of whole antibodies or those synthesized de novo using
recombinant DNA methodologies. It also includes polyclonal
antibodies, monoclonal antibodies, chimeric antibodies, humanized
antibodies, or single chain antibodies. "Fc" portion of an antibody
refers to that portion of an immunoglobulin heavy chain that
comprises one or more heavy chain constant region domains, CH1, CH2
and CH3, but does not include the heavy chain variable region.
[0770] The functional fragments of antibodies, such as Fab,
F(ab')2, and Fv that are capable of binding to macrophages, are
described as follows: (1) Fab, the fragment which contains a
monovalent antigen-binding fragment of an antibody molecule, can be
produced by digestion of whole antibody with the enzyme papain to
yield an intact light chain and a portion of one heavy chain; (2)
Fab', the fragment of an antibody molecule that can be obtained by
treating whole antibody with pepsin, followed by reduction, to
yield an intact light chain and a portion of the heavy chain; two
Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the
fragment of the antibody that can be obtained by treating whole
antibody with the enzyme pepsin without subsequent reduction;
F(ab')2 is a dimer of two Fab' fragments held together by two
disulfide bonds; (4) Fv, defined as a genetically engineered
fragment containing the variable region of the light chain and the
variable region of the heavy chain expressed as two chains; and (5)
Single chain antibody ("SCA"), a genetically engineered molecule
containing the variable region of the light chain and the variable
region of the heavy chain, linked by a suitable polypeptide linker
as a genetically fused single chain molecule.
[0771] Methods of producing polyclonal and monoclonal antibodies as
well as fragments thereof are well known in the art (See for
example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold
Spring Harbor Laboratory, New York, 1988, incorporated herein by
reference).
[0772] Antibody fragments according to the present invention can be
prepared by proteolytic hydrolysis of the antibody or by expression
in E. coli or mammalian cells (e.g. Chinese hamster ovary cell
culture or other protein expression systems) of DNA encoding the
fragment. Antibody fragments can be obtained by pepsin or papain
digestion of whole antibodies by conventional methods. For example,
antibody fragments can be produced by enzymatic cleavage of
antibodies with pepsin to provide a 5S fragment denoted F(ab')2.
This fragment can be further cleaved using a thiol reducing agent,
and optionally a blocking group for the sulfhydryl groups resulting
from cleavage of disulfide linkages, to produce 3.5S Fab'
monovalent fragment's. Alternatively, an enzymatic cleavage using
pepsin produces two monovalent Fab' fragments and an Fc fragment
directly. These methods are described, for example, by Goldenberg,
U.S. Pat. Nos. 4,036,945 and 4,331,647, and references contained
therein, which patents are hereby incorporated by reference in
their entirety. See also Porter, R. R. [Biochem. J. 73: 119-126
(1959)]. Other methods of cleaving antibodies, such as separation
of heavy chains to form monovalent light-heavy chain fragments,
further cleavage of fragments, or other enzymatic, chemical, or
genetic techniques may also be used, so long as the fragments bind
to the antigen that is recognized by the intact antibody.
[0773] Fv fragments comprise an association of VH and VL chains.
This association may be noncovalent, as described in Inbar et al.
[Proc. Nat'l Acad. Sci. USA 69:2659-62 (19720]. Alternatively, the
variable chains can be linked by an intermolecular disulfide bond
or cross-linked by chemicals such as glutaraldehyde. Preferably,
the Fv fragments comprise VH and VL chains connected by a peptide
linker. These single-chain antigen binding proteins (sFv) are
prepared by constructing a structural gene comprising DNA sequences
encoding the VH and VL domains connected by an oligonucleotide. The
structural gene is inserted into an expression vector, which is
subsequently introduced into a host cell such as E. coli. The
recombinant host cells synthesize a single polypeptide chain with a
linker peptide bridging the two V domains. Methods for producing
sFvs are described, for example, by [Whitlow and Filpula, Methods
2: 97-105 (1991); Bird et al., Science 242:423-426 (1988); Pack et
al., Bio/Technology 11:1271-77 (1993); and U.S. Pat. No. 4,946,778,
which is hereby incorporated by reference in its entirety.
[0774] Another form of an antibody fragment is a peptide coding for
a single complementarity-determining region (CDR). CDR peptides
("minimal recognition units") can be obtained by constructing genes
encoding the CDR of an antibody of interest. Such genes are
prepared, for example, by using the polymerase chain reaction to
synthesize the variable region from RNA of antibody-producing
cells. See, for example, Larrick and Fry [Methods, 2: 106-10
(1991)].
[0775] Humanized forms of non-human (e.g., murine) antibodies are
chimeric molecules of immunoglobulins, immunoglobulin chains or
fragments thereof (such as Fv, Fab, Fab', F(ab') or other
antigen-binding subsequences of antibodies) which contain minimal
sequence derived from non-human immunoglobulin. Humanized
antibodies include human immunoglobulins (recipient antibody) in
which residues from a complementary determining region (CDR) of the
recipient are replaced by residues from a CDR of a non-human
species (donor antibody) such as mouse, rat or rabbit having the
desired specificity, affinity and capacity. In some instances, Fv
framework residues of the human immunoglobulin are replaced by
corresponding non-human residues. Humanized antibodies may also
comprise residues which are found neither in the recipient antibody
nor in the imported CDR or framework sequences. In general, the
humanized antibody will comprise substantially all of at least one,
and typically two, variable domains, in which all or substantially
all of the CDR regions correspond to those of a non-human
immunoglobulin and all or substantially all of the FR regions are
those of a human immunoglobulin consensus sequence. The humanized
antibody optimally also will comprise at least a portion of an
immunoglobulin constant region (Fc), typically that of a human
immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann
et al., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct.
Biol., 2:593-596 (1992)].
[0776] Methods for humanizing non-human antibodies are well known
in the art. Generally, a humanized antibody has one or more amino
acid residues introduced into it from a source which is non-human.
These non-human amino acid residues are often referred to as import
residues, which are typically taken from an import variable domain.
Humanization can be essentially performed following the method of
Winter and co-workers [Jones et al., Nature, 321:522-525 (1986);
Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al.,
Science, 239:1534-1536 (1988)], by substituting rodent CDRs or CDR
sequences for the corresponding sequences of a human antibody.
Accordingly, such humanized antibodies are chimeric antibodies
(U.S. Pat. No. 4,816,567), wherein substantially less than an
intact human variable domain has been substituted by the
corresponding sequence from a non-human species. In practice,
humanized antibodies are typically human antibodies in which some
CDR residues and possibly some FR residues are substituted by
residues from analogous sites in rodent antibodies.
[0777] Human antibodies can also be produced using various
techniques known in the art, including phage display libraries
[Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et
al., J. Mol. Biol., 222:581 (1991)]. The techniques of Cole et al.
and Boerner et al. are also available for the preparation of human
monoclonal antibodies (Cole et al., Monoclonal Antibodies and
Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J.
Immunol., 147(1):86-95 (1991)]. Similarly, human antibodies can be
made by introduction of human immunoglobulin loci into transgenic
animals, e.g., mice in which the endogenous immunoglobulin genes
have been partially or completely inactivated. Upon challenge,
human antibody production is observed, which closely resembles that
seen in humans in all respects, including gene rearrangement,
assembly, and antibody repertoire. This approach is described, for
example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825;
5,625,126; 5,633,425; 5,661,016, and in the following scientific
publications: Marks et al., Bio/Technology 10,: 779-783 (1992);
Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368
812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51
(1996); Neuberger, Nature Biotechnology 14: 826 (1996); and Lonberg
and Huszar, Intern. Rev. Immunol. 13, 65-93 (1995).
[0778] Preferably, the antibody of this aspect of the present
invention specifically binds at least one epitope of the
polypeptide variants of the present invention. As used herein, the
term "epitope" refers to any antigenic determinant on an antigen to
which the paratope of an antibody binds.
[0779] Epitopic determinants usually consist of chemically active
surface groupings of molecules such as amino acids or carbohydrate
side chains and usually have specific three dimensional structural
characteristics, as well as specific charge characteristics.
[0780] Optionally, a unique epitope may be created in a variant due
to a change in one or more post-translational modifications,
including but not limited to glycosylation and/or phosphorylation,
as described below. Such a change may also cause a new epitope to
be created, for example through removal of glycosylation at a
particular site.
[0781] An epitope according to the present invention may also
optionally comprise part or all of a unique sequence portion of a
variant according to the present invention in combination with at
least one other portion of the variant which is not contiguous to
the unique sequence portion in the linear polypeptide itself, yet
which are able to form an epitope in combination. One or more
unique sequence portions may optionally combine with one or more
other non-contiguous portions of the variant (including a portion
which may have high homology to a portion of the known protein) to
form an epitope.
Immunoassays
[0782] In another embodiment of the present invention, an
immunoassay can be used to qualitatively or quantitatively detect
and analyze markers in a sample. This method comprises: providing
an antibody that specifically binds to a marker; contacting a
sample with the antibody; and detecting the presence of a complex
of the antibody bound to the marker in the sample.
[0783] To prepare an antibody that specifically binds to a marker,
purified protein markers can be used. Antibodies that specifically
bind to a protein marker can be prepared using any suitable methods
known in the art.
[0784] After the antibody is provided, a marker can be detected
and/or quantified using any of a number of well recognized
immunological binding assays. Useful assays include, for example,
an enzyme immune assay (EIA) such as enzyme-linked immunosorbent
assay (ELISA), a radioimmune assay (RIA), a Western blot assay, or
a slot blot assay see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110;
4,517,288; and 4,837,168). Generally, a sample obtained from a
subject can be contacted with the antibody that specifically binds
the marker.
[0785] Optionally, the antibody can be fixed to a solid support to
facilitate washing and subsequent isolation of the complex, prior
to contacting the antibody with a sample. Examples of solid
supports include but are not limited to glass or plastic in the
form of, e.g., a microtiter plate, a stick, a bead, or a microbead.
Antibodies can also be attached to a solid support.
[0786] After incubating the sample with antibodies, the mixture is
washed and the antibody-marker complex formed can be detected. This
can be accomplished by incubating the washed mixture with a
detection reagent. Alternatively, the marker in the sample can be
detected using an indirect assay, wherein, for example, a second,
labeled antibody is used to detect bound marker-specific antibody,
and/or in a competition or inhibition assay wherein, for example, a
monoclonal antibody which binds to a distinct epitope of the marker
are incubated simultaneously with the mixture.
[0787] Throughout the assays, incubation and/or washing steps may
be required after each combination of reagents. Incubation steps
can vary from about 5 seconds to several hours, preferably from
about 5 minutes to about 24 hours. However, the incubation time
will depend upon the assay format, marker, volume of solution,
concentrations and the like. Usually the assays will be carried out
at ambient temperature, although they can be conducted over a range
of temperatures, such as 10.degree. C. to 40.degree. C.
[0788] The immunoassay can be used to determine a test amount of a
marker in a sample from a subject. First, a test amount of a marker
in a sample can be detected using the immunoassay methods described
above. If a marker is present in the sample, it will form an
antibody-marker complex with an antibody that specifically binds
the marker under suitable incubation conditions described above.
The amount of an antibody-marker complex can optionally be
determined by comparing to a standard. As noted above, the test
amount of marker need not be measured in absolute units, as long as
the unit of measurement can be compared to a control amount and/or
signal.
[0789] Preferably used are antibodies which specifically interact
with the polypeptides of the present invention and not with wild
type proteins or other isoforms thereof, for example. Such
antibodies are directed, for example, to the unique sequence
portions of the polypeptide variants of the present invention,
including but not limited to bridges, heads, tails and insertions
described in greater detail below. Preferred embodiments of
antibodies according to the present invention are described in
greater detail with regard to the section entitled
"Antibodies".
[0790] Radio-immunoassay (RIA): In one version, this method
involves precipitation of the desired substrate and in the methods
detailed hereinbelow, with a specific antibody and radiolabelled
antibody binding protein (e.g., protein A labeled with I.sup.125)
immobilized on a precipitable carrier such as agarose beads. The
number of counts in the precipitated pellet is proportional to the
amount of substrate.
[0791] In an alternate version of the RIA, a labeled substrate and
an unlabelled antibody binding protein are employed. A sample
containing an unknown amount of substrate is added in varying
amounts. The decrease in precipitated counts from the labeled
substrate is proportional to the amount of substrate in the added
sample.
[0792] Enzyme linked immunosorbent assay (ELISA): This method
involves fixation of a sample (e.g., fixed cells or a proteinaceous
solution) containing a protein substrate to a surface such as a
well of a microtiter plate. A substrate specific antibody coupled
to an enzyme is applied and allowed to bind to the substrate.
Presence of the antibody is then detected and quantitated by a
colorimetric reaction employing the enzyme coupled to the antibody.
Enzymes commonly employed in this method include horseradish
peroxidase and alkaline phosphatase. If well calibrated and within
the linear range of response, the amount of substrate present in
the sample is proportional to the amount of color produced. A
substrate standard is generally employed to improve quantitative
accuracy.
[0793] Western blot: This method involves separation of a substrate
from other protein by means of an acrylamide gel followed by
transfer of the substrate to a membrane (e.g., nylon or PVDF).
Presence of the substrate is then detected by antibodies specific
to the substrate, which are in turn detected by antibody binding
reagents. Antibody binding reagents may be, for example, protein A,
or other antibodies. Antibody binding reagents may be radiolabelled
or enzyme linked as described hereinabove. Detection may be by
autoradiography, colorimetric reaction or chemiluminescence. This
method allows both quantitation of an amount of substrate and
determination of its identity by a relative position on the
membrane which is indicative of a migration distance in the
acrylamide gel during electrophoresis.
[0794] Immunohistochemical analysis: This method involves detection
of a substrate in situ in fixed cells by substrate specific
antibodies. The substrate specific antibodies may be enzyme linked
or linked to fluorophores. Detection is by microscopy and
subjective evaluation. If enzyme linked antibodies are employed, a
colorimetric reaction may be required.
[0795] Fluorescence activated cell sorting (FACS): This method
involves detection of a substrate in situ in cells by substrate
specific antibodies. The substrate specific antibodies are linked
to fluorophores. Detection is by means of a cell sorting machine
which reads the wavelength of light emitted from each cell as it
passes through a light beam. This method may employ two or more
antibodies simultaneously.
Radio-Imaging Methods
[0796] These methods include but are not limited to, positron
emission tomography (PET) single photon emission computed
tomography (SPECT). Both of these techniques are non-invasive, and
can be used to detect and/or measure a wide variety of tissue
events and/or functions, such as detecting cancerous cells for
example. Unlike PET, SPECT can optionally be used with two labels
simultaneously. SPECT has some other advantages as well, for
example with regard to cost and the types of labels that can be
used. For example, U.S. Pat. No. 6,696,686 describes the use of
SPECT for detection of breast cancer, and is hereby incorporated by
reference as if fully set forth herein.
Display Libraries
[0797] According to still another aspect of the present invention
there is provided a display library comprising a plurality of
display vehicles (such as phages, viruses or bacteria) each
displaying at least 6, at least 7, at least 8, at least 9, at least
10, 10-15, 12-17, 15-20, 15-30 or 20-50 consecutive amino acids
derived from the polypeptide sequences of the present
invention.
[0798] Methods of constructing such display libraries are well
known in the art. Such methods are described in, for example, Young
A C, et al., "The three-dimensional structures of a polysaccharide
binding antibody to Cryptococcus neoformans and its complex with a
peptide from a phage display library: implications for the
identification of peptide mimotopes" J Mol Biol 1997 Dec. 12;
274(4):622-34; Giebel L B et al. "Screening of cyclic peptide phage
libraries identifies ligands that bind streptavidin with high
affinities" Biochemistry 1995 Nov. 28; 34(47):15430-5; Davies E L
et al., "Selection of specific phage-display antibodies using
libraries derived from chicken immunoglobulin genes" J Immunol
Methods 1995 Oct. 12; 186(1):125-35; Jones C R T al. "Current
trends in molecular recognition and bioseparation" J Chromatogr A
1995 Jul. 14; 707(1):3-22; Deng S J et al. "Basis for selection of
improved carbohydrate-binding single-chain antibodies from
synthetic gene libraries" Proc Natl Acad Sci USA 1995 May 23;
92(11):4992-6; and Deng S J et al. "Selection of antibody
single-chain variable fragments with improved carbohydrate binding
by phage display" J Biol Chem 1994 Apr. 1; 269(13):9533-8, which
are incorporated herein by reference.
[0799] The following sections relate to Candidate Marker Examples
(first section) and to Experimental Data for these Marker Examples
(second section).
Candidate Marker Examples Section
[0800] This Section relates to Examples of sequences according to
the present invention, including illustrative methods of selection
thereof.
[0801] Description of the methodology undertaken to uncover the
biomolecular sequences of the present invention
[0802] Human ESTs and cDNAs were obtained from GenBank versions 136
(Jun. 15, 2003 ftp dot ncbi dot nih dot gov/genbank/release dot
notes/gb136 dot release dot notes); NCBI genome assembly of April
2003; RefSeq sequences from June 2003; Genbank version 139
(December 2003); Human Genome from NCBI (Build 34) (from October
2003); and RefSeq sequences from December 2003; and from the
LifeSeq library of Incyte Corporation (ESTs only; Wilmington, Del.,
USA). With regard to GenBank sequences, the human EST sequences
from the EST (GBEST) section and the human mRNA sequences from the
primate (GBPRI) section were used; also the human nucleotide RefSeq
mRNA sequences were used (see for example dot ncbi dot nlm dot nih
dot gov/Genbank/GenbankOverview dot html and for a reference to the
EST section, see dot ncbi dot nlm dot nih dot gov/dbEST/; a general
reference to dbEST, the EST database in GenBank, may be found in
Boguski et al, Nat Genet. 1993 August; 4(4):332-3; all of which are
hereby incorporated by reference as if fully set forth herein).
[0803] Novel splice variants were predicted using the LEADS
clustering and assembly system as described in Sorek, R., Ast, G.
& Graur, D. Alu-containing exons are alternatively spliced.
Genome Res 12, 1060-7 (2002); U.S. Pat. No. 6,625,545; and U.S.
patent application No. 10/426,002, published as US20040101876 on
May 27, 2004; all of which are hereby incorporated by reference as
if fully set forth herein. Briefly, the software cleans the
expressed sequences from repeats, vectors and immunoglobulins. It
then aligns the expressed sequences to the genome taking
alternatively splicing into account and clusters overlapping
expressed sequences into "clusters" that represent genes or partial
genes.
[0804] These were annotated using the GeneCarta (Compugen,
Tel-Aviv, Israel) platform. The GeneCarta platform includes a rich
pool of annotations, sequence information (particularly of spliced
sequences), chromosomal information, alignments, and additional
information such as SNPs, gene ontology terms, expression profiles,
functional analyses, detailed domain structures, known and
predicted proteins and detailed homology reports.
[0805] A brief explanation is provided with regard to the method of
selecting the candidates. However, it should noted that this
explanation is provided for descriptive purposes only, and is not
intended to be limiting in any way. The potential markers were
identified by a computational process that was designed to find
genes and/or their splice variants that are over-expressed in tumor
tissues, by using databases of expressed sequences. Various
parameters related to the information in the EST libraries,
determined according to a manual classification process, were used
to assist in locating genes and/or splice variants thereof that are
over-expressed in cancerous tissues. The detailed description of
the selection method is presented in Example 1 below. The cancer
biomarkers selection engine and the following wet validation stages
are schematically summarized in FIG. 1.
Example 1
Identification of Differentially Expressed Gene
Products--Algorithm
[0806] In order to distinguish between differentially expressed
gene products and constitutively expressed genes (i.e., house
keeping genes) an algorithm based on an analysis of frequencies was
configured. A specific algorithm for identification of transcripts
over expressed in cancer is described hereinbelow.
[0807] Dry analysis
[0808] Library annotation--EST libraries are manually classified
according to: [0809] Tissue origin [0810] Biological
source--Examples of frequently used biological sources for
construction of EST libraries include cancer cell-lines; normal
tissues; cancer tissues; fetal tissues; and others such as normal
cell lines and pools of normal cell-lines, cancer cell-lines and
combinations thereof. A specific description of abbreviations used
below with regard to these tissues/cell lines etc is given above.
[0811] Protocol of library construction--various methods are known
in the art for library construction including normalized library
construction; non-normalized library construction; subtracted
libraries; ORESTES and others. It will be appreciated that at times
the protocol of library construction is not indicated.
[0812] The following rules are followed:
[0813] EST libraries originating from identical biological samples
are considered as a single library.
[0814] EST libraries which included above-average levels of
contamination, such as DNA contamination for example, were
eliminated. The presence of such contamination was determined as
follows. For each library, the number of unspliced ESTs that are
not fully contained within other spliced sequences was counted. If
the percentage of such sequences (as compared to all other
sequences) was at least 4 standard deviations above the average for
all libraries being analyzed, this library was tagged as being
contaminated and was eliminated from further consideration in the
below analysis (see also Sorek, R. & Safer, H. M. A novel
algorithm for computational identification of contaminated EST
libraries. Nucleic Acids Res 31, 1067-74 (2003) for further
details).
[0815] Clusters (genes) having at least five sequences including at
least two sequences from the tissue of interest were analyzed.
Splice variants were identified by using the LEADS software package
as described above.
Example 2
Identification of Genes Over Expressed in Cancer.
[0816] Two different scoring algorithms were developed.
[0817] Libraries score--candidate sequences which are supported by
a number of cancer libraries, are more likely to serve as specific
and effective diagnostic markers.
[0818] The basic algorithm--for each cluster the number of cancer
and normal libraries contributing sequences to the cluster was
counted. Fisher exact test was used to check if cancer libraries
are significantly over-represented in the cluster as compared to
the total number of cancer and normal libraries.
[0819] Library counting: Small libraries (e.g., less than 1000
sequences) were excluded from consideration unless they participate
in the cluster. For this reason, the total number of libraries is
actually adjusted for each cluster.
[0820] Clones no. score--Generally, when the number of ESTs is much
higher in the cancer libraries relative to the normal libraries it
might indicate actual over-expression.
[0821] The algorithm--
[0822] Clone counting: For counting EST clones each library
protocol class was given a weight based on our belief of how much
the protocol reflects actual expression levels:
[0823] (i) non-normalized: 1
[0824] (ii) normalized: 0.2
[0825] (iii) all other classes: 0.1
[0826] Clones number score--The total weighted number of EST clones
from cancer libraries was compared to the EST clones from normal
libraries. To avoid cases where one library contributes to the
majority of the score, the contribution of the library that gives
most clones for a given cluster was limited to 2 clones.
[0827] The score was computed as
c + 1 C / n + 1 N ##EQU00001##
[0828] where:
[0829] c--weighted number of "cancer" clones in the cluster.
[0830] C--weighted number of clones in all "cancer" libraries.
[0831] n--weighted number of "normal" clones in the cluster.
[0832] N--weighted number of clones in all "normal" libraries.
[0833] Clones number score significance--Fisher exact test was used
to check if EST clones from cancer libraries are significantly
over-represented in the cluster as compared to the total number of
EST clones from cancer and normal libraries.
[0834] Two search approaches were used to find either general
cancer-specific candidates or tumor specific candidates. [0835]
Libraries/sequences originating from tumor tissues are counted as
well as libraries originating from cancer cell-lines ("normal"
cell-lines were ignored). [0836] Only libraries/sequences
originating from tumor tissues are counted
Example 3
Identification of Tissue Specific Genes
[0837] For detection of tissue specific clusters, tissue
libraries/sequences were compared to the total number of
libraries/sequences in cluster. Similar statistical tools to those
described in above were employed to identify tissue specific genes.
Tissue abbreviations are the same as for cancerous tissues, but are
indicated with the header "normal tissue".
[0838] The algorithm--for each tested tissue T and for each tested
cluster the following were examined:
[0839] 1. Each cluster includes at least 2 libraries from the
tissue T. At least 3 clones (weighed--as described above) from
tissue T in the cluster; and
[0840] 2. Clones from the tissue T are at least 40% from all the
clones participating in the tested cluster
[0841] Fisher exact test P-values were computed both for library
and weighted clone counts to check that the counts are
statistically significant.
Example 4
[0842] Identification of Splice Variants Over Expressed in Cancer
of Clusters which are Not Over Expressed in Cancer
[0843] Cancer-specific splice variants containing a unique region
were identified.
[0844] Identification of Unique Sequence Regions in Splice
Variants
[0845] A Region is defined as a group of adjacent exons that always
appear or do not appear together in each splice variant.
[0846] A "segment" (sometimes referred also as "seg" or "node") is
defined as the shortest contiguous transcribed region without known
splicing inside.
[0847] Only reliable ESTs were considered for region and segment
analysis. An EST was defined as unreliable if:
[0848] (i) Unspliced;
[0849] (ii) Not covered by RNA;
[0850] (iii) Not covered by spliced ESTs; and
[0851] (iv) Alignment to the genome ends in proximity of long
poly-A stretch or starts in proximity of long poly-T stretch.
[0852] Only reliable regions were selected for further scoring.
Unique sequence regions were considered reliable if:
[0853] (i) Aligned to the genome; and
[0854] (ii) Regions supported by more than 2 ESTs.
[0855] The Algorithm
[0856] Each unique sequence region divides the set of transcripts
into 2 groups:
[0857] (i) Transcripts containing this region (group TA).
[0858] (ii) Transcripts not containing this region (group TB).
[0859] The set of EST clones of every cluster is divided into 3
groups:
[0860] (i) Supporting (originating from) transcripts of group TA
(S1).
[0861] (ii) Supporting transcripts of group TB (S2).
[0862] (iii) Supporting transcripts from both groups (S3).
[0863] Library and clones number scores described above were given
to S1 group.
[0864] Fisher Exact Test P-values were used to check if:
[0865] S1 is significantly enriched by cancer EST clones compared
to S2; and
[0866] S1 is significantly enriched by cancer EST clones compared
to cluster background (S1+S2+S3).
[0867] Identification of unique sequence regions and division of
the group of transcripts accordingly is illustrated in FIG. 2. Each
of these unique sequence regions corresponds to a segment, also
termed herein a "node".
[0868] Region 1: common to all transcripts, thus it is not
considered for detecting variants; Region 2: specific to Transcript
1; Region 3: specific to Transcripts 2 and 3; Region 4: specific to
Transcript 3; Region 5: specific to Transcript 1 and 2; Region 6:
specific to Transcript 1.
Example 5
[0869] Identification of Cancer Specific Splice Variants of Genes
Over Expressed in Cancer
[0870] A search for EST supported (no mRNA) regions for genes
of:
[0871] (i) known cancer markers
[0872] (ii) Genes shown to be over-expressed in cancer in published
micro-array experiments.
[0873] Reliable EST supported-regions were defined as supported by
minimum of one of the following:
[0874] (i) 3 spliced ESTs; or
[0875] (ii) 2 spliced ESTs from 2 libraries;
[0876] (iii) 10 unspliced ESTs from 2 libraries, or
[0877] (iv) 3 libraries.
Actual Marker Examples
[0878] The following examples relate to specific actual marker
examples.
Experimental Examples Section
[0879] This Section relates to Examples describing experiments
involving these sequences, and illustrative, non-limiting examples
of methods, assays and uses thereof. The materials and experimental
procedures are explained first, as all experiments used them as a
basis for the work that was performed.
[0880] The markers of the present invention were tested with regard
to their expression in various cancerous and non-cancerous tissue
samples. A description of the samples used in the lung cancer panel
is provided in Tables 2 and 2.sub.--1, below. A description of the
samples used in the normal tissue panel is provided in Tables 3 and
3.sub.--1, below. The key for Table 2.sub.--1 is provided in Table
2.sub.--1.sub.--1 below. Tests were then performed as described in
the "Materials and Experimental Procedures" section below.
TABLE-US-00003 TABLE 2 Tissue samples in testing panel sample
rename Lot No. source pathology Grade gender/age 1-B-Adeno G1
A504117 Biochain Adenocarcinoma 1 F/29 2-B-Adeno G1 A504118
Biochain Adenocarcinoma 1 M/64 95-B-Adeno G1 A610063 Biochain
Adenocarcinoma 1 F/54 12-B-Adeno G2 A504119 Biochain Adenocarcinoma
2 F/74 75-B-Adeno G2 A609217 Biochain Adenocarcinoma 2 M/65
77-B-Adeno G2 A608301 Biochain Adenocarcinoma 2 M/44 13-B-Adeno
G2-3 A504116 Biochain Adenocarcinoma 2-3 M/64 89-B-Adeno G2-3
A609077 Biochain Adenocarcinoma 2-3 M/62 76-B-Adeno G3 A609218
Biochain Adenocarcinoma 3 M/57 94-B-Adeno G3 A610118 Biochain
Adenocarcinoma 3 M/68 3-CG-Adeno CG-200 Ichilov Adenocarcinoma NA
14-CG-Adeno CG-111 Ichilov Adenocarcinoma M/68 15-CG-Bronch adeno
CG-244 Ichilov Bronchioloalveolar M/74 adenocarcinoma 45-B-Alvelous
Adeno A501221 Biochain Alveolus F/50 carcinoma 44-B-Alvelous Adeno
G2 A501123 Biochain Alveolus 2 F/61 carcinoma 19-B-Squamous G1
A408175 Biochain Squamous 1 M/78 carcinoma 16-B-Squamous G2 A409091
Biochain Squamous 2 F/68 carcinoma 17-B-Squamous G2 A503183
Biochain Squamous 2 M/57 carcinoma 21-B-Squamous G2 A503187
Biochain Squamous 2 M/52 carcinoma 78-B-Squamous G2 A607125
Biochain Squamous Cell 2 M/62 Carcinoma 80-B-Squamous G2 A609163
Biochain Squamous Cell 2 M/74 Carcinoma 18-B-Squamous G2-3 A503387
Biochain Squamous Cell 2-3 M/63 Carcinoma 81-B-Squamous G3 A609076
Biochain Squamous 3 m/53 Carcinoma 79-B-Squamous G3 A609018
Biochain Squamous Cell 3 M/67 Carcinoma 20-B-Squamous A501121
Biochain Squamous M/64 Carcinoma 22-B-Squamous A503386 Biochain
Squamous M/48 Carcinoma 88-B-Squamous A609219 Biochain Squamous
Cell M/64 Carcinoma 100-B-Squamous A409017 Biochain Squamous M/64
Carcinoma 23-CG-Squamous CG-109 (1) Ichilov Squamous M/65 Carcinoma
24-CG-Squamous CG-123 Ichilov Squamous M/76 Carcinoma
25-CG-Squamous CG-204 Ichilov Squamous M/72 Carcinoma 87-B-Large
cell G3 A609165 Biochain Large Cell 3 F/47 Carcinoma 38-B-Large
cell A504113 Biochain Large cell M/58 39-B-Large cell A504114
Biochain Large cell F/35 82-B-Large cell A609170 Biochain Large
Cell M/68 Neuroendocrine Carcinoma 30-B-Small cell carci G3 A501389
Biochain small cell 3 M/34 31-B-Small cell carci G3 A501390
Biochain small cell 3 F/59 32-B-Small cell carci G3 A501391
Biochain small cell 3 M/30 33-B-Small cell carci G3 A504115
Biochain small cell 3 M 86-B-Small cell carci G3 A608032 Biochain
Small Cell 3 F/52 Carcinoma 83-B-Small cell carci A609162 Biochain
Small Cell F/47 Carcinoma 84-B-Small cell carci A609167 Biochain
Small Cell F/59 Carcinoma 85-B-Small cell carci A609169 Biochain
Small Cell M/66 Carcinoma 46-B-N M44 A501124 Biochain Normal M44
F/61 47-B-N A503205 Biochain Normal PM M/26 48-B-N A503206 Biochain
Normal PM M/44 49-B-N A503384 Biochain Normal PM M/27 50-B-N
A503385 Biochain Normal PM M/28 90-B-N A608152 Biochain Normal
(Pool 2) pool 2 PM 91-B-N A607257 Biochain Normal (Pool 2) pool 2
PM 92-B-N A503204 Biochain Normal PM m/28 93-Am-N 111P0103A Ambion
Normal PM F/61 96-Am-N 36853 Ambion Normal PM F/43 97-Am-N 36854
Ambion Normal PM M/46 98-Am-N 36855 Ambion Normal PM F/72 99-Am-N
36856 Ambion Normal PM M/31
TABLE-US-00004 TABLE 2_1 Lung cancer testing panel sample id (GCI)/
case id TISSUE RNA (Asterand)/ ID ID lot (GCI)/ (GCI)/ no. specimen
Sample Source/ sample (old ID ID Diag Specimen Tum Tissue Delivery
name samples) (Asterand) (Asterand) Diag remarks location Gr TNM CS
% Gen LC GCI 1-GC- 7Z9V4 7Z9V4AYM Aden BC IA 80 F BAC- SIA LC GCI
2-GC- ZW2AQ ZW2AQARP Aden BC IB 70 F BAC- SIB LC Bioch 72- A501123
AC 2 UN F (44)- Bc- BAC LC Bioch 73- A501221 AC UN UN F (45)- Bc-
BAC LC GCI 4-GC- 3MOPL 3MOPLA79 Aden IA 60 M Adeno- SIA LC GCI
5-GC- KOJXD KOJXDAV4 Aden IA 90 F Adeno- SIA LC GCI 6-GC- X2Q44
X2Q44A79 Aden IA 85 M Adeno- SIA LC GCI 7-GC- 6BACZ 6BACZAP5 Aden
IA 60 F Adeno- SIA LC GCI 8-GC- BS9AF BS9AFA3E Aden IA 55 F Adeno-
SIA LC GCI 9-GC- UCLOA UCLOAA9L Aden IA 80 F Adeno- SIA LC GCI
10-GC- BVYK3 BVYK3A7Z Aden IA 60 F Adeno- SIA LC GCI 11-GC- U4DM4
U4DM4AFZ Aden IB 65 F Adeno- SIB LC GCI 12-GC- OWX5Y OWX5YA3S Aden
IB 90 M Adeno- SIB LC GCI 13-GC- XYY96 XYY96A6B Aden IIA 70 F
Adeno- SIIA LC GCI 14-GC- SO7B1 SO7B1AIJ Aden IIA 70 M Adeno- SIIA
LC GCI 15-GC- QANSY QANSYACD Aden IIIA 65 F Adeno- SIIIA LC Bioch
16- A610063 Aden 1 UN F (95)- BC- Adeno LC Bioch 17- A609077 Aden
2-3 UN M (89)- Bc- Adeno LC Bioch 18- A609218 Aden 3 UN M (76)- Bc-
Adeno LC Bioch 74-(2)- A504118 Aden 1 UN M Bc- Adeno LC Bioch 76-
A609217 Aden 2 UN M (75)- Bc- Adeno LC Bioch 77- A504119 Aden 2 UN
F (12)- Bc- Adeno LC Bioch 78- A504116 Aden 2-3 UN M (13)- Bc-
Adeno LC Bioch 79- A610118 Aden 3 UN M (94)- Bc- Adeno LC Ichilov
80-(3)- CG- Aden UN UN F Ic- 200 Adeno LC Ichilov 81- CG- Aden UN
UN M (14)-Ic- 111 Adeno LC Aster 19-As- 9220 9418 9418A1 SQ 1
TXN0M0 Occult 80 M Sq-S0 LC GCI 20-GC- U2QHS U2QHSA2N SQ IA 55 F
Sq-SIA LC GCI 21-GC- TRQR7 TRQR7ACD SQ IB 75 M Sq-SIB LC Aster
22-As- 17581 32603 32603B1 SQ 3 T2N0M0 IB 90 M Sq-SIB LC Aster
23-As- 18309 41454 41454B1 SQ 2 T2N0MX IB 100 M Sq-SIB LC Aster
24-As- 9217 9415 9415B1 SQ 2 T2N0M0 IB 90 M Sq-SIB LC GCI 25-GC-
RXQ1P RXQ1PAEA SQ IIB 55 F Sq-SIIB LC GCI 26-GC- KB5KH KB5KHA6X SQ
IIB 65 M Sq-SIIB LC GCI 27-GC- LAYMB LAYMBALF SQ IIIA 65 F Sq-
SIIIA LC Ichilov 28- CG- SQ UN UN M (23)-Ic- 109 (1) Sq LC Ichilov
29- CG- SQ UN UN M (25)-Ic- 204 Sq LC Bioch 30- A408175 SQ 1 UN M
(19)- Bc-Sq LC Bioch 31- A607125 SQ 2 UN M (78)- Bc-Sq LC Bioch 32-
A409091 SQ 2 UN F (16)- Bc-Sq LC Bioch 33- A609163 SQ 2 UN M (80)-
Bc-Sq LC Bioch 34- A503387 SQ 2-3 UN M (18)- Bc-Sq LC Bioch 35-
A609076 SQ 3 UN M (81)- Bc-Sq LC Bioch 82- A503187 SQ 2 UN M (21)-
Bc-Sq LC Bioch 83- A503183 SQ 2 UN M (17)- Bc-Sq LC Bioch 84-
A609018 SQ 3 UN M (79)- Bc-Sq LC Bioch 85- A503386 SQ UN UN M (22)-
Bc-Sq LC Bioch 86- A501121 SQ UN UN M (20)- Bc-Sq LC Bioch 87-
A609219 SQ UN UN M (88)- Bc-Sq LC Bioch 88- A409017 SQ UN UN M
(100)- Bc-Sq LC Ichilov 89- CG- SQ UN UN M (24)-Ic- 123 Sq LC GCI
36-GC- AF8AL AF8ALAAL LCC IA 85 M LCC- SIA LC GCI 37-GC- O62XU
O62XUA1X LCC IB 75 F LCC- SIB LC GCI 38-GC- OLOIM OLOIMAS1 LCC IB
70 M LCC- SIB LC GCI 39-GC- 1ZWSV 1ZWSVAB9 LCC IIB 50 M LCC- SIIB
LC GCI 40-GC- 2YHOD 2YHODA1H LCC NSCC . . . IIB 95 M LCC- SIIB LC
GCI 41-GC- 38B4D 38B4DAQK LCC IIB 90 F LCC- SIIB LC Bioch 90-
A504114 LCC UN UN F (39)- Bc- LCC LC Bioch 91- A609165 LCC 3 UN F
(87)- Bc- LCC LC Bioch 92- A504113 LCC UN UN M (38)- Bc- LCC LC
Bioch 93- A609170 LCNC UN UN M (82)- Bc- LCC LC GCI 42-GC- QPJQL
QPJQLAF6 SCC NC 3 IB 65 F SCC- SIB LC Bioch 43- A501391 SCC UN M
(32)- Bc- SCC LC Bioch 44- A501389 SCC 3 UN M (30)- Bc- SCC LC
Bioch 45- A609162 SCC UN UN F (83)- Bc- SCC LC Bioch 46- A608032
SCC 3 UN F (86)- Bc- SCC LC Bioch 47- A501390 SCC UN F (31)- Bc-
SCC LC Bioch 48- A609167 SCC UN UN F (84)- Bc- SCC LC Bioch 49-
A609169 SCC UN UN M (85)- Bc- SCC LC Bioch 50- A504115 SCC UN M
(33)- Bc- SCC LN Aster 51-As- 9078 9275 9275B1 Norm-L PS M N-PS LN
Aster 52-As- 8757 8100 8100B1 Norm-L PM (Right), F N-PM Lobe
Inferior LN Aster 53-As- 6692 6161 6161A1 Norm-L PM M N-PM LN Aster
54-As- 7900 7180 7180F1 Norm-L PM F N-PM LN Aster 55-As- 8771 8163
8163A1 Norm-L PM (Left), M
N-PM Lobe Superior LN Aster 56-As- 13094 19763 19763A1 Norm-L PM M
N-PM LN Aster 57-As- 19174 40654 40654A2 Norm-L PM F N-PM LN Aster
58-As- 13128 19642 19642A1 Norm-L PM F N-PM LN Aster 59-As- 14374
20548 20548C1 Norm-L PM (Right), F N-PM Lobe Superior LN Amb 60-
36856 N- PM M (99)- PM Am-N PM LN Amb 61- 36853 N- PM F (96)- PM
Am-N PM LN Amb 62- 36854 N- PM M (97)- PM Am-N PM LN Amb 63-
111P0103A N- PM- F (93)- PM ICH Am-N PM LN Amb 64- 36855 N- PM F
(98)- PM Am-N PM LN Bioch 67- A503385 N- PM M (50)- PM Bc-N PM LN
Bioch 68- A503204 N- PM M (92)- PM Bc-N PM LN Bioch 69- A607257
N-P2- PM P2 (91)- PM Bc-N PM LN Bioch 70- A608152 N-P2 PM P2 (90)-
PM Bc-N PM LN Bioch 71- A503206 N- PM M (48)- PM Bc-N PM # of # Y.
Cig. Use # Y. Cause Smoking Per of off Sm Sm Dr # Recovery of Exc.
Tissue age Ethnic B Status day Tobacco Tobacco PY? ppl Al Dr Type
Death Y. LC 63 WCAU Prev 20 15 27 N -- Y 0 Surg 2001 U. LC 56 WCAU
Prev 15 28 10 Y 1 Y 6 Surg 2002 U. LC 61 LC 50 LC 68 WCAU Nev U. --
-- -- N -- N -- Surg 2001 LC 64 WCAU Prev 15 40 7 Y 1 N 0 Surg 2003
U. LC 58 WCAU Prev 10 47 0 Y 2 N -- Surg 2004 U. LC 65 WCAU Curr 6
30 -- Y 1 N -- Surg 2004 U. LC 59 WCAU Curr 20 40 -- N -- N -- Surg
2004 U. LC 69 WCAU Curr 30 52 -- Y 4 N -- Surg 2005 U. LC 60 WCAU
Curr 40 40 -- N -- N -- Surg 2002 U. LC 68 WCAU Prev 5 4 43 N -- N
-- Surg 2003 U. LC 69 WCAU Curr 10 -- -- -- N -- Surg 2002 U. LC 62
WCAU Prev 6 40 6 N -- Y 0 Surg 2004 U. LC 56 WCAU Curr 30 25 -- Y 1
N -- Surg 2001 U. LC 61 WCAU Curr 30 36 -- Y 1 N -- Surg 2004 U. LC
54 LC 62 LC 57 LC 64 LC 65 LC 74 LC 64 LC 68 LC 56 LC 68 LC 67 CAU
Curr 11-20 31-40 O Surg 2003 U. LC 68 WCAU Prev 10 20 0 N -- N --
Surg 2004 U. LC 62 WCAU Prev 20 50 0 Y 5 N -- Surg 2005 U. LC 73
CAU Prev O Surg 2004 U. LC 66 CAU Prev. 11-20 45 P Surg 2005 U. LC
65 CAU Curr 6-10 41-50 O Surg 2002 U. LC 44 WCAU Prev 20 20 0 Y 2 N
-- Surg 2004 U. LC 68 WCAU Prev 40 40 0 Y 2 N -- Surg 2004 U. LC 58
WCAU Prev 50 40 1 Y 2 N -- Surg 2004 U. LC 65 LC 72 LC 78 LC 62 LC
68 LC 74 LC 63 LC 53 LC 52 LC 57 LC 67 LC 48 LC 64 LC 64 LC 64 LC
76 LC 45 WCAU Prev 45 33 0 Y 2 Y 28 Surg 2004 U. LC 60 WCAU Prev 30
45 0 Y 3 N -- Surg 2004 U. LC 68 WCAU Prev -- 55 -- Y -- N -- Surg
2001 U. LC 51 WCAU Prev 20 12 22 Y 1 N -- Surg 2004 U. LC 62 WCAU
Prev 40 40 0 Y 2 Y 12 Surg 2004 U. LC 70 WCAU Prev 30 50 -- Y 2 Y
13 Surg 2002 U. LC 35 LC 47 LC 58 LC 68 LC 62 WCAU Prev 20 35 0.15
Y 2 N -- Surg 2003 U. LC 30 LC 34 LC 47 LC 52 LC 59 LC 59 LC 66 LC
LN 22 CAU Nev U. NU Surg 2003 LN 26 CAU Nev U. O Aut CA 2003 LN 37
CAU Nev U. C Aut MCE 2002 LN 76 CAU Prev Aut CPulA 2002 U. LN 81
CAU Prev 41 or 31-40 O Aut CA 2003 U. more LN 0 CAU Prev 21-40
41-50 P Aut IC U. LN 69 CAU Curr 21-40 31-40 P Aut CPulA 2005 U. LN
75 CAU Aut CPulA 2004 LN 75 CAU Aut CerA 2004 LN 31 LN 43 LN 46 LN
61 LN 72 LN 28 LN 28 LN 24, 29 LN 27, 28 LN 44
TABLE-US-00005 TABLE 2_1_1 Key Full Name # Cig. Per day Number of
Cigarettes per day # Dr Number of Drinks # of Y. Use of Tobacco
Number of Years Using Tobacco # Y. off Tobacco Number of Years Off
Tobacco AC Alveolus carcinoma Aden ADENOCARCINOMA Amb Ambion Aster
Asterand Aut Autopsy BC BRONCHIOLOALVEOLAR CARCINOMA Bioch Biochain
C Current Use CA Cardiac arrest CAU Caucasian Cer A Cerebrovascular
accident CPul A Cardiopulmonary arrest CS Cancer Stage Curr U.
Current Use Diag Diagnosis Dr Al Drink Alcohol? Exc Y. Excision
Year Gen Gender Gr Grade Height HT IC Ischemic cardiomyopathy LC
Lung Cancer LCC LARGE CELL CARCINOMA LCNC Large Cell Neuroendocrine
Carcinoma LN Lung Normal MCE Massive cerebral edema N No NC
NEUROENDOCRINE CARCINOMA Nev. U. Never Used Norm-L Normal Lung
N-P2-PM Normal (Pool 2)-PM N-PM Normal-PM NSCC . . . NON-SMALL CELL
CARCINOMA WITH SARCOMUTOUS TRANSFORMTAIO NU Never used O Occasional
Use P Previous Use P2 Pool 2 Prev U. Previous Use SQ Squamous Cell
Carcinoma Sm P Y? Have people at home smoked in past 15 yr Sm ppl
If yes, how many? SCC SMALL CELL CARCINOMA SMOKE_GROWING_UP Did
people smoke at home while growing up Surg Surgical Tum % Tumor
Percentage WCAU White Caucasian Y Yes
TABLE-US-00006 TABLE 3 Tissue samples in normal panel: Lot no.
Source Tissue Pathology Sex/Age 1-Am-Colon (C71) 071P10B Ambion
Colon PM F/43 2-B-Colon (C69) A411078 Biochain Colon PM-Pool of 10
M&F 3-Cl-Colon (C70) 1110101 Clontech Colon PM-Pool of 3
M&F 4-Am-Small Intestine 091P0201A Ambion Small Intestine PM
M/75 5-B-Small Intestine A501158 Biochain Small Intestine PM M/63
6-B-Rectum A605138 Biochain Rectum PM M/25 7-B-Rectum A610297
Biochain Rectum PM M/24 8-B-Rectum A610298 Biochain Rectum PM M/27
9-Am-Stomach 110P04A Ambion Stomach PM M/16 10-B-Stomach A501159
Biochain Stomach PM M/24 11-B-Esophagus A603814 Biochain Esophagus
PM M/26 12-B-Esophagus A603813 Biochain Esophagus PM M/41
13-Am-Pancreas 071P25C Ambion Pancreas PM M/25 14-CG-Pancreas
CG-255-2 Ichilov Pancreas PM M/75 15-B-Lung A409363 Biochain Lung
PM F/26 16-Am-Lung (L93) 111P0103A Ambion Lung PM F/61 17-B-Lung
(L92) A503204 Biochain Lung PM M/28 18-Am-Ovary (O47) 061P43A
Ambion Ovary PM F/16 19-B-Ovary (O48) A504087 Biochain Ovary PM
F/51 20-B-Ovary (O46) A504086 Biochain Ovary PM F/41 21-Am-Cervix
101P0101A Ambion Cervix PM F/40 22-B-Cervix A408211 Biochain Cervix
PM F/36 23-B-Cervix A504089 Biochain Cervix PM-Pool of 5 M&F
24-B-Uterus A411074 Biochain Uterus PM-Pool of 10 M&F
25-B-Uterus A409248 Biochain Uterus PM F/43 26-B-Uterus A504090
Biochain Uterus PM-Pool of 5 M&F 27-B-Bladder A501157 Biochain
Bladder PM M/29 28-Am-Bladder 071P02C Ambion Bladder PM M/20
29-B-Bladder A504088 Biochain Bladder PM-Pool of 5 M&F
30-Am-Placenta 021P33A Ambion Placenta PB F/33 31-B-Placenta
A410165 Biochain Placenta PB F/26 32-B-Placenta A411073 Biochain
Placenta PB-Pool of 5 M&F 33-B-Breast (B59) A607155 Biochain
Breast PM F/36 34-Am-Breast (B63) 26486 Ambion Breast PM F/43
35-Am-Breast (B64) 23036 Ambion Breast PM F/57 36-Cl-Prostate (P53)
1070317 Clontech Prostate PB-Pool of 47 M&F 37-Am-Prostate
(P42) 061P04A Ambion Prostate PM M/47 38-Am-Prostate (P59) 25955
Ambion Prostate PM M/62 39-Am-Testis 111P0104A Ambion Testis PM
M/25 40-B-Testis A411147 Biochain Testis PM M/74 41-Cl-Testis
1110320 Clontech Testis PB-Pool of 45 M&F 42-CG-Adrenal
CG-184-10 Ichilov Adrenal PM F/81 43-B-Adrenal A610374 Biochain
Adrenal PM F/83 44-B-Heart A411077 Biochain Heart PB-Pool of 5
M&F 45-CG-Heart CG-255-9 Ichilov Heart PM M/75 46-CG-Heart
CG-227-1 Ichilov Heart PM F/36 47-Am-Liver 081P0101A Ambion Liver
PM M/64 48-CG-Liver CG-93-3 Ichilov Liver PM F/19 49-CG-Liver
CG-124-4 Ichilov Liver PM F/34 50-Cl-BM 1110932 Clontech Bone
Marrow PM-Pool of 8 M&F 51-CGEN-Blood WBC#5 CGEN Blood M
52-CGEN-Blood WBC#4 CGEN Blood M 53-CGEN-Blood WBC#3 CGEN Blood M
54-CG-Spleen CG-267 Ichilov Spleen PM F/25 55-CG-Spleen 111P0106B
Ambion Spleen PM M/25 56-CG-Spleen A409246 Biochain Spleen PM F/12
56-CG-Thymus CG-98-7 Ichilov Thymus PM F/28 58-Am-Thymus 101P0101A
Ambion Thymus PM M/14 59-B-Thymus A409278 Biochain Thymus PM M/28
60-B-Thyroid A610287 Biochain Thyroid PM M/27 61-B-Thyroid A610286
Biochain Thyroid PM M/24 62-CG-Thyroid CG-119-2 Ichilov Thyroid PM
F/66 63-Cl-Salivary Gland 1070319 Clontech Salivary Gland PM-Pool
of 24 M&F 64-Am-Kidney 111P0101B Ambion Kidney PM-Pool of 14
M&F 65-Cl-Kidney 1110970 Clontech Kidney PM-Pool of 14 M&F
66-B-Kidney A411080 Biochain Kidney PM-Pool of 5 M&F
67-CG-Cerebellum CG-183-5 Ichilov Cerebellum PM M/74
68-CG-Cerebellum CG-212-5 Ichilov Cerebellum PM M/54 69-B-Brain
A411322 Biochain Brain PM M/28 70-Cl-Brain 1120022 Clontech Brain
PM-Pool of 2 M&F 71-B-Brain A411079 Biochain Brain PM-Pool of 2
M&F 72-CG-Brain CG-151-1 Ichilov Brain PM F/86 73-Am-Skeletal
Muscle 101P013A Ambion Skeletal Muscle PM F/28 74-Cl-Skeletal
Muscle 1061038 Clontech Skeletal Muscle PM-Pool of 2 M&F
TABLE-US-00007 TABLE 3_1 Sample id (GCI)/case id Tissue id Sample
id (Asterand) (GCI)/Specimen (Asterand)/RNA old sample name sample
name Source Lot no. id (Asternd) id (GCI) 7-B-Rectum
1-(7)-Bc-Rectum Biochain A610297 8-B-Rectum 2-(8)-Bc-Rectum
Biochain A610298 new colon 3-GC-Colon GCI CDSUV CDSUVNR3 new colon
4-As-Colon Asterand 16364 31802 31802B1 new colon 5-As-Colon
Asterand 22900 74446 74446B1 new small bowl 6-GC-Small bowl GCI
V9L7D V9L7DN6Z new small bowl 7-GC-Small bowl GCI M3GVT M3GVTN5R
new small bowl 8-GC-Small bowl GCI 196S2 196S2AJN 9-Am-Stomach
9-(9)-Am-Stomach Ambion 110P04A 10-B-Stomach 10-(10)-Bc-Stomach
Biochain A501159 11-B-Esophagus 11-(11)-Bc-Esoph Biochain A603814
12-B-Esophagus 12-(12)-Bc-Esoph Biochain A603813 new pancreas
13-As-Panc Asterand 8918 9442 9442C1 new pancreas 14-As-Panc
Asterand 10082 11134 11134B1 48-CG-Liver 15-(48)-Ic-Liver Ichilov
CG-93-3 new liver 16-As-Liver Asterand 7916 7203 7203B1
28-Am-Bladder 17-(28)-Am-Bladder Ambion 071P02C 29-B-Bladder
18-(29)-Bc-Bladder Biochain A504088 64-Am-Kidney 19-(64)-Am-Kidney
Ambion 111P0101B 65-Cl-Kidney 20-(65)-Cl-Kidney Clontech 1110970
66-B-Kidney 21-(66)-Bc-Kidney Biochain A411080 new kidney
22-GC-Kidney GCI N1EVZ N1EVZN91 new kidney 23-GC-Kidney GCI BMI6W
BMI6WN9F 42-CG-Adrenal 24-(42)-Ic-Adrenal Ichilov CG-184-10
43-B-Adrenal 25-(43)-Bc-Adrenal Biochain A610374 16-Am-Lung (L93)
26-(16)-Am-Lung Ambion 111P0103A 17-B-Lung (L92) 27-(17)-Bc-Lung
Biochain A503204 new lung 28-As-Lung Asterand 9078 9275 9275B1 new
lung 29-As-Lung Asterand 6692 6161 6161A1 new lung 30-As-Lung
Asterand 7900 7180 7180F1 75-G-Ovary 31-(75)-GC-Ovary GCI L629FRV1
76-G-Ovary 32-(76)-GC-Ovary GCI DWHTZRQX 77-G-Ovary
33-(77)-GC-Ovary GCI FDPL9NJ6 78-G-Ovary 34-(78)-GC-Ovary GCI
GWXUZN5M 21-Am-Cervix 35-(21)-Am-Cerix Ambion 101P0101A new cervix
36-GC-cervix GCI E2P2N E2P2NAP4 24-B-Uterus 37-(24)-Bc-Uterus
Biochain A411074 26-B-Uterus 38-(26)-Bc-Uterus Biochain A504090
30-Am-Placenta 39-(30)-Am-Placen Ambion 021P33A 32-B-Placenta
40-(32)-Bc-Placen Biochain A411073 new breast 41-GC-Breast GCI
DHLR1 new breast 42-GC-Breast GCI TG6J6 new breast 43-GC-Breast GCI
E6UDD E6UDDNCF 38-Am-Prostate (P59) 44-(38)-Am-Prostate Ambion
25955 add prostate from 45-Bc-Prostate Biochain A609258 prostate
panel new testis 46-As-Testis Asterand 13071 19567 19567B1 new
testis 47-As-Testis Asterand 19671 42120 42120A1 ARTERY
48-GC-Artery GCI 7FUUP 7FUUPAMP ARTERY 49-GC-Artery GCI YGTVY
YGTVYAIN blood cells 50-Th-Blood-PBMC Tel-Hashomer 52497 blood
cells 51-Th-Blood-PBMC Tel-Hashomer 31055 blood cells
52-Th-Blood-PBMC Tel-Hashomer 31058 54-CG-Spleen 53-(54)-Ic-Spleen
Ichilov CG-267 55-Am-Spleen 54-(55)-Am-Spleen Ambion 111P0106B
57-CG-Thymus 55-(57)-Ic-Thymus Ichilov CG-98-7 58-Am-Thymus
56-(58)-Am-Thymus Ambion 101P0101A 60-B-Thyroid 57-(60)-Bc-Thyroid
Biochain A610287 62-CG-Thyroid 58-(62)-Ic-Thyroid Ichilov CG-119-2
new salivary gland 59-Gc-Sali gland GCI NNSMV NNSMVNJC
67-CG-Cerebellum 60-(67)-Ic-Cerebellum Ichilov CG-183-5
68-CG-Cerebellum 61-(68)-Ic-Cerebellum Ichilov CG-212-5 69-B-Brain
62-(69)-Bc-Brain Biochain A411322 71-B-Brain 63-(71)-Bc-Brain
Biochain A411079 72-CG-Brain 64-(72)-Ic-Brain Ichilov CG-151-1
44-B-Heart 65-(44)-Bc-Heart Biochain A411077 46-CG-Heart
66-(46)-Ic-Heart Ichilov CG-227-1 45-CG-Heart (Fibrotic)
67-(45)-Ic-Heart (Fibrotic) Ichilov CG-255-9 new skeletal muscle
68-GC-Skel Mus GCI T8YZS T8YZSN7O new skeletal muscle 69-GC-Skel
Mus GCI Q3WKA Q3WKANCJ new skeletal muscle 70-As-Skel Mus Asterand
8774 8235 8235G1 new skeletal muscle 71-As-Skel Mus Asterand 8775
8244 8244A1 new skeletal muscle 72-As-Skel Mus Asterand 10937 12648
12648C1 new skeletal muscle 73-As-Skel Mus Asterand 6692 6166
6166A1
Materials and Experimental Procedures
[0881] RNA preparation--RNA was obtained from Clontech (Franklin
Lakes, N.J. USA 07417, dot clontech dot com), BioChain Inst. Inc.
(Hayward, Calif. 94545 USA dot biochain dot com), ABS (Wilmington,
Del. 19801, USA, dot absbioreagents dot com) or Ambion (Austin,
Tex. 78744 USA, dot ambion dot com). Alternatively, RNA was
generated from tissue samples using TRI-Reagent (Molecular Research
Center), according to Manufacturer's instructions. Tissue and RNA
samples were obtained from patients or from postmortem. Total RNA
samples were treated with DNaseI (Ambion) and purified using RNeasy
columns (Qiagen).
[0882] RT PCR--Purified RNA (1 .mu.g) was mixed with 150 ng Random
Hexamer primers (Invitrogen) and 500 .mu.M dNTP in a total volume
of 15.6 .mu.l. The mixture was incubated for 5 min at 65.degree. C.
and then quickly chilled on ice. Thereafter, 5 .mu.l of
5.times.SuperscriptII first strand buffer (Invitrogen), 2.4 .mu.l
0.1M DTT and 40 units RNasin (Promega) were added, and the mixture
was incubated for 10 min at 25.degree. C., followed by further
incubation at 42.degree. C. for 2 min. Then, 1 .mu.l (200 units) of
SuperscriptII (Invitrogen) was added and the reaction (final volume
of 25 .mu.l) was incubated for 50 min at 42.degree. C. and then
inactivated at 70.degree. C. for 15 min. The resulting cDNA was
diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8).
[0883] Real-Time RT-PCR analysis--cDNA (5 .mu.l), prepared as
described above, was used as a template in Real-Time PCR reactions
using the SYBR Green I assay (PE Applied Biosystem) with specific
primers and UNG Enzyme (Eurogentech or ABI or Roche). The
amplification was effected as follows: 50.degree. C. for 2 min,
95.degree. C. for 10 min, and then 40 cycles of 95.degree. C. for
15 sec, followed by 60.degree. C. for 1 min. Detection was
performed by using the PE Applied Biosystem SDS 7000. The cycle in
which the reactions achieved a threshold level (Ct) of fluorescence
was registered and was used to calculate the relative transcript
quantity in the RT reactions. The relative quantity was calculated
using the equation Q=efficiency .sup.-Ct. The efficiency of the PCR
reaction was calculated from a standard curve, created by using
serial dilutions of several reverse transcription (RT) reactions.
To minimize inherent differences in the RT reaction, the resulting
relative quantities were normalized to normalization factor
calculated in one of the following methods as indicated in the
text:
[0884] Method 1--the geometric mean of the relative quantities of
the selected housekeeping (HSKP) genes was used as normalization
factor.
[0885] Method 2--The expression of several housekeeping (HSKP)
genes was checked on every panel. The relative quantity (Q) of each
housekeeping gene in each sample, calculted as described above, was
diveded by the median quantity of this gene in all panel samples to
obtain the "relative Q rel to MED". Then, for each sample the
median of the "relative Q rel to MED" of the selected housekeeping
genes was calculted and served as normalization factor of this
sample for further calculations. Unless defined otherwise, the
normalization of the Real-Time RT-PCR analysis results described
herein was carried out according to method 1 above.
[0886] Schematic summary of quantitative real-time PCR analysis is
presented in FIG. 3. As shown, the x-axis shows the cycle number.
The C.sub.T=Threshold Cycle point, which is the cycle that the
amplification curve crosses the fluorescence threshold that was set
in the experiment. This point is a calculated cycle number in which
PCR product signal is above the background level (passive dye ROX)
and still in the Geometric/Exponential phase (as shown, once the
level of fluorescence crosses the measurement threshold, it has a
geometrically increasing phase, during which measurements are most
accurate, followed by a linear phase and a plateau phase; for
quantitative measurements, the latter two phases do not provide
accurate measurements). The y-axis shows the normalized reporter
fluorescence. It should be noted that this type of analysis
provides relative quantification.
[0887] The sequences of the housekeeping genes measured in all the
examples in testing panel were as follows:
TABLE-US-00008 Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO: 1711)) Ubiquitin Forward primer (SEQ ID NO: 326):
ATTTGGGTCGCGGTTCTTG Ubiquifin Reverse primer (SEQ ID NO: 327):
TGCCTTGACATTCTCGATGGT Ubiquitin-amplicon (SEQ ID NO: 328)
ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAA
TGCAGATCTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGGTT
GAGCCCAGTGACACCATCGAGAATGTCAAGGCA SDHA (GenBank Accession No.
NM_004168 (SEQ ID NO: 1712)) SDHA Forward primer (SEQ ID NO: 329):
TGGGAACAAGAGGGCATCTG SDHA Reverse primer (SEQ ID NO: 330):
CCACCACTGCATCAAATTCATG SDHA-amplicon (SEQ ID NO: 331):
TGGGAACAAGAGGGCATGTGCTAAAGTTTCAGATTCCATTTCTGCTCAGT
ATCCAGTAGTGGATCATGAATTTGATGCAGTGGTGG PBGD (GenBank Accession No.
BC019323 (SEQ ID NO: 1713)), PBGD Forward primer (SEQ ID NO: 332):
TGAGAGTGATTCGCGTGGG PBGD Reverse primer (SEQ ID NO: 333):
CCAGGGTACGAGGCTTTCAAT PBGD-amplicon (SEQ ID NO: 334):
TGAGAGTGATTCGCGTGGGTACCCGCAAGAGCCAGCTTGCTCGCATACAG
ACGGACAGTGTGGTGGCAACATTGAAAGCCTCGTACCCTGG HPRT1 (Genflank Accession
No. NM_000194 (SEQ ID NO: 1714)), HPRT1 Forward primer (SEQ ID NO:
1295): TGACACTGGCAAAACAATGCA HPRT1 Reverse primer (SEQ ID NO:
1296): GGTCCTTTTCACCAGCAAGCT HPRT1-amplicon (SEQ ID NO: 1297):
TGACACTGGCAAAACAATGCAGACTTTGCTTTCCTTGGTCAGGCAGTATA
ATCCAAAGATGGTCAAGGTCGCAAGCTTGCTGGTGAAAAGGACC
[0888] The sequences of the housekeeping genes measured in all the
examples on normal tissue samples panel were as follows:
TABLE-US-00009 RPL19 (GenBank Accession No. NM_000981 (SEQ ID NO:
1715)), RPL19 Forward primer (SEQ ID NO: 1298):
TGGCAAGAAGAAGGTCTGGTTAG RPL19 Reverse primer (SEQ ID NO: 1420):
TGATCAGCCCATCTTTGATGAG RPL19-amplicon (SEQ ID NO: 1630):
TGGCAAGAAGAAGGTCTGGTTAGACCCCAATGAGACCAATGAAATCGCCA
ATGCCAACTCCCGTCAGCAGATCCGGAAGCTCATCAAAGATGGGCTGATC A TATA box
(GenBank Accession No. NM_003194 (SEQ ID NO: 1716)), TATA box
Forward primer (SEQ ID NO: 1631): CGGTTTGCTGCGGTAATCAT TATA box
Reverse primer (SEQ ID NO: 1632): TTTCTTGCTGCCAGTCTGGAC TATA
box-amplicon (SEQ ID NO: 1633):
CGGTTTGCTGCGGTAATCATGAGGATAAGAGAGCCACGAACCACGGCACT
GATTTTCAGTTCTGGGAAAATGGTGTGCACAGGAGCCAAGAGTGAAGAAC
AGTCCAGACTGGCAGCAAGAAA Ubiquitin (GenBank Accession No. BC000449
(SEQ ID NO: 1711)) Ubiquitin Forward primer (SEQ ID NO: 326):
ATTTGGGTCGCGGTTCTTG Ubiquitin Reverse primer (SEQ ID NO: 327):
TGCCTTGACATTCTCGATGGT Ubiquitin-amplicon (SEQ ID NO: 328)
ATTTGGGTCGCGGTTCTTGTTTGTGGATCGCTGTGATCGTCACTTGACAA
TGCAGATCTTCGTGAAGACTCTGACTGGTAAGACCATCACCCTCGAGG
TTGAGCCCAGTGACACCATCGAGAATGTCAAGGCA SDHA (GenBank Accession No.
NM_004168 (SEQ ID NO: 1712)) SDHA Forward primer (SEQ ID NO: 329):
TGGGAACAAGAGGGCATCTG SDHA Reverse primer (SEQ ID NO: 330):
CCACCACTGCATCAAATTCATG SDHA-amplicon (SEQ ID NO: 331):
TGGGAACAAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGT
ATCCAGTAGTGGATCATGAATTTGATGCAGTGGTGG
[0889] Oligonucleotide-Based Micro-Array Experiment Protocol--
Microarray Fabrication
[0890] Microarrays (chips) were printed by pin deposition using the
MicroGrid II MGII 600 robot from BioRobotics Limited (Cambridge,
UK). 50-mer oligonucleotides target sequences were designed by
Compugen Ltd (Tel-Aviv, IL) as described by A. Shoshan et al,
"Optical technologies and informatics", Proceedings of SPIE. Vol
4266, pp. 86-95 (2001). The designed oligonucleotides were
synthesized and purified by desalting with the Sigma-Genosys system
(The Woodlands, Tex., US) and all of the oligonucleotides were
joined to a C6 amino-modified linker at the 5' end, or being
attached directly to CodeLink slides (Cat #25-6700-01. Amersham
Bioscience, Piscataway, N.J., US). The 50-mer oligonucleotides,
forming the target sequences, were first suspended in Ultra-pure
DDW (Cat #01-866-1A Kibbutz Beit-Haemek, Israel) to a concentration
of 50 .mu.M. Before printing the slides, the oligonucleotides were
resuspended in 300 mM sodium phosphate (pH 8.5) to final
concentration of 150 mM and printed at 35-40% relative humidity at
21.degree. C.
[0891] Each slide contained a total of 9792 features in 32
subarrays. Of these features, 4224 features were sequences of
interest according to the present invention and negative controls
that were printed in duplicate. An additional 288 features (96
target sequences printed in triplicate) contained housekeeping
genes from Human Evaluation Library2, Compugen Ltd, Israel. Another
384 features are E. coli spikes 1-6, which are oligos to E-Coli
genes which are commercially available in the Array Control product
(Array control--sense oligo spots, Ambion Inc. Austin, Tex. Cat
#1781, Lot #112K06).
Post-Coupling Processing of Printed Slides
[0892] After the spotting of the oligonucleotides to the glass
(CodeLink) slides, the slides were incubated for 24 hours in a
sealed saturated NaCl humidification chamber (relative humidity
70-75%).
[0893] Slides were treated for blocking of the residual reactive
groups by incubating them in blocking solution at 50.degree. C. for
15 minutes (10 ml/slide of buffer containing 0.1M Tris, 50 mM
ethanolamine, 0.1% SDS). The slides were then rinsed twice with
Ultra-pure DDW (double distilled water). The slides were then
washed with wash solution (10 ml/slide. 4.times.SSC, 0.1% SDS)) at
50.degree. C. for 30 minutes on the shaker. The slides were then
rinsed twice with Ultra-pure DDW, followed by drying by
centrifugation for 3 minutes at 800 rpm.
[0894] Next, in order to assist in automatic operation of the
hybridization protocol, the slides were treated with Ventana
Discovery hybridization station barcode adhesives. The printed
slides were loaded on a Bio-Optica (Milan, Italy) hematology
staining device and were incubated for 10 minutes in 50m1 of
3-Aminopropyl Triethoxysilane (Sigma A3648 lot #122K589). Excess
fluid was dried and slides were then incubated for three hours in
20 mm/Hg in a dark vacuum desiccator (Pelco 2251, Ted Pella, Inc.
Redding Calif.).
[0895] The following protocol was then followed with the Genisphere
900-RP (random primer), with mini elute columns on the Ventana
Discovery HybStation.TM., to perform the microarray experiments.
Briefly, the protocol was performed as described with regard to the
instructions and information provided with the device itself. The
protocol included cDNA synthesis and labeling. cDNA concentration
was measured with the TBS-380 (Turner Biosystems. Sunnyvale,
Calif.) PicoFlour, which is used with the OliGreen ssDNA
Quantitation reagent and kit.
[0896] Hybridization was performed with the Ventana Hybridization
device, according to the provided protocols (Discovery
Hybridization Station Tuscon Ariz.).
[0897] The slides were then scanned with GenePix 4000B dual laser
scanner from Axon Instruments Inc, and analyzed by GenePix Pro 5.0
software.
[0898] Schematic summary of the oligonucleotide based microarray
fabrication and the experimental flow is presented in FIGS. 4 and
5.
[0899] Briefly, as shown in FIG. 4, DNA oligonucleotides at 25 uM
were deposited (printed) onto Amersham `CodeLink` glass slides
generating a well defined `spot`. These slides are covered with a
long-chain, hydrophilic polymer chemistry that creates an active
3-D surface that covalently binds the DNA oligonucleotides 5'-end
via the C6-amine modification. This binding ensures that the full
length of the DNA oligonucleotides is available for hybridization
to the cDNA and also allows lower background, high sensitivity and
reproducibility.
[0900] FIG. 5 shows a schematic method for performing the
microarray experiments. It should be noted that stages on the
left-hand or right-hand side may optionally be performed in any
order, including in parallel, until stage 4 (hybridization).
Briefly, on the left-hand side, the target oligonucleotides are
being spotted on a glass microscope slide (although optionally
other materials could be used) to form a spotted slide (stage 1).
On the right hand side, control sample RNA and cancer sample RNA
are Cy3 and Cy5 labeled, respectively (stage 2), to form labeled
probes. It should be noted that the control and cancer samples come
from corresponding tissues (for example, normal prostate tissue and
cancerous prostate tissue). Furthermore, the tissue from which the
RNA was taken is indicated below in the specific examples of data
for particular clusters, with regard to overexpression of an
oligonucleotide from a "chip" (microarray), as for example
"prostate" for chips in which prostate cancerous tissue and normal
tissue were tested as described above. In stage 3, the probes are
mixed. In stage 4, hybridization is performed to form a processed
slide. In stage 5, the slide is washed and scanned to form an image
file, followed by data analysis in stage 6.
[0901] The following clusters were found to be overexpressed in
lung cancer: [0902] W60282_PEA.sub.--1 [0903] F05068_PEA.sub.--1
[0904] H38804_PEA.sub.--1 [0905] HSENA78 [0906] T39971 [0907]
(R00299) [0908] H14624 [0909] Z41644_PEA.sub.--1 [0910]
Z25299_PEA.sub.--2 [0911] HSSTROL3 [0912] HUMTREFAC_PEA.sub.--2
[0913] HSS100PCB [0914] HSU33147_PEA.sub.--1 [0915] HUMCA1XIA
[0916] H61775 [0917] HUMGRP5E [0918] HUMODCA [0919] AA161187 [0920]
R66178 [0921] D56406_PEA.sub.--1 [0922] M85491_PEA.sub.--1 [0923]
Z21368_PEA.sub.--1 [0924] HUMCA1XIA [0925] R20779 [0926]
R38144_PEA.sub.--2 [0927] Z44808_PEA.sub.--1 [0928]
HUMOSTRO_PEA.sub.--1_PEA.sub.--1 [0929] R11723_PEA.sub.--3 [0930]
Al076020 [0931] T23580 [0932] M79217_PEA.sub.--1 [0933]
M62096_PEA.sub.--1 [0934] M78076_PEA.sub.--1 [0935]
T99080_PEA.sub.--4 [0936] T08446_PEA.sub.--1 [0937]
R16276_PEA.sub.--1
[0938] The following clusters were found to be overexpressed in
lung small cell cancer:
[0939] H61775
[0940] HUMGRP5E
[0941] M85491_PEA.sub.--1
[0942] Z44808_PEA.sub.--1
[0943] AA161187
[0944] R66178
[0945] HUMPHOSLIP_PEA.sub.--2
[0946] Al076020
[0947] T23580
[0948] M79217_PEA.sub.--1
[0949] M62096_PEA.sub.--1
[0950] M78076_PEA.sub.--1
[0951] T99080_PEA.sub.--4
[0952] T08446_PEA.sub.--1
[0953] The following clusters were found to be overexpressed in
lung adenocarcinoma:
[0954] R00299
[0955] M85491_PEA.sub.--1
[0956] Z21368_PEA.sub.--1
[0957] HUMCA1XIA
[0958] AA161187
[0959] R66178
[0960] T11628_PEA.sub.--1
[0961] The following clusters were found to be overexpressed in
lung squamous cell:
[0962] HUMODCA
[0963] R00299
[0964] D56406_PEA.sub.--1
[0965] Z44808_PEA.sub.--1
[0966] Z21368_PEA.sub.--1
[0967] HUMCA1XIA
[0968] AA161187
[0969] R66178
[0970] HUMCEA_PEA.sub.--1
[0971] R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1
Description for Cluster H61775
[0972] Cluster H61775 features 2 transcript(s) and 6 segment(s) of
interest, the names for which are given in Tables 4 and 5,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
6.
TABLE-US-00010 TABLE 4 Transcripts of interest Transcript Name
Sequence ID No. H61775_T21 1 H61775_T22 2
TABLE-US-00011 TABLE 5 Segments of interest Segment Name Sequence
ID No. H61775_node_2 151 H61775_node_4 152 H61775_node_6 153
H61775_node_8 154 H61775_node_0 155 H61775_node_5 156
TABLE-US-00012 TABLE 6 Proteins of interest Protein Name Sequence
ID No. H61775_P16 1281 H61775_P17 1282
[0973] Cluster H61775 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 6 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[0974] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 6 and Table 7. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: brain malignant tumors and a mixture of
malignant tumors from different tissues.
TABLE-US-00013 TABLE 7 Normal tissue distribution Name of Tissue
Number bladder 0 brain 0 colon 0 epithelial 10 general 3 breast 8
muscle 0 ovary 0 pancreas 0 prostate 0 uterus 0
TABLE-US-00014 TABLE 8 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 3.1e-01
3.8e-01 3.2e-01 2.5 4.6e-01 1.9 brain 8.8e-02 6.5e-02 1 3.5 4.1e-04
5.8 colon 5.6e-01 6.4e-01 1 1.1 1 1.1 epithelial 3.0e-02 1.3e-01
2.3e-02 2.1 3.2e-01 1.2 general 1.3e-06 4.9e-05 1.0e-07 6.3 1.5e-06
4.3 breast 4.7e-01 3.7e-01 3.3e-01 2.0 4.6e-01 1.6 muscle 2.3e-01
2.9e-01 1.5e-01 6.8 3.9e-01 2.6 ovary 3.8e-01 4.2e-01 1.5e-01 2.4
2.6e-01 1.9 pancreas 3.3e-01 4.4e-01 4.2e-01 2.4 5.3e-01 1.9
prostate 7.3e-01 7.8e-01 6.7e-01 1.5 7.5e-01 1.3 uterus 1.0e-01
2.6e-01 2.9e-01 2.6 5.1e-01 1.8
[0975] As noted above, contig H61775 features 2 transcript(s),
which were listed in Table 4 above. A description of each variant
protein according to the present invention is now provided.
[0976] Variant protein H61775_P16 (SEQ ID NO:1281) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) H61775_T21 (SEQ ID
NO:1). One or more alignments to one or more previously published
protein sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[0977] Comparison report between H61775_P16 (SEQ ID NO:1281) and
Q9P2J2 (SEQ ID NO:1694):
[0978] 1. An isolated chimeric polypeptide encoding for H61775_P16
(SEQ ID NO:1281), comprising a first amino acid sequence being at
least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFGLY-
SPRI DPDYVG corresponding to amino acids 11-93 of Q9P2J2 (SEQ ID
NO:1694), which also corresponds to amino acids 1-83 of H61775_P16
(SEQ ID NO:1281), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCS-
VTLQV (SEQ ID NO: 1754) corresponding to amino acids 84-152 of
H61775_P16 (SEQ ID NO:1281), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[0979] 2. An isolated polypeptide encoding for a tail of H61775_P16
(SEQ ID NO:1281), comprising a polypeptide begin at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCS-
VTLQV (SEQ ID NO: 1754) in H61775_P16 (SEQ ID NO:1281).
[0980] Comparison report between H61775_P16 (SEQ ID NO:1281) and
AAQ88495 (SEQ ID NO:1695):
[0981] 1. An isolated chimeric polypeptide encoding for H61775_P16
(SEQ ID NO:1281), comprising a first amino acid sequence being at
least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLKFIQFGLYS-
PRI DPDYVG corresponding to amino acids 11-83 of AAQ88495 (SEQ ID
NO:1695), which also corresponds to amino acids 1-83 of H61775_P16
(SEQ ID NO:1281), and a second amino acid sequence being at least
70%, optionally at least 80% preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCSVTLQV
(SEQ ID NO: 1754) corresponding to amino acids 84-152 of H61775_P16
(SEQ ID NO:1281), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[0982] 2. An isolated polypeptide encoding for a tail of H61775_P16
(SEQ ID NO:1281), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence
DCGFPAFRELKRAETVSPVFFTRRCIWEDLKSTGFSPAGGGRPPGGGPRTQEDSGLPCWRSSCS-
VTLQV (SEQ ID NO: 1754) in H61775_P16 (SEQ ID NO:1281).
[0983] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[0984] Variant protein H61775_P16 (SEQ ID NO:1281) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 9, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein H61775_P16 (SEQ ID NO:1281)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00015 TABLE 9 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
14 I -> T No 138 G -> R No 34 G -> E Yes 48 G -> R No
91 R -> * Yes
[0985] Variant protein H61775_P16 (SEQ ID NO:1281) is encoded by
the following transcript(s): H61775_T21 (SEQ ID NO:1), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript H61775_T21 (SEQ ID NO:1) is shown in
bold; this coding portion starts at position 261 and ends at
position 716. The transcript also has the following SNPs as listed
in Table 10 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein H61775_P16 (SEQ ID NO:1281) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00016 TABLE 10 Nucleic acid SNPs SNP position Alternative
on nucleotide sequence nucleic acid Previously known SNP? 117 T
-> C Yes 200 T -> C No 672 G -> C No 222 T -> C Yes 301
T -> C No 361 G -> A Yes 377 G -> A No 400 -> C No 402
G -> C No 531 C -> T Yes 566 T -> C No
[0986] Variant protein H61775_P17 (SEQ ID NO:1282) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) H61775_T22 (SEQ ID
NO:2). One or more alignments to one or more previously published
protein sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[0987] Comparison report between H61775_P17 (SEQ ID NO:1282) and
Q9P2J2 (SEQ ID NO:1694):
[0988] 1. An isolated chimeric polypeptide encoding for H61775_P17
(SEQ ID NO:1282), comprising a first amino acid sequence being at
least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFGLY-
SPRI DPDYVG corresponding to amino acids 11-93 of Q9P2J2 (SEQ ID
NO:1694), which also corresponds to amino acids 1-83 of H61775_P17
(SEQ ID NO:1282).
[0989] Comparison report between H61775_P17 (SEQ ID NO:1282) and
AAQ88495 (SEQ ID NO:1695):
[0990] 1. An isolated chimeric polypeptide encoding for H61775_P17
(SEQ ID NO:1282), comprising a first amino acid sequence being at
least 90% homologous to
MVWCLGLAVLSLVISQGADGRGKPEVVSVVGRAGESVVLGCDLLPPAGRPPLHVIEWLRFGFLLPIFIQFGLY-
SPRI DPDYVG corresponding to amino acids 1-83 of AAQ88495 (SEQ ID
NO:1695), which also corresponds to amino acids 1-83 of H61775_P17
(SEQ ID NO:1282).
[0991] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[0992] Variant protein H61775_P17 (SEQ ID NO:1282) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 11, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein H61775_P17 (SEQ ID NO:1282)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00017 TABLE 11 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
14 I -> T No 34 G -> E Yes 48 G -> R No
[0993] Variant protein H61775_P17 (SEQ ID NO:1282) is encoded by
the following transcript(s): H61775_T22 (SEQ ID NO:2), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript H61775_T22 (SEQ ID NO:2) is shown in
bold; this coding portion starts at position 261 and ends at
position 509. The transcript also has the following SNPs as listed
in Table 12 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein H61775_P17 (SEQ ID NO:1282) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00018 TABLE 12 Nucleic acid SNPs SNP position Alternative
on nucleotide sequence nucleic acid Previously known SNP? 117 T
-> C Yes 200 T -> C No 222 T -> C Yes 301 T -> C No 361
G -> A Yes 377 G -> A No 400 -> C No 402 G -> C No 596
T -> A Yes
[0994] As noted above, cluster H61775 features 6 segment(s), which
were listed in Table 5 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[0995] Segment cluster H61775_node.sub.--2 (SEQ ID NO:1022)
according to the present invention is supported by 17 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H61775_T21 (SEQ ID NO:1) and H61775_T22 (SEQ ID NO:2). Table 13
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00019 TABLE 13 Segment location on transcripts Segment
Segment Transcript name starting position ending position
H61775_T21 (SEQ ID NO: 1) 87 318 H61775_T22 (SEQ ID NO: 2) 87
318
[0996] Segment cluster H61775_node.sub.--4 (SEQ ID NO:1023)
according to the present invention is supported by 20 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H61775_T21 (SEQ ID NO:1) and H61775_T22 (SEQ ID NO:2). Table 14
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00020 TABLE 14 Segment location on transcripts Segment
Segment Transcript name starting position ending position
H61775_T21 (SEQ ID NO: 1) 319 507 H61775_T22 (SEQ ID NO: 2) 319
507
[0997] Segment cluster H61775_node.sub.--6 (SEQ ID NO:1024)
according to the present invention is supported by 1 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): H61775_T22
(SEQ ID NO:2). Table 15 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00021 TABLE 15 Segment location on transcripts Segment
Segment Transcript name starting position ending position
H61775_T22 (SEQ ID NO: 2) 515 715
[0998] Segment cluster H61775_node.sub.--8 (SEQ ID NO:1025)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): H61775_T21
(SEQ ID NO:1). Table 16 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00022 TABLE 16 Segment location on transcripts Segment
Segment Transcript name starting position ending position
H61775_T21 (SEQ ID NO: 1) 508 1205
[0999] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 bp in length, and so
are included in a separate description.
[1000] Segment cluster H61775_node.sub.--0 (SEQ ID NO:1026)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): H61775_T21
(SEQ ID NO:1) and H61775_T22 (SEQ ID NO:2). Table 17 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00023 TABLE 17 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H61775_T21 (SEQ ID NO: 1) 1 86 H61775_T22 (SEQ ID NO: 2) 1 86
[1001] Segment cluster H61775_node.sub.--5 (SEQ ID NO:1027)
according to the present invention can be found in the following
transcript(s): H61775_T22 (SEQ ID NO:2). Table 18 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00024 TABLE 18 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H61775_T22 (SEQ ID NO: 2) 508 514
[1002] Microarray (chip) data is also available for this gene as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (with
regard to lung cancer), shown in Table 19.
TABLE-US-00025 TABLE 19 Oligonucleotides related to this gene
Overexpressed Chip Oligonucleotide name in cancers reference
H61775_0_11_0 (SEQ ID NO: 204) Lung cancer Lung
[1003] Variant protein alignment to the previously known
protein:
TABLE-US-00026 Sequence name: /tmp/Psw0RJLCti/aLAXQjXh07:Q9P2J2
(SEQ ID NO:1694) Sequence documentation: Alignment of: H61775_P16
(SEQ ID NO:1281) x Q9P2J2 (SEQ ID NO:1694) .. Alignment segment
1/1: Quality: 803.00 Escore: 0 Matching length: 83 Total length: 83
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Indentity:
100.00 Gaps: 0 Alignment: . . . . . ##STR00001## . . . ##STR00002##
Sequence name: /tmp/Psw0RJLCti/aLAXQjXh07:AAQ88495 (SEQ ID NO:1695)
Sequence documentation: Alignment of: H61775_P16 (SEQ ID NO:1281) x
AAQ88495 (SEQ ID NO:1695) .. Alignment segment 1/1: Quality: 803.00
Escore: 0 Matching length: 83 Total length: 83 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00003## . . . ##STR00004## Sequence name:
/tmp/naab8yR3GC/pSM4l2IL5o:Q9P2J2 (SEQ ID NO:1694) Sequence
documentation: Alignment of: H61775_P17 (SEQ ID NO:1282) x Q9P2J2
(SEQ ID NO:1694) .. Alignment segment 1/1: Quality: 803.0 Escore: 0
Matching length: 83 Total length: 83 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: . . . . .
##STR00005## . . . ##STR00006## Sequence name:
/tmp/naab8yR3GC/pSM4l2IL5o:AAQ88495 (SEQ ID NO:1695) Sequence
documentation: Alignment of: H61775_P17 (SEQ ID NO:1282) x AAQ88495
(SEQ ID NO:1695) .. Alignment segment 1/1: Quality: 803.00 Escore:
0 Matching length: 83 Total length: 83 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment: . . . . .
##STR00007## . . . ##STR00008##
Expression of immunoglobulin superfamily, member 9, H61775
transcripts which are detectable by amplicon as depicted in
sequence name H61775seg8 (SEQ ID NO: 1636) in normal and cancerous
lung tissues
[1004] Expression of immunoglobulin superfamily, member 9
transcripts detectable by or according to seg8, H61775seg8 amplicon
(SEQ ID NO: 1636) and H61775seg8F2 (SEQ ID NO: 1634) and
H61775seg8R2 (SEQ ID NO: 1635) primers was measured by real time
PCR. In parallel the expression of four housekeeping genes--PBGD
(GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--PBGD-amplicon, SEQ ID NO:334, primers SEQ ID NOs 332 and
333), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID
NO:1714); amplicon--HPRT1-amplicon, SEQ ID NO:1297; primers SEQ ID
NOs 1295 and 1296), Ubiquitin (GenBank Accession No. BC000449 (SEQ
ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328, primers
SEQ ID NOs 326 and 327) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SDHA-amplicon, SEQ ID
NO:331; primers SEQ ID NOs 329 and 330) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel"), to obtain a value of fold up-regulation for each
sample relative to median of the normal PM samples.
[1005] FIG. 7 is a histogram showing over expression of the
above-indicated immunoglobulin superfamily, member 9 transcripts in
cancerous lung samples relative to the normal samples. The number
and percentage of samples that exhibit at least 5 fold
over-expression, out of the total number of samples tested, is
indicated in the bottom. As is evident from FIG. 7, the expression
of immunoglobulin superfamily, member 9 transcripts detectable by
the above amplicon(s) in cancer samples was significantly higher
than in the non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99,
Table 2 "Tissue samples in testing panel"). Notably an
over-expression of at least 5 fold was found in 11 out of 15
adenocarcinoma samples, 12 out of 16 squamous cell carcinoma
samples, 1 out of 4 samples of large cell carcinoma samples and in
8 out of 8 small cell carcinoma samples.
[1006] Statistical analysis was applied to verify the significance
of these results, as described below.
[1007] The P value for the difference in the expression levels of
immunoglobulin superfamily, member 9 transcripts detectable by the
above amplicon in lung cancer samples versus the normal tissue
samples was determined by T test as 6.5E-02. In adenocarcinoma, the
minimum values were 7.62E-03 in squamous cell adenocarcinoma cancer
and 1.5E-03 in small cell carcinoma.
[1008] Threshold of 5 fold overexpression was found to
differentiate between cancer and normal samples with P value of
9.62E-04 in adenocarcinoma, 5.9E-04 in squamous cell carcinoma, and
a threshold of 10 fold overexpression was found to differentiate
between small cell adenocarcinoma cancer and normal samples with P
value of 7.14E-05 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[1009] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: H61775seg8F2
forward primer (SEQ ID NO: 1634); and H61775seg8R2 reverse primer
(SEQ ID NO: 1635).
[1010] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: H6177seg8 (SEQ ID NO: 1636).
TABLE-US-00027 H61775seg8F2 (SEQ ID NO: 1634)
GAAGGCTCTTGTCACTTACTAGCCAT H61775seg8R2 (SEQ ID NO: 1635)
TGTCACCATATTTAATCCTCCCAA H61775seg8 (SEQ ID NO: 1636)
GAAGGCTCTTGTCACTTACTAGCCATGTGATTTTGGAAAGAAACTTAACA
TTAATTCCTTCAGCTACAATGGAATTCTTGGGAGGATTAAATATGGTGAC A
Expression of immunoglobulin superfamily, member 9, H61775
transcripts which are detectable by amplicon as depicted in
sequence name H61775seg8 (SEQ ID NO: 1636) in different normal
tissues.
[1011] Expression of immunoglobulin superfamily, member 9
transcripts detectable by or according to H61775 seg8 amplicon (SEQ
ID NO: 1636) and H61775 seg8F2 (SEQ ID NO: 1634) and H61775 seg8R2
(SEQ ID NO: 1635) was measured by real time PCR. In parallel the
expression of four housekeeping genes--RPL19 (GenBank Accession No.
NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ ID NO:1630),
TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:1716);
TATA amplicon, SEQ ID NO:1633), Ubiquitin (GenBank Accession No.
BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the ovary samples
(Sample Nos. 18-20, Table 4, "Tissue sample in normal panel",
above), to obtain a value of relative expression of each sample
relative to median of the ovary samples.
TABLE-US-00028 H61775seg8F2 (SEQ ID NO: 1634)
GAAGGCTCTTGTCACTTACTAGCCAT H61775seg8R2 (SEQ ID NO: 1635)
TGTCACCATATTTAATCCTCCCAA H61775seg8 (SEQ ID NO: 1636)
GAAGGCTCTTGTCACTTACTAGCCATGTGATTTTGGAAAGAAACTTAACA
TTAATTCCTTCAGCTACAATGGAATTCTTGGGAGGATTAAATATGGTGAC A
The results are demonstrated in FIG. 8, showing expression of
immunoglobulin superfamily, member 9, H61775 transcripts, which are
detectable by amplicon as depicted in sequence name H61775seg8 (SEQ
ID NO: 1636), in different normal tissues.
Description for Cluster M85491
[1012] Cluster M85491 features 2 transcript(s) and 11 segment(s) of
interest, the names for which are given in Tables 20 and 21,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
22.
TABLE-US-00029 TABLE 20 Transcripts of interest Transcript Name
Sequence ID No. M85491_PEA_1_T16 3 M85491_PEA_1_T20 4
TABLE-US-00030 TABLE 21 Segments of interest Segment Name Sequence
ID No. M85491_PEA_1_node_0 157 M85491_PEA_1_node_13 158
M85491_PEA_1_node_21 159 M85491_PEA_1_node_23 160
M85491_PEA_1_node_24 161 M85491_PEA_1_node_8 162
M85491_PEA_1_node_9 163 M85491_PEA_1_node_10 164
M85491_PEA_1_node_18 165 M85491_PEA_1_node_19 166
M85491_PEA_1_node_6 167
TABLE-US-00031 TABLE 22 Proteins of interest Protein Name Sequence
ID No. M85491_PEA_1_P13 1283 M85491_PEA_1_P14 1284
[1013] These sequences are variants of the known protein Ephrin
type-B receptor 2 [precursor] (SwissProt accession identifier
EPB2_HUMAN; known also according to the synonyms EC 2.7.1.112;
Tyrosine-protein kinase receptor EPH-3; DRT; Receptor
protein-tyrosine kinase HEK5; ERK), SEQ ID NO: 1417, referred to
herein as the previously known protein.
[1014] Protein Ephrin type-B receptor 2 [precursor] (SEQ ID
NO:1417) is known or believed to have the following function(s):
Receptor for members of the ephrin-B family. The sequence for
protein Ephrin type-B receptor 2 [precursor] is given at the end of
the application, as "Ephrin type-B receptor 2 [precursor] amino
acid sequence" (SEQ ID NO:1417). Known polymorphisms for this
sequence are as shown in Table 23.
TABLE-US-00032 TABLE 23 Amino acid mutations for Known Protein
SNPposition(s) on amino acid sequence Comment 671 A -> R. /FTId
= VAR_004162. 1-20 MALRRLGAALLLLPLLAAVE -> MWVPVLALPVCTYA 923 E
-> K 956 L -> V 958 V -> L 154 G -> D 476 K -> KQ
495-496 Missing 532 E -> D 568 R -> RR 589 M -> I 788 I
-> F 853 S -> A
[1015] Protein Ephrin type-B receptor 2 [precursor] (SEQ ID
NO:1417) localization is believed to be Type I membrane
protein.
[1016] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: protein amino acid
phosphorylation; transmembrane receptor protein tyrosine kinase
signaling pathway; neurogenesis, which are annotation(s) related to
Biological Process; protein tyrosine kinase; receptor;
transmembrane-ephrin receptor; ATP binding; transferase, which are
annotation(s) related to Molecular Function; and integral membrane
protein, which are annotation(s) related to Cellular Component.
[1017] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1018] Cluster M85491 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 9 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1019] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 9 and Table 24. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors and a mixture
of malignant tumors from different tissues.
TABLE-US-00033 TABLE 24 Normal tissue distribution Name of Tissue
Number Bladder 0 Bone 0 Brain 10 Colon 31 epithelial 10 General 12
Kidney 0 Liver 0 Lung 5 Breast 8 Muscle 5 Ovary 36 pancreas 10 Skin
0 Stomach 0
TABLE-US-00034 TABLE 25 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Bladder 5.4e-01
6.0e-01 3.2e-01 2.5 4.6e-01 1.9 Bone 1 2.8e-01 1 1.0 7.0e-01 1.8
Brain 3.4e-01 3.6e-01 1.2e-01 2.9 1.8e-02 2.7 Colon 3.4e-02 5.7e-02
8.2e-02 2.8 2.0e-01 2.1 epithelial 1.7e-03 3.5e-03 2.0e-03 2.8
1.1e-02 2.2 General 4.8e-04 5.2e-04 6.7e-04 2.3 1.3e-03 1.9 Kidney
4.3e-01 3.7e-01 1 1.1 7.0e-01 1.5 Liver 1 4.5e-01 1 1.0 6.9e-01 1.5
Lung 2.2e-01 2.7e-01 6.9e-02 3.6 3.4e-02 3.6 Breast 8.2e-01 7.3e-01
6.9e-01 1.2 6.8e-01 1.2 Muscle 9.2e-01 4.8e-01 1 0.8 1.5e-01 3.2
Ovary 8.5e-01 7.3e-01 9.0e-01 0.7 6.7e-01 1.0 pancreas 5.5e-01
2.0e-01 6.7e-01 1.2 3.5e-01 1.8 Skin 2.9e-01 4.7e-01 1.4e-01 7.0
6.4e-01 1.6 Stomach 1.5e-01 3.2e-01 1 1.0 8.0e-01 1.3
As noted above, cluster M85491 features 2 transcript(s), which were
listed in Table 20 above. These transcript(s) encode for protein(s)
which are variant(s) of protein Ephrin type-B receptor 2
[precursor] (SEQ ID NO:1417). A description of each variant protein
according to the present invention is now provided.
[1020] Variant protein M85491_PEA.sub.--1_P13 (SEQ ID NO:1283)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M85491_PEA.sub.--1_T16 (SEQ ID NO:3). An alignment is given to the
known protein (Ephrin type-B receptor 2 [precursor] (SEQ ID
NO:1417)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1021] Comparison report between M85491_PEA.sub.--1_P13 (SEQ ID
NO:1283) and EPB2_HUMAN (SEQ ID NO:1417):
[1022] 1. An isolated chimeric polypeptide encoding for
M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), comprising a first amino
acid sequence being at least 90% homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWL
RTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADES-
FSQ
VDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSL-
VAARGSC
IANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCRGCPSGTFKANQGDEACTHCPIN-
SRTTSEGAT
NCVCRNGYYRADLDPLDMPCTTIPSAPQAVISSVNETSLMLEWTPPRDSGGREDLVYNIICKSC-
GSGRGACTRCGD
NVQYAPRQLGLTEPRIYISDLLAHTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSIMHQVSRTVD-
SITLS WSQPDQPNGVILDYELQYYEK corresponding to amino acids 1-476 of
EPB2_HUMAN (SEQ ID NO:1417), which also corresponds to amino acids
1-476 of M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VPIGWVLSPSPTSLRAPLPG (SEQ ID NO: 1755) corresponding to
amino acids 477-496 of M85491_PEA.sub.--1_P13 (SEQ ID NO:1283),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1023] 2. An isolated polypeptide encoding for a tail of
M85491_PEA.sub.--1_P13 (SEQ ID NO:1283), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VPIGWVLSPSPTSLRAPLPG (SEQ ID NO: 1755) in M85491_PEA.sub.--1_P13
(SEQ ID NO:1283).
[1024] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1025] Variant protein M85491_PEA.sub.--1_P13 (SEQ ID NO:1283) is
encoded by the following transcript(s): M85491_PEA.sub.--1_T16 (SEQ
ID NO:3), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M85491_PEA.sub.--1_T16 (SEQ ID NO:3) is shown in bold; this coding
portion starts at position 143 and ends at position 1630. The
transcript also has the following SNPs as listed in Table 26 (given
according to their position on the nucleotide sequence, with the
alternative nucleic acid listed; the last column indicates whether
the SNP is known or not; the presence of known SNPs in variant
protein M85491_PEA.sub.--1_P13 (SEQ ID NO:1283) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00035 TABLE 26 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
799 G -> A Yes 1066 C -> T Yes 1519 A -> G Yes 1872 C
-> T Yes 2044 T -> C Yes 2156 G -> A Yes 2606 C -> A
Yes 2637 G -> C Yes
[1026] Variant protein M85491_PEA.sub.--1_P14 (SEQ ID NO:1284)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). An alignment is given to the
known protein (Ephrin type-B receptor 2 [precursor] (SEQ ID
NO:1417)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1027] Comparison report between M85491_PEA.sub.--1_P14 (SEQ ID
NO:1284) and EPB2_HUMAN (SEQ ID NO:1417):
[1028] 1. An isolated chimeric polypeptide encoding for
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), comprising a first amino
acid sequence being at least 90% homologous to
MALRRLGAALLLLPLLAAVEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWL
RTKFIRRRGAHRIHVEMKFSVRDCSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADES-
FSQ
VDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYGGCMSLIAVRVFYRKCPRIIQNGAIFQETLSGAESTSL-
VAARGSC IANAEEVDVPIKLYCNGDGEWLVPIGRCMCKAGFEAVENGTVCR corresponding
to amino acids 1-270 of EPB2_HUMAN (SEQ ID NO:1417), which also
corresponds to amino acids 1-270 of M85491_PEA.sub.--1_P14 (SEQ ID
NO:1284), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL
(SEQ ID NO: 1756) corresponding to amino acids 271-301 of
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1029] 2. An isolated polypeptide encoding for a tail of
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ERQDLTMLSRLVLNSWPQMILPPQPPKVLEL (SEQ ID NO: 1756) in
M85491_PEA.sub.--1_P14 (SEQ ID NO:1284).
[1030] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1031] Variant protein M85491_PEA.sub.--1_P14 (SEQ ID NO:1284) is
encoded by the following transcript(s): M85491_PEA.sub.--1_T20 (SEQ
ID NO:4), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M85491_PEA.sub.--1_T20 (SEQ ID NO:4) is shown in bold; this coding
portion starts at position 143 and ends at position 1045. The
transcript also has the following SNPs as listed in Table 27 (given
according to their position on the nucleotide sequence, with the
alternative nucleic acid listed; the last column indicates whether
the SNP is known or not; the presence of known SNPs in variant
protein M85491_PEA.sub.--1_P14 (SEQ ID NO:1284) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00036 TABLE 27 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
799 G -> A Yes 1135 T -> C Yes 1160 T -> C Yes 1172 A
-> C Yes 1176 T -> A Yes
[1032] As noted above, cluster M85491 features 11 segment(s), which
were listed in Table 21 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1033] Segment cluster M85491_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1028) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3) and
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). Table 28 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00037 TABLE 28 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 1 203 M85491_PEA_1_T20 (SEQ ID NO:
4) 1 203
[1034] Segment cluster M85491_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:1029) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491PEA.sub.--1_T20 (SEQ ID NO:4). Table 29 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00038 TABLE 29 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T20 (SEQ ID NO: 4) 954 1182
[1035] Segment cluster M85491_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:1030) according to the present invention is supported by 18
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3). Table 30 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00039 TABLE 30 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 1110 1445
[1036] Segment cluster M85491_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:1031) according to the present invention is supported by 18
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3). Table 31 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00040 TABLE 31 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 1446 1570
[1037] Segment cluster M85491_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1032) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3). Table 32 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00041 TABLE 32 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 1571 2875
[1038] Segment cluster M85491_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1033) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3) and
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). Table 33 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00042 TABLE 33 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 269 672 M85491_PEA_1_T20 (SEQ ID
NO: 4) 269 672
[1039] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 34.
TABLE-US-00043 TABLE 34 Oligonucleotides related to this segment
Overexpressed Chip Oligonucleotide name in cancers reference
M85491_0_14_0 (SEQ ID NO: 206) lung malignant LUN tumors
[1040] Segment cluster M85491_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:1034) according to the present invention is supported by 20
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3) and
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). Table 35 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00044 TABLE 35 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 673 856 M85491_PEA_1_T20 (SEQ ID
NO: 4) 673 856
[1041] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 bp in length, and so
are included in a separate description.
[1042] Segment cluster M85491_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:1035) according to the present invention is supported by 17
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3) and
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). Table 36 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00045 TABLE 36 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 857 953 M85491_PEA_1_T20 (SEQ ID
NO: 4) 857 953
[1043] Segment cluster M85491_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:1036) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3). Table 37 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00046 TABLE 37 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 954 1044
[1044] Segment cluster M85491_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:1036) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3). Table 38 below
describes the staring and ending position of this segment on each
transcript.
TABLE-US-00047 TABLE 38 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 1045 1109
[1045] Segment cluster M85491_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1038) according to the present invention is supported by 11
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M85491_PEA.sub.--1_T16 (SEQ ID NO:3) and
M85491_PEA.sub.--1_T20 (SEQ ID NO:4). Table 39 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00048 TABLE 39 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M85491_PEA_1_T16 (SEQ ID NO: 3) 204 268 M85491_PEA_1_T20 (SEQ ID
NO: 4) 204 268
Variant protein alignment to the previously known protein:
TABLE-US-00049 Sequence name: /tmp/qfmsU9VtxS/DylcLC9j8v:EPB2_HUMAN
(SEQ ID NO:1417) Sequence documentation: Alignment of:
M85491_PEA_1_P13 (SEQ ID NO:1283) x EPB2_HUMAN (SEQ ID NO:1417)
Alignment segment 1/1: Quality: 4726.00 Escore: 0 Matching length:
476 Total length: 476 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Aligmnment: . . . . . ##STR00009##
. . . . . ##STR00010## . . . . . ##STR00011## . . . . .
##STR00012## . . . . . ##STR00013## . . . . . ##STR00014## . . . .
. ##STR00015## . . . . . ##STR00016## . . . . . ##STR00017## . .
##STR00018## Sequence name: /tmp/rmnzuDbot6/GiHbjeU8iR:EPB2_HUMAN
(SEQ ID NO:1417) Sequence documentation: Alignment of:
M85491_PEA_1_P14 (SEQ ID NO:1284) x EPB2_HUMAN (SEQ ID NO:1417) ..
Alignment segment 1/1: Quality: 2673.00 Escore: 0 Matching length:
270 Total length: 270 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: . . . . . ##STR00019##
. . . . . ##STR00020## . . . . . ##STR00021## . . . . .
##STR00022## . . . . . ##STR00023## . . ##STR00024##
Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112)
(Tyrosine-protein kinase receptor EPH-3) M85491 transcripts which
are detectable by amplicon as depicted in sequence name M85491seg24
(SEQ ID NO: 1639) in normal and cancerous lung tissues
[1046] Expression of Ephrin type-B receptor 2 precursor (EC
2.7.1.112) (Tyrosine-protein kinase receptor EPH-3) transcripts
detectable by or according to seg24, M85491seg24 amplicon (SEQ ID
NO: 1639) and M85491seg24F (SEQ ID NO: 1637) and M85491seg24R (SEQ
ID NO: 1638) primers was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334),
HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2 above, "Tissue samples in
testing panel"), to obtain a value of fold up-regulation for each
sample relative to median of the normal PM samples.
[1047] FIG. 10 below is a histogram showing over expression of the
above-indicated Ephrin type-B receptor 2 precursor (EC 2.7.1.112)
(Tyrosine-protein kinase receptor EPH-3) transcripts in cancerous
lung samples relative to the normal samples. Values represent the
average of duplicate experiments. Error bars indicate the minimal
and maximal values obtained. The number and percentage of samples
that exhibit at least 3 fold over-expression, out of the total
number of samples tested, is indicated in the bottom.
[1048] As is evident from FIG. 10, the expression of Ephrin type-B
receptor 2 precursor (EC 2.7.1.112) (Tyrosine-protein kinase
receptor EPH-3) transcripts detectable by the above ampliconin
cancer samples was significantly higher than in the non-cancerous
samples (Sample Nos. 47-50, 90-93, 96-99 Table 2, "Tissue samples
in testing panel".). Notably an over-expression of at least 3 fold
was found in 9 out of 15 adenocarcinoma samples and in 4 out of 8
small cell carcinoma samples.
[1049] Statistical analysis was applied to verify the significance
of these results, as described below.
[1050] Threshold of 3 fold overexpression was found to
differentiate between cancer and normal samples with P value of
7.42E-03 in adenocarcinoma and 5.69E-02 in small cell carcinoma as
checked by exact fisher test. The above values demonstrate
statistical significance of the results.
[1051] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: M85491seg24F
forward primer (SEQ ID NO: 1637); and M85491seg24Rreverse primer
(SEQ ID NO: 1638).
[1052] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: M85491seg24 (SEQ ID NO: 1639).
TABLE-US-00050 M85491seg24F (SEQ ID NO: 1637)-
GGCGTCTTTCTCCCTCTGAAC M85491seg24R (SEQ ID NO: 1638)-
GTCCCATTCTGGGTGCTGTG M85491seg24 (SEQ ID NO: 1639)-
GGCGTCTTTCTCCCTCTGAACCTCAGTTrCCACCTGTGTCGAGTGTGGGT
GAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGC
ACCCAGAATGGGAC
Expression of Ephrin type-B receptor 2 precursor (EC 2.7.1.112)
(Tyrosine-protein kinase receptor EPH-3)M85491 transcripts which
are detectable by amplicon as depicted in sequence name M85491
seg24 (SEQ ID NO: 1639) in different normal tissues
[1053] Expression of Ephrin type-B receptor 2 precursor transcripts
detectable by or according to M85491 seg24 amplicon (SEQ ID NO:
1639) and M85491 seg24F (SEQ ID NO: 1637) and M85491 seg24R (SEQ ID
NO: 1638) was measured by real time PCR. In parallel the expression
of four housekeeping genes--RPL19 (GenBank Accession No.
NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ ID NO:1630),
TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:1716);
TATA amplicon, SEQ ID NO:1633), Ubiquitin (GenBank Accession No.
BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the lung samples
(Sample Nos. 15-17, Table 2, "Tissue sample on normal panel",
above), to obtain a value of relative expression of each sample
relative to median of the lung samples.
TABLE-US-00051 M85491seg24F (SEQ ID NO: 1637)-
GGCGTCTTTCTCCCTCTGAAC M85491seg24R (SEQ ID NO: 1638)-
GTCCCATTCTGGGTGCTGTG M85491seg24 (SEQ ID NO: 1639)-
GGCGTCTTTCTCCCTCTGAACCTCAGTTTCCACCTGTGTCGAGTGTGGGT
GAGACCCCTCGCGGGGAGCTATGCAGGTTACGGAGAAAAGGCAGCACAGC
ACCCAGAATGGGAC
The results are shown in FIG. 11, demonstrating the expression of
Ephrin type-B receptor 2 precursor (Tyrosine-protein kinase
receptor EPH-3) M85491 transcripts which are detectable by amplicon
as depicted in sequence name M85491seg24 (SEQ ID NO: 1639) in
different normal tissues.
Description for Cluster T39971
[1054] Cluster T39971 features 4 transcript(s) and 28 segment(s) of
interest, the names for which are given in Tables 40 and 41,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
42.
TABLE-US-00052 TABLE 40 Transcripts of interest Transcript Name
Sequence ID No. T39971_T10 5 T39971_T12 6 T39971_T16 7 T39971_T5
8
TABLE-US-00053 TABLE 41 Segments of interest Segment Name Sequence
ID No. T39971_node_0 168 T39971_node_18 169 T39971_node_21 170
T39971_node_22 171 T39971_node_23 172 T39971_node_31 173
T39971_node_33 174 T39971_node_7 175 T39971_node_1 176
T39971_node_10 177 T39971_node_11 178 T39971_node_12 179
T39971_node_15 180 T39971_node_16 181 T39971_node_17 182
T39971_node_26 183 T39971_node_27 184 T39971_node_28 185
T39971_node_29 186 T39971_node_3 187 T39971_node_30 188
T39971_node_34 189 T39971_node_35 190 T39971_node_36 191
T39971_node_4 192 T39971_node_5 193 T39971_node_8 194 T39971_node_9
195
TABLE-US-00054 TABLE 42 Proteins of interest Protein Name Sequence
ID No. T39971_P6 1285 T39971_P9 1286 T39971_P11 1287 T39971_P12
1288
[1055] These sequences are variants of the known protein
Vitronectin precursor (SwissProt accession identifier VTNC_HUMAN;
known also according to the synonyms Serum spreading factor;
S-protein; V75), SEQ ID NO: 1418, referred to herein as the
previously known protein.
[1056] Protein Vitronectin precursor (SEQ ID NO:1418) is known or
believed to have the following function(s): Vitronectin is a cell
adhesion and spreading factor found in serum and tissues.
Vitronectin interacts with glycosaminoglycans and proteoglycans. Is
recognized by certain members of the integrin family and serves as
a cell-to-substrate adhesion molecule. Inhibitor of the
membrane-damaging effect of the terminal cytolytic complement
pathway. The sequence for protein Vitronectin precursor is given at
the end of the application, as "Vitronectin precursor amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 4.
TABLE-US-00055 TABLE 43 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 122 A -> S./FTId =
VAR_012983. 268 R -> Q./FTId = VAR_012984. 400 T -> M./FTId =
VAR_012985. 50 C -> N 225 S -> N 366 A -> T
[1057] Protein Vitronectin precursor (SEQ ID NO:1418) localization
is believed to be Extracellular.
[1058] The previously known protein also has the following
indication(s) and/or potential therapeutic use(s): Cancer,
melanoma. It has been investigated for clinical/therapeutic use in
humans, for example as a target for an antibody or small molecule,
and/or as a direct therapeutic; available information related to
these investigations is as follows. Potential pharmaceutically
related or therapeutically related activity or activities of the
previously known protein are as follows: Alphavbeta3 integrin
antagonist; Apoptosis agonist. A therapeutic role for a protein
represented by the cluster has been predicted. The cluster was
assigned this field because there was information in the drug
database or the public databases (e.g., described herein above)
that this protein, or part thereof, is used or can be used for a
potential therapeutic indication: Anticancer.
[1059] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: immune response;
cell adhesion, which are annotation(s) related to Biological
Process; protein binding; heparin binding, which are annotation(s)
related to Molecular Function; and extracellular space, which are
annotation(s) related to Cellular Component.
[1060] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1061] Cluster T39971 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 12 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1062] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 12 and Table 44. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: liver cancer, lung malignant tumors and
pancreas carcinoma.
TABLE-US-00056 TABLE 44 Normal tissue distribution Name of Tissue
Number adrenal 60 bladder 0 Bone 0 Brain 9 Colon 0 epithelial 79
general 29 Liver 2164 Lung 0 Lymph nodes 0 Breast 0 pancreas 0
prostate 0 Skin 0 Uterus 0
TABLE-US-00057 TABLE 45 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 6.9e-01
7.4e-01 2.0e-02 2.3 5.3e-02 1.8 bladder 5.4e-01 6.0e-01 5.6e-01 1.8
6.8e-01 1.5 Bone 1 6.7e-01 1 1.0 7.0e-01 1.4 Brain 8.0e-01 8.6e-01
3.0e-01 1.9 5.3e-01 1.2 Colon 4.2e-01 4.8e-01 7.0e-01 1.6 7.7e-01
1.4 epithelial 6.6e-01 5.7e-01 1.0e-01 0.8 8.7e-01 0.6 general
5.1e-01 3.8e-01 9.2e-08 1.6 8.3e-04 1.3 Liver 1 6.7e-01 2.3e-03 0.3
1 0.2 Lung 2.4e-01 9.1e-02 1.7e-01 4.3 8.1e-03 5.0 Lymph nodes 1
5.7e-01 1 1.0 5.8e-01 2.3 Breast 1 6.7e-01 1 1.0 8.2e-01 1.2
pancreas 9.5e-02 1.8e-01 1.5e-11 6.5 8.2e-09 4.6 prostate 7.3e-01
6.0e-01 6.7e-01 1.5 5.6e-01 1.7 Skin 1 4.4e-01 1 1.0 6.4e-01 1.6
Uterus 5.0e-01 2.6e-01 1 1.1 8.0e-01 1.4
[1063] As noted above, cluster T39971 features 4 transcript(s),
which were listed in Table 40 above. These transcript(s) encode for
protein(s) which are variant(s) of protein Vitronectin precursor
(SEQ ID NO:1418). A description of each variant protein according
to the present invention is now provided.
[1064] Variant protein T39971_P6 (SEQ ID NO:1285) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) T39971_T5 (SEQ ID
NO:8). An alignment is given to the known protein (Vitronectin
precursor (SEQ ID NO:1418)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1065] Comparison report between T39971_P6 (SEQ ID NO:1285) and
VTNC_HUMAN (SEQ ID NO:1418):
[1066] 1. An isolated chimeric polypeptide encoding for T39971_P6
(SEQ ID NO:1285), comprising a first amino acid sequence being at
least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFKGSQ YWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKG
corresponding to amino acids 1-276 of VTNC_HUMAN (SEQ ID NO:1418),
which also corresponds to amino acids 1-276 of T39971_P6 (SEQ ID
NO:1285), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence TQGVVGD (SEQ ID NO: 1757)
corresponding to amino acids 277-283 of T39971_P6 (SEQ ID NO:1285),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1067] 2. An isolated polypeptide encoding for a tail of T39971_P6
(SEQ ID NO:1285), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence TQGVVGD (SEQ ID NO: 1757) in
T39971_P6 (SEQ ID NO:1285).
[1068] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1069] Variant protein T39971_P6 (SEQ ID NO:1285) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 46, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein T39971_P6 (SEQ ID NO:1285)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00058 TABLE 46 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
122 A -> S Yes 145 G -> No 268 R -> Q Yes 280 V -> A
Yes 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No
211 T -> No 267 G -> No 267 G -> A No 268 R -> No
[1070] Variant protein T39971_P6 (SEQ ID NO:1285) is encoded by the
following transcript(s): T39971_T5 (SEQ ID NO:8), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript T39971_T5 (SEQ ID NO:8) is shown in bold;
this coding portion starts at position 756 and ends at position
1604. The transcript also has the following SNPs as listed in Table
47 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T39971_P6 (SEQ ID NO:1285) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00059 TABLE 47 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No
1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No
1558 G -> A Yes 1594 T -> C Yes 1642 T -> C Yes 1770 C
-> T Yes 529 G -> T Yes 1982 A -> G No 2007 G -> No
2029 T -> C No 2094 T -> C No 2117 C -> G No 2123 C ->
T Yes 2152 C -> T Yes 2182 G -> T No 2185 A -> C No 2297 T
-> C Yes 1119 G -> T Yes 2411 G -> No 2411 G -> T No
2487 T -> C Yes 1188 G -> No 1295 C -> No 1295 C -> G
No 1324 -> T No 1331 C -> No 1381 C -> No
[1071] Variant protein T39971_P9 (SEQ ID NO:1286) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) T39971_T10 (SEQ ID
NO:5). An alignment is given to the known protein (Vitronectin
precursor (SEQ ID NO:1418)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1072] Comparison report between T39971_P9 (SEQ ID NO:1286) and
VTNC_HUMAN (SEQ ID NO:1418):
[1073] 1. An isolated chimeric polypeptide encoding for T39971_P9
(SEQ ID NO:1286), comprising a first amino acid sequence being at
least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFKGSQ
YWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE-
CEGSSLSAV FEHFAMMQRDSWEDIFELLFWGRT corresponding to amino acids
1-325 of VTNC_HUMAN (SEQ ID NO:1418), which also corresponds to
amino acids 1-325 of T39971.sup.--P9 (SEQ ID NO:1286), and a second
amino acid sequence being at least 90% homologous to
SGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRATWLSLFSSEESNLGANNYDDYRMDWLVPAT-
C EPIQSVFFFSGDKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to
amino acids 357-478 of VTNC_HUMAN (SEQ ID NO:1418), which also
corresponds to amino acids 326-447 of T39971_P9 (SEQ ID NO:1286),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1074] 2. An isolated chimeric polypeptide encoding for an edge
portion of T39971_P9 (SEQ ID NO:1286), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise TS, having a structure as follows: a sequence
starting from any of amino acid numbers 325-x to 325; and ending at
any of amino acid numbers 326+((n-2)-x), in which x varies from 0
to n-2.
[1075] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1076] Variant protein T39971_P9 (SEQ ID NO:1286) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 48, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein T39971_P9 (SEQ ID NO:1286)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00060 TABLE 48 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
122 A -> S Yes 145 G -> No 268 R -> Q Yes 328 M -> T No
350 S -> P No 369 T -> M Yes 379 S -> I No 380 N -> T
No 180 C -> No 180 C -> W No 192 Y -> No 209 A -> No
211 T -> No 267 G -> No 267 G -> A No 268 R -> No
[1077] Variant protein T39971_P9 (SEQ ID NO:1286) is encoded by the
following transcript(s): T39971_T10 (SEQ ID NO:5), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript T39971_T10 (SEQ ID NO:5) is shown in bold;
this coding portion starts at position 756 and ends at position
2096. The transcript also has the following SNPs as listed in Table
49 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T39971_P9 (SEQ ID NO:1286) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00061 TABLE 49 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No
1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No
1558 G -> A Yes 1738 T -> C No 1803 T -> C No 1826 C ->
G No 529 G -> T Yes 1832 C -> T Yes 1861 C -> T Yes 1891 G
-> T No 1894 A -> C No 2006 T -> C Yes 2120 G -> No
2120 G -> T No 2196 T -> C Yes 1119 G -> T Yes 1188 G
-> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C
-> No 1381 C -> No
[1078] Variant protein T39971_P11 (SEQ ID NO:1287) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) T39971_T12 (SEQ ID
NO:6). An alignment is given to the known protein (Vitronectin
precursor (SEQ ID NO:1418)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1079] Comparison report between T39971_P11 (SEQ ID NO:1287) and
VTNC_HUMAN (SEQ ID NO:1418):
[1080] 1. An isolated chimeric polypeptide encoding for T39971_P11
(SEQ ID NO:1287), comprising a first amino acid sequence being at
least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFKGSQ
YWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE-
CEGSSLSAV FEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids
1-326 of VTNC_HUMAN (SEQ ID NO:1418), which also corresponds to
amino acids 1-326 of T39971_P11 (SEQ ID NO:1287), and a second
amino acid sequence being at least 90% homologous to
DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL corresponding to amino acids
442-478 of VTNC_HUMAN (SEQ ID NO:1418), which also corresponds to
amino acids 327-363 of T39971_P11 (SEQ ID NO:1287), wherein said
first and second amino acid sequences are contiguous and in a
sequential order.
[1081] 2. An isolated chimeric polypeptide encoding for an edge
portion of T39971_P11 (SEQ ID NO:1287), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise SD, having a structure as follows: a sequence
starting from any of amino acid numbers 326-x to 326; and ending at
any of amino acid numbers 327+((n-2)-x), in which x varies from 0
to n-2.
[1082] Comparison report between T39971_P11 (SEQ ID NO:1287) and
Q9BSH7 (SEQ ID NO:1696):
[1083] 1. An isolated chimeric polypeptide encoding for T39971_P11
(SEQ ID NO:1287), comprising a first amino acid sequence being at
least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFKGSQ
YWRFEDGVLDPDYPRNISDGFDGIPDNVDAALALPAHSYSGRERVYFFKGKQYWEYQFQHQPSQEE-
CEGSSLSAV FEHFAMMQRDSWEDIFELLFWGRTS corresponding to amino acids
1-326 of Q9BSH7, which also corresponds to amino acids 1-326 of
T39971_P11 (SEQ ID NO:1287), and a second amino acid sequence being
at least 90% homologous to DKYYRVNLRTRRVDTVDPPYPRSIAQYWLGCPAPGHL
corresponding to amino acids 442-478 of Q9BSH7, which also
corresponds to amino acids 327-363 of T39971_P11 (SEQ ID NO:1287),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1084] 2. An isolated chimeric polypeptide encoding for an edge
portion of T39971_P11 (SEQ ID NO:1287), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise SD, having a structure as follows: a sequence
starting from any of amino acid numbers 326-x to 326; and ending at
any of amino acid numbers 327 +((n-2)-x), in which x varies from 0
to n-2.
[1085] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1086] Variant protein T39971_P11 (SEQ ID NO:1287) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 50, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein T39971_P11 (SEQ ID NO:1287)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00062 TABLE 50 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
122 A -> S Yes 145 G -> No 268 R -> Q Yes 180 C -> No
180 C -> W No 192 Y -> No 209 A -> No 211 T -> No 267 G
-> No 267 G -> A No 268 R -> No
[1087] Variant protein T39971_P11 (SEQ ID NO:1287) is encoded by
the following transcript(s): T39971_T12 (SEQ ID NO:6), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript T39971_T12 (SEQ ID NO:6) is shown in
bold; this coding portion starts at position 756 and ends at
position 1844. The transcript also has the following SNPs as listed
in Table 51 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein T39971_P11 (SEQ ID NO:1287) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00063 TABLE 51 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No
1406 -> G No 1555 G -> No 1555 G -> C No 1558 G -> No
1558 G -> A Yes 1754 T -> C Yes 1868 G -> No 1868 G ->
T No 529 G -> T Yes 1944 T -> C Yes 1119 G -> T Yes 1188 G
-> No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C
-> No 1381 C -> No
[1088] Variant protein T39971_P12 (SEQ ID NO:1288) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) T39971_T16 (SEQ ID
NO:7). An alignment is given to the known protein (Vitronectin
precursor (SEQ ID NO:1418)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1089] Comparison report between T39971_P12 (SEQ ID NO:1288) and
VTNC_HUMAN (SEQ ID NO:1418):
[1090] 1. An isolated chimeric polypeptide encoding for T39971_P12
(SEQ ID NO:1288), comprising a first amino acid sequence being at
least 90% homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFK corresponding to amino acids 1-223 of VTNC_HUMAN (SEQ ID
NO:1418), which also corresponds to amino acids 1-223 of T39971_P12
(SEQ ID NO:1288), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence VPGAVGQGRKHLGRV (SEQ ID NO:
1758) corresponding to amino acids 224-238 of T39971_P12 (SEQ ID
NO:1288), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1091] 2. An isolated polypeptide encoding for a tail of T39971_P12
(SEQ ID NO:1288), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO: 1758) in
T39971_P12 (SEQ ID NO:1288).
[1092] Comparison report between T39971_P12 (SEQ ID NO:1288) and
Q9BSH7:
[1093] 1. An isolated chimeric polypeptide encoding for T39971_P12
(SEQ ID NO:1288), comprising a first amino acid sequence being at
least 90 homologous to
MAPLRPLLILALLAWVALADQESCKGRCTEGFNVDKKCQCDELCSYYQSCCTDYTAECKPQVTRGDVFTMPED-
E
YTVYDDGEEKNNATVHEQVGGPSLTSDLQAQSKGNPEQTPVLKPEEEAPAPEVGASKPEGIDSRPETLHPGR-
PQPP
AEEELCSGKPFDAFTDLKNGSLFAFRGQYCYELDEKAVRPGYPKLIRDVWGIEGPIDAAFTRINCQGKT-
YLFK corresponding to amino acids 1-223 of Q9BSH7, which also
corresponds to amino acids 1-223 of T39971_P12 (SEQ ID NO:1288),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence VPGAVGQGRKHLGRV (SEQ ID NO: 1758) corresponding to
amino acids 224-238 of T39971_P12 (SEQ ID NO:1288), wherein said
first and second amino acid sequences are contiguous and in a
sequential order.
[1094] 2. An isolated polypeptide encoding for a tail of T39971_P12
(SEQ ID NO:1288), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence VPGAVGQGRKHLGRV (SEQ ID NO: 1758) in
T39971_P12 (SEQ ID NO:1288).
[1095] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1096] Variant protein T39971_P12 (SEQ ID NO:1288) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 52, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein T39971_P12 (SEQ ID NO:1288)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00064 TABLE 52 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
122 A -> S Yes 145 G -> No 180 C -> No 180 C -> W No
192 Y -> No 209 A -> No 211 T -> No
[1097] Variant protein T39971_P12 (SEQ ID NO:1288) is encoded by
the following transcript(s): T39971_T16 (SEQ ID NO:7), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript T39971_T16 (SEQ ID NO:7) is shown in
bold; this coding portion starts at position 756 and ends at
position 1469. The transcript also has the following SNPs as listed
in Table 53 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein T39971_P12 (SEQ ID NO:1288) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00065 TABLE 53 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
417 G -> C Yes 459 T -> C Yes 1387 C -> No 1406 -> A No
1406 -> G No 529 G -> T Yes 1119 G -> T Yes 1188 G ->
No 1295 C -> No 1295 C -> G No 1324 -> T No 1331 C ->
No 1381 C -> No
[1098] As noted above, cluster T39971 features 28 segment(s), which
were listed in Table 41 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1099] Segment cluster T39971_node.sub.--0 (SEQ ID NO:1039)
according to the present invention is supported by 76 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971.sub.--10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16
(SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 54 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00066 TABLE 54 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1 810 T39971_T12 (SEQ ID NO: 6) 1 810
T39971_T16 (SEQ ID NO: 7) 1 810 T39971_T5 (SEQ ID NO: 8) 1 810
[1100] Segment cluster T39971_node.sub.--18 (SEQ ID NO:1040)
according to the present invention is supported by 1 libraries The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): T39971_T16
(SEQ ID NO:7). Table 55 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00067 TABLE 55 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T16 (SEQ ID NO: 7) 1425 1592
[1101] Segment cluster T3997_node.sub.--21 (SEQ ID NO:1041)
according to the present invention is supported by 99 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6) and T39971_T5
(SEQ ID NO:8). Table 56 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00068 TABLE 56 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1425 1581 T39971_T12 (SEQ ID NO: 6) 1425
1581 T39971_T5 (SEQ ID NO: 8) 1425 1581
[1102] Segment cluster T39971_node.sub.--22 (SEQ ID NO:1042)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): T39971_T5 (SEQ
ID NO:8). Table 57 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00069 TABLE 57 Segment location on transcripts Segment
Segment starting ending Transcript name position position T39971_T5
(SEQ ID NO: 8) 1582 1779
[1103] Segment cluster T39971_node.sub.--23 (SEQ ID NO:1043)
according to the present invention is supported by 101 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6) and T39971_T5
(SEQ ID NO:8). Table 56 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00070 TABLE 58 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1582 1734 T39971_T12 (SEQ ID NO: 6) 1582
1734 T39971_T5 (SEQ ID NO: 8) 1780 1932
[1104] Segment cluster T39971_node.sub.--31 (SEQ ID NO:1044)
according to the present invention is supported by 94 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5) and T39971_T5 (SEQ ID NO:8). Table 59
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00071 TABLE 59 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1847 1986 T39971_T5 (SEQ ID NO: 8) 2138
2277
[1105] Segment cluster T139971_node.sub.--33 (SEQ ID NO:1045)
according to the present invention is supported by 77 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6) and T39971_T5
(SEQ ID NO:8). Table 60 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00072 TABLE 60 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1987 2113 T39971_T12 (SEQ ID NO: 6) 1735
1861 T39971_T5 (SEQ ID NO: 8) 2278 2404
[1106] Segment cluster T39971_node.sub.--7 (SEQ ID NO:1046)
according to the present invention is supported by 87 libraries The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): T39971_T10
(SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ ID NO:7)
and T39971_T5 (SEQ ID NO:8). Table 61 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00073 TABLE 61 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 940 1162 T39971_T12 (SEQ ID NO: 6) 940
1162 T39971_T16 (SEQ ID NO: 7) 940 1162 T39971_T5 (SEQ ID NO: 8)
940 1162
[1107] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1108] Segment cluster T39971_node.sub.--1 (SEQ ID NO:1047)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 62
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00074 TABLE 62 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 811 819 T39971_T12 (SEQ ID NO: 6) 811 819
T39971_T16 (SEQ ID NO: 7) 811 819 T39971_T5 (SEQ ID NO: 8) 811
819
[1109] Segment cluster T39971_node.sub.--10 (SEQ ID NO:1048)
according to the present invention is supported by 77 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 63 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00075 TABLE 63 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1189 1232 T39971_T12 (SEQ ID NO: 6) 1189
1232 T39971_T16 (SEQ ID NO: 7) 1189 1232 T39971_T5 (SEQ ID NO: 8)
1189 1232
[1110] Segment cluster T39971_node.sub.--11 (SEQ ID NO:1049)
according to the present invention is supported by 79 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 64 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00076 TABLE 64 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1233 1270 T39971_T12 (SEQ ID NO: 6) 1233
1270 T39971_T16 (SEQ ID NO: 7) 1233 1270 T39971_T5 (SEQ ID NO: 8)
1233 1270
[1111] Segment cluster T39971_node.sub.--12 (SEQ ID NO:1050)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 65
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00077 TABLE 65 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1271 1284 T39971_T12 (SEQ ID NO: 6) 1271
1284 T39971_T16 (SEQ ID NO: 7) 1271 1284 T39971_T5 (SEQ ID NO: 8)
1271 1284
[1112] Segment cluster T39971_node.sub.--15 (SEQ ID NO:1051)
according to the present invention is supported by 79 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 66 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00078 TABLE 66 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1285 1316 T39971_T12 (SEQ ID NO: 6) 1285
1316 T39971_T16 (SEQ ID NO: 7) 1285 1316 T39971_T5 (SEQ ID NO: 8)
1285 1316
[1113] Segment cluster T399771_node.sub.--16 (SEQ ID NO:1052)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 67
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00079 TABLE 67 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1317 1340 T39971_T12 (SEQ ID NO: 6) 1317
1340 T39971_T16 (SEQ ID NO: 7) 1317 1340 T39971_T5 (SEQ ID NO: 8)
1317 1340
[1114] Segment cluster T39971_node.sub.--17 (SEQ ID NO:1053)
according to the present invention is supported by 86 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 68 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00080 TABLE 68 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1341 1424 T39971_T12 (SEQ ID NO: 6) 1341
1424 T39971_T16 (SEQ ID NO: 7) 1341 1424 T39971_T5 (SEQ ID NO: 8)
1341 1424
[1115] Segment cluster T39971_node.sub.--26 (SEQ ID NO:1054)
according to the present invention is supported by 85 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971.sub.--15 (SEQ ID NO:8). Table 69 below describes the
starting and ending position of this segment each transcript.
TABLE-US-00081 TABLE 69 Segment location on transcripts Segment
Segment starting ending Transcript name position position T39971_T5
(SEQ ID NO: 8) 1933 1974
[1116] Segment cluster T39971_node.sub.--27 (SEQ ID NO:1055)
according to the present invention is supported by 90 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): T39971_T5
(SEQ ID NO:8). Table 70 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00082 TABLE 70 Segment location on transcripts Segment
Segment starting ending Transcript name position position T39971_T5
(SEQ ID NO: 8) 1975 2025
[1117] Segment cluster T39971_node.sub.--28 (SEQ ID NO:1056)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5) and T39971_T5 (SEQ ID
NO:8). Table 71 below describes the starting and ending position of
this segment on each transcript.
TABLE-US-00083 TABLE 71 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1735 1743 T39971_T5 (SEQ ID NO: 8) 2026
2034
[1118] Segment cluster T39971_node.sub.--29 (SEQ ID NO:1057)
according to the present invention is supported by 99 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5) and T39971_T5 (SEQ ID NO:8). Table 72
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00084 TABLE 72 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1744 1838 T39971_T5 (SEQ ID NO: 8) 2035
2129
[1119] Segment cluster T39971_node.sub.--3 (SEQ ID NO:1058)
according to the present invention is supported by 78 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 73 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00085 TABLE 73 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 820 861 T39971_T12 (SEQ ID NO: 6) 820 861
T39971_T16 (SEQ ID NO: 7) 820 861 T39971_T5 (SEQ ID NO: 8) 820
861
[1120] Segment cluster T39971_node.sub.--30 (SEQ ID NO:1059)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5) and T39971_T5 (SEQ ID
NO:8). Table 74 below describes the starting and ending position of
this segment on each transcript.
TABLE-US-00086 TABLE 74 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 1839 1846 T39971_T5 (SEQ ID NO: 8) 2130
2137
[1121] Segment cluster T39971_node.sub.--34 (SEQ ID NO:1060)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6)
and T39971_T5 (SEQ ID NO:8). Table 75 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00087 TABLE 75 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 2114 2120 T39971_T12 (SEQ ID NO: 6) 1862
1868 T39971_T5 (SEQ ID NO: 8) 2405 2411
[1122] Segment cluster T39971_node.sub.--35 (SEQ ID NO:1061)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6)
and T39971_T5 (SEQ ID NO:8). Table 76 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00088 TABLE 76 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 2121 2137 T39971_T12 (SEQ ID NO: 6) 1869
1885 T39971_T5 (SEQ ID NO: 8) 2412 2428
[1123] Segment cluster T39971_node.sub.--36 (SEQ ID NO:1062)
according to the present invention is supported by 51 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6) and T39971_T5
(SEQ ID NO:8). Table 77 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00089 TABLE 77 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 2138 2199 T39971_T12 (SEQ ID NO: 6) 1886
1947 T39971_T5 (SEQ ID NO: 8) 2429 2490
[1124] Segment cluster T39971_node.sub.--4 (SEQ ID NO:1063)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 78
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00090 TABLE 78 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 862 881 T39971_T12 (SEQ ID NO: 6) 862 881
T39971_T16 (SEQ ID NO: 7) 862 881 T39971_T5 (SEQ ID NO: 8) 862
881
[1125] Segment cluster T39971_node.sub.--5 (SEQ ID NO:1064)
according to the present invention is supported by 80 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6), T39971_T16 (SEQ
ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 79 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00091 TABLE 79 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T39971_T10 (SEQ ID NO: 5) 882 939 T39971_T12 (SEQ ID NO: 6) 882 939
T39971_T16 (SEQ ID NO: 7) 882 939 T39971_T5 (SEQ ID NO: 8) 882
939
[1126] Segment cluster T39971_node.sub.--8 (SEQ ID NO:1065)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 80
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00092 TABLE 80 Segment location on transcripts Segment
Segment Transcript name starting position ending position
T39971_T10 (SEQ ID NO: 5) 1163 1168 T39971_T12 (SEQ ID NO: 6) 1163
1168 T39971_T16 (SEQ ID NO: 7) 1163 1168 T39971_T5 (SEQ ID NO: 8)
1163 1168
[1127] Segment cluster T39971_node.sub.--9 (SEQ ID NO:1066)
according to the present invention can be found in the following
transcript(s): T39971_T10 (SEQ ID NO:5), T39971_T12 (SEQ ID NO:6),
T39971_T16 (SEQ ID NO:7) and T39971_T5 (SEQ ID NO:8). Table 81
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00093 TABLE 81 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T39971_T10 (SEQ ID NO: 5) 1169 1188 T39971_T12 (SEQ ID NO: 6) 1169
1188 T39971_T16 (SEQ ID NO: 7) 1169 1188 T39971_T5 (SEQ ID NO: 8)
1169 1188
[1128] Variant protein alignment to the previously known
protein:
TABLE-US-00094 Sequence name: /tmp/ckraCL2OcZ/43L7YcPH7x:VTNC_HUMAN
(SEQ ID NO:1418) Sequence documentation: Alignment of: T39971_P6
(SEQ ID NO:1285) x VTNC_HUMAN (SEQ ID NO:1418) .. Alignment segment
1/1: Quality: 2774.00 Escore: 0 Matching length: 278 Total length:
278 Matching percent Similarity: 99.64 Matching Percent Identity:
99.64 Total Percent Similarity: 99.64 Total Percent Identity: 99.64
Gaps: 0 Alignment: . . . . . ##STR00025## . . . . . ##STR00026## .
. . . . ##STR00027## . . . . . ##STR00028## . . . . . ##STR00029##
. . ##STR00030## Sequence name:
/tmp/X4DeeuSlB4/yMubSR5FPs:VTNC_HUMAN (SEQ ID NO:1418) Sequence
documentation: Alignment of: T39971_P9 (SEQ ID NO:1286) x
VTNC_HUMAN (SEQ ID NO:1418 .. Alignment segment 1/1: Quality:
4430.00 Escore: 0 Matching length: 447 Total length: 478 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 93.51 Total Percent Identity: 93.51 Gaps: 1
Alignment: . . . . . ##STR00031## . . . . . ##STR00032## . . . . .
##STR00033## . . . . . ##STR00034## . . . . . ##STR00035## . . . .
. ##STR00036## . . . . . ##STR00037## . . . . . ##STR00038## . . .
. . ##STR00039## . . ##STR00040## Sequence name:
/tmp/jvp1VtnxNy/wxNSeFVZZw:VTNC_HUMAN (SEQ ID NO:1418) Sequence
documentation: Alignment of: T39971_P11 (SEQ ID NO:1287) x
VTNC_HUMAN (SEQ ID NO:1418) Alignment segment 1/1: Quality: 3576.00
Escore: 0 Matching length: 363 Total length: 478 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 75.94 Total Percent Identity: 75.94 Gaps: 1 Alignment:
. . . . . ##STR00041## . . . . . ##STR00042## . . . . .
##STR00043## . . . . . ##STR00044## . . . . . ##STR00045## . . . .
. ##STR00046## . . . . . ##STR00047## . . . . . 326
.................................................. 326 351
AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAT 400 . . . . .
##STR00048## . . ##STR00049## Sequence name:
/tmp/jvp1VtnxNy/wxNSeFVZZw:Q9BSH7 Sequence documentation: Alignment
of: T39971_P11 (SEQ ID NO:1287) x Q9BSH7 .. Alignment segment 1/1:
Quality: 3576.00 Escore: 0 Matching length: 363 Total length: 478
Matching Percent Similarity: 100.00 Metching Percent Identity:
100.00 Total Percent Similarity: 75.94 Total Percent Identity:
75.94 Gaps: 1 Alignment: . . . . . ##STR00050## . . . . .
##STR00051## . . . . . ##STR00052## . . . . . ##STR00053## . . . .
. ##STR00054## . . . . . ##STR00055## . . . . . ##STR00056## . . .
. . 326 .................................................. 326 351
AGRIYISGMAPRPSLAKKQRFRHRNRKGYRSQRGHSRGRNQNSRRPSRAM 400 . . . . .
##STR00057## . . ##STR00058## Sequence name:
/tmp/fgebv7ir4i/48bTBMziJ0:VTNC_HUMAN (SEQ ID NO:1418) Sequence
documentation: Alignment of: T39971_P12 (SEQ ID NO:1288) x
VTNC_HUMAN (SEQ ID NO:1418) Alignment segment 1/1: Quality: 2237.00
Escore: 0 Matching length: 223 Total length: 223 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00059## . . . . . ##STR00060## . . . . .
##STR00061## . . . . . ##STR00062## . . ##STR00063## Sequence name:
/tmp/fgebv7ir4i/48bTBMziJ0:Q9BSH7 Sequence documentation: Alignment
of: T39971_P12 (SEQ ID NO:1288) x Q9BSH7 .. Alignment segment 1/1:
Quality: 2237.00 Escore: 0 Matching length: 223 Totallength: 223
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: . . . . . ##STR00064## . . . . .
##STR00065## . . . . . ##STR00066## . . . . . ##STR00067## . .
##STR00068##
Description for Cluster Z21368
[1129] Cluster Z21368 features 7 transcript(s) and 34 segment(s) of
interest, the names for which are given in Tables 82 and 83,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
84.
TABLE-US-00095 TABLE 82 Transcripts of interest Transcript Name
Sequence ID No. Z21368_PEA_1_T10 9 Z21368_PEA_1_T11 10
Z21368_PEA_1_T23 11 Z21368_PEA_1_T24 12 Z21368_PEA_1_T5 13
Z21368_PEA_1_T6 14 Z21368_PEA_1_T9 15
TABLE-US-00096 TABLE 83 Segments of interest Segment Name Sequence
ID No. Z21368_PEA_1_node_0 1067 Z21368_PEA_1_node_15 1068
Z21368_PEA_1_node_19 1069 Z21368_PEA_1_node_2 1070
Z21368_PEA_1_node_21 1071 Z21368_PEA_1_node_33 1072
Z21368_PEA_1_node_36 1073 Z21368_PEA_1_node_37 1074
Z21368_PEA_1_node_39 1075 Z21368_PEA_1_node_4 1076
Z21368_PEA_1_node_41 1077 Z21368_PEA_1_node_43 1078
Z21368_PEA_1_node_45 1079 Z21368_PEA_1_node_53 1080
Z21368_PEA_1_node_56 1081 Z21368_PEA_1_node_58 1082
Z21368_PEA_1_node_66 1083 Z21368_PEA_1_node_67 1084
Z21368_PEA_1_node_69 1085 Z21368_PEA_1_node_11 1086
Z21368_PEA_1_node_12 1087 Z21368_PEA_1_node_16 1088
Z21368_PEA_1_node_17 1089 Z21368_PEA_1_node_23 1090
Z21368_PEA_1_node_24 1091 Z21368_PEA_1_node_30 1092
Z21368_PEA_1_node_31 1093 Z21368_PEA_1_node_38 1094
Z21368_PEA_1_node_47 1095 Z21368_PEA_1_node_49 1096
Z21368_PEA_1_node_51 1097 Z21368_PEA_1_node_61 1098
Z21368_PEA_1_node_68 1099 Z21368_PEA_1_node_7 1100
TABLE-US-00097 TABLE 84 Proteins of interest Protein Name Sequence
ID No. Z21368_PEA_1_P2 1289 Z21368_PEA_1_P5 1290 Z21368_PEA_1_P15
1291 Z21368_PEA_1_P16 1292 Z21368_PEA_1_P22 1293 Z21368_PEA_1_P23
1294
[1130] These sequences are variants of the known protein
Extracellular sulfatase Sulf-1 precursor (SwissProt accession
identifier SUL1_HUMAN; known also according to the synonyms EC
3.1.6.-; HSulf-1), SEQ ID NO: 1419, referred to herein as the
previously known protein.
[1131] Protein Extracellular sulfatase Sulf-1 precursor(SEQ ID
NO:1419) is known or believed to have the following function(s):
Exhibits arylsulfatase activity and highly specific
endoglucosamine-6-sulfatase activity. It can remove sulfate from
the C-6 position of glucosamine within specific subregions of
intact heparin. Diminishes HSPG (heparan sulfate proteoglycans)
sulfation, inhibits signaling by heparin-dependent growth factors,
diminishes proliferation, and facilitates apoptosis in response to
exogenous stimulation. The sequence for protein Extracellular
sulfatase Sulf-1 precursor is given at the end of the application,
as "Extracellular sulfatase Sulf-1 precursor amino acid sequence".
Known polymorphisms for this sequence are as shown in Table 85.
TABLE-US-00098 TABLE 85 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 87-88 CC->AA: LOSS OF
ARYLSULFATASE ACTIVITY AND LOSS OF ABILITY TO MODULATE APOPTOSIS.
49 L -> P 728 K -> R
[1132] Protein Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419) localization is believed to be Endoplasmic reticulum and
Golgi stack. Also localized on the cell surface (By
similarity).
[1133] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: apoptosis;
metabolism; heparan sulfate proteoglycan metabolism, which are
annotation(s) related to Biological Process;
[1134] arylsulfatase; hydrolase, which are annotation(s) related to
Molecular Function; and extracellular space; endoplasmic reticulum;
Golgi apparatus, which are annotation(s) related to Cellular
Component.
[1135] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1136] Cluster Z21368 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 13 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1137] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 13 and Table 86. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues and pancreas carcinoma.
TABLE-US-00099 TABLE 86 Normal tissue distribution Name of Tissue
Number bladder 123 Bone 557 Brain 34 Colon 94 epithelial 56 general
68 head and neck 0 kidney 35 Lung 22 Lymph nodes 0 Breast 52 muscle
31 Ovary 0 pancreas 0 prostate 44 Skin 67 stomach 109 T cells 0
Thyroid 0 Uterus 140
TABLE-US-00100 TABLE 87 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 5.4e-01
6.6e-01 6.4e-01 1.0 8.5e-01 0.7 Bone 4.5e-01 8.2e-01 9.1e-01 0.4 1
0.3 Brain 5.5e-01 7.3e-01 1.5e-01 1.5 5.0e-01 0.9 Colon 1.4e-01
2.8e-01 1.0e-01 2.0 3.0e-01 1.4 epithelial 1.1e-03 1.5e-01 1.2e-07
2.1 1.0e-01 1.1 general 1.4e-05 5.3e-02 1.9e-06 1.6 6.7e-01 0.8
head and neck 2.4e-02 7.1e-02 4.6e-01 2.5 7.5e-01 1.4 kidney
8.9e-01 9.0e-01 1 0.4 1 0.4 Lung 3.5e-01 4.1e-01 7.2e-03 2.6
1.0e-01 1.6 Lymph nodes 7.7e-02 3.1e-01 2.3e-02 8.5 1.9e-01 3.2
Breast 4.0e-01 6.1e-01 5.4e-02 2.3 3.0e-01 1.3 muscle 7.5e-02
3.5e-02 1 1.0 1.7e-01 1.7 Ovary 3.8e-01 4.2e-01 2.2e-01 2.9 3.4e-01
2.2 pancreas 2.2e-02 6.9e-02 1.4e-08 6.5 1.4e-06 4.6 prostate
8.3e-01 8.9e-01 3.1e-01 1.4 5.2e-01 1.1 Skin 6.1e-01 8.1e-01
6.0e-01 1.2 1 0.3 stomach 4.4e-02 5.0e-01 5.0e-01 0.8 9.7e-01 0.4 T
cells 5.0e-01 6.7e-01 3.3e-01 3.1 7.2e-01 1.4 Thyroid 3.6e-01
3.6e-01 1 1.1 1 1.1 Uterus 3.5e-01 7.8e-01 4.6e-01 0.9 9.1e-01
0.5
[1138] As noted above, cluster Z21368 features 7 transcript(s),
which were listed in Table 82 above. These transcript(s) encode for
protein(s) which are variant(s) of protein Extracellular sulfatase
Sulf-1 precursor (SEQ ID NO:1419). A description of each variant
protein according to the present invention is now provided.
[1139] Variant protein Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1140] Comparison report between Z21368_PEA.sub.--1_P2 (SEQ ID
NO:1289) and SUL1_HUMAN (SEQ ID NO:1419):
[1141] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT
FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNE-
YNGS
YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVI-
SHAAPH
GPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDS-
VERLYNML
VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLA-
PTILDIAGLDTPPDV
DGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTA-
CE
QPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRASRSQRKSQRQFLR-
NQGT
PKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRML-
ADSSNAV
GPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKP-
EECSCSKQSY
YNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLT-
CFTHDNNHWQT APFWN corresponding to amino acids 1-761 of SUL1_HUMAN
(SEQ ID NO:1419), which also corresponds to amino acids 1-761 of
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO: 1759) corresponding to
amino acids 762-790 of Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1142] 2. An isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PHKYSAHGRTRHFESATRTTNGAQKLSRI (SEQ ID NO: 1759) in
Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289).
[1143] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1144] Variant protein Z21368_PEA.sub.--1_P2 (SEQ ID NO:1289) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z21368_PEA.sub.--1_T5
(SEQ ID NO:13) is shown in bold; this coding portion starts at
position 529 and ends at position 2898.
[1145] Variant protein Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1146] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID
NO:1290) and Q7Z2W2 (SEQ ID NO:1697):
[1147] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 90 homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL
corresponding to amino acids 1-57 of Q7Z2W2 (SEQ ID NO:1697), which
also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5 (SEQ
ID NO:1290), second bridging amino acid sequence comprising A, and
a third amino acid sequence being at least 90% homologous to
FFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYP-
HRP
VMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQ-
TLMSV
DDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQ-
IVLNIDLAPTI
LDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERV-
KEL
CQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGYRAS-
RSQRK
SQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDL-
QASSGGNR
GRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNL-
REVRGHLKRR
KPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQ-
RKGEECSLPGLT
CFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVE-
R GILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG
corresponding to amino acids 139-871 of Q7Z2W2 (SEQ ID NO:1697),
which also corresponds to amino acids 59-791 of Z21368.sub.--1_P5
(SEQ ID NO:1290), wherein said first, second and third amino acid
sequences are contiguous and in a sequential order.
[1148] 2. An isolated polypeptide encoding for an edge portion of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least three amino
acids comprise LAF, the sequence having a structure as follows
(numbering according to Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290)): a
sequence starting from any of amino acid numbers 57-x to 57; and
ending at any of amino acid numbers 59+((n-2)-x), in which x varies
from 0 to n-2.
[1149] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID
NO:1290) and AAH12997 (SEQ ID NO:1698):
[1150] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIP-
PGWR
EWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHG-
PEDSAP
QFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNM-
LVETGELE
NTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIA-
GLDTPPDVDGKSVL
KLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQ-
K
WQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGEHDKDKECSCRESGYRASRSQRKSQRQFLRNQGTPK-
YKP
RFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNA-
VGPPTT
VRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCS-
KQSYYNKEK
GVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDN-
NHWQTAPFWN
LGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQ-
LHVQLME (SEQ ID NO: 1760) corresponding to amino acids 1-751 of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), and a second amino acid
sequence being at least 90% homologous to
LRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG corresponding to amino
acids 1-40 of AAH12997 (SEQ ID NO:1698), which also corresponds to
amino acids 752-791 of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1151] 2. An isolated polypeptide encoding for a head of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELAFFGKYLNEYNGSYIP-
PGWR
EQLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVISHAAPHG-
PEDSAP
QFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDSVERLYNM-
LVETGELE
NTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLAPTILDIA-
GLDTPPDVDGKSVL
KLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKYERVKELCQQARYQTACEQPGQ-
K
WQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDGECSCRESGYRASRSQRKSQRQFLRNQGTPK-
YKP
RFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGPRDLQASSGGNRGRMLADSSNA-
VGPPT
VRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKIKNLREVRGHLKRRKPEECSCSK-
QSYYNKEK
GVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEKRRQRKGEECSLPGLTCFTHDNN-
HWQTAPFWN
LGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTVHTVERGILNQL-
HVQLME (SEQ ID NO: 1760) of Z21368_PEA.sub.--1_P5 (SEQ ID
NO:1290).
[1152] Comparison report between Z21368_PEA.sub.--1_P5 (SEQ ID
NO:1290) and SUL1_HUMAN (SEQ ID NO:1419):
[1153] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a first amino
acid sequence being at least 90 homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVEL
corresponding to amino acids 1-57 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-57 of Z21368_PEA.sub.--1_P5
(SEQ ID NO:1290), and a second amino acid sequence being at least
90% homologous to
AFFGKYLNEYNGSYIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSK-
RMYPH
RPVMMVISHAAPHGPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQR-
KRLQTLM
SVDDSVERLYNMLVETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGS-
IVPQIVLNIDLA
PTILDIAGLDTPPDVDGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERGKFLRKKEESSKNIQQSNHLPKY-
ERV
KELCQQARYQTACEQPGQKWQCIEDTSGKLRIHKCKGPSDLLTVRQSTRNLYARGFHDKDKECSCRESGY-
RASRS
QRKSQRQFLRNQGTPKYKPRFVHTRQTRSLSVEFEGEIYDINLEEEEELQVLQPRNIAKRHDEGHKGP-
RDLQASSG
GNRGRMLADSSNAVGPPTTVRVTHKCFILPNDSIHCERELYQSARAWKDHKAYIDKEIEALQDKI-
KNLREVRGHL
KRRKPEECSCSKQSYYNKEKGVKKQEKLKSHLHPFKEAAQEVDSKLQLFKENNRRRKKERKEK-
RRQRKGEECSL
PGLTCFTHDNNHWQTAPFWNLGSFCACTSSNNNTYWCLRTVNETHNFLFCEFATGFLEYFDMNTDPYQLTNTV-
H TVERGILNQLHVQLMELRSCQGYKQCNPRPKNLDVGNKDGGSYDLHRGQLWDGWEG
corresponding to amino acids 138-871 of SUL1_HUMAN (SEQ ID
NO:1419), which also corresponds to amino acids 58-791 of
Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1154] 2. An isolated chimeric polypeptide encoding for an edge
portion of Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise LA, having a structure as follows: a
sequence starting from any of amino acid numbers 57-x to 57; and
ending at any of amino acid numbers 58 +((n-2)-x), in which x
varies from 0 to n-2.
[1155] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1156] Variant protein Z21368_PEA.sub.--1_P5 (SEQ ID NO:1290) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T9 (SEQ
ID NO:15), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z21368_PEA.sub.--1_T9
(SEQ ID NO:15) is shown in bold; this coding portion starts at
position 556 and ends at position 2928.
[1157] Variant protein Z21368_PEA.sub.--1_P15 (SEQ ID NO:1291)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T23 (SEQ ID NO:11). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1158] Comparison report between Z21368_PEA.sub.--1_P15 (SEQ ID
NO:1291) and SUL1_HUMAN (SEQ ID NO:1419):
[1159] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA1_P15 (SEQ ID NO:1291), comprising a first amino acid
sequence being at least 90 homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT
FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNE-
YNGS
YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVI-
SHAAPH
GPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDS-
VERLYNML
VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLA-
PTILDIAGLDTPPDV DGKSVLKLLDPEKPGNRFRTNKKAKIWRDTFLVERG corresponding
to amino acids 1-416 of SUL1_HUMAN (SEQ ID NO:1419), which also
corresponds to amino acids 1-416 of Z21368_PEA.sub.--1_P15 (SEQ ID
NO:1291).
[1160] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1161] Variant protein Z21368_PEA.sub.--1_P15 (SEQ ID NO:1291) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
Z21368_PEA.sub.--1_T23 (SEQ ID NO:11) is shown in bold; this coding
portion starts at position 691 and ends at position 1938.
[1162] Variant protein Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T24 (SEQ ID NO:12). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1163] Comparison report between Z21368_PEA.sub.--1_P16 (SEQ ID
NO:1292) and SUL1_HUMAN (SEQ ID NO:1419):
[1164] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT
FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNE-
YNGS
YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAKDYFTDLITNESINYFKMSKRMYPHRPVMMVI-
SHAAPH
GPEDSAPQFSKLYPNASQHITPSYNYAPNMDKHWIMQYTGPMLPIHMEFTNILQRKRLQTLMSVDDS-
VERLYNML
VETGELENTYIIYTADHGYHIGQFGLVKGKSMPYDFDIRVPFFIRGPSVEPGSIVPQIVLNIDLA-
PTILDIAGLDTPPDV DGKSVLKLLDPEKPGNR corresponding to amino acids
1-397 of SUL1_HUMAN (SEQ ID NO:1419), which also corresponds to
amino acids 1-397 of Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence CVIVPPLSQPQIH (SEQ ID NO: 1761) corresponding to amino
acids 398-410 of Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), wherein
said first and second amino acid sequences are contiguous and in a
sequential order.
[1165] 2. An isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
CVIVPPLSQPQIH (SEQ ID NO: 1761) in Z21368_PEA.sub.--1_P16 (SEQ ID
NO:1292).
[1166] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1167] Variant protein Z21368_PEA.sub.--1_P16 (SEQ ID NO:1292) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T24 (SEQ
ID NO:12), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
Z21368_PEA.sub.--1_T24 (SEQ ID NO:12) is shown in bold; this coding
portion starts at position 691 and ends at position 1920.
[1168] Variant protein Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T10 (SEQ ID NO:9). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1169] Comparison report between Z21368_PEA.sub.--1_P22 (SEQ ID
NO:1293) and SUL1_HUMAN (SEQ ID NO:1419):
[1170] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT
FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRTAFFGKYLNE-
YNGS YIPPGWREWLGLIKNSRFYNYTVCRNGIKEKHGFDYAK corresponding to amino
acids 1-188 of SUL1_HUMAN (SEQ ID NO:1419), which also corresponds
to amino acids 1-188 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO: 1762) corresponding
to amino acids 189-210 of Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1171] 2. An isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ARYDGDQPRCAPRPRGLSPTVF (SEQ ID NO: 1762) in Z21368_PEA.sub.--1_P22
(SEQ ID NO:1293).
[1172] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1173] Variant protein Z21368_PEA.sub.--1_P22 (SEQ ID NO:1293) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ
ID NO:9), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
Z21368_PEA.sub.--1_T10 (SEQ ID NO:9) is shown in bold; this coding
portion starts at position 691 and ends at position 1320.
[1174] Variant protein Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10). An alignment is given to the
known protein (Extracellular sulfatase Sulf-1 precursor (SEQ ID
NO:1419)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1175] Comparison report between Z21368_PEA.sub.--1_P23 (SEQ ID
NO:1294) and Q7Z2W2 (SEQ ID NO:1697):
[1176] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a first amino
ac id sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT
corresponding to amino acids 1-137 of Q7Z2W2 (SEQ ID NO:1697),
which also corresponds to amino acids 1-137 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GLLHRLNH
(SEQ ID NO: 1763) corresponding to amino acids 138-145 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1177] 2. An isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GLLHRLNH
(SEQ ID NO: 1763) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294).
[1178] Comparison report between Z21368_PEA.sub.--1_P23 (SEQ ID
NO:1294) and SUL1_HUMAN (SEQ ID NO:1419):
[1179] 1. An isolated chimeric polypeptide encoding for
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a first amino
acid sequence being at least 90% homologous to
MKYSCCALVLAVLGTELLGSLCSTVRSPRFRGRIQQERKNIRPNIILVLTDDQDVELGSLQVMNKTRKIMEHG-
GAT FINAFVTTPMCCPSRSSMLTGKYVHNHNVYTNNENCSSPSWQAMHEPRTFAVYLNNTGYRT
corresponding to amino acids 1-137 of SUL1_HUMAN (SEQ ID NO:1419),
which also corresponds to amino acids 1-137 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GLLHRLNH
(SEQ ID NO: 1763) corresponding to amino acids 138-145 of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1180] 2. An isolated polypeptide encoding for a tail of
Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GLLHRLNH
(SEQ ID NO: 1763) in Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294).
[1181] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1182] Variant protein Z21368_PEA.sub.--1_P23 (SEQ ID NO:1294) is
encoded by the following transcript(s): Z21368_PEA.sub.--1_T11 (SEQ
ID NO:10), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10) is shown in bold; this coding
portion starts at position 691 and ends at position 1125.
[1183] As noted above, cluster Z21368 features 34 segment(s), which
were listed in Table 83 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1184] Segment cluster Z21368_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1067) according to the present invention libraries. The number
of libraries was determined as previously described. This segment
can be found in the following transcript(s): Z21368_PEA.sub.--1_T9
(SEQ ID NO:15). Table 88 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00101 TABLE 88 Segment location on transcripts Segment
Segment Transcript name starting position ending position
Z21368_PEA_1_T9 (SEQ ID NO: 1 327 15)
[1185] Segment cluster Z21368_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:1068) according to the present invention is supported by 26
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 89 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00102 TABLE 89 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 631 807 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 631 807 Z21368_PEA_1_T23 (SEQ ID NO: 11) 631 807
Z21368_PEA_1_T24 (SEQ ID NO: 12) 631 807 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 469 645 Z21368_PEA_1_T6 (SEQ ID NO: 14) 469 645
Z21368_PEA_1_T9 (SEQ ID NO: 15) 496 672
[1186] Segment cluster Z21368_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:1069) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:14). Table 90 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00103 TABLE 90 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 863 1102 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 863 1102 Z21368_PEA_1_T23 (SEQ ID NO: 11) 863 1102
Z21368_PEA_1_T24 (SEQ ID NO: 12) 863 1102 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 701 940 Z21368_PEA_1_T6 (SEQ ID NO: 14) 701 940
[1187] Segment cluster Z21368_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1070) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13) and Z21368_PEA.sub.--1_T6 (SEQ
ID NO:14). Table 91 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00104 TABLE 91 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1 300 Z21368_PEA_1_T11 (SEQ ID NO:
10) 1 300 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1 300 Z21368_PEA_1_T24
(SEQ ID NO: 12) 1 300 Z21368_PEA_1_T5 (SEQ ID NO: 13) 1 300
Z21368_PEA_1_T6 (SEQ ID NO: 14) 1 300
[1188] Segment cluster Z21368_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:1071) according to the present invention is supported by 37
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T23 (SEQ ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ
ID NO:12), Z21368_PEA.sub.--1_T5 (SEQ ID NO:13),
Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and Z21368_PEA.sub.--1_T9 (SEQ
ID NO:15). Table 92 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00105 TABLE 92 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1103 1254 Z21368_PEA_1_T23 (SEQ ID
NO: 11) 1103 1254 Z21368_PEA_1_T24 (SEQ ID NO: 12) 1103 1254
Z21368_PEA_1_T5 (SEQ ID NO: 13) 941 1092 Z21368_PEA_1_T6 (SEQ ID
NO: 14) 941 1092 Z21368_PEA_1_T9 (SEQ ID NO: 15) 728 879
[1189] Segment cluster Z21368_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:1072) according to the present invention is supported by 45
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 93 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00106 TABLE 93 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1502 1677 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1424 1599 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1576 1751
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1576 1751 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1414 1589 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1414 1589
Z21368_PEA_1_T9 (SEQ ID NO: 15) 1201 1376
[1190] Segment cluster Z21368_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:1073) according to the present invention is supported by 44
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 94 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00107 TABLE 94 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1678 1806 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1600 1728 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1752 1880
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1752 1880 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1590 1718 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1590 1718
Z21368_PEA_1_T9 (SEQ ID NO: 15) 1377 1505
[1191] Segment cluster Z21368_PEA.sub.--1_node.sub.--37 (SEQ ID
NO:1074) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T24 (SEQ ID NO:12). Table 95
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00108 TABLE 95 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1881 2159
[1192] Segment cluster Z21368_PEA.sub.--1_node.sub.--39 (SEQ ID
NO:1075) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T23 (SEQ ID NO:11) and
Z21368_PEA.sub.--1_T24 (SEQ ID NO:12). Table 96 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00109 TABLE 96 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T23 (SEQ ID NO: 11) 1938 2790 Z21368_PEA_1_T24 (SEQ ID
NO: 12) 2217 3069
[1193] Segment cluster Z21368_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1076) according to the present invention is supported by 13
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ ID
NO:11) and Z21368_PEA.sub.--1_T24 (SEQ ID NO:12). Table 97 below
describes the starting and encoding position of this segment on
each transcript.
TABLE-US-00110 TABLE 97 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 301 462 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 301 462 Z21368_PEA_1_T23 (SEQ ID NO: 11) 301 462
Z21368_PEA_1_T24 (SEQ ID NO: 12) 301 462
[1194] Segment cluster Z21368_PEA.sub.--1_node.sub.--41 (SEQ ID
NO:1077) according to the present invention is supported by 49
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 98 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00111 TABLE 98 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1864 1993 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1786 1915 Z21368_PEA_1_T5 (SEQ ID NO: 13) 1776 1905
Z21368_PEA_1_T6 (SEQ ID NO: 14) 1776 1905 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 1563 1692
[1195] Segment cluster Z21368_PEA.sub.--1_node.sub.--43 (SEQ ID
NO:1078) according to the present invention is supported by 52
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368 PEA 1 T5 (SEQ ID
NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 99 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00112 TABLE 99 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1994 2210 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1916 2132 Z21368_PEA_1_T5 (SEQ ID NO: 13) 1906 2122
Z21368_PEA_1_T6 (SEQ ID NO: 14) 1906 2122 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 1693 1909
[1196] Segment cluster Z21368_PEA.sub.--1_node.sub.--45 (SEQ ID
NO:1079) according to the present invention is supported by 64
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 100 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00113 TABLE 100 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2211 2466 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2133 2388 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2123 2378
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2123 2378 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 1910 2165
[1197] Segment cluster Z21368_PEA.sub.--1_node.sub.--53 (SEQ ID
NO:1080) according to the present invention is supported by 60
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 101 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00114 TABLE 101 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2725 2900 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2647 2822 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2637 2812
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2637 2812 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2424 2599
[1198] Segment cluster Z21368_PEA.sub.--1_node.sub.--56 (SEQ ID
NO:1081) according to the present invention is supported by 50
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10) and Z21368_PEA.sub.--1_T9
(SEQ ID NO:15). Table 102 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00115 TABLE 102 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2901 3043 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2823 2965 Z21368_PEA_1_T9 (SEQ ID NO: 15) 2600 2742
[1199] Segment cluster Z21368_PEA.sub.--1_node.sub.--58 (SEQ ID
NO:1082) according to the present invention is supported by 71
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1.sub.--1_T11 (SEQ ID NO:10),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 103
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00116 TABLE 103 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 3044 3167 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2966 3089 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2813 2936
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2813 2936 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2743 2866
[1200] Segment cluster Z21368_PEA.sub.--1_node.sub.--66 (SEQ ID
NO:1083) according to the present invention is supported by 142
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 104 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00117 TABLE 104 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 3202 3789 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 3124 3711 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2971 3558
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2971 3558 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2901 3488
[1201] Segment cluster Z21368_PEA.sub.--1_node.sub.--67 (SEQ ID
NO:1084) according to the present invention is supported by 181
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA1_T6 (SEQ ID NO:14) and Z21368_PEA.sub.--1_T9
(SEQ ID NO:15). Table 105 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00118 TABLE 105 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 3790 4374 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 3712 4296 Z21368_PEA_1_T5 (SEQ ID NO: 13) 3559 4143
Z21368_PEA_1_T6 (SEQ ID NO: 14) 3559 4143 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 3489 4073
[1202] Segment cluster Z21368_PEA.sub.--1_node.sub.--69 (SEQ ID
NO:1085) according to the present invention is supported by 150
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 106 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00119 TABLE 106 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 4428 4755 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 4350 4677 Z21368_PEA_1_T5 (SEQ ID NO: 13) 4197 5384
Z21368_PEA_1_T6 (SEQ ID NO: 14) 4197 4524 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 4127 4454
[1203] According to an optional embodiment or the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1204] Segment cluster Z21368_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:1086) according to the present invention is supported by 26
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 107 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00120 TABLE 107 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 558 602 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 558 602 Z21368_PEA_1_T23 (SEQ ID NO: 11) 558 602
Z21368_PEA_1_T24 (SEQ ID NO: 12) 558 602 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 396 440 Z21368_PEA_1_T6 (SEQ ID NO: 14) 396 440
Z21368_PEA_1_T9 (SEQ ID NO: 15) 423 467
[1205] Segment cluster Z21368_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:1087) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 108 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00121 TABLE 108 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 603 630 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 603 630 Z21368_PEA_1_T23 (SEQ ID NO: 11) 603 630
Z21368_PEA_1_T24 (SEQ ID NO: 12) 603 630 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 441 468 Z21368_PEA_1_T6 (SEQ ID NO: 14) 441 468
Z21368_PEA_1_T9 (SEQ ID NO: 15) 468 495
[1206] Segment cluster Z21368_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:1088) according to the present invention can be found in the
following transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA1_T24 (SEQ ID NO:12), Z21368_PEA.sub.--1_T5
(SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 109 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00122 TABLE 109 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 808 822 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 808 822 Z21368_PEA_1_T23 (SEQ ID NO: 11) 808 822
Z21368_PEA_1_T24 (SEQ ID NO: 12) 808 822 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 646 660 Z21368_PEA_1_T6 (SEQ ID NO: 14) 646 660
Z21368_PEA_1_T9 (SEQ ID NO: 15) 673 687
[1207] Segment cluster Z21368_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:1089) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 110 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00123 TABLE 110 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 823 862 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 823 862 Z21368_PEA_1_T23 (SEQ ID NO: 11) 823 862
Z21368_PEA_1_T24 (SEQ ID NO: 12) 823 862 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 661 700 Z21368_PEA_1_T6 (SEQ ID NO: 14) 661 700
Z21368_PEA_1_T9 (SEQ ID NO: 15) 688 727
[1208] Segment cluster Z21368_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:1090) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T11 (SEQ ID NO:10),
Z21368_PEA.sub.--1_T23 (SEQ ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ
ID NO:12), Z21368_PEA.sub.--1_T5 (SEQ ID NO:13),
Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and Z21368_PEA.sub.--1_T9 (SEQ
ID NO:15). Table 111 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00124 TABLE 111 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z21368_PEA_1_T11 (SEQ ID NO: 10) 1103 1176 Z21368_PEA_1_T23 (SEQ ID
NO: 11) 1255 1328 Z21368_PEA_1_T24 (SEQ ID NO: 12) 1255 1328
Z21368_PEA_1_T5 (SEQ ID NO: 13) 1093 1166 Z21368_PEA_1_T6 (SEQ ID
NO: 14) 1093 1166 Z21368_PEA_1_T9 (SEQ ID NO: 15) 880 953
[1209] Segment cluster Z21368_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1091) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 112 below
describes the starting segment on each transcript.
TABLE-US-00125 TABLE 112 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1255 1350 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1177 1272 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1329 1424
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1329 1424 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1167 1262 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1167 1262
Z21368_PEA_1_T9 (SEQ ID NO: 15) 954 1049
[1210] Segment cluster Z21368_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:1092) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 113 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00126 TABLE 113 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1351 1409 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1273 1331 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1425 1483
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1425 1483 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1263 1321 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1263 1321
Z21368_PEA_1_T9 (SEQ ID NO: 15) 1050 1108
[1211] Segment cluster Z21368_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:1093) according to the present invention is supported by 40
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 114 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00127 TABLE 114 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1410 1501 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1332 1423 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1484 1575
Z21368_PEA_1_T24 (SEQ ID NO: 12) 1484 1575 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1322 1413 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1322 1413
Z21368_PEA_1_T9 (SEQ ID NO: 15) 1109 1200
[1212] Segment cluster Z21368_PEA.sub.--1_node.sub.--38 (SEQ ID
NO:1094) according to the present invention is supported by 45
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1.sub.--19 (SEQ ID NO:15). Table 115
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00128 TABLE 115 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 1807 1863 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 1729 1785 Z21368_PEA_1_T23 (SEQ ID NO: 11) 1881 1937
Z21368_PEA_1_T24 (SEQ ID NO: 12) 2160 2216 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 1719 1775 Z21368_PEA_1_T6 (SEQ ID NO: 14) 1719 1775
Z21368_PEA_1_T9 (SEQ ID NO: 15) 1506 1562
[1213] Segment cluster Z21368_PEA.sub.--1_node.sub.--47 (SEQ ID
NO:1095) according to the present invention is supported by 61
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 116 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00129 TABLE 116 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2467 2563 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2389 2485 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2379 2475
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2379 2475 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2166 2262
[1214] Segment cluster Z21368_PEA.sub.--1_node.sub.--49 (SEQ ID
NO:1096) according to the present invention is supported by 57
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 117 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00130 TABLE 117 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2564 2658 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2486 2580 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2476 2570
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2476 2570 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2263 2357
[1215] Segment cluster Z21368_PEA.sub.--1_node.sub.--51 (SEQ ID
NO:1097) according to the present invention is supported by 46
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 118 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00131 TABLE 118 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 2659 2724 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 2581 2646 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2571 2636
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2571 2636 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2358 2423
[1216] Segment cluster Z21368_PEA.sub.--1_node.sub.--61 (SEQ ID
NO:1098) according to the present invention is supported by 61
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 119 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00132 TABLE 119 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 3168 3201 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 3090 3123 Z21368_PEA_1_T5 (SEQ ID NO: 13) 2937 2970
Z21368_PEA_1_T6 (SEQ ID NO: 14) 2937 2970 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 2867 2900
[1217] Segment cluster Z21368_PEA.sub.--1_node.sub.--68 (SEQ ID
NO:1099) according to the present invention is supported by 87
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T5 (SEQ
ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID NO:14) and
Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 120 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00133 TABLE 120 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 4375 4427 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 4297 4349 Z21368_PEA_1_T5 (SEQ ID NO: 13) 4144 4196
Z21368_PEA_1_T6 (SEQ ID NO: 14) 4144 4196 Z21368_PEA_1_T9 (SEQ ID
NO: 15) 4074 4126
[1218] Segment cluster Z21368_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:1100) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z21368_PEA.sub.--1_T10 (SEQ ID NO:9),
Z21368_PEA.sub.--1_T11 (SEQ ID NO:10), Z21368_PEA.sub.--1_T23 (SEQ
ID NO:11), Z21368_PEA.sub.--1_T24 (SEQ ID NO:12),
Z21368_PEA.sub.--1_T5 (SEQ ID NO:13), Z21368_PEA.sub.--1_T6 (SEQ ID
NO:14) and Z21368_PEA.sub.--1_T9 (SEQ ID NO:15). Table 121 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00134 TABLE 121 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z21368_PEA_1_T10 (SEQ ID NO: 9) 463 557 Z21368_PEA_1_T11 (SEQ ID
NO: 10) 463 557 Z21368_PEA_1_T23 (SEQ ID NO: 11) 463 557
Z21368_PEA_1_T24 (SEQ ID NO: 12) 463 557 Z21368_PEA_1_T5 (SEQ ID
NO: 13) 301 395 Z21368_PEA_1_T6 (SEQ ID NO: 14) 301 395
Z21368_PEA_1_T9 (SEQ ID NO: 15) 328 422
[1219] Overexpression of at least a portion of this cluster was
determined according to oligonucleotides and one or more chips. The
results were as follows: Oligonucleotide
Z21368.sub.--0.sub.--0.sub.--61857 (SEQ ID NO: 207) was on the TAA
chip and was found to be overexpressed in Lung cancer (general), in
Lung adenocarcinoma, and in Lung squamous cell cancer.
Variant protein alignment to the previously known protein:
TABLE-US-00135 Sequence name: /tmp/5ER3vIMKE2/9L0Y7lDlTQ:SUL1_HUMAN
(SEQ ID NO:1419) Sequence documentation: Alignment of:
Z21368_PEA_1_P2 (SEQ ID NO:1289) x SULl_HUMAN (SEQ ID NO:1419)
Alignmeent segment 1/1: Quality: 7664.00 Escore: 0 Matching length:
761 Total length: 761 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: . . . . . ##STR00069##
. . . . . ##STR00070## . . . . . ##STR00071## . . . . .
##STR00072## . . . . . ##STR00073## . . . . . ##STR00074## . . . .
. ##STR00075## . . . . . ##STR00076## . . . . . ##STR00077## . . .
. . ##STR00078## . . . . . ##STR00079## . . . . . ##STR00080## . .
. . . ##STR00081## . . . . . ##STR00082## . . . . . ##STR00083## .
##STR00084## Sequence name: /tmp/tt3yfXIUKV/YxSTFWr66h:Q7Z2W2 (SEQ
ID NO:1697) Sequence documentation: Alignment of: Z21368_PEA_1_P5
(SEQ ID NO:1290) x Q8Z2W2 (SEQ ID NO:1697) Alignment segment 1/1:
Quality: 7869.00 Escore: 0 Matching length: 791 Total length: 871
Matching Percent Similarity: 99.87 Matching Percent Identity: 99.87
Total Percent Similarity: 90.70 Total Percent Identity: 90.70 Gaps:
1 Alignment: . . . . . ##STR00085## . . . . . ##STR00086## . . . .
. ##STR00087## . . . . . ##STR00088## . . . . . ##STR00089## . . .
. . ##STR00090## . . . . . ##STR00091## . . . . . ##STR00092## . .
. . . ##STR00093## . . . . . ##STR00094## . . . . . ##STR00095## .
. . . . ##STR00096## . . . . . ##STR00097## . . . . . ##STR00098##
. . . . . ##STR00099## . . . . . ##STR00100## . . . . .
##STR00101## . . ##STR00102## Sequence name:
/tmp/tt3yfXIUKV/YxSTFWr66h:AAH12997 (SEQ ID NO:1698) Sequence
documentation: Alignment of: Z21368_PEA_1_P5 (SEQ ID NO:1290) x
AAH12997 (SEQ ID NO:1698) Alignment segment 1/1: Quality: 420.00
Escore: 0 Matching length: 40 Total length: 40 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . ##STR00103## Sequence name:
/tmp/tt3yfXIUKV/YxSTFWr66h:SUL1_HUMAN (SEQ ID NO:1419) Sequence
documentation: Alignment of: Z21368_PEA_1_P5 (SEQ ID NO:1290) x
SUL1_HUMAN (SEQ ID NO:1419) Alignment segment 1/1: Quality: 7878.00
Escore: 0 Matching length: 791 Total length: 871 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 90.82 Total Percent Identity: 90.82 Gaps: 1 Alignment:
. . . . . ##STR00104## . . . . . ##STR00105## . . . . .
##STR00106## . . . . . ##STR00107## . . . . . ##STR00108## . . . .
. ##STR00109## . . . . . ##STR00110## . . . . . ##STR00111## . . .
. . ##STR00112## . . . . . ##STR00113## . . . . . ##STR00114## . .
. . . ##STR00115## . . . . . ##STR00116## . . . . . ##STR00117## .
. . . . ##STR00118## . . . . . ##STR00119## . . . . . ##STR00120##
. . ##STR00121## Sequence name:
/tmp/AVAZGWHuF0/RzHFOnHIsT:SUL1_HUMAN (SEQ ID NO:1419) Sequence
documentation: Alignment of: Z21368_PEA_1_P15 (SEQ ID NO:1291) x
SUL1_HUMAN (SEQ ID NO:1419) Alignment segment 1/1: Quality: 4174.00
Escore: 0 Matching length: 416 Total length: 416 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00122## . . . . . ##STR00123## . . . . .
##STR00124## . . . . . ##STR00125## . . . . . ##STR00126## . . . .
. ##STR00127## . . . . . ##STR00128## . . . . . ##STR00129## .
##STR00130## Sequence name: /tmp/JhwgRdKqmt/kqSmjxkWWk:SUL1_SUMAN
(SEQ ID NO:1419) Sequence documentation: Alignment of:
Z21368_PEA_1_P16 (SEQ ID NO:1292) x SUL1_HUMAN (SEQ ID NO:1419)
Alignment segment 1/1: Quality: 3985.00 Escore: 0 Matching length:
397 Total length: 397 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: . . . . . ##STR00131##
. . . . . ##STR00132## . . . . . ##STR00133## . . . . .
##STR00134## . . . . . ##STR00135## . . . . . ##STR00136## . . . .
. ##STR00137## . . . . ##STR00138## Sequence name:
/tmp/GPlnIw3BOg/zXFdxqG4ow:SUL1_HUMAN (SEQ ID NO:1419) Sequence
documentation: Alignment of: Z21368_PEA_a_P22 (SEQ ID NO:1293) x
SUL1_HUMAN (SEQ ID NO:1419) Alignment segment 1/1: Quality: 1897.00
Escore: 0 Matching length: 188 Total length: 188 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00139## . . . . . ##STR00140## . . . . .
##STR00141## . . . ##STR00142## Sequence name:
/tmp/oji5Fs74fB/8xeB9KrGjp:Q7Z2W2 (SEQ ID NO:1697) Sequence
documentation: Alignment of: Z21368_PEA_1_P23 (SEQ ID NO:1294) x
Q7Z2W2 (SEQ ID NO:1697) Alignment segment 1/1: Quality: 1368.00
Escore: 0.000511 Matching length: 137 Total length: 137 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00143## . . . . . ##STR00144## . . .
##STR00145## Sequence name: /tmp/oji5Fs74fB/8xeB9KrGjp:SUL1_HUMAN
(SEQ ID NO:1419) Sequence documentation: Alignment of:
Z21368_PEA_1_P23 (SEQ ID NO:1294) x SUL1_HUMAN (SEQ ID NO:1419)
Alignment segment 1/1: Quality: 1368.00 Escore: 0.000511 Matching
length: 137 Total length: 137 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00
Gaps: 0 Alignment . . . . . ##STR00146## . . . . . ##STR00147## . .
. ##STR00148##
Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368
transcripts which are detectable by amplicon as depicted in
sequence name Z21368junc17-21 (SEQ ID NO: 1642) in normal and
cancerous lung tissues
[1220] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts detectable by or according to junc17-21 segment,
Z21368junc17-21 amplicon (SEQ ID NO: 1642) and Z21368junc17-21F
(SEQ ID NO: 1640) Z21368junc17-21R (SEQ ID NO: 1641) primers was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[1221] FIG. 14 is a histogram showing over expression of the
above-indicated SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts in cancerous lung samples relative to the normal
samples. Values represent the average of duplicate experiments.
Error bars indicate the minimal and maximal values obtained. As is
evident from FIG. 14, the expression of SUL1_HUMAN--Extracellular
sulfatase Sulf-1 transcripts detectable by the above amplicon in
cancer samples was significantly higher than in the non-cancerous
samples (Sample Nos. 47-50, 90-93, 96-99 Table 2, "Tissue samples
in testing panel"). Notably an over-expression of at least 5 fold
was found in 10 out of 15 adenocarcinoma samples, 7 out of 16
squamous cell carcinoma samples, 0 out of 4 large cell carcinoma
samples and in 0 out of 8 small cells carcinoma samples.
Threshold of 5 fold over-expression was found to differentiate
between cancer and normal samples with P value of 3.56E-04 in
adenocarcinoma, 9.66E-03 in squamous cell carcinomas checked by
exact fisher test. The above values demonstrate statistical
significance of the results.
[1222] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair:
Z21368junc17-21F forward primer (SEQ ID NO: 1640); and
Z21368junc17-21 R reverse primer (SEQ ID NO: 1641).
[1223] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z21368junc17-21 (SEQ ID NO: 1642).
TABLE-US-00136 Forward primer (SEQ ID NO: 1640):
GGACGGATACAGCAGGAACG Reverse amplicon (SEQ ID NO: 1641):
TATTTTCCAAAAAAGGCCAGCTC Amplicon (SEQ ID NO: 1642):
GGACGGATACAGCAGGAACGAAAAAACATCCGACCCAACATTATTCTTGT
GCTTACCGATGATCAAGATGTGGAGCTGGCCTTTTTTGGAAAATA
Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368
transcripts, which are detectable by amplicon as depicted in
sequence name Z21368 junc17-21 (SEQ ID NO: 1642) in different
normal tissues
[1224] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts detectable by or according to Z21368 junc17-21 amplicon
(SEQ ID NO: 1642) and Z21368 junc17-21F (SEQ ID NO: 1640) and
Z21368 junc17-21R (SEQ ID NO: 1641) was measured by real time PCR.
In parallel the expression of four housekeeping genes--RPL19
(GenBank Accession No. NM.sub.--000981 (SEQ ID NO:1715); RPL19
amplicon, SEQ ID NO:1630), TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO:1716); TATA amplicon, SEQ ID NO:1633),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the breast samples (Sample Nos. 33-35
Table 3, "Tissue samples in normal panel", above), to obtain a
value of relative expression of each sample relative to median of
the breast samples.
TABLE-US-00137 Forward primer (SEQ ID NO: 1640):
GGACGGATACAGCAGGAACG Reverse amplicon (SEQ ID NO: 1641):
TATTTTCCAAAAAAGGCCAGCTC Amplicon (SEQ ID NO: 1642):
GGACGGATACAGCAGGAACGAAAAAACATCCGACCCAACATTATTCTTGT
GCTTACCGATGATCAAGATGTGGAGGTGGCCTTTTTTGGAAAATA
[1225] The results are shown in FIG. 15, demonstrating the
expression of Extracellular sulfatase Sulf-1Z21368 transcripts,
which are detectable by amplicon as depicted in sequence name
Z21368 junc17-21 (SEQ ID NO: 1642), in different normal
tissues.
Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1 Z21368
transcripts which are detectable by amplicon as depicted in
sequence name Z21368seg39 (SEQ ID NO: 1645) in normal and cancerous
lung tissues
[1226] Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts detectable by or according to seg39, Z21368seg39
amplicon (SEQ ID NO: 1645) and primers Z21368seg39F (SEQ ID NO:
1643) and Z21368seg39R (SEQ ID NO: 1644) was measured by real time
PCR. In parallel the expression of four housekeeping genes--PBGD
(GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO:1714); amplicon--HPRT1-amplicon, SEQ
ID NO:1297), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel"), to obtain a value of fold up-regulation for each
sample relative to median of the normal PM samples.
[1227] FIG. 16 is a histogram showing over expression of the
above-indicated SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts in cancerous lung samples relative to the normal
samples. Values represent the average of duplicate experiments.
Error bars indicate the minimal and maximal values obtained.
As is evident from FIG. 16, the expression of
SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable
by the above amplicon in cancer samples was higher than in the
non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99 Table 2,
"Tissue samples in testing panel"). Notably an over-expression of
at least 5 fold was found in 8 out of 15 adenocarcinoma samples, 5
out of 16 squamous cell carcinoma samples and 1 out of 4 large cell
carcinoma samples.
[1228] Statistical analysis was applied to verify the significance
of these results, as described below.
[1229] The P value for the difference in the expression levels of
SUL1_HUMAN--Extracellular sulfatase Sulf-1 transcripts detectable
by the above amplicon in lung cancer samples versus the normal
tissue samples was determined by T test as 2.17E-04 in
adenocarcinoma, 9.94E-03 in squamous cell carcinoma and 2.17E-01 in
large cell carcinoma.
[1230] Threshold of 5fold overexpression was found to differentiate
between cancer and normal samples with P value of 1.74E-02 in
adenocarcinoma, 1.58E-01 in squamous cell carcinoma and 4.33E-01 in
large cell carcinoma as checked by exact fisher test. The above
values demonstrate statistical significance of the results.
[1231] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: Z21368seg39F
forward primer (SEQ ID NO: 1643); and Z21368seg39R reverse primer
(SEQ ID NO: 1644).
[1232] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z21368seg39 (SEQ ID NO: 1645).
TABLE-US-00138 Forward primer Z21368seg39F (SEQ ID NO: 1643):
GTTGCATTTCTCAGTGCTGGTTT Reverse primer Z21368seg39R (SEQ ID NO:
1644): AGGGTGCCGGGTGAGG Amplicon Z21368seg39 (SEQ ID NO: 1645):
GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGATTGAGTTTCT
CTACCATCCTCCCCACGTTCTTCTCTAAGCTGCCTCCAAGCCTCACCCGG CACCCT
Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1Z21368
transcripts which are detectable by amplicon as depicted in
sequence name Z21368seg39 (SEQ ID NO: 1645) in different normal
tissues Expression of SUL1_HUMAN--Extracellular sulfatase Sulf-1
transcripts detectable by or according to Z21368seg39 amplicon (SEQ
ID NO: 1645) and Z21368seg39F (SEQ ID NO: 1643) Z21368seg39R (SEQ
ID NO: 1644) was measured by real time PCR. In parallel the
expression of four housekeeping genes--[RPL19 (GenBank Accession
No. NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ ID
NO:1630), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID
NO:1716); TATA amplicon, SEQ ID NO:1633), UBC (GenBank Accession
No. BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the breast samples
(Sample Nos. 33-35 Table 3, above), to obtain a value of relative
expression of each sample relative to median of the breast
samples.
TABLE-US-00139 Forward primer Z21368seg39F (SEQ ID NO: 1643):
GTTGCATTTCTCAGTGCTGGTTT Reverse primer Z21368seg39R (SEQ ID NO:
1644): AGGGTGCCGGGTGAGG Amplicon Z21368seg39 (SEQ ID NO: 1645):
GTTGCATTTCTCAGTGCTGGTTTCTAATCAGACCAGTGGATTGAGTTTCT
CTACCATCCTCCCCACGTTCTTCTCTAAGCTGCCTCCAAGCCTCACCCGG CACCCT
[1233] The results are demonstrated in FIG. 17, showing expression
of SUL1_HUMAN--Extracellular sulfatase Sulf-1, Z21368 transcripts,
which are detectable by amplicon as depicted in sequence name
Z21368seg39 (SEQ ID NO: 1645), in different normal tissues.
Expression of SULF1 Z21368 Transcripts which are Detectable by
Amplicon as Depicted in Sequence Name Z21368junc59-64F1R1 (SEQ ID
NO: 1801) in Normal and Cancerous Lung Tissues
[1234] Expression of SULF1 transcripts detectable by or according
to junc59-64--Z21368_junc59-64F1R1 (SEQ ID NO: 1801) amplicon (SEQ
ID NO: 1801) and primers Z21368_junc59-64F1 (SEQ ID NO: 1799) and
Z21368_junc59-64R1 (SEQ ID NO: 1800) was measured by real time PCR.
In parallel the expression of several housekeeping genes--HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO: 1714);
amplicon--HPRT1-amplicon (SEQ ID NO: 1297)), PBGD (GenBank
Accession No. BC019323 (SEQ ID NO: 1713); amplicon--PBGD-amplicon
(SEQ ID NO: 334)), SDHA (GenBank Accession No. NM.sub.--004168 (SEQ
ID NO: 1712); amplicon--SDHA-amplicon (SEQ ID NO: 331)) and
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO: 1711);
amplicon--Ubiquitin-amplicon (SEQ ID NO: 328)) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the normalization factor calculated from the
expression of these house keeping genes as described in
normalization method 2 in the "materials and methods" section. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal samples (sample numbers
51-64, 69 and 70, Table 2.sub.--1 above), to obtain a value of fold
up-regulation for each sample relative to median of the normal
samples.
[1235] FIG. 114 is a histogram showing over expression of the
above-indicated SULF1 transcripts in cancerous Lung samples
relative to the normal samples.
[1236] As is evident from FIG. 114, the expression of SULF1
transcripts detectable by the above amplicon in non-small cell
carcinoma samples--adenocarcinoma, squamous cell carcinoma and
large cell carcinoma was significantly higher than in the
non-cancerous samples (sample numbers 51-64, 69 and 70, Table
2.sub.--1 above). Notably an over-expression of at least 5 fold was
found in 20 out of 57 non-small cell carcinoma samples--9 out of 23
adenocarcinoma samples, 7 out of 24 squamous cell carcinoma samples
and 4 out of 10 large cell carcinoma samples.
[1237] Statistical analysis was applied to verify the significance
of these results, as described below.
[1238] The P value for the difference in the expression levels of
SULF1 transcripts detectable by the above amplicon in Lung
non-small cell carcinoma samples versus the normal tissue samples
was determined by T test as 1.60e-009. The P value for the
difference in the expression levels of SULF1 transcripts detectable
by the above amplicon in Lung adenocarcinoma samples, Lung squamous
cell carcinoma samples and Lung large cell carcinoma samples versus
the normal tissue samples was determined by T test as 1.18e-005,
1.16e-004 and 9.83e-003, respectively.
[1239] Threshold of 5 fold over expression was found to
differentiate between non-small cell carcinoma and normal samples
with P value of 2.82e-003 as checked by exact Fisher test.
Threshold of 5 fold over expression was found to differentiate
between adenocarcinoma and normal samples with P value of 3.86e-003
as checked by exact Fisher test. Threshold of 5 fold over
expression was found to differentiate between squamous cell
carcinoma and normal samples with P value of 1.86e-002 as checked
by exact Fisher test. Threshold of 5 fold over expression was found
to differentiate between large cell carcinoma and normal samples
with P value of 1.40e-002 as checked by exact Fisher test.
[1240] The above values demonstrate statistical significance of the
results.
[1241] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair:
Z21368_junc59-64F1 forward primer (SEQ ID NO: 1799); and
Z21368_junc59-64R1 reverse primer (SEQ ID NO: 1800).
[1242] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z21368_junc59-64F1R1 (SEQ ID NO: 1801).
TABLE-US-00140 Forward Primer (Z21368_unc59-64F1) (SEQ ID NO:
1799): AACAACCGTAGGAGGAAGAAGGA Reverse Primer (Z21368_junc59-64R1)
(SEQ ID NO: 1800): GTGTGCACTGTATTTGTGAGGGTTC Amplicon
(Z21368_junc59-64F1R1) (SEQ ID NO: 1801):
AACAACCGTAGGAGGAAGAAGGAGAGGAAGGAGAAGAGACGGCAGAGGAA
GGGGGAAGAGTGCAGCCTGCCTGGCCTCAGTTGCTTCACGCATGACAACA
ACCACTGGCAGACAGCCCCGTTCTGGAACCCTCACAAATACAGTGCACAC
Expression of SULF1 Z21368 Transcripts which are Detectable by
Amplicon as Depicted in Sequence Name Z21368_junc59-64F1R1 (SEQ ID
NO: 1801) in Different Normal Tissues
[1243] Expression of SULF1 transcripts detectable by or according
to junc59-64--Z21368_junc59-64F1R1 amplicon (SEQ ID NO: 1801) and
primers Z21368_junc59-64F1 (SEQ ID NO: 1799) and Z21368_junc59-64R1
(SEQ ID NO: 1800) was measured by real time PCR. Non-detected
samples (sample no. 51) were assigned Ct value of 41 and were
calculated accordingly. In parallel the expression of several
housekeeping genes--SDHA (GenBank Accession No. NM.sub.--004168
(SEQ ID NO: 1712); amplicon--SDHA-amplicon (SEQ ID NO: 331)),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO: 1711);
amplicon--Ubiquitin-amplicon (SEQ ID NO: 328)), RPL19 (GenBank
Accession No. NM.sub.--000981 (SEQ ID NO: 1715); RPL19 amplicon
(SEQ ID NO: 1630)) and TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO: 1716); TATA amplicon (SEQ ID NO: 1633))
was measured similarly. For each RT sample, the expression of the
above amplicon was normalized to the normalization factor
calculated from the expression of these house keeping genes as
described in normalization method 2 in the "materials and methods"
section. The normalized quantity of each RT sample was then divided
by the median of the quantities of the lung samples (sample numbers
26, 28, 29 and 30, Table 3.sub.--1 above), to obtain a value of
relative expression of each sample relative to median of the lung
samples.
TABLE-US-00141 Forward Primer (Z21368_junc59-64F1) (SEQ ID NO:
1799): AACAACCGTAGGAGGAAGAAGGA Reverse Primer (Z21368_junc59-64R1)
(SEQ ID NO: 1800): GTGTGCACTGTATTTGTGAGGGTTC Amplicon
(Z21368_junc59-64F1R1) (SEQ ID NO: 1801):
AACAACCGTAGGAGGAAGAAGGAGAGGAAGGAGAAGAGACGGCAGAGGAA
GGGGGAAGAGTGCAGCCTGCCTGGCCTCACTTGCTTCACGCATGACAACA
ACCACTGGCAGACAGCCCCGTTCTGGAACCCTCACAAATACAGTGCACAC
[1244] FIG. 115 is a histogram showing the expression of SULF1
Z21368 transcripts which are detectable by amplicon as depicted in
sequence name Z21368_junc59-64F1R1 (SEQ ID NO: 1801) in different
normal tissues.
Description for Cluster HUMGRP5E
[1245] Cluster HUMGRP5E features 2 transcript(s) and 5 segment(s)
of interest, the names for which are given in Tables 122 and 123,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
124.
TABLE-US-00142 TABLE 122 Transcripts of interest Transcript Name
Sequence ID No. HUMGRP5E_T4 20 HUMGRP5E_T5 21
TABLE-US-00143 TABLE 123 Segments of interest Segment Name Sequence
ID No. HUMGRP5E_node_0 335 HUMGRP5E_node_2 336 HUMGRP5E_node_8 337
HUMGRP5E_node_3 338 HUMGRP5E_node_7 339
TABLE-US-00144 TABLE 124 Proteins of interest Protein Name Sequence
ID No. HUMGRP5E_P4 1299 HUMGRP5E_P5 1300
[1246] These sequences are variants of the known protein
Gastrin-releasing peptide precursor (SwissProt accession identifier
GRP_HUMAN; known also according to the synonyms GRP; GRP-10), SEQ
ID NO: 1421, referred to herein as the previously known protein.
Known isoforms of the GRP protein are described in
sp_vs|P07492-2|GRP_HUMAN Isoform 2 (SEQ ID NO: 1788) and
sp_vs|P07492-3|GRP_HUMAN Isoform 3 (SEQ ID NO: 1789).
[1247] Gastrin-releasing peptide is known or believed to have the
following function(s): stimulates gastrin release as well as other
gastrointestinal hormones. The sequence for protein
Gastrin-releasing peptide precursor (SEQ ID NO:1421) is given at
the end of the application, as "Gastrin-releasing peptide precursor
amino acid sequence". Known polymorphisms for this sequence are as
shown in Table 125.
TABLE-US-00145 TABLE 125 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 4 S -> R
[1248] Protein Gastrin-releasing peptide localization is believed
to be Secreted.
[1249] The previously known protein also has the following
indication(s) and/or potential therapeutic use(s): Diabetes, Type
II. It has been investigated for clinical/therapeutic use in
humans, for example as a target for an antibody or small molecule,
and/or as a direct therapeutic; available information related to
these investigations is as follows. Potential pharmaceutically
related or therapeutically related activity or activities of the
previously known protein are as follows: Bombesin antagonist;
Insulinotropin agonist. A therapeutic role for a protein
represented by the cluster has been predicted. The cluster was
assigned this field because there was information in the drug
database or the public databases (e.g., described herein above)
that this protein, or part thereof, is used or can be used for a
potential therapeutic indication: Anorectic/Antiobesity; Releasing
hormone; Anticancer; Respiratory; Antidiabetic.
[1250] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: signal
transduction; neuropeptide signaling pathway, which are
annotation(s) related to Biological Process; growth factor, which
are annotation(s) related to Molecular Function; and secreted,
which are annotation(s) related to Cellular Component.
[1251] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1252] As noted above, cluster HUMGRP5E features 2 transcript(s),
which were listed in Table 122 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Gastrin-releasing
peptide precursor (SEQ ID NO:1421). A description of each variant
protein according to the present invention is now provided.
[1253] Variant protein HUMGRP5E_P4 (SEQ ID NO:1299) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HUMGRP5E_T4
(SEQ ID NO:20). An alignment is given to the known protein
(Gastrin-releasing peptide precursor (SEQ ID NO:1421)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1254] Comparison report between HUMGRP5E_P4 (SEQ ID NO:1299) and
GRP_HUMAN (SEQ ID NO:1421):
[1255] 1. An isolated chimeric polypeptide encoding for HUMGRP5E_P4
(SEQ ID NO:1299), comprising a first amino acid sequence being at
least 90% homologous to
MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTGESSSVSERGSLKQQLRE-
Y IRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSEDSSNFKDVGSKGK
corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:1421),
which also corresponds to amino acids 1-127 of HUMGRP5E_P4 (SEQ ID
NO:1299), and a second amino acid sequence being at least 90%
homologous to GSQREGRNPQLNQQ corresponding to amino acids 135-148
of GRP_HUMAN (SEQ ID NO:1421), which also corresponds to amino
acids 128-141 of HUMGRP5E_P4 (SEQ ID NO:1299), wherein said first
and second amino acid sequences are contiguous and in a sequential
order.
[1256] 2. An isolated chimeric polypeptide encoding for an edge
portion of HUMGRP5E_P4 (SEQ ID NO:1299), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise KG, having a structure as follows: a sequence
starting from any of amino acid numbers 127-x to 127; and ending at
any of amino acid numbers 128+((n-2)-x), in which x varies from 0
to n-2.
[1257] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1258] Variant protein HUMGRP5E_P4 (SEQ ID NO:1299) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 126, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMGRP5E_P4 (SEQ ID NO:1299)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00146 TABLE 126 Amino acid mutations SNP position(s) on
amino Alternative amino acid sequence acid(s) Previously known SNP?
4 S -> R Yes
[1259] Variant protein HUMGRP5E_P4 (SEQ ID NO:1299) is encoded by
the following transcript(s): HUMGRP5E_T4 (SEQ ID NO:20), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript HUMGRP5E_T4 (SEQ ID NO:20) is shown in
bold; this coding portion starts at position 622 and ends at
position 1044. The transcript also has the following SNPs as listed
in Table 127 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMGRP5E_P4 (SEQ ID NO:1299) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00147 TABLE 127 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
541 -> T No 542 G -> T No 631 A -> C Yes 672 G -> A Yes
1340 C -> No 1340 C -> A No 1341 A -> No 1341 A -> G
No
[1260] Variant protein HUMGRP5E_P5 (SEQ ID NO:1300) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HUMGRP5E_T5
(SEQ ID NO:21). An alignment is given to the known protein
(Gastrin-releasing peptide precursor (SEQ ID NO:1421)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1261] Comparison report between HUMGRP5E_P5 (SEQ ID NO:1300) and
GRP_HUMAN (SEQ ID NO:1421):
[1262] 1. An isolated chimeric polypeptide encoding for HUMGRP5E_P5
(SEQ ID NO:1300), comprising a first amino acid sequence being at
least 90% homologous to
MRGSELPLVLLALVLCLAPRGRAVPLPAGGGTVLTKMYPRGNHWAVGHLMGKKSTGESSSVSERGSLKQQLRE-
Y IRWEEAARNLLGLIEAKENRNHQPPQPKALGNQQPSWDSEDSSNFKDVGSKGK
corresponding to amino acids 1-127 of GRP_HUMAN (SEQ ID NO:1421),
which also corresponds to amino acids 1-127 of HUMGRP5E_P5 (SEQ ID
NO:1300), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DSLLQVLNVKEGTPS (SEQ ID NO: 1764)
corresponding to amino acids 128-142 of HUMGRP5E_P5 (SEQ ID
NO:1300), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1263] 2. An isolated polypeptide encoding for a tail of
HUMGRP5E_P5 (SEQ ID NO:1300), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence DSLLQVLNVKEGTPS (SEQ ID
NO: 1764) in HUMGRP5E_P5 (SEQ ID NO:1300).
[1264] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1265] Variant protein HUMGRP5E_P5 (SEQ ID NO:1300) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 128, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMGRP5E_P5 (SEQ ID NO:1300)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00148 TABLE 128 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
4 S -> R Yes
[1266] Variant protein HUMGRP5E_P5 (SEQ ID NO:1300) is encoded by
the following transcript(s): HUMGRP5E_T5 (SEQ ID NO:21), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript HUMGRP5E_T5 (SEQ ID NO:21) is shown in
bold; this coding portion starts at position 622 and ends at
position 1047. The transcript also has the following SNPs as listed
in Table 129 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMGRP5E_P5 (SEQ ID NO:1300) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00149 TABLE 129 Nucleic acid SNPs Previously Alternative
known SNP position on nucleotide sequence nucleic acid SNP? 541
-> T No 542 G -> T No 631 A -> C Yes 672 G -> A Yes
1354 C -> No 1354 C -> A No 1355 A -> No 1355 A -> G
No
[1267] As noted above, cluster HUMGRP5E features 5 segment(s),
which were listed in Table 123 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[1268] Segment cluster HUMGRP5E_node.sub.--0 (SEQ ID NO:1130)
according to the present invention is supported by 21 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMGRP5E_T4 (SEQ ID NO:20) and HUMGRP5E_T5 (SEQ ID NO:21). Table
130 below starting and ending position of this segment on each
transcript.
TABLE-US-00150 TABLE 130 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMGRP5E_T4 (SEQ ID NO: 20) 1 760 HUMGRP5E_T5 (SEQ ID NO: 21) 1
760
[1269] Segment cluster HUMGRP5E_node.sub.--2 (SEQ ID NO:1131)
according to the present invention is supported by 27 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMGRP5E_T4 (SEQ ID NO:20) and HUMGRP5E_T5 (SEQ ID NO:21). Table
131 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00151 TABLE 131 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMGRP5E_T4 (SEQ ID NO: 20) 761 984 HUMGRP5E_T5 (SEQ ID NO: 21) 761
984
[1270] Segment cluster HUMGRP5E_node.sub.--8 (SEQ ID NO:1132)
according to the present invention is supported by 26 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMGRP5E_T4 (SEQ ID NO:20) and HUMGRP5E_T5 (SEQ ID NO:21). Table
132 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00152 TABLE 132 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMGRP5E_T4 (SEQ ID NO: 20) 1004 1362 HUMGRP5E_T5 (SEQ ID NO: 21)
1018 1376
[1271] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1272] Segment cluster HUMGRP5E_node.sub.--3 (SEQ ID NO:1133)
according to the present invention can be found in the following
transcript(s): HUMGRP5E_T4 (SEQ ID NO:20) and HUMGRP5E_T5 (SEQ ID
NO:21). Table 133 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00153 TABLE 133 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMGRP5E_T4 (SEQ ID NO: 20) 985 1003 HUMGRP5E_T5 (SEQ ID NO: 21)
985 1003
[1273] Segment cluster HUMGRP5E_node.sub.--7 (SEQ ID NO:1134)
according to the present invention can be found in the following
transcript(s): HUMGRP5E_T5 (SEQ ID NO:21). Table 134 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00154 TABLE 134 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMGRP5E_T5 (SEQ ID NO: 21) 1004 1017
[1274] Microarray (chip) data is also available for this gene as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (with
regard to lung cancer), shown in Table 135.
TABLE-US-00155 TABLE 135 Oligonucleotides related to this gene
Overexpressed Chip Oligonucleotide name in cancers reference
HUMGRP5E_0_0_16630 (SEQ ID NO: Lung cancer Lung 208) HUMGRP5E_0_2_0
(SEQ ID NO: 209) Lung cancer Lung
[1275] Variant protein alignment to the previously known
protein:
TABLE-US-00156 Sequence name: /tmp/412zs2mwyT/B0wj)UAX0d:GRP_HUMAN
(SEQ ID NO:1421) Sequence documentation: Alignmeent of: HUMGRP5E_P4
(SEQ ID NO:1299) x GRP_HUMAN (SEQ ID NO:1421) Alignment segment
1/1: Quality: 1291.00 Escore: 0 Matching length: 141 Total length:
148 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 95.27 Total Percent Identity:
95.27 Gaps: 1 Alignment: . . . . . ##STR00149## . . . . .
##STR00150## . . . . ##STR00151## Sequence name:
/tmp/1me9ldnvfv/KbP5io8PtU:GRP_HUMAN (SEQ ID NO:1421) Sequence
documentation: Alignment of: HUMGRP5E_P5 (SEQ ID NO:1300) x
GRP_HUMAN (SEQ ID NO:1421) Alignment segment 1/1: Quality: 1248.00
Escore: 0 Matching length: 127 Total length: 127 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: . . . . . ##STR00152## . . . . . ##STR00153## . .
##STR00154##
[1276] The data given below shows that HUMGRP5E splice variants of
the present invention can be used as useful diagnostic agents for
lung cancer. In particular, differential overexpression in Small
Cell Lung Cancer cells (as opposed to normal lung cells and normal
tissue of other types) was demonstrated through determination of
mRNA expression, while antibodies selective for HUMGRP5E_P5 (SEQ ID
NO: 1300) splice variant were found to be capable of detecting
HUMGRP5E_P5 (SEQ ID NO: 1300) splice variant in human serum (blood
samples), further confirming the existence of HUMGRP5E_P5 (SEQ ID
NO: 1300) splice variant protein and its specific, differential
expression in patients with Cell lung cancer. Antibodies raised
against HUMGRP5E_P5 (SEQ ID NO: 1300) splice variant showed that
HUMGRP5E_P5 (SEQ ID NO: 1300) splice variant is differentially
detected in serum samples taken from subjects suffering from small
cell lung carcinoma as compared to healthy subjects, thereby
supporting the utility of HUMGRP5E_P5 (SEQ ID NO: 1300) splice
variant as a diagnostic agent for lung cancer. The experiments were
performed as described in greater detail below.
Expression of GRP_HUMAN--Gastrin-Releasing Peptide (HUMGRP5E)
Transcripts which are Detectable by Amplicon as Depicted in
Sequence Name HUMGRP5Ejunc3-7 (SEQ ID NO: 1648) in Normal and
Cancerous Lung Tissues
[1277] Expression of GRP_HUMAN--gastrin-releasing peptide
transcripts detectable by or according to HUMGRP5Ejunc3-7 amplicon
(SEQ ID NO: 1648) and HUMGRP5Ejunc3-7F (SEQ ID NO: 1646) and
HUMGRP5Ejunc3-7R (SEQ ID NO: 1647) primers was measured by real
time PCR. In parallel the expression of four housekeeping genes
PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO:1714); amplicon--HPRT1-amplicon, SEQ
ID NO:1297), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing sample",), to obtain a value of fold up-regulation for each
sample relative to median of the normal PM samples.
[1278] FIG. 19 is a histogram showing over expression of the
above-indicated GRP_HUMAN--gastrin-releasing peptide transcripts in
several cancerous lung samples relative to the normal samples. As
is evident from FIG. 19, the expression of
GRP_HUMAN--gastrin-releasing peptide transcripts detectable by the
above amplicon in several cancer samples was significantly higher
than in the non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99,
Table 2, "Tissue samples in testing sample"). Notably an
over-expression of at least 10 fold was found in 2 out of 15
adenocarcinoma samples, and in 7 out of 8 small cells carcinoma
samples.
[1279] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair:
HUMGRP5Ejunc3-7F forward primer (SEQ ID NO: 1646); and
HUMGRP5Ejunc3-7R reverse primer (SEQ ID NO: 1647).
[1280] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: HUMGRP5Ejunc3-7 (SEQ ID NO: 1648).
TABLE-US-00157 HUMGRP5Ejunc3-7F (SEQ ID NO: 1646):
ACCAGCCACCTCAACCCA HUMGRP5Ejunc3-7R (SEQ ID NO: 1647):
CTGGAGGAGAGAGTCTTTGCCT HUMGRP5Ejunc3-7 (SEQ ID NO: 1648):
ACCAGCCACCTCAACCCAAGGCCCTGGGCAATCAGCAGCCTTCGTGGGAT
TCAGAGGATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTC TCTGCTCCAG
Expression of GRP_HUMAN--gastrin-releasing peptide (HUMGRP5E)
transcripts which are detectable by amplicon as depicted in
sequence name HUMGRP5Ejunc3-7 (SEQ ID NO: 1648) in different normal
tissues
[1281] Expression of GRP_HUMAN--gastrin-releasing peptide
transcripts detectable by or according to HUMGRP5E junc3-7 amplicon
(SEQ ID NO: 1648) and HUMGRP5E junc3-7F (SEQ ID NO: 1646) and
HUMGRP5E junc3-7R (SEQ ID NO: 1647) was measured by real time PCR.
In parallel the expression of four housekeeping genes--RPL19
(GenBank Accession No. NM.sub.--000981 (SEQ ID NO:1715); RPL19
amplicon, SEQ ID NO:1630), TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO:1716); TATA amplicon, SEQ ID NO:1633),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the breast samples (Sample Nos. 33-35,
Table 3, "Tissue samples on normal panel", above), to obtain a
value of relative expression of each sample relative to median of
the breast samples.
TABLE-US-00158 HUMGRP5Ejunc3-7F (SEQ ID NO: 1646):
ACCAGCCACCTCAACCCA HUMGRP5Ejunc3-7R (SEQ ID NO: 1647):
CTGGAGCAGAGAGTCTTTGCCT HUMGRP5Ejunc3-7 (SEQ ID NO: 1648):
ACCAGCCACCTCAACCCAAGGCCCTGGGCAATCAGCAGCCTTCGTGGGAT
TCAGAGGATAGCAGCAACTTCAAAGATGTAGGTTCAAAAGGCAAAGACTC TCTGCTCCAG
[1282] The results are shown in FIG. 20, demonstrating the
expression of GRP_HUMAN--gastrin-releasing peptide (HUMGRP5E)
transcripts which are detectable by amplicon as depicted in
sequence name HUMGRP5Ejunc3-7 in different normal tissues.
[1283] Differential Expression of HUMGRP5E_P5 (SEQ ID NO:1300) in
Small Cell Lung Carcinoma Patients as Compared to Healthy
Subjects.
[1284] HUMGRP5E_P5 (SEQ ID NO: 1300) variant of the present
invention results from alternative splicing of the GRP gene and it
contains 142 amino acids. The first 121 amino acids from the
N-terminal are shared with WT GRP 1 (SEQ ID NO:1421), WT GRP 2 (SEQ
ID NO:1788) and WT GRP 3 (SEQ ID NO:1789). The next 6 amino acids
are absent in WT GRP 2 (SEQ ID NO:1788), but appear in the other
two known isoforms. In WT GRP 2 (SEQ ID NO:1788), shared 121
N-terminal region is followed by two amino acids which are absent
in HUMGRP5E_P5 (SEQ ID NO: 1300) and in the two other known
isoforms (SEQ ID NOs: 1421 and 1789). In addition, WT GRP 2 (SEQ ID
NO:1788) shares with HUMGRP5E_P5 (SEQ ID NO: 1300) splice variant
of the present invention a tail of 15 C-terminal amino acids. Thus,
HUMGRP5E_P5 (SEQ ID NO: 1300) splice variant of the present
invention has a novel bridge connecting the 127 amino acids head of
WT GRP isoforms 1 (SEQ ID NO:1421) and 3 (SEQ ID NO:1789) and the
15 amino acids tail of WT GRP isoform 2 (SEQ ID NO:1788).
[1285] The alignment comparison of the known GRP isoforms and the
HUMGRP5E_P5 (SEQ ID NO: 1300) is presented in FIG. 98. In FIG. 98,
the first N-terminal 127 amino acids common for HUMGRP5E_P5 (SEQ ID
NO: 1300) splice variant, WT GRP 1 (SEQ ID NO:1421) and WT GRP 3
(SEQ ID NO:1789) are shown in bold: 2 amino acids that appear in
the WT GRP 2 (SEQ ID NO:1788) and absent in the HUMGRP5E_P5 (SEQ ID
NO: 1300) are double underlined: 15 amino acids common for
HUMGRP5E_P5 (SEQ ID NO: 1300) and WT GRP isoform 2 (SEQ ID NO:1788)
are underlined.
[1286] 1. Protein Production of HUMGRP5E P5 (SEQ ID NO: 1300), WT
GRP 1 (SEQ ID NO:1421) and HUMGRP5E P5 Representing Fragment (SEQ
ID NO: 1794)
[1287] As a tool for antibody development and ELISA assay
development, the following recombinant proteins were produced:
HUMGRP5E_P5 splice variant (GRP.sub.--142) (SEQ ID NO: 1793) and WT
GRP 1 (GRP.sub.--148) (SEQ ID NO:1792) proteins. In addition, a
peptide representing the 15 amino acids (SEQ ID NO: 1794) from the
C-terminals tail of WT GRP 2 (SEQ ID NO:1788) and HUMGRP5E_P5 (SEQ
ID NO: 1300) was synthesized, to be used as a negative selection
tool.
1.1 Cloning and Expression in Mammalian Cells
1.1.1. Cloning of HUMGRP5E P5 (SEQ ID NO: 1793) (GRP-142) and WT
GRP 1 (GRP-148) (SEQ ID NO:1792)
[1288] GRP sequences starting from the predicted protein cleavage
site (corresponding to amino acid at position 54) were codon
optimized to boost protein expression in mammalian cells. In
addition, bacterial low-usage codons were eliminated to enable
bacterial expression of the variants using the same DNA
fragment.
[1289] The optimized genes were chemically synthesized at GeneArt
(Germany) using their proprietary gene synthesis technology, with
the addition of DNA sequences encoding a 8.times. His tag
downstream to the ectopic IL6 signal peptide. The resulting DNA
sequences for GRP-148 (SEQ ID NO: 1790) and GRP142 (SEQ ID NO:
1791) are shown in FIGS. 99a and 99b, respectively. The IL6 signal
peptide was added to enable secretion from mammalian cells, while
the His-tag was added to facilitate protein purification. Flanking
EcoRI and NotI sites were introduced at the 5' and 3' ends of the
DNA fragments respectively (underlined in FIGS. 99a and 99b).
Protein sequences for GRP-148 (SEQ ID NO: 1792) and GRP-142 (SEQ ID
NO: 1793) are shown in FIGS. 100a and 100b, respectively.
[1290] The DNA fragments were cloned into EcoRI and NotI sites of
pIRESpuro3 (Clontech, cat #PT3646-5) and the DNA sequence was
verified. Plasmid maps are shown in FIGS. 101a and 101b.
[1291] The expected MWs of the 2 mammalian proteins are: [1292]
GRP142 (SEQ ID NO: 1793) 11.4 kDa [1293] GRP148 (SEQ ID NO: 1792)
12.0 kDa
[1294] 1.1.2. Mammalian Expression of GRP Proteins
[1295] GRP constructs were transfected into HEK-293T cells (ATCC
catalog number CRL-11268) as follows: One day prior to
transfection, one well in a 6 well plate was plated with 500,000
cells in 2 ml DMEM (Dulbecco's modified Eagle's medium; Biological
Industries, Cat#: 01-055-1A) containing 10% FBS and incubated at
37.degree. C. in a 5% CO2 humidified incubator. Transfection was
done by FuGENE 6 Transfection Reagent (Roche, Cat#: 1-814-443)
according to manufacturer's protocol. Following 48h, transfected
cells were split and subjected to antibiotic selection using 5
microgram/ml puromycin. The surviving cells were propagated for 2-3
weeks.
[1296] Expression of the recombinant proteins in supernatant of
transfected cells was verified by Western Blot (WB) analysis using
anti His antibodies (Serotec, Cat. #MCA1396) as shown in FIG. 102,
lanes 6 and 7.
[1297] 1.2. Production and Purification of GRP-148 (SEQ ID NO:
1792)
[1298] 1.2.1. Mammalian Production of the GRP-148 (SEQ ID NO:
1792)
[1299] In order to produce sufficient amounts of the protein,
HEK293T cells expressing GRP-148 (SEQ ID NO: 1792) were further
propagated in serum-free medium as described below. Cells were
taken from a T-80 flask containing serum supplemented medium after
trypsinization, and were transferred into shake flasks containing
serum free medium (EX-CELL293, JRH)) supplemented with 4 mM
glutamine and selection antibiotics (5 ug/ml puromycin). Cultures
were incubated at 37.degree. C. on a shaker, at 100 RPM, and were
diluted into a consecutive shake flask containing fresh medium when
cell density reached 2-3.1.times.10.sup.6 cell/ml. After several
passages in serum-free medium the adapted cells served as an
inoculum for production.
[1300] Production of GRP 148 (SEQ ID NO: 1792) was carried out in
stirred-tank bioreactor equipped with an acoustic cell retention
device (ADI Autoclavable Glass Bioreactor, Applikon and BioSep10,
Applisens), operated in perfusion mode. The bioreactor was seeded
with cell density of 1.1.times.10.sup.6 cells/ml, in a final
working volume of 3.5 L. After growth phase of 4 days, a production
phase of 17 days in serum-free medium supplemented with 4 mM
glutamine (without selection antibiotics) was carried out during
which the growth temperature was reduced from 37.degree. C. to
34.degree. C. During production phase, cell density reached
2.6.times.10.sup.7 cells/ml and the culture was fed at perfusion
rate of 1-3 replacements per day. The total of 112 L of harvest
collected was filtered through a 0.22 um filter and used for
protein purification. GRP 148 (SEQ ID NO: 1792) harvest was
concentrated approximately 10 fold and the buffer was exchanged to
diafiltration buffer(50 mM NaH.sub.2PO4, 0.3 M NaCl, pH 8.0) using
PALL ultrafiltration system. Imidazole solution (2M pH 8.0) was
added to a final concentration of 10 mM, the harvest was filtered
through 0.22 um filter).
[1301] 1.2. 2 Purification of the GRP-148 (SEQ ID NO: 1792).
[1302] Purification process was carried out using a gravity-flow
column(Econo-pac 20 ml, BioRad) for binding, and AKTA Explorer (GE
Healthcare) for washing and elution. 1 ml Ni-NTA was washed and
equilibrated in a gravity-flow column. The resin was transferred
into a 250 ml vessel, the treated harvest (total volume 0.2L) was
added and incubated over night rolling at 4.degree. C. to allow
binding of the protein. On the following day the resin was packed
in a 5/50 Tricorn column (GE Healthcare). The column was connected
to the AKTA system and washed with 15 CV (column volumes) of buffer
A (50 mM NaH.sub.2PO4, 0.3 M NaCl, 10 mM Imidazole, pH 8.0) at flow
rate of 1 ml/min. Elution was carried out with 10 CV of buffer of
buffer B (50 mM NaH.sub.2PO4, 0.3 M NaCl, 250 mM Imidazole, pH 8.0
at a flow-rate of 0.4 ml/min. The eluted fractions were pooled and
dialyzed against dialysis buffer (Dulbecco's Phosphate buffers
saline pH 7.4 (w/o Ca, w/o Mg)) over night at 4.degree. C. with 3
buffer exchanges of 5L each. The dialyzed protein was filtered
through 0.45 um filter, aliquoted and stored at -70.degree. C.
Samples of the purified proteins were analyzed by SDS-PAGE stained
by Coomassie, as shown in FIG. 103. The identity of the purified
protein was verified by mass spectrometry analysis.
[1303] 1.3. Mammalian Production and Purification of the GRP-142
(SEQ ID NO: 1793)
[1304] 4.3.1 Mammalian Production of the GRP-142 (SEQ ID NO:
1793)
[1305] In order to produce sufficient amounts of the protein, the
HEK293T cells expressing GRP-142 (SEQ ID NO: 1793) cells were
further propagated in serum-free medium as described below. HEK293T
cells expressing GRP-142 (SEQ ID NO: 1793) were taken from a T-80
flask containing serum supplemented medium after trypsinization,
and were transferred into shake flasks containing serum free medium
(EX-CELL293, JRH) supplemented with 4 mM glutamine and selection
antibiotics (5 ug/ml puromycin). Cultures were incubated at
37.degree. C. on a shaker, 100 RPM, and when cell density reached
2-4.times.10.sup.6 cell/ml, the cells were diluted into a
consecutive shake flask containing fresh medium. After several
passages in serum-free medium the adapted cells served as an
inoculum for production.
[1306] Production-phase growth of GRP-142 (SEQ ID NO: 1793) was
carried out in a hollow-fiber bioreactor (Accusyst-Maximizer,
Biovest) operated in perfusion mode. The hollow-fiber cultureware
(1.5 m.sup.2, cellulose acetate double column) was inoculated with
8.5.times.10.sup.9 viable cells. The culture was fed with basal
medium (IMDM supplemented with additional 2 mM glutamine) on the
non-cell side of the fibers (intra-capillary), and with a complete
serum-free-medium (EX-CELL293, JRH) on the cell side of the fibers
(extra-capillary).
The production was carried out for 75 days, during which a total of
325 L of harvest were collected. Due to the low size of the
GRP-142, it passed through the fiber. Hence, harvest was collected
from both the intra-capillary (11 L) and the extra-capillary (314
L) fluids. All harvest batches were filtered through a 0.22 um
filter and used for protein purification.
[1307] 1.3.2 Purification of the GRP-142 (SEQ ID NO: 1793)
[1308] The purification process was carried out using a gravity
column for binding, and AKTA Explorer (GE Healthcare) for washing
and elution. 1ml Ni-NTA was washed and equilibrated in a 20m1
gravity column. The resin was transferred into a 500 ml vessel, the
treated harvest (total volume of 0.54 L) was added and incubated
over night on a roller at 4.degree. C. to allow binding of the
protein. On the following day the resin was packed in a 5/50
Tricorn column. The column was connected to the AKTA system and
washed with buffer A at flow rate of 1 ml/min 15 CV. Elution was
carried out by applying buffer 10 CV of buffer at a flow-rate of
0.4 ml/min. The eluted fractions were pooled and dialyzed against
dialysis buffer over night at 4.degree. C. with 3 volume exchange
of 5 L each. The dialyzed protein was filtered through 0.45 um
filter, aliquoted and stored at -70.degree. C.
The identity of the purified proteins was verified by mass
spectrometry analysis. Samples of the purified proteins obtained in
all above purification bathes were analyzed by SDS-PAGE stained by
Coomassie, as shown in FIG. 104.
1.4. HUMGRP5E P5 C-Terminal Peptide Tail (SEQ ID NO: 1794)
[1309] A peptide of 16 amino acids (SEQ ID NO: 1794) comprising of
15 amino acids common to HUMGRP5E_P5 (SEQ ID NO: 1300) splice
variant and WT GRP 2 (SEQ ID NO: 1788) isoform and C-terminal Cys
(added to facilitate copling to BSA and agarose beads) was
synthesized by Sigma-Aldrich Israel-LTD with a purity of
.gtoreq.95%.
TABLE-US-00159 HUMGRP5E_P5 C-termianl peptide tail sequence
(DSPS16) (SEQ ID NO: 1794):
H-Asp-Ser-Leu-Leu-Gln-Val-Leu-Asn-Val-Lys-Glu-Gly-
Thr-Pro-Ser-Cys-OH
[1310] 2. Antibody Development
[1311] In order to test HUMGRP5E_P5 (SEQ ID NO: 1300) protein
expression pattern in serum samples of diseased and healthy
individuals, specific polyclonal antibodies were developed as
described below.
The antibody of interest had to recognize specifically HUMGRP5E_P5
(SEQ ID NO: 1300), without recognizing WT GRP 1 (SEQ ID NO:1421)
and without recognizing the HUMGRP5E_P5 C-terminal peptide tail
(SEQ ID NO:1794), common to the HUMGRP5E_P5 variant of the present
invention (SEQ ID NO:1300) and to the known GRP-2 isoform (SEQ ID
NO:1788). Therefore, serum titers as well as resultant antibodies
were tested against all three protein/peptide preparations
following a successful recognition of the HUMGRP5E_P5 (SEQ ID NO:
1300)-specific immunogen.
[1312] Peptide Design and Synthesis
[1313] One peptide was selected as HUMGRP5E_P5 (SEQ ID NO:
1300)-specific immunogen for polyclonal antibody development. The
peptide sequence in the area of the unique bridge was used as a
template.
[1314] Selected HUMGRP5E_P5 (SEQ ID NO: 1300)-specific immunogen:
The primary sequence of the immunogen peptide (CGEN0601 (SEQ ID NO:
1795)) is shown below. Terminal cysteine residue was used to
facilitate coupling via m-maleimidobenzoyl-N-hydroxysuccinimide
ester (MBS) to Keyhole Limpet Hemocyanin (KLH).
Peptide CGEN0601 (SEQ ID NO: 1795): Ac-SKGKDSLLQVL-Ahx-C-amide
[1315] This peptide represents an internal region of the protein
sequence and it was therefore blocked at the amino terminal end by
acetylation and at its carboxy end by amidation. The illustration
in FIG. 105 shows the sequence of the selected immunogen marked on
the primary sequence of the HUMGRP5E_P5 (SEQ ID NO: 1300)
protein.
[1316] The immunogen peptide was synthesized using a conventional
technology (50 mg; purity .gtoreq.90%). The peptide was conjugated
to Keyhole Limpet Hemocyanin (KLH) and Bovine Serum Albumin (BSA)
using an m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS)
linker.
[1317] 2.2 Rabbit Polyclonal Antibody Development
[1318] 2.2.1. Rabbit Immunization and Sera Testing
[1319] Three New Zealand White Rabbits (8346, 8348 and 8349) were
immunized with CGEN0601 (SEQ ID NO: 1795) conjugated with KLH.
Immunization schedule and production bleed schedules are summarized
in Tables 136 and 137, respectively.
TABLE-US-00160 TABLE 136 Summary of rabbit immunization and test
bleed schedule. Scheduled Date Initial Injection Boost #1 Boost #2
Boost #3 (500 .mu.g (250 .mu.g (250 .mu.g (250 .mu.g Test Bleed
Rabbit # Pre Bleed ID/CFA) ID/IFA) SC/IFA) SC/IFA) #1 8346 Jun. 12,
2006 Jun. 16, 2006 Jun. 23, 2006 Jun. 30, 2006 Jul. 14, 2006 Jul.
24, 2006 8348 Jun. 12, 2006 Jun. 16, 2006 Jun. 23, 2006 Jun. 30,
2006 Jul. 14, 2006 Jul. 24, 2006 8349 Jun. 12, 2006 Jun. 16, 2006
Jun. 23, 2006 Jun. 30, 2006 Jul. 14, 2006 Jul. 24, 2006
TABLE-US-00161 TABLE 137 Summary of rabbit production bleed
schedule. Scheduled Date Production Production Production
Production Production Production Production Rabbit # Bleed #1 Bleed
#2 Bleed #3 Bleed #4 Bleed #5 Bleed #6 Bleed #7 8346 Aug. 3, 2006
Aug. 14, 2006 Aug. 21, 2006 Sep. 25, 2006 8348 Aug. 3, 2006 Aug.
14, 2006 Aug. 21, 2006 Sep. 11, 2006 Sep. 18, 2006 Sep. 25, 2006
Oct. 9, 2006 8349 Aug. 3, 2006 Aug. 14, 2006 Aug. 21, 2006 Sep. 11,
2006 Sep. 18, 2006 Sep. 25, 2006 Oct. 9, 2006 Production Production
Production Production Production Production Production Rabbit #
Bleed #8 Bleed #9 Bleed #10 Bleed #11 Bleed #12 Bleed #13 Bleed #14
8346 8348 Oct. 16, 2006 Nov. 13, 2006 Nov. 20, 2006 Nov. 27, 2006
Dec. 11, 2006 Dec. 18, 2006 Dec. 25, 2006 8349 Oct. 16, 2006 Nov.
13, 2006 Nov. 20, 2006 Nov. 27, 2006 Dec. 11, 2006 Dec. 18, 2006
Dec. 25, 2006 Production Production Production Terminal Rabbit #
Bleed #15 Bleed #16 Bleed #17 Bleed 8346 Oct. 30, 2007 8348 Jan. 2,
2007 8349 Jan. 2, 2007 Jan. 8, 2007 Jan. 15, 2007 XXXXX
[1320] Production bleeds were collected and antibody titers were
determined by ELISA using CGEN0601 (SEQ ID NO: 1795) peptide
conjugated with BSA, recombinant HUMGRP5E_P5 (SEQ ID NO: 1793)
splice variant, WT GRP 1 protein (SEQ ID NO:1792) and HUMGRP5E_P5
C-terminal peptide tail (SEQ ID NO: 1794).
[1321] Rabbit 8346 showed a lower antibody titer against the splice
variant (SEQ ID N):1793) (SVr) protein as compared to rabbits 8348
and 8349, therefore only few production bleeds were collected from
this rabbit and its bleeds were not purified.
[1322] 2.2.2 Rabbit Polyclonal Antibody Affinity Purification
[1323] Affinity purification was performed on all production bleeds
collected from the two rabbits (8348 and 8349) using a CGEN0601
(SEQ ID NO: 1795) immunoaffinity resin. Two passes of PBS diluted
antiserum (1:1) were run on immunoaffinity resin prepared by
coupling 10 mg Peptide CGEN0601 (SEQ ID NO: 1795) (Lot
06-2996-2137) [Sequence: Ac-SKGKDSLLQVL-Ahx-C-amide] to agarose
beads. The purified product was concentrated to approximately 1
mg/ml and dialyzed against 1.times.PBS. The yield obtained from
these purifications is summarized in Table 138 below.
TABLE-US-00162 TABLE 138 Total Lot Number Rabbit Concentration
Volume Yield Buffer 18878C 8349 1.10 mg/ml 37.0 ml 40.7 mg 0.02 M
Potassium Phosphate, 0.15 M Sodium Chloride, pH 7.2 18980C 8348 1.0
mg/ml 82.0 ml 82.0 mg 0.02 M Potassium Phosphate, 0.15 M Sodium
Chloride, pH 7.2
Purified antibodies were assayed by ELISA for reactivity towards
the immunogen (SEQ ID NO: 1795) conjugated to BSA, splice variant
protein (SEQ ID NO: 1793), wild type protein (SEQ ID NO:1792), and
HUMGRP5E_P5 C-terminal peptide tail (SEQ ID NO: 1794) conjugated to
BSA. Results are summarized in FIGS. 106 and 107.
[1324] Reactivity of the purified antibodies to both the splice
variant and the wild type proteins was also tested by a Western
blot analysis of both purified antibody preparations. The results
suggested a good recognition of the HUMGRP5E_P5 (SEQ ID NO: 1793)
splice variant and no recognition of the WT GRP 1 (SEQ ID NO:1792)
protein. The data is shown in FIGS. 108 and 109.
[1325] The two antibody preparations described above showed a good
binding to HUMGRP5E_P5 (SEQ ID NO:1793) splice variant and low
recognition of the WT GRP 1 protein (SEQ ID NO:1792). The binding
of the purified antibodies to HUMGRP5E_P5 C-terminal peptide tail
(SEQ ID NO:1794) was high in both preparations.
[1326] Rabbit 8349 (Lot #18878C) had higher titers against
HUMGRP5E_P5 (SEQ ID NO: 1793) splice variant and lower titers
against HUMGRP5E_P5 C-terminal peptide tail (SEQ ID NO:1794) as
compared to Rb8348 (Lot #18980). Therefore, this lot was selected
for cross absorption against the HUMGRP5E_P5 C-terminal peptide
tail (SEQ ID NO:1794) in order to significantly decrease its
recognition to known GRP isoforms.
[1327] The affinity purified antibody from rabbit 8349 was run over
an immunoaffinity resin prepared by coupling 10.0 mg of
GRP-negative control Peptide (DSPS16) (SEQ ID NO: 1794) to agarose
beads. The flow through was collected as the affinity purified
cross adsorbed product. The eluant was collected as the pan
reactive antibody. All purified products were concentrated to 1.0
mg/ml and dialyzed against 1.times.PBS. Prior to final vialing,
each antibody was filter sterilized (0.22 .mu.m). The cross
absorbed product prepared from lot 18878C was named lot 18978C. The
eluant--pan reactive antibody was named 18979C. Antibody yield from
cross adsorption is presented in Table 139 below.
TABLE-US-00163 TABLE 139 Yield from cross adsorption of Rabbit 8349
(Lot 18878C). Lot Number Rabbit Concentration Volume Total Yield
Buffer Rb 8439 Cross 8349 1.5 mg/ml 18.0 ml 27.0 mg 0.02 M
Potassium Phosphate, 0.15 M absorbed Sodium Chloride, pH 7.2
product Lot 18978C Rb 8349 Pan 8349 1.37 mg/ml 2.3 ml 3.1 mg 0.02 M
Potassium Phosphate, 0.15 M Reactive Sodium Chloride, pH 7.2 Lot
18979C
[1328] Antibodies prepared by cross absorption (Rb 8349 cross
absorbed product, lot#18978C) were assayed for reactivity towards
the immunogen (SEQ ID NO:1795) conjugated to BSA, splice variant
protein (SEQ ID NO:1793), wild type protein (SEQ ID NO:1792), and
HUMGRP5E_P5 C-terminal peptide tail (SEQ ID NO:1794) conjugated to
BSA. Results presented in FIG. 110.
[1329] The cross absorbed antibodies possessed a good recognition
of HUMGRP5E_P5 (SEQ ID NO:1793) splice variant and a low
recognition of both, WT GRP 1 (SEQ ID NO:1792) and the HUMGRP5E_P5
C-terminal peptide tail (SEQ ID NO:1794). Therefore, this
preparation was later used for assay development.
[1330] 3. HUMGRP5E P5 (SEQ ID NO: 1300) Assay Development
[1331] Assay Development stage of HUMGRP5E_P5 (SEQ ID NO: 1300) was
carried out through CommonWealth Biotechnologies (CBI), Inc., a
US-based service provider, using serum samples of Lung Cancer
patients.
[1332] For assay development purposes polyclonal antibody
preparation (Rockland polyclonal, Rabbit 8349 that was cross
absorbed on the GRP-negative control peptide) was used. As
indicated above, this antibody was developed against a synthetic
peptide Acetyl-SKGKDSLLQVL-amide (SEQ ID NO: 1795), comprising the
unique bridge specific for HUMGRP5E_P5 (SEQ ID NO: 1300) splice
variant.
[1333] Three ELISA formats were developed in order to identify the
most sensitive assay format for the detection of HUMGRP5E_P5 (SEQ
ID NO: 1300) protein in serum:
[1334] a Sandwich ELISA
[1335] a Antibody capture competitive ELISA
[1336] Antigen capture competitive ELISA
3.1 Sandwich ELISA
[1337] In order to develop a sandwich ELISA test, the cross
absorbed polyclonal antibody (Rb8349 cross absorbed product) has
been tested both as a capture and a detector antibody. For serving
as a detector, antibody was labeled with biotin. The sandwich assay
format was not able to detect HUMGRP5E_P5 (SEQ ID NO: 1793) spiked
in serum in all the concentrations that were tested (.ltoreq.1
ug/ml).
3.2 Antibody Capture Competitive ELISA
[1338] ELISA plates were coated with the antibody and its binding
to biotin-labeled HUMGRP5E_P5 (SEQ ID NO: 1793) spiked in serum
samples was assessed. Non-labeled HUMGRP5E_P5 (SEQ ID NO: 1793) was
tested as a competing antigen. The antibody capture assay format
was the following (Format 1):
[1339] Coat: Rabbit 8349, cross absorbed product
[1340] Detector: HUMGRP5E_P5 (SEQ ID NO: 1793) biotin-labeled
protein
[1341] LOD for HUMGRP5E_P5 (SEQ ID NO: 1793): .about.14 ng/ml
3.3 Antigen Capture Competitive ELISA
[1342] ELISA plates were coated with HUMGRP5E_P5 (SEQ ID NO: 1793)
splice variant protein and its binding to antibody pre-incubated
with peptide-spiked serum samples was assessed. The antigen capture
assay was the following (Format 2):
[1343] Coat: HUMGRP5E_P5 (SEQ ID NO: 1793) protein
[1344] Detector: Rabbit 8349, Cross absorbed product
[1345] LOD for HUMGRP5E_P5 (SEQ ID NO: 1793): .about.10 ng/ml
[1346] The results observed with the various assay formats showed a
comparable performance of both antigen and antibody capture
competitive tests, with a slightly lower LOD for the format 2. This
format 2 did not recognize spiked WT GRP 1 (SEQ ID NO:1792) and
HUMGRP5E_P5 C-terminal peptide tail (SEQ ID NO: 1794) samples (up
to concentration of 0.88 nmol/ml which is equivalent to 10 ug/ml of
the HUMGRP5E_P5 (SEQ ID NO: 1793)).
It was therefore decided to continue with the antigen capture
competitive assay format for serum samples testing.
4. Serum Screening
[1347] Serum of Small Cell Lung Cancer (SCLC) patient's sera and
control sera (ProMedDx) were tested by HUMGRP5E_P5 antigen
competitive assay described above.
[1348] 4.1 Serum Samples Screening
Sera from eight Small Cell Lung Cancer (SCLC) patients and 21
gender-matched control sera (Mean age: 65y.times.7; 50 y.+-.2,
respectively) were assayed using optimized HUMGRP5E_P5 (SEQ ID NO:
1300) antigen capture competitive assay (Format 2, above). The
results are presented in Table 140 as well and in FIG. 111.
TABLE-US-00164 TABLE 140 Concentration of CgenGRP in control and
SCLC patients' sera. Serum screening 7.1 CgenGRP Cgen GRP Lung
cancer concentration, Normal controls concentration, Sample ID
ng/ml Sample ID ng/ml 11069742 * 11069756 61 11069783 * 11069722 43
11069743 48 11069803 4 11069725 10 11069754 * 11069769 ** 11069784
* 11069785 * 11069794 * 11069758 * P132 28 11069739 * P220 95
11069736 * P490 65 11069745 18 P8 41 11069765 18 P805 55 11069767
15 P873 55 11069790 13 P90 32 11069780 * P93 55 11069771 * Mean 53
Mean 11 St. Dev. 21 St. Dev. 18 * Below LOD ** Detected, but below
LOQL
[1349] The results revealed that HUMGRP5E_P5 (SEQ ID NO: 1300)
concentrations detected in SCLC sera are relatively higher than
HUMGRP5E_P5 (SEQ ID NO: 1300) concentrations detected in the
control sera. The mean concentration level of HUMGRP5E_P5 (SEQ ID
NO: 1300) levels was 53.2.+-.21.4 ng/ml for patients and
11.0.+-.18.1 ng/ml for controls. Three control samples (out of the
21 tested) showed positive signals in the range observed for
patients and 6 control samples showed signals lower than the range
observed for patients. The remaining 12 controls had no signal. The
results indicate that HUMGRP5E_P5 (SEQ ID NO: 1300) can serve as a
serum marker for the detection of SCLC patients.
[1350] The antibodies specific for HUMGRP5E_P5 (SEQ ID NO: 1300)
splice variant were able to detect HUMGRP5E_P5 (SEQ ID NO: 1300)
variant protein in serum samples, including in Small Cell lung
cancer patients serum, however, sensitivity and reproducibility of
the results were hampered by apparent low levels of the protein in
serum and also by technical problems with the assays, according to
additional results that are not shown.
Description for Cluster D56406
[1351] Cluster D56406 features 3 transcript(s) and 10 segment(s) of
interest, the names for which are given in Tables 141 and 142,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
143.
TABLE-US-00165 TABLE 141 Transcripts of interest Transcript Name
Sequence ID No. D56406_PEA_1_T3 22 D56406_PEA_1_T6 23
D56406_PEA_1_T7 24
TABLE-US-00166 TABLE 142 Segments of interest Segment Name Sequence
ID No. D56406_PEA_1_node_0 340 D56406_PEA_1_node_13 341
D56406_PEA_1_node_11 342 D56406_PEA_1_node_2 343
D56406_PEA_1_node_3 344 D56406_PEA_1_node_5 345 D56406_PEA_1_node_6
346 D56406_PEA_1_node_7 347 D56406_PEA_1_node_8 348
D56406_PEA_1_node_9 349
TABLE-US-00167 TABLE 143 Proteins of interest Protein Name Sequence
ID No. D56406_PEA_1_P2 1301 D56406_PEA_1_P5 1302 D56406_PEA_1_P6
1303
[1352] These sequences are variants of the known protein
Neurotensin/neuromedin N precursor [Contains: Large neuromedin N
(NmN-125); Neuromedin N (NmN) (NN); Neurotensin (NT); Tail peptide]
(SwissProt accession identifier NEUTHUMAN), SEQ ID NO: 1422,
referred to herein as the previously known protein.
[1353] Protein Neurotensin/neuromedin N precursor is known or
believed to have the following function(s): Neurotensin may play an
endocrine or paracrine role in the regulation of fat metabolism. It
causes contraction of smooth muscle. The sequence for protein
Neurotensin/neuromedin N precursor is given at the end of the
application, as "Neurotensin/neuromedin N precursor [Contains:
Large neuromedin N (NmN-125); Neuromedin N (NmN) (NN); Neurotensin
(NT); Tail peptide] amino acid sequence". Protein
Neurotensin/neuromedin N precursor localization is believed to be
Secreted; Packaged within secretory vesicles.
[1354] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: signal
transduction, which are annotation(s) related to Biological
Process; neuropeptide hormone, which are annotation(s) related to
Molecular Function; and extracellular; soluble fraction, which are
annotation(s) related to Cellular Component.
[1355] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot
ncbinlmdot nih dot gov/projects/LocusLink/>.
[1356] As noted above, cluster D56406 features 3 transcript(s),
which were listed in Table 141 above. These transcript(s) encode
for protein(s) which are variant(s) of protein
Neurotensin/neuromedin N precursor. A description of each variant
protein according to the present invention is now provided.
[1357] Variant protein D56406_PEA.sub.--1_P2 (SEQ ID NO:1301)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
D56406_PEA.sub.--1_T3 (SEQ ID NO:22). An alignment is given to the
known protein (Neurotensin/neuromedin N precursor) at the end of
the application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1358] Comparison report between D56406_PEA.sub.--1_P2 (SEQ ID
NO:1301) and NEUT_HUMAN (SEQ ID NO:1422):
[1359] 1. An isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLCSDSEEEMKALEADFLTNMHTSKISKAHVPSWKMTLLNVCSLVNNL
NSPAEETGEVHEEELVARRKLPTALDGFSLEAMLTIYQLHKICHSRAFQHWE corresponding
to amino acids 1-120 of NEUT_HUMAN (SEQ ID NO:1422), which also
corresponds to amino acids 1-120 of D56406_PEA.sub.--1_P2 (SEQ ID
NO:1301), second amino acid sequence being at least 70%, optionally
at least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence ARWLTPVIPALWEAETGGSRGQEMETIPANT (SEQ ID NO: 1773)
corresponding to amino acids 121-151 of D56406_PEA.sub.--1_P2 (SEQ
ID NO:1301), and a third amino acid sequence being at least 90%
homologous to LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY
corresponding to amino acids 121-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 152-201 of
D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[1360] 2. An isolated polypeptide encoding for an edge portion of
D56406_PEA.sub.--1_P2 (SEQ ID NO:1301), comprising an amino acid
sequence being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
encoding for ARWLTPVIPALWEAETGGSRGQEMETIPANT (SEQ ID NO: 1773),
corresponding to D56406_PEA.sub.--1_P2 (SEQ ID NO:1301).
[1361] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1362] Variant protein D56406_PEA.sub.--1_P2 (SEQ ID NO:1301) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 144, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein D56406_PEA.sub.--1_P2
(SEQ ID NO:1301) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00168 TABLE 144 Amino acid mutations SNP position(s) on
amino Alternative amino acid sequence acid(s) Previously known SNP?
30 M -> V No 44 S -> P No 84 V -> No 84 V -> A No
[1363] Variant protein D56406_PEA.sub.--1_P2 (SEQ ID NO:1301) is
encoded by the following transcript(s): D56406_PEA.sub.--1_T3 (SEQ
ID NO:22), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript D56406_PEA.sub.--1_T3
(SEQ ID NO:22) is shown in bold; this coding portion position 106
and ends at position 708. The transcript also has the following
SNPs as listed in Table 145 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein D56406_PEA.sub.--1_P2
(SEQ ID NO:1301) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00169 TABLE 145 Nucleic acid SNPs SNP position on
nucleotide Previously sequence Alternative nucleic acid known SNP?
94 G -> T No 95 A -> T No 858 T -> G Yes 103 A -> G Yes
193 A -> G No 235 T -> C No 339 T -> C No 356 T -> No
356 T -> C No 417 A -> T No 757 T -> No
[1364] Variant protein D56406_PEA.sub.--1_P5 (SEQ ID NO:1302)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
D56406PEA.sub.--1_T6 (SEQ ID NO:23). An alignment is given to the
known protein (Neurotensin/neuromedin N precursor) at the end of
the application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1365] Comparison report between D56406_PEA.sub.--1_P5 (SEQ ID
NO:1302) and NEUT_HUMAN (SEQ ID NO:1422):
[1366] 1. An isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLC corresponding to amino acids 1-23 of
NEUT_HUMAN (SEQ ID NO:1422), which also corresponds to amino acids
1-23 of D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), and a second amino
acid sequence being at least 90% homologous to
SEEEMKALEADFLTNMHTSKISKAHVPSWKMTLLNVCSLVNNLNSPAEETGEVHEEELVARRKLPTALDG
FSLEAMLTIYQLHKICHSRAFQHWELIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDS
YYY corresponding to amino acids 26-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 24-168 of
D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1367] 2. An isolated chimeric polypeptide encoding for an edge
portion of D56406_PEA.sub.--1_P5 (SEQ ID NO:1302), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise CS, having a structure as follows: a
sequence starting from any of amino acid numbers 23-x to 23; and
ending at any of amino acid numbers 24+((n-2)-x), in which x varies
from 0 to n-2.
[1368] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1369] Variant protein D56406PEA.sub.--1_P5 (SEQ ID NO:1302) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 146, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein D56406_PEA.sub.--1_P5
(SEQ ID NO:1302) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00170 TABLE 146 Amino acid mutations SNP position(s) on
amino acid Previously sequence Alternative amino acid(s) known SNP?
28 M -> V No 42 S -> P No 82 V -> No 82 V -> A No
[1370] Variant protein D56406_PEA.sub.--1_P5 (SEQ ID NO:1302) is
encoded by the following transcript(s): D56406_PEA.sub.--1_T6 (SEQ
ID NO:23), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript D56406_PEA.sub.--1_T6
(SEQ ID NO:23) is shown in bold; this coding portion starts at
position 106 and ends at position 609. The transcript also has the
following SNPs as listed in Table 147 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
D56406_PEA.sub.--1_P5 (SEQ ID NO:1302) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00171 TABLE 147 Nucleic acid SNPs SNP position on
nucleotide Previously sequence Alternative nucleic acid known SNP?
94 G -> T No 95 A -> T No 759 T -> G Yes 806 G -> A Yes
1014 T -> G No 1178 T -> G No 103 A -> G Yes 187 A -> G
No 229 T -> C No 333 T -> C No 350 T -> No 350 T -> C
No 411 A -> T No 658 T -> No
[1371] Variant protein D56406_PEA.sub.--1_P6 (SEQ ID NO:1303)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
D56406_PEA.sub.--1_T7 (SEQ ID NO:24). An alignment is given to the
known protein (Neurotensin/neuromedin N precursor) at the end of
the application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1372] Comparison report between D56406_PEA.sub.--1_P6 (SEQ ID
NO:1303) and NEUT_HUMAN (SEQ ID NO:1422):
[1373] 1. An isolated chimeric polypeptide encoding for
D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), comprising a first amino
acid sequence being at least 90% homologous to
MMAGMKIQLVCMLLLAFSSWSLCSDSEEEMKALEADFLTNMHTSK corresponding to
amino acids 1-45 of NEUT_HUMAN (SEQ ID NO:1422), which also
corresponds to amino acids 1-45 of D56406_PEA.sub.--1_P6 (SEQ ID
NO:1303), and a second amino acid sequence being at least 90%
homologous to LIQEDILDTGNDKNGKEEVIKRKIPYILKRQLYENKPRRPYILKRDSYYY
corresponding to amino acids 121-170 of NEUT_HUMAN (SEQ ID
NO:1422), which also corresponds to amino acids 46-95 of
D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1374] 2. An isolated chimeric polypeptide encoding for an edge
portion of D56406_PEA.sub.--1_P6 (SEQ ID NO:1303), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KL, having a structure as follows: a
sequence starting from any of amino acid numbers 45-x to 45; and
ending at any of amino acid numbers 46+((n-2)-x), in which x varies
from 0 to n-2.
[1375] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1376] Variant protein D56406_PEA.sub.--1_P6 (SEQ ID NO:1303) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 148, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein D56406_PEA.sub.--1_P6
(SEQ ID NO:1303) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00172 TABLE 148 Amino acid mutations SNP position(s) on
amino acid Previously sequence Alternative amino acid(s) known SNP?
30 M -> V No 44 S -> P No
[1377] Variant protein D56406_PEA.sub.--1_P6 (SEQ ID NO:1303) is
encoded by the following transcript(s): D56406_PEA.sub.--1_T7 (SEQ
ID NO:24), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript D56406_PEA.sub.--1_T7
(SEQ ID NO:24) is shown in bold; this coding portion starts at
position 106 and ends at position 390. The transcript also has the
following SNPs as listed in Table 149 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
D56406_PEA.sub.--1_P6 (SEQ ID NO:1303) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00173 TABLE 149 Nucleic acid SNPs SNP position on
nucleotide Previously sequence Alternative nucleic acid known SNP?
94 G -> T No 95 A -> T No 103 A -> G Yes 193 A -> G No
235 T -> C No 439 T -> No 540 T -> G Yes 587 G -> A Yes
795 T -> G No 959 T -> G No
[1378] As noted above, cluster D56406 features 10 segment(s), which
were listed in Table 142 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1379] Segment cluster D56406PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1135) according to the present invention is supported by 48
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22),
D56406_PEA.sub.--1_T6 (SEQ ID NO:23) and D56406_PEA.sub.--1_T7 (SEQ
ID NO:24). Table 150 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00174 TABLE 150 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 1 178 (SEQ ID NO: 22) D56406_PEA_1_T6 1 178 (SEQ ID
NO: 23) D56406_PEA_1_T7 1 178 (SEQ ID NO: 24)
[1380] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (with
regard to lung cancer), shown in Table 151.
TABLE-US-00175 TABLE 151 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
D56406_0_5_0 lung malignant tumors LUN (SEQ ID NO: 210)
[1381] Segment cluster D56406_PEA.sub.--1_node.sub.--13 according
to the present invention is supported by 43 libraries. The number
of libraries was determined as previously described. This segment
can be found in the following transcript(s): D56406_PEA.sub.--1_T3
(SEQ ID NO:22), D56406_PEA.sub.--1_T6 (SEQ ID NO:23) and
D56406_PEA.sub.--1_T7 (SEQ ID NO:24). Table 152 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00176 TABLE 152 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 559 902 (SEQ ID NO: 22) D56406_PEA_1_T6 460 1239
(SEQ ID NO: 23) D56406_PEA_1_T7 241 1020 (SEQ ID NO: 24)
[1382] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1383] Segment cluster D56406_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:1137) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22). Table 153
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00177 TABLE 153 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 466 558 (SEQ ID NO: 22)
[1384] Segment cluster D56406_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1138) according to the present invention can found in the
following transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22) and
D56406_PEA.sub.--1_T7 (SEQ ID NO:24). Table 154 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00178 TABLE 154 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 179 184 (SEQ ID NO: 22) D56406_PEA_1_T7 179 184
(SEQ ID NO: 24)
[1385] Segment cluster D56406_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:1139) according to the present invention is supported by 46
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22),
D56406_PEA.sub.--1_T6 (SEQ ID NO:23) and D56406_PEA.sub.--1_T7 (SEQ
ID NO:24). Table 155 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00179 TABLE 155 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 185 240 (SEQ ID NO: 22) D56406_PEA_1_T6 179 234
(SEQ ID NO: 23) D56406_PEA_1_T7 185 240 (SEQ ID NO: 24)
[1386] Segment cluster D56406_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1140) according to the present invention is supported by 48
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22) and
D56406_PEA.sub.--1_T6 (SEQ ID NO:23). Table 156 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00180 TABLE 156 Segment location on transcripts Segment
Transcript name starting position Segment ending position
D56406_PEA_1_T3 241 355 (SEQ ID NO: 22) D56406_PEA_1_T6 235 349
(SEQ ID NO: 23)
[1387] Segment cluster D56406_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1141) according to the present invention is supported by 34
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22) and
D56406_PEA.sub.--1_T6 (SEQ ID NO:23). Table 157 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00181 TABLE 157 Segment location on transcripts Segment
starting Transcript name position Segment ending position
D56406_PEA_1_T3 356 389 (SEQ ID NO: 22) D56406_PEA_1_T6 350 383
(SEQ ID NO: 23)
[1388] Segment cluster D56406_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:1142) according to the present invention is supported by 32
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1 T3 (SEQ ID NO:22) and
D56406_PEA.sub.--1_T6 (SEQ ID NO:23). Table 158 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00182 TABLE 158 Segment location on transcripts Segment
starting Transcript name position Segment ending position
D56406_PEA_1_T3 390 415 (SEQ ID NO: 22) D56406_PEA_1_T6 384 409
(SEQ ID NO: 23)
[1389] Segment cluster D56406_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1143) according to the present invention can be found in the
following transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22) and
D56406_PEA.sub.--1_T6 (SEQ ID NO:23). Table 159 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00183 TABLE 159 Segment location on transcripts Segment
starting Transcript name position Segment ending position
D56406_PEA_1_T3 416 423 (SEQ ID NO: 22) D56406_PEA_1_T6 410 417
(SEQ ID NO: 23)
[1390] Segment cluster D56406_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:1144) according to the present invention is supported by 31
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): D56406_PEA.sub.--1_T3 (SEQ ID NO:22) and
D56406PEA.sub.--1_T6 (SEQ ID NO:23). Table 160 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00184 TABLE 160 Segment location on transcripts Segment
starting Transcript name position Segment ending position
D56406_PEA_1_T3 424 465 (SEQ ID NO: 22) D56406_PEA_1_T6 418 459
(SEQ ID NO: 23)
Variant protein alignment to the previously known protein:
TABLE-US-00185 Sequence name: /tmp/jU49325aMA/8F0XuN7La5:NEUT_HUMAN
(SEQ ID NO:1422) Sequence documentation: Alignment of:
D56406_PEA_1_P2 (SEQ ID NO:1301) x NEUT_HUMAN (SEQ ID NO:1422)
Alignment segment 1/1: Quality: 1591.00 Escore: 0 Matching length:
170 Total length: 201 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 84.58 Total
Percent Identity: 84.58 Gaps: 1 Alignment: . . . . . ##STR00155## .
. . . . ##STR00156## . . . . . ##STR00157## . . . . . ##STR00158##
##STR00159## Sequence name: /tmp/wWui8Kd4y9/zbf3ihRwnR:NEUT_HUMAN
(SEQ ID NO:1422) Sequence documentation: Alignment of:
D56406_PEA_1_P5 (SEQ ID NO:1302) x NEUT_HUMAN (SEQ ID NO:1422)
Alignment segment 1/1: Quality: 1572.00 Escore: 0 Matching length:
168 Total length: 170 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 98.82 Total
Percent Identity: 98.82 Gaps: 1 Alignment: . . . . . ##STR00160## .
. . . . ##STR00161## . . . . . ##STR00162## . . ##STR00163##
Sequence name: /tmp/f5d07fF5D7/E4N5xjUIAN:NEUT_HUMAN (SEQ ID
NO:1422) Alignment segment 1/1: Quality: 844.00 Escore: 0 Matching
length: 95 Total length: 170 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 55.88
Total Percent Identity: 55.88 Gaps: 1 Alignment: . . . . .
##STR00164## . . . . . 45
.................................................. 45 51
VPSWKMTLLNVCSLVNNLNSPAEETGEVHEEELVARRKLPTALDGFSLEA 100 . . . . .
##STR00165## . . ##STR00166##
Expression of NTS D56406 Transcripts which are Detectable by
Amplicon as Depicted in Sequence Name D56406_seg7-9F2R2 (SEQ ID NO:
1798) in Normal and Cancerous Lung Tissues
[1391] Expression of NTS transcripts detectable by or according to
seg7-9F2R2--D56406_seg7-9F2R2 amplicon (SEQ ID NO: 1798) and
primers D56406_seg7-9F2 (SEQ ID NO: 1796) and D56406_seg7-9R2 (SEQ
ID NO: 1797) was measured by real time PCR. In parallel the
expression of several housekeeping genes--HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO: 1714); amplicon--HPRT1-amplicon
(SEQ ID NO: 1297)), PBGD (GenBank Accession No. BC019323 (SEQ ID
NO: 1713); amplicon--PBGD-amplicon (SEQ ID NO: 334)), SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO: 1712);
amplicon--SDHA-amplicon (SEQ ID NO: 331)) and Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO: 1711);
amplicon--Ubiquitin-amplicon (SEQ ID NO: 328)) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the normalization factor calculated from the
expression of these house keeping genes as described in
normalization method 2 in the "materials and methods" section. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal samples (sample numbers
51-64, 69 and 70, Table 2.sub.--1 above), to obtain a value of fold
up-regulation for each sample relative to median of the normal
samples.
[1392] FIG. 112 is a histogram showing over expression of the
above-indicated NTS transcripts in cancerous Lung samples relative
to the normal samples.
[1393] As is evident from FIG. 112, the expression of NTS
transcripts detectable by the above amplicon in non-small cell
carcinoma samples, specifically in squamous cell carcinoma was
significantly higher than in the non-cancerous samples (sample
numbers 51-64, 69 and 70, Table 2.sub.--1 above). Notably an
over-expression of at least fold was found in 12 out of 39
non-small cell carcinoma samples and in 8 out of 16 squamous cell
carcinoma samples.
[1394] Statistical analysis was applied to verify the significance
of these results, as described below.
[1395] The P value for the difference in the expression levels of
NTS transcripts detectable by the above amplicon in Lung non-small
cell carcinoma samples versus the normal tissue samples was
determined by T test as 1.47e-002. The P value for the difference
in the expression levels of NTS transcripts detectable by the above
amplicon in Lung squamous cell carcinoma samples versus the normal
tissue samples was determined by T test as 1.46e-002.
[1396] Threshold of 5 fold over expression was found to
differentiate between non-small cell carcinoma and normal samples
with P value of 8.91e-003 as checked by exact Fisher test.
Threshold of 5 fold over expression was found to differentiate
between squamous cell carcinoma and normal samples with P value of
1.22e-003 as checked by exact Fisher test.
[1397] The above values demonstrate statistical significance of the
results.
[1398] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair:
D56406_seg7-9F2 forward primer (SEQ ID NO: 1796); and
D56406_seg7-9R2 reverse primer (SEQ ID NO: 1797).
[1399] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: D56406_seg7-9F2R2 (SEQ ID NO: 1798).
TABLE-US-00186 Forward Primer (D56406_seg7-9F2 (SEQ ID NO: 1796)):
AGCTCCACAAAATCTGTCACAGC Reverse Primer (D56406_seg7-9R2 (SEQ ID NO:
1797)): TGATCCGCCCGTCTCG Amplicon (D56406_seg7-9F2R2 (SEQ ID NO:
1798)): AGCTCCACAAAATCTGTCACAGCAGGGCTTTTCAACACTGGGAGGCACGG
TGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGACGGGCGGATC A
[1400] Expression of NTS D56406 Transcripts which are Detectable by
Amplicon as Depicted in Sequence Name D56406_seg7-9F2R2 (SEQ ID NO:
1798) in Different Normal Tissues
[1401] Expression of NTS transcripts detectable by or according to
seg7-9F2R2--D56406_seg7-9F2R2 amplicon (SEQ ID NO: 1798) and
primers D56406_seg7-9F2 (SEQ ID NO: 1796) and D56406_seg7-9R2 (SEQ
ID NO: 1797) was measured by real time PCR. In parallel the
expression of several housekeeping genes--SDHA (GenBank Accession
No. NM.sub.--004168 (SEQ ID NO: 1712); amplicon--SDHA-amplicon (SEQ
ID NO: 331)), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:
1711); amplicon--Ubiquitin-amplicon (SEQ ID NO: 328)), RPL19
(GenBank Accession No. NM.sub.--000981 (SEQ ID NO: 1715); RPL19
amplicon (SEQ ID NO: 1630)) and TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO: 1716); TATA amplicon (SEQ ID NO: 1633))
was measured similarly. For each RT sample, the expression of the
above amplicon was normalized to the normalization factor
calculated from the expression of these house keeping genes as
described in normalization method 2 in the "materials and methods"
section. The normalized quantity of each RT sample was then divided
by the median of the quantities of the lung samples (sample numbers
28, 29 and 30, Table 3.sub.--1 above), to obtain a value of
relative expression of each sample relative to median of the lung
samples.
TABLE-US-00187 Forward Primer (D56406_seg7-9F2) (SEQ ID NO: 1796):
AGCTCCACAAAATCTGTCACAGC Reverse Primer (D56406_seg7-9R2) (SEQ ID
NO: 1797): TGATCCGCCCGTCTCG Amplicon (D56406_seg7-9F2R2) (SEQ ID
NO: 1798): AGCTCCACAAAATCTGTCACAGCAGGGCTTTTCAACACTGGGAGGCACGG
TGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGACGGGCGGATC A
[1402] FIG. 113 shows a histogram showing the expression of NTS
D56406 transcripts which are detectable by amplicon as depicted in
sequence name D56406_seg7-9F2R2 (SEQ ID NO: 1798) in different
normal tissues.
Description for Cluster F05068
[1403] Cluster F05068 features 3 transcript(s) and 12 segment(s) of
interest, the names for which are given in Tables 161 and 162,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
163.
TABLE-US-00188 TABLE 161 Transcripts of interest Transcript Name
Sequence ID No. F05068_PEA_1_T3 25 F05068_PEA_1_T4 26
F05068_PEA_1_T6 27
TABLE-US-00189 TABLE 162 Segments of interest Segment Name Sequence
ID No. F05068_PEA_1_node_0 350 F05068_PEA_1_node_10 351
F05068_PEA_1_node_12 352 F05068_PEA_1_node_13 353
F05068_PEA_1_node_4 354 F05068_PEA_1_node_8 355
F05068_PEA_1_node_11 356 F05068_PEA_1_node_3 357
F05068_PEA_1_node_5 358 F05068_PEA_1_node_6 359 F05068_PEA_1_node_7
360 F05068_PEA_1_node_9 361
TABLE-US-00190 TABLE 163 Proteins of interest Protein Name Sequence
ID No. F05068_PEA_1_P7 1304 F05068_PEA_1_P8 1305
[1404] These sequences are variants of the known protein ADM
precursor [Contains: Adrenomedullin (AM); Proadrenomedullin N-20
terminal peptide (ProAM-N20) (ProAM N-terminal 20 peptide) (PAMP)]
(SwissProt accession identifier ADML_HUMAN), SEQ ID NO:1423,
referred to herein as the previously known protein.
[1405] Protein ADM precursor is known or believed to have the
following function(s): AM and PAMP are potent hypotensive and
vasodilatator agents. Numerous actions have been reported, most
related to the physiologic control of fluid and electrolyte
homeostasis. In the kidney, AM is diuretic and natriuretic, and
both AM and PAMP inhibit aldosterone secretion by direct adrenal
actions. In pituitary gland, both peptides at physiologically
relevant doses inhibit basal ACTH secretion. Both peptides appear
to act in brain and pituitary gland to facilitate the loss of
plasma volume, actions which complement their hypotensive effects
in blood vessels. The sequence for protein ADM precursor is given
at the end of the application, as "ADM precursor [Contains:
Adrenomedullin (AM); Proadrenomedullin N-20 terminal peptide
(ProAM-N20) (ProAM N-terminal 20 peptide) (PAMP)] amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 164.
TABLE-US-00191 TABLE 164 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 50 S -> R (in dbSNP:
5005). /FTId = VAR_014861.
[1406] Protein ADM precursor localization is believed to be
Secreted.
[1407] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: cAMP biosynthesis;
progesterone biosynthesis; signal transduction; cell-cell
signaling; pregnancy;
[1408] excretion; circulation; response to wounding, which are
annotation(s) related to Biological Process; ligand; hormone, which
are annotation(s) related to Molecular Function; and extracellular
space; soluble fraction, which are annotation(s) related to
Cellular Component.
[1409] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1410] Cluster F05068 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 21 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1411] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 21 and Table 165. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: uterine malignancies.
TABLE-US-00192 TABLE 165 Normal tissue distribution Name of Tissue
Number bladder 164 bone 259 brain 26 colon 66 epithelial 73 general
67 head and neck 0 kidney 49 liver 0 lung 51 lymph nodes 0 breast
87 ovary 0 pancreas 30 skin 295 stomach 0 Thyroid 0 uterus 13
TABLE-US-00193 TABLE 166 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 7.6e-01
8.0e-01 9.4e-01 0.5 9.9e-01 0.4 bone 7.5e-01 8.8e-01 1 0.1 1 0.3
brain 5.2e-01 6.1e-01 7.0e-04 2.1 1.1e-02 1.4 colon 6.2e-01 6.1e-01
9.7e-01 0.5 9.6e-01 0.6 epithelial 1.0e-01 3.0e-02 7.8e-01 0.7
5.8e-01 0.9 general 3.7e-01 2.6e-01 8.5e-01 0.8 9.0e-01 0.8 head
and neck 2.1e-01 1.1e-01 1 1.0 3.2e-01 2.3 kidney 3.8e-01 3.9e-01
6.6e-02 1.8 1.2e-02 2.2 liver 1.8e-01 1.2e-01 2.3e-01 4.3 2.3e-01
2.6 lung 6.2e-01 4.3e-01 8.5e-01 0.7 3.8e-01 1.0 lymph nodes 1
3.1e-01 1 1.0 1 1.3 breast 7.8e-01 5.8e-01 9.1e-01 0.6 8.9e-01 0.7
ovary 3.8e-01 2.6e-01 3.2e-01 2.4 1.6e-01 2.5 pancreas 5.1e-01
3.3e-01 7.0e-01 0.9 1.0e-01 1.4 skin 6.0e-01 5.2e-01 9.7e-01 0.3 1
0.1 stomach 3.6e-01 3.0e-01 1 1.0 4.1e-01 1.8 Thyroid 5.0e-01
5.0e-01 6.7e-01 1.7 6.7e-01 1.7 uterus 1.1e-01 2.6e-01 2.1e-03 3.2
2.3e-02 2.2
[1412] As noted above, cluster F05068 features 3 transcript(s),
which were listed in Table 161 above. These transcript(s) encode
for protein(s) which are variant(s) of protein ADM precursor. A
description of each variant protein according to the present
invention is now provided.
[1413] Variant protein F05068_PEA.sub.--1_P7 (SEQ ID NO:1304)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
F05068_PEA.sub.--1_T3 (SEQ ID NO:25) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). An alignment is given to the known protein (ADM
precursor) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1414] Comparison report between F05068_PEA.sub.--1_P7 (SEQ ID
NO:1304) and ADML_HUMAN (SEQ ID NO:1423):
[1415] 1. An isolated chimeric polypeptide encoding for
F05068_PEA.sub.--1_P7 (SEQ ID NO:1304), comprising a first amino
acid sequence being at least 90% homologous to
MKLVSVALMYLGSLAFLGADTARLDVASEFRKK corresponding to amino acids 1-33
of ADML_HUMAN (SEQ ID NO:1423), which also corresponds to amino
acids 1-33 of F05068_PEA.sub.--1_P7 (SEQ ID NO:1304).
[1416] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1417] Variant protein F05068_PEA.sub.--1_P7 (SEQ ID NO:1304) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 167, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein F05068_PEA.sub.--1_P7
(SEQ ID NO:1304) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00194 TABLE 167 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
4 V -> F No 10 Y -> C No
[1418] Variant protein F05068PEA.sub.--1_P7 (SEQ ID NO:1304) is
encoded by the following transcript(s): F05068_PEA.sub.--1_T3 (SEQ
ID NO:25) and F05068_PEA.sub.--1_T6 (SEQ ID NO:27), for which the
sequence(s) is/are given at the end of the application.
[1419] The coding portion of transcript F05068_PEA.sub.--1_T3 (SEQ
ID NO:25) is shown in bold; this coding portion starts at position
267 and ends at position 365. The transcript also has the following
SNPs as listed in Table 168 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein F05068_PEA.sub.--1_P7
(SEQ ID NO:1304) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00195 TABLE 168 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
26 C -> T Yes 164 T -> No 593 G -> C Yes 860 C -> No
860 C -> A No 1022 G -> A No 1023 G -> A No 1023 G -> C
Yes 1084 G -> A Yes 1088 C -> No 1088 C -> A No 1106 C
-> No 177 T -> No 1106 C -> A No 1149 G -> No 1154 C
-> No 1171 T -> G Yes 1192 G -> No 1224 C -> No 1266 C
-> No 1282 C -> T No 1381 G -> A No 1450 T -> No 206 C
-> T Yes 1457 T -> G No 1534 C -> No 1535 C -> No 1554
A -> G Yes 1572 A -> C No 1572 A -> G No 1655 A -> C
Yes 1669 T -> C Yes 1721 C -> T No 245 G -> No 259 C ->
No 276 G -> T No 295 A -> G No 317 A -> C Yes 566 C ->
G Yes
[1420] The coding portion of transcript F05068_PEA.sub.--1_T6 (SEQ
ID NO:27) is shown in bold; this coding portion starts at position
267 and ends at position 365. The transcript also has the following
SNPs as listed in Table 169 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein F05068_PEA.sub.--1_P7
(SEQ ID NO:1304) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00196 TABLE 169 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
26 C -> T Yes 164 T -> No 593 G -> C Yes 739 C -> G Yes
1093 C -> No 1093 C -> A No 1255 G -> A No 1256 G -> A
No 1256 G -> C Yes 1317 G -> A Yes 1321 C -> No 1321 C
-> A No 177 T -> No 1339 C -> No 1339 C -> A No 1382 G
-> No 1387 C -> No 1404 T -> G Yes 1425 G -> No 1457 C
-> No 1499 C -> No 1515 C -> T No 1614 G -> A No 206 C
-> T Yes 1683 T -> No 1690 T -> G No 1767 C -> No 1768
C -> No 1787 A -> G Yes 1805 A -> C No 1805 A -> G No
1888 A -> C Yes 1902 T -> C Yes 1954 C -> T No 245 G ->
No 259 C -> No 276 G -> T No 295 A -> G No 317 A -> C
Yes 566 C -> G Yes
[1421] Variant protein F05068_PEA.sub.--1_P8 (SEQ ID NO:1305)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
F05068_PEA.sub.--1_T4 (SEQ ID NO:26). An alignment is given to the
known protein (ADM precursor) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1422] Comparison report between F05068_PEA.sub.--1_P8 (SEQ ID
NO:1305) and ADML_HUMAN (SEQ ID NO:1423):
[1423] 1. An isolated chimeric polypeptide encoding for
F05068_PEA.sub.--1_P8 (SEQ ID NO:1305), comprising a first amino
acid sequence being at least 90% homologous to
MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSSSYPTGLADVKAGPAQTLI
RPQDMKGASRSPED corresponding to amino acids 1-82 of ADML_HUMAN (SEQ
ID NO:1423), which also corresponds to amino acids 1-82 of
F05068_PEA.sub.--1_P8 (SEQ ID NO:1305), and a second amino acid
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence R corresponding to
amino acids 83-83 of F05068_PEA.sub.--1_P8 (SEQ ID NO:1305),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1424] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1425] Variant protein F05068_PEA.sub.--1_P8 (SEQ ID NO:1305) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 170, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein F05068PEA.sub.--1_P8 (SEQ
ID NO:1305) sequence provides support for the deduced sequence of
this variant protein according to the present invention).
TABLE-US-00197 TABLE 170 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
4 V -> F No 50 S -> R Yes 10 Y -> C No
[1426] Variant protein F05068_PEA.sub.--1_P8 (SEQ ID NO:1305) is
encoded by the following transcript(s): F05068_PEA.sub.--1_T4 (SEQ
ID NO:26), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript F05068_PEA.sub.--1_T4
(SEQ ID NO:26) is shown in bold; this coding portion position 267
and ends at position 515. The transcript also has the following
SNPs as listed in Table 171 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein F05068_PEA.sub.--1_P8
(SEQ ID NO:1305) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00198 TABLE 171 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
26 C -> T Yes 164 T -> No 443 G -> C Yes 589 C -> G Yes
943 C -> No 943 C -> A No 1105 G -> A No 1106 G -> A No
1106 G -> C Yes 1167 G -> A Yes 1171 C -> No 1171 C ->
A No 177 T -> No 1189 C -> No 1189 C -> A No 1232 G ->
No 1237 C -> No 1254 T -> G Yes 1275 G -> No 1307 C ->
No 1349 C -> No 1365 C -> T No 1464 G -> A No 206 C ->
T Yes 1533 T -> No 1540 T -> G No 1617 C -> No 1618 C
-> No 1637 A -> G Yes 1655 A -> C No 1655 A -> G No
1738 A -> C Yes 1752 T -> C Yes 1804 C -> T No 245 G ->
No 259 C -> No 276 G -> T No 295 A -> G No 317 A -> C
Yes 416 C -> G Yes
[1427] As noted above, cluster F05068 features 12 segment(s), which
were listed in Table 162 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1428] Segment cluster F05068_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1145) according to the present invention is supported by 143
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 172 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00199 TABLE 172 Segment location on transcripts Segment
Transcript name starting position Segment ending position
F05068_PEA_1_T3 1 245 (SEQ ID NO: 25) F05068_PEA_1_T4 1 245 (SEQ ID
NO: 26) F05068_PEA_1_T6 1 245 (SEQ ID NO: 27)
[1429] Segment cluster F05068_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:1146) according to the present invention is supported by 127
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 173 below describes the starting and ending
position segment on each transcript.
TABLE-US-00200 TABLE 173 Segment location on transcripts Segment
Transcript name starting position Segment ending position
F05068_PEA_1_T3 749 909 (SEQ ID NO: 25) F05068_PEA_1_T4 832 992
(SEQ ID NO: 26) F05068_PEA_1_T6 982 1142 (SEQ ID NO: 27)
[1430] Segment cluster F05068_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:1147) according to the present invention is supported by 123
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 174 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00201 TABLE 174 Segment location on transcripts Segment
Transcript name starting position Segment ending position
F05068_PEA_1_T3 986 1106 (SEQ ID NO: 25) F05068_PEA_1_T4 1069 1189
(SEQ ID NO: 26) F05068_PEA_1_T6 1219 1339 (SEQ ID NO: 27)
[1431] Segment cluster F05068_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:1148) according to the present invention is supported by 181
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 175 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00202 TABLE 175 Segment location on transcripts Segment
Transcript name starting position Segment ending position
F05068_PEA_1_T3 1107 1737 (SEQ ID NO: 25) F05068_PEA_1_T4 1190 1820
(SEQ ID NO: 26) F05068_PEA_1_T6 1340 1970 (SEQ ID NO: 27)
[1432] Segment cluster F05068_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1149) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25) and
F05068_PEA.sub.--1_T6 (SEQ ID NO:27). Table 176 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00203 TABLE 176 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 365 514 F05068_PEA_1_T6 (SEQ ID NO:
27) 365 514
[1433] Segment cluster F05068_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1150) according to the present invention is supported by 13
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and
F05068_PEA.sub.--1_T6 (SEQ ID NO:27). Table 177 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00204 TABLE 177 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T4 (SEQ ID NO: 26) 515 747 F05068_PEA_1_T6 (SEQ ID NO:
27) 665 897
[1434] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1435] Segment cluster F05068_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:1151) according to the present invention is supported by 112
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 178 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00205 TABLE 178 SegmentSegment location on transcripts
Segment starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 910 985 F05068_PEA_1_T4 (SEQ ID NO:
26) 993 1068 F05068_PEA_1_T6 (SEQ ID NO: 27) 1143 1218
[1436] Segment cluster F05068_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:1152) according to the present invention is supported by 145
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 179 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00206 TABLE 179 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 246 364 F05068_PEA_1_T4 (SEQ ID NO:
26) 246 364 F05068_PEA_1_T6 (SEQ ID NO: 27) 246 364
[1437] Segment cluster F05068_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1153) according to the present invention is supported by 124
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1T6 (SEQ
ID NO:27). Table 180 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00207 TABLE 180 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 515 573 F05068_PEA_1_T4 (SEQ ID NO:
26) 365 423 F05068_PEA_1_T6 (SEQ ID NO: 27) 515 573
[1438] Segment cluster F05068_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1154) according to the present invention is supported by 110
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 181 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00208 TABLE 181 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 574 613 F05068_PEA_1_T4 (SEQ ID NO:
26) 424 463 F05068_PEA_1_T6 (SEQ ID NO: 27) 574 613
[1439] Segment cluster F05068_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:1155) according to the present invention is supported by 109
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 182 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00209 TABLE 182 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 614 664 F05068_PEA_1_T4 (SEQ ID NO:
26) 464 514 F05068_PEA_1_T6 (SEQ ID NO: 27) 614 664
[1440] Segment cluster F05068_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:1156) according to the present invention is supported by 114
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): F05068_PEA.sub.--1_T3 (SEQ ID NO:25),
F05068_PEA.sub.--1_T4 (SEQ ID NO:26) and F05068_PEA.sub.--1_T6 (SEQ
ID NO:27). Table 183 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00210 TABLE 183 Segment location on transcripts Segment
starting Segment ending Transcript name position position
F05068_PEA_1_T3 (SEQ ID NO: 25) 665 748 F05068_PEA_1_T4 (SEQ ID NO:
26) 748 831 F05068_PEA_1_T6 (SEQ ID NO: 27) 898 981
Variant protein alignment to the previously known protein:
TABLE-US-00211 Sequence name: /tmp/kEsi3RWsCN/lsvdhjfiNV:ADML_HUMAN
(SEQ ID NO:1423) Sequence documentation: Alignment of:
F05068_PEA_1_P7 (SEQ ID NO:1304) x ADML_HUMAN (SEQ ID NO:1423)
Alignment segment 1/1: Quality: 304.00 Escore: 0 Matching length:
33 Total length: 33 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: . . . ##STR00167##
Sequence name: /tmp/tcrlWIx4kg/aghbr8Eh8n:ADML_HUMAN (SEQ ID
NO:1423) Sequence documentation: Alignment of: F05068_PEA_1_P8 (SEQ
ID NO:1305) x ADML_HUMAN (SEQ ID NO:1423) Alignment segment 1/1:
Quality: 791.00 Escore: 0 Matching length: 82 Total length: 82
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Matching Percent Similarity: 100.00 Total Percent IDentity:
100.00 Gaps: 0 Alignment: . . . . . ##STR00168## . . .
##STR00169##
Description for Cluster H14624
[1441] Cluster H14624 features 1 transcript(s) and 15 segment(s) of
interest, the names for which are given in Tables 184 and 185,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
186.
TABLE-US-00212 TABLE 184 Transcripts of interest Transcript Name
Sequence ID No. H14624_T20 28
TABLE-US-00213 TABLE 185 Segments of interest Segment Name Sequence
ID No. H14624_node_0 362 H14624_node_16 363 H14624_node_3 364
H14624_node_10 365 H14624_node_11 366 H14624_node_12 367
H14624_node_13 368 H14624_node_14 370 H14624_node_15 371
H14624_node_4 372 H14624_node_5 373 H14624_node_6 374 H14624_node_7
375 H14624_node_8 376 H14624_node_9 377
TABLE-US-00214 TABLE 186 Proteins of interest Protein Name Sequence
ID No. H14624_P15 1306
[1442] Cluster H14624 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 22 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1443] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 22 and Table 187. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: colorectal cancer, epithelial malignant
tumors, a mixture of malignant tumors from different tissues, lung
malignant tumors and pancreas carcinoma.
TABLE-US-00215 TABLE 187 Normal tissue distribution Name of Tissue
Number adrenal 0 bladder 410 bone 71 brain 42 colon 6 epithelial 91
general 74 head and neck 0 kidney 0 lung 30 breast 949 ovary 7
pancreas 2 prostate 94 stomach 3 Thyroid 128 uterus 54
TABLE-US-00216 TABLE 188 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 4.2e-01
4.6e-01 4.6e-01 2.2 5.3e-01 1.9 bladder 5.4e-01 6.0e-01 1.2e-02 1.6
2.2e-01 1.0 bone 4.9e-01 8.5e-01 1.8e-01 1.3 7.5e-01 0.6 brain
4.7e-01 7.0e-01 6.3e-05 2.3 9.4e-03 1.4 colon 4.4e-02 9.9e-02
4.5e-03 5.4 2.0e-02 3.9 epithelial 7.7e-03 3.6e-01 1.5e-11 2.0
2.9e-02 1.1 general 5.1e-03 5.9e-01 8.3e-21 2.2 1.5e-04 1.2 head
and neck 1.4e-01 2.8e-01 4.6e-01 2.2 7.5e-01 1.3 kidney 6.5e-01
7.2e-01 5.8e-01 1.7 7.0e-01 1.4 lung 6.1e-02 1.4e-01 3.3e-05 5.8
8.1e-03 2.9 breast 2.4e-01 4.1e-01 1 0.3 1 0.2 ovary 8.5e-01
7.3e-01 6.8e-01 1.2 1.6e-01 1.6 pancreas 7.5e-03 4.9e-02 1.2e-21
22.4 2.4e-16 15.1 prostate 8.3e-01 8.9e-01 7.2e-01 0.8 8.8e-01 0.6
stomach 4.6e-01 8.5e-01 1.0e-03 2.7 1.1e-01 1.4 Thyroid 7.0e-01
7.0e-01 5.9e-01 1.0 5.9e-01 1.0 uterus 4.1e-01 7.3e-01 2.3e-01 1.2
6.2e-01 0.7
[1444] As noted above, contig H14624 features 1 transcript(s),
which were listed in Table 184 above. A description of each variant
protein according to the present invention is now provided.
[1445] Variant protein H14624 P15 (SEQ ID NO:1306) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) H14624_T20 (SEQ ID
NO:28). One or more alignments to one or more previously published
protein sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1446] Comparison report between H14624_P15 (SEQ ID NO:1306) and
Q9HAP5 (SEQ ID NO:1701):
[1447] 1. An isolated chimeric polypeptide encoding for H14624 P15
(SEQ ID NO:1306), comprising a first amino acid sequence being at
least 90% homologous to
MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLCHGIEYQNMRLPNLLGHETMKE
VLEQAGAWIPVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCVQVKDRCAPVMSAFGFPWPDML
ECDRFPQDNDLCIPLASSDHLLPATEE corresponding to amino acids 1-167 of
Q9HAP5 (SEQ ID NO:1701), which also corresponds to amino acids
1-167 of H14624_P15 (SEQ ID NO:1306), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
GKPSLLLPHSLLG (SEQ ID NO: 1765) corresponding to amino acids
168-180 of H14624 P15 (SEQ ID NO:1306), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1448] 2. An isolated polypeptide encoding for a tail of H14624_P15
(SEQ ID NO:1306), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence GKPSLLLPHSLLG (SEQ ID NO: 1765) in
H14624_P15 (SEQ ID NO:1306).
[1449] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1450] Variant protein H14624 P15 (SEQ ID NO:1306) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 189, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein H14624_P15 (SEQ ID NO:1306)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00217 TABLE 189 Amino acid mutations SNP position(s) on
amino Alternative amino acid sequence acid(s) Previously known SNP?
11 L -> No 170 P -> S Yes 28 F -> No 29 G -> No 38 S
-> No 45 A -> V Yes 60 L -> No
[1451] Variant protein H14624_P15 (SEQ ID NO:1306) is encoded by
the following transcript(s): H14624_T20 (SEQ ID NO:28), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript H14624_T20 (SEQ ID NO:28) is shown in
bold; this coding portion starts at position 857 and ends at
position 1396. The transcript also has the following SNPs as listed
in Table 190 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein H14624_P15 (SEQ ID NO:1306) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00218 TABLE 190 Nucleic acid SNPs SNP position on
Alternative nucleic nucleotide sequence acid Previously known SNP?
389 A -> G No 476 C -> T No 969 G -> No 988 G -> T Yes
990 C -> T Yes 1034 C -> No 1168 C -> T Yes 1364 C -> T
Yes 488 T -> C No 819 C -> G Yes 851 C -> No 887 C ->
No 922 G -> A Yes 934 C -> T Yes 938 T -> No 943 C ->
No
[1452] As noted above, cluster H14624 features 15 segment(s), which
were listed in Table 185 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1453] Segment cluster H14624_node.sub.--0 (SEQ ID NO:1157)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): H14624_T20
(SEQ ID NO:28). Table 191 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00219 TABLE 191 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1 573
[1454] Segment cluster H14624_node.sub.--16 (SEQ ID NO:1158)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): H14624_T20
(SEQ ID NO:28). Table 192 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00220 TABLE 192 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1359 1745
[1455] Segment cluster H14624_node.sub.--3 (SEQ ID NO:1159)
according to the present invention is supported by 67 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 193 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00221 TABLE 193 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 574 822
[1456] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1457] Segment cluster H14624_node.sub.--10 (SEQ ID NO:1160)
according to the present invention can be found in the following
transcript(s): H14624_T20 (SEQ ID NO:28). Table 194 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00222 TABLE 194 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1070 1079
[1458] Segment cluster H14624_node.sub.--11 (SEQ ID NO:1161)
according to the present invention is supported by 99 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 195 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00223 TABLE 195 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1080 1114
[1459] Segment cluster H14624_node.sub.--12 (SEQ ID NO:1162)
according to the present invention can be found in the following
transcript(s): H14624_T20 (SEQ ID NO:28). Table 196 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00224 TABLE 196 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1115 1135
[1460] Segment cluster H14624_node.sub.--13 (SEQ ID NO:1163)
according to the present invention is supported by 124 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 197 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00225 TABLE 197 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1136 1227
[1461] Segment cluster H14624_node.sub.--14 (SEQ ID NO:1164)
according to the present invention is supported by 114 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 198 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00226 TABLE 198 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1228 1287
[1462] Segment cluster H14624_node.sub.--15 (SEQ ID NO:1165)
according to the present invention is supported by 124 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 199 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00227 TABLE 199 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1288 1358
[1463] Segment cluster H14624_node.sub.--4 (SEQ ID NO:1166)
according to the present invention is supported by 65 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 200 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00228 TABLE 200 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 823 892
[1464] Segment cluster H14624_node.sub.--5 (SEQ ID NO:1167)
according to the present invention can be found in the following
transcript(s): H14624_T20 (SEQ ID NO:28). Table 201 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00229 TABLE 201 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 893 903
[1465] Segment cluster H14624_node.sub.--6 (SEQ ID NO:1168)
according to the present invention can be found in the following
transcript(s): H14624_T20 (SEQ ID NO:28). Table 202 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00230 TABLE 202 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 904 927
[1466] Segment cluster H14624_node.sub.--7 (SEQ ID NO:1169)
according to the present invention can be found in the following
transcript(s): H14624_T20 (SEQ ID NO:28). Table 203 below describes
the starting and ending position of this segment on
each,transcript.
TABLE-US-00231 TABLE 203 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 928 934
[1467] Segment cluster H14624_node.sub.--8 (SEQ ID NO:1170)
according to the present invention is supported by 85 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 204 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00232 TABLE 204 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 935 1014
[1468] Segment cluster H14624_node.sub.--9 (SEQ ID NO:1171)
according to the present invention is supported by 87 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
H14624_T20 (SEQ ID NO:28). Table 205 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00233 TABLE 205 Segment location on transcripts Segment
starting Segment ending Transcript name position position
H14624_T20 (SEQ ID NO: 28) 1015 1069
[1469] Variant protein alignment to the previously known
protein:
TABLE-US-00234 Sequence name: /tmp/Upb1SbFkrj/N4PrGQAB2V:Q9HAP5
(SEQ ID NO: 1701) Sequence documentation: Alignment of: H14624_P15
(SEQ ID NO: 1306) .times. Q9HAP5 (SEQ ID NO: 1701) . . . Alignment
segment 1/1: Quality: 1702.00 Escore: 0 Matching length: 167 Total
length: 167 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00170## ##STR00171##
##STR00172## ##STR00173##
Description for Cluster H38804
[1470] Cluster H38804 features 2 transcript(s) and 20 segment(s) of
interest, the names for which are given in Tables 206 and 207,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
208.
TABLE-US-00235 TABLE 206 Transcripts of interest Transcript name
Sequence ID No. H38804_PEA_1_T24 29 H38804_PEA_1_T8 30
TABLE-US-00236 TABLE 207 Segments of interest Segment Name Sequence
ID No. H38804_PEA_1_node_0 378 H38804_PEA_1_node_1 379
H38804_PEA_1_node_16 380 H38804_PEA_1_node_19 381
H38804_PEA_1_node_24 382 H38804_PEA_1_node_25 383
H38804_PEA_1_node_28 384 H38804_PEA_1_node_29 385
H38804_PEA_1_node_30 386 H38804_PEA_1_node_10 387
H38804_PEA_1_node_12 388 H38804_PEA_1_node_13 389
H38804_PEA_1_node_14 390 H38804_PEA_1_node_2 391
H38804_PEA_1_node_20 392 H38804_PEA_1_node_23 393
H38804_PEA_1_node_26 394 H38804_PEA_1_node_3 395
H38804_PEA_1_node_4 396 H38804_PEA_1_node_5 397
TABLE-US-00237 TABLE 208 Proteins of interest Segment Name Sequence
ID No. H38804_PEA_1_P5 1307 H38804_PEA_1_P17 1308
[1471] These sequences are variants of the known protein Mitotic
checkpoint protein BUB3 (SwissProt accession identifier
BUB3_HUMAN), SEQ ID NO:1424, referred to herein as the previously
known protein. Protein Mitotic checkpoint protein BUB3 (SEQ ID
NO:1424) is known or believed to have the following function(s):
Required for kinetochore localization of BUB1. The sequence for
protein Mitotic checkpoint protein BUB3 is given at the end of the
application, as "Mitotic checkpoint protein BUB3 amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 209
TABLE-US-00238 TABLE 209 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 326-327 Missing
[1472] Protein Mitotic checkpoint protein BUB3 (SEQ ID NO:1424)
localization is believed to be Nuclear.
[1473] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: mitosis; mitotic
checkpoint; mitotic spindle checkpoint; cell proliferation, which
are annotation(s) related to Biological Process; and nucleus, which
are annotation(s) related to Cellular Component.
[1474] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1475] Cluster H38804 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 23 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1476] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 23 and Table 210. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: transitional cell carcinoma, brain
malignant tumors, a mixture of malignant tumors from different
tissues and gastric carcinoma.
TABLE-US-00239 TABLE 210 Normal tissue distribution Name of Tissue
Number adrenal 124 bladder 0 bone 64 brain 40 colon 75 epithelial
86 general 79 head and neck 334 kidney 69 liver 14 lung 125 lymph
nodes 218 breast 263 bone marrow 62 muscle 27 ovary 109 pancreas 43
prostate 32 skin 53 stomach 0 T cells 557 Thyroid 257 uterus
113
TABLE-US-00240 TABLE 211 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 6.3e-01
5.4e-01 1.8e-01 1.4 5.0e-02 1.9 bladder 7.0e-02 2.6e-02 3.2e-02 4.9
9.9e-03 6.2 bone 3.7e-01 2.3e-01 7.9e-01 0.9 3.2e-01 1.6 brain
3.1e-02 4.2e-03 5.3e-01 1.2 1.1e-02 2.1 colon 2.4e-01 1.1e-01
2.0e-01 1.7 1.6e-01 1.8 epithelial 1.1e-01 2.2e-02 1.5e-01 1.2
8.6e-03 1.3 general 2.3e-02 2.3e-04 9.0e-02 1.2 4.7e-05 1.4 head
and neck 4.4e-01 4.7e-01 9.2e-01 0.6 8.9e-01 0.5 kidney 8.2e-01
8.4e-01 9.0e-01 0.8 3.5e-01 1.0 liver 8.3e-01 1.5e-01 1 0.8 5.3e-02
2.8 lung 6.9e-01 8.1e-01 5.1e-01 1.1 6.0e-01 0.8 lymph nodes
5.1e-01 6.9e-01 5.0e-01 0.9 9.5e-01 0.5 breast 4.9e-01 4.2e-01
9.7e-01 0.5 9.5e-01 0.5 bone marrow 6.7e-01 5.4e-01 1 1.5 3.3e-02
2.6 muscle 8.5e-01 6.1e-01 1 0.4 6.3e-01 1.0 ovary 3.4e-01 3.3e-01
2.5e-01 1.5 4.7e-01 1.1 pancreas 4.3e-01 4.9e-01 6.3e-01 1.0
6.9e-01 0.9 prostate 7.4e-01 6.5e-01 1.5e-01 1.9 1.0e-01 2.0 skin
6.0e-01 1.7e-01 5.4e-01 1.4 2.7e-02 1.2 stomach 4.5e-02 9.9e-03
2.5e-01 3.1 4.3e-02 4.3 T cells 5.0e-01 6.7e-01 1 0.3 9.8e-01 0.5
Thyroid 5.7e-01 5.7e-01 1 0.4 1 0.4 uterus 5.7e-01 6.7e-01 9.2e-01
0.6 8.7e-01 0.5
[1477] As noted above, cluster H38804 features 2 transcript(s),
which were listed in Table 206 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Mitotic checkpoint
protein BUB3 (SEQ ID NO:1424). A description of each variant
protein according to the present invention is now provided. Variant
protein H38804_PEA.sub.--1_P5 (SEQ ID NO:1307) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s)
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). An alignment is given to the
known protein (Mitotic checkpoint protein BUB3 (SEQ ID NO:1424)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1478] Comparison report between H38804_PEA.sub.--1_P5 (SEQ ID
NO:1307) and BUB3_HUMAN (SEQ ID NO:1424):
[1479] 1. An isolated chimeric polypeptide encoding for
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ
(SEQ ID NO: 1766) corresponding to amino acids 1-57 of
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), and a second amino acid
sequence being at least 90% homologous to
[1480]
MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMRLKYQHTGAVLDCAFYDP-
THA
WSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPE
KVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYL
DPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIA
SLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPK corresponding to amino
acids 1-324 of BUB3_HUMAN (SEQ ID NO:1424), which also corresponds
to amino acids 58-381 of H38804_PEA.sub.--1_P5 (SEQ ID NO:1307),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1481] 2. An isolated polypeptide encoding for a head of
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ (SEQ ID
NO: 1766) of H38804_PEA.sub.--1_P5 (SEQ ID NO:1307).
[1482] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Signal peptide,NN:NO) predicts that this
protein has a signal peptide.
[1483] Variant protein H38804_PEA.sub.--1_P5 (SEQ ID NO:1307) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 212, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein H38804_PEA.sub.--1_P5
(SEQ ID NO:1307) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00241 TABLE 212 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 126 H -> Y No 129 S -> R Yes 256 I -> No 256 I ->
N No 258 G -> No 266 D -> No 266 D -> E No 266 D -> N
Yes 296 A -> G No 296 A -> V No 306 F -> C No 314 F ->
No 215 R -> K No 361 T -> A No 381 K -> No 217 L -> No
220 D -> No 220 D -> E No 245 F -> No 245 F -> V No 248
K -> No 248 K -> Q No
[1484] Variant protein H38804_PEA.sub.--1_P5 (SEQ ID NO:1307) is
encoded by the following transcript(s): H38804_PEA.sub.--1_T8 (SEQ
ID NO:30), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript H38804_PEA.sub.--1_T8
(SEQ ID NO:30) is shown in bold; this coding portion starts at
position 475 and ends at position 1617. The transcript also has the
following SNPs as listed in Table 213 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
H38804_PEA.sub.--1_P5 (SEQ ID NO:1307) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00242 TABLE 213 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 161 C
-> No 167 C -> No 1118 G -> A No 1123 T -> No 1134 C
-> No 1134 C -> A No 1207 T -> No 1207 T -> G No 1216 A
-> No 1216 A -> C No 1241 T -> No 1241 T -> A No 167 C
-> A No 1248 C -> No 1248 C -> G No 1270 G -> A Yes
1272 C -> No 1272 C -> A No 1361 C -> G No 1361 C -> T
No 1391 T -> G No 1414 T -> No 1419 A -> G No 192 T ->
No 1555 A -> G No 1615 A -> No 1642 G -> A Yes 1846 T
-> C Yes 2090 A -> G No 2356 C -> G No 2712 G -> No
2909 T -> C No 2909 T -> G No 3020 T -> G No 208 C -> T
Yes 3251 T -> No 3306 T -> No 3307 T -> G No 3354 T ->
No 3521 -> G No 3601 C -> No 3601 C -> G No 3633 T ->
No 3633 T -> G No 3638 A -> No 849 G -> T No 3638 A ->
C No 3674 C -> T Yes 3812 T -> G No 3862 G -> A Yes 3864 T
-> A No 3865 T -> A No 3990 T -> G No 4096 T -> G No
4152 G -> A Yes 850 C -> T No 855 C -> T Yes 861 T -> G
Yes 1098 T -> C No
[1485] Variant protein H38804_PEA.sub.--1_P17 (SEQ ID NO:1308)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
H38804_PEA.sub.--1_T24 (SEQ ID NO:29). An alignment is given to the
known protein (Mitotic checkpoint protein BUB3 (SEQ ID NO:1424)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1486] Comparison report between H38804_PEA.sub.--1_P17 (SEQ ID
NO:1308) and BUB3_HUMAN (SEQ ID NO:1424):
[1487] 1. An isolated chimeric polypeptide encoding for
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ
(SEQ ID NO: 1766) corresponding to amino acids 1-57 of
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), and a second amino acid
sequence being at least 90% homologous to
MTGSNEFKLNQPPEDGISSVKFSPNTSQFLLVSSWDTSVRLYDVPANSMRLKYQHTGAVLDCAFYDPTHA
WSGGLDHQLKMHDLNTDQENLVGTHDAPIRCVEYCPEVNVMVTGSWDQTVKLWDPRTPCNAGTFSQPE
KVYTLSVSGDRLIVGTAGRRVLVWDLRNMGYVQQRRESSLKYQTRCIRAFPNKQGYVLSSIEGRVAVEYL
DPSPEVQKKKYAFKCHRLKENNIEQIYPVNAISFHNIHNTFATGGSDGFVNIWDPFNKKRLCQFHRYPTSIA
SLAFSNDGTTLAIASSYMYEMDDTEHPEDGIFIRQVTDAETKPKSPCT corresponding to
amino acids 1-328 of BUB3_HUMAN (SEQ ID NO:1424), which also
corresponds to amino acids 58-385 of H38804_PEA.sub.--1_P17 (SEQ ID
NO:1308), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1488] 2. An isolated polypeptide encoding for a head of
H38804_PEA.sub.--1_P17 (SEQ ID NO:1308), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGRVRTLAGECSAQAQAQSLLAVVLSAPPSGGTPSARLSVRSPSPRDPWGLWAPVLQ (SEQ ID
NO: 1766) of H38804_PEA.sub.--1_P17 (SEQ ID NO:1308).
[1489] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Signal peptide,NN:NO) predicts that this
protein has a signal peptide.
[1490] Variant protein H38804_PEA.sub.--1_P17 (SEQ ID NO:1308) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 214, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein H38804_PEA.sub.--1_P17
(SEQ ID NO:1308) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00243 TABLE 214 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 126 H -> Y No 129 S -> R Yes 256 I -> No 256 I ->
N No 258 G -> No 266 D -> No 266 D -> E No 266 D -> N
Yes 296 A -> G No 296 A -> V No 306 F -> C No 314 F ->
No 215 R -> K No 361 T -> A No 381 K -> No 217 L -> No
220 D -> No 220 D -> E No 245 F -> No 245 F -> V No 248
K -> No 248 K -> Q No
[1491] Variant protein H38804_PEA.sub.--1_P17 (SEQ ID NO:1308) is
encoded by the following transcript(s): H38804.sub.--l
PEA.sub.--1_T24 (SEQ ID NO:29), for which the sequence(s) is/are
given at the end of the application. The coding portion of
transcript H38804_PEA.sub.--1_T24 (SEQ ID NO:29) is shown in bold;
this coding portion stars at position 475 and ends at position
1629. The transcript also has the following SNPs as listed in Table
215 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein H38804_PEA.sub.--1_P17 (SEQ ID NO:1308) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00244 TABLE 215 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 161 C
-> No 167 C -> No 1118 G -> A No 1123 T -> No 1134 C
-> No 1134 C -> A No 1207 T -> No 1207 T -> G No 1216 A
-> No 1216 A -> C No 1241 T -> No 1241 T -> A No 167 C
-> A No 1248 C -> No 1248 C -> G No 1270 G -> A Yes
1272 C -> No 1272 C -> A No 1361 C -> G No 1361 C -> T
No 1391 T -> G No 1414 T -> No 1419 A -> G No 192 T ->
No 1555 A -> G No 1615 A -> No 1721 G -> No 1918 T -> C
No 1918 T -> G No 2029 T -> G No 2260 T -> No 2315 T ->
No 2316 T -> G No 2363 T -> No 208 C -> T Yes 2530 -> G
No 2610 C -> No 2610 C -> G No 2642 T -> No 2642 T -> G
No 2647 A -> No 2647 A -> C No 2683 C -> T Yes 2821 T
-> G No 2871 G -> A Yes 849 G -> T No 2873 T -> A No
2874 T -> A No 2999 T -> G No 3105 T -> G No 3161 G ->
A Yes 850 C -> T No 855 C -> T Yes 861 T -> G Yes 1098 T
-> C No
[1492] As noted above, cluster H38804 features 20 segment(s), which
were listed in Table 2 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1493] Segment cluster H38804_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1172) according to the present invention is supported by 125
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 216 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00245 TABLE 216 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1 213 H38804_PEA_1_T8 (SEQ ID NO:
30) 1 213
[1494] Segment cluster H38804_PEA.sub.--1_node.sub.--1 (SEQ ID
NO:1173) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 217 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00246 TABLE 217 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 214 645 H38804_PEA_1_T8 (SEQ ID
NO: 30) 214 645
[1495] Segment cluster H38804_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:1174) according to the present invention is supported by 214
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 218 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00247 TABLE 218 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1063 1221 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1063 1221
[1496] Segment cluster H38804_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:1175) according to the present invention is supported by 198
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 219 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00248 TABLE 219 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1222 1360 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1222 1360
[1497] Segment cluster H38804_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1176) according to the present invention is supported by 180
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 220 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00249 TABLE 220 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1421 1616 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1421 1616
[1498] Segment cluster H38804_PEA.sub.--1_node.sub.--25 (SEQ ID
NO.1177) according to the present invention is supported by 28
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 221
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00250 TABLE 221 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T8 (SEQ ID NO: 30) 1617 1969
[1499] Segment cluster H38804_PEA.sub.--1_node.sub.--28 (SEQ ID
NO:1178) according to the present invention is supported by 38
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 222
below describes the staring and ending position of this segment on
each transcript.
TABLE-US-00251 TABLE 222 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T8 (SEQ ID NO: 30) 2018 2607
[1500] Segment cluster H38804_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:1179) according to the present invention is supported by 259
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 223 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00252 TABLE 223 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1617 2844 H38804_PEA_1_T8 (SEQ ID
NO: 30) 2608 3835
[1501] Segment cluster H38804_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:1180) according to the present invention is supported by 169
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 224 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00253 TABLE 224 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 2845 3170 H38804_PEA_1_T8 (SEQ ID
NO: 30) 3836 4161
[1502] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1503] Segment cluster H38804_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:1181) according to the present invention is supported by 179
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 225 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00254 TABLE 225 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 841 910 H38804_PEA_1_T8 (SEQ ID
NO: 30) 841 910
[1504] Segment cluster H38804_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:1182) according to the present invention is supported by 181
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 226 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00255 TABLE 226 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 911 949 H38804_PEA_1_T8 (SEQ ID
NO: 30) 911 949
[1505] Segment cluster H38804_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:1183) according to the present invention is supported by 187
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 227 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00256 TABLE 227 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 950 1028 H38804_PEA_1_T8 (SEQ ID
NO: 30) 950 1028
[1506] Segment cluster H38804_PEA.sub.--1_node.sub.--14 (SEQ ID
NO:1184) according to the present invention is supported by 179
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 228 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00257 TABLE 228 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1029 1062 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1029 1062
[1507] Segment cluster H38804_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1185) according to the present invention is supported by 156
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 229 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00258 TABLE 229 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 646 678 H38804_PEA_1_T8 (SEQ ID
NO: 30) 646 678
[1508] Segment cluster H38804_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:1186) according to the present invention is supported by 162
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 230 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00259 TABLE 230 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1361 1399 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1361 1399
[1509] Segment cluster H38804_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:1187) according to the present invention can be found in the
following transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 231 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00260 TABLE 231 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 1400 1420 H38804_PEA_1_T8 (SEQ ID
NO: 30) 1400 1420
[1510] Segment cluster H38804_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:1188) according to the present invention is supported by 21
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804PEA.sub.--1_T8 (SEQ ID NO:30). Table 232 below
describes the stargin and ending position of this segment on each
transcript.
TABLE-US-00261 TABLE 232 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T8 (SEQ ID NO: 30) 1970 2017
[1511] Segment cluster H38804_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:1189) according to the present invention is supported by 162
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 233 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00262 TABLE 233 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 679 716 H38804_PEA_1_T8 (SEQ ID
NO: 30) 679 716
[1512] Segment cluster H38804_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1190) according to the present invention is supported by 172
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 234 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00263 TABLE 234 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 717 827 H38804_PEA_1_T8 (SEQ ID
NO: 30) 717 827
[1513] Segment cluster H38804_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1191) according to the present invention can be found in the
following transcript(s): H38804_PEA.sub.--1_T24 (SEQ ID NO:29) and
H38804_PEA.sub.--1_T8 (SEQ ID NO:30). Table 235 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00264 TABLE 235 Segment location on transcripts Segment
Segment ending Transcript name starting position position
H38804_PEA_1_T24 (SEQ ID NO: 29) 828 840 H38804_PEA_1_T8 (SEQ ID
NO: 30) 828 840
[1514] Variant protein alignment to the previously known
protein:
TABLE-US-00265 Sequence name: /tmp/RR4oV8zYLg/QlORqeqpIp:BUB3_HUMAN
(SEQ ID NO: 1424) Sequence documentation: Alignment of:
H38804_PEA_1_P5 (SEQ ID NO: 1307) .times. BUB3_HUMAN (SEQ ID NO:
1424) Alignment segment 1/1: Quality: 3244.00 Escore: 0 Matching
length: 324 Total length: 324 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00174##
##STR00175## ##STR00176## ##STR00177## ##STR00178## ##STR00179##
##STR00180## Sequence name: /tmp/Db0dQEpSuo/Lr8HPXaeBg:BUB3_HUMAN
(SEQ ID NO: 1424) Sequence documentation: Alignment of:
H38804_PEA_1_P17 (SEQ ID NO: 1308) .times. BUB3_HUMAN (SEQ ID NO:
1424) . . . Alignment segment 1/1: Quality: 3288.00 Escore: 0
Matching length: 328 Total length: 328 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00181## ##STR00182## ##STR00183## ##STR00184## ##STR00185##
##STR00186## ##STR00187##
Description for Cluster HSENA78
[1515] Cluster HSENA78 features 1 transcript(s) and 7 segment(s) of
interest, the names for which are given in Tables 236 and 237,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
238.
TABLE-US-00266 TABLE 236 Transcripts of interest Transcript Name
Sequence ID No. HSENA78_T5 31
TABLE-US-00267 TABLE 237 Segments of interest Segment Name Sequence
ID No. HSENA78_node_0 398 HSENA78_node_2 399 HSENA78_node_6 400
HSENA78_node_9 401 HSENA78_node_3 402 HSENA78_node_4 403
HSENA78_node_8 404
TABLE-US-00268 TABLE 238 Proteins of interest Protein Name Sequence
ID No. HSENA78_P2 1309
[1516] These sequences are variants of the known protein Small
inducible cytokine B5 precursor (SwissProt accession identifier
SZ05_HUMAN; known also according to the synonyms CXCL5;
Epithelial-derived neutrophil activating protein 78;
Neutrophil-activating peptide ENA-78), SEQ ID NO: 1425, referred to
herein as the previously known protein.
[1517] Protein Small inducible cytokine B5 precursor (SEQ ID
NO:1425) is known or believed to have the following function(s):
Involved in neutrophil activation. The sequence for protein Small
inducible cytokine B5 precursor is given at the end of the
application, as "Small inducible cytokine B5 precursor amino acid
sequence". Protein Small inducible cytokine B5 precursor
localization is believed to be Secreted.
[1518] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: chemotaxis; signal
transduction; cell-cell signaling; positive control of cell
proliferation, which are annotation(s) related to Biological
Process; and chemokine, which are annotation(s) related to
Molecular Function.
[1519] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1520] Cluster HSENA78 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 24 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1521] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 24 and Table 239. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors and lung
malignant tumors.
TABLE-US-00269 TABLE 239 Normal tissue distribution Name of Tissue
Number colon 0 epithelial 2 general 38 kidney 0 lung 3 breast 8
skin 0 stomach 36 uterus 4
TABLE-US-00270 TABLE 240 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 colon 2.6e-01
3.3e-01 1.7e-01 2.7 2.7e-01 2.2 epithelial 2.5e-01 9.0e-02 3.2e-03
4.1 8.5e-07 5.5 general 8.4e-01 7.2e-01 1 0.3 1 0.4 kidney 1
7.2e-01 1 1.0 1.7e-01 1.9 lung 8.5e-01 4.8e-01 4.1e-01 1.9 4.0e-05
3.8 breast 9.5e-01 8.7e-01 1 0.8 6.8e-01 1.2 skin 2.9e-01 4.7e-01
1.4e-01 7.0 6.4e-01 1.6 stomach 5.0e-01 4.3e-01 7.5e-01 1.0 4.3e-01
1.3 uterus 7.1e-01 8.5e-01 6.6e-01 1.3 8.0e-01 1.0
[1522] As noted above, cluster HSENA78 features 1 transcnpt(s),
which were listed in Table 236 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Small inducible
cytokine B5 precursor (SEQ ID NO:1425). A description of each
variant protein according to the present invention is now
provided.
[1523] Variant protein HSENA78_P2 (SEQ ID NO:1309) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) HSENA78_T5 (SEQ ID
NO:31). An alignment is given to the known protein (Small inducible
cytokine B5 precursor (SEQ ID NO:1425)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1524] Comparison report between HSENA78_P2 (SEQ ID NO:1309) and
SZ05_HUMAN (SEQ ID NO:1425):
[1525] 1. An isolated chimeric polypeptide encoding for HSENA78_P2
(SEQ ID NO:1309), comprising a first amino acid sequence being at
least 90% homologous to
MSLLSSRAARVPGPSSSLCALLVLLLLLTQPGPIASAGPAAAVLRELRCVCLQTTQGVHPKMISNLQVFAIG
PQCSKVEVV corresponding to amino acids 1-81 of SZ05_HUMAN (SEQ ID
NO:1425), which also corresponds to amino acids 1-81 of HSENA78_P2
(SEQ ID NO:1309).
[1526] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1527] Variant protein HSENA78_P2 (SEQ ID NO:1309) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 241, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSENA78_P2 (SEQ ID NO:1309)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00271 TABLE 241 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
80 V -> No 81 V -> No
[1528] Variant protein HSENA78_P2 (SEQ ID NO:1309) is encoded by
the following transcript(s): HSENA78_T5 (SEQ ID NO:31), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript HSENA78_T5 (SEQ ID NO:31) is shown in
bold; this coding portion starts at position 149 and ends at
position 391. The transcript also has the following SNPs as listed
in Table 242 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HSENA78_P2 (SEQ ID NO:1309) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00272 TABLE 242 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
92 C -> T Yes 144 C -> T No 1151 A -> T Yes 1389 T -> C
No 1867 C -> G Yes 145 C -> T No 181 C -> T Yes 316 G
-> A Yes 388 G -> No 390 T -> No 605 T -> No 972 C
-> T Yes 1105 A -> G Yes
[1529] As noted above, cluster HSENA78 features 7 segment(s), which
were listed in Table 237 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1530] Segment cluster HSENA78_node.sub.--0 (SEQ ID NO:1192)
according to the present invention is supported by 24 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSENA78_T5 (SEQ ID NO:31). Table 243 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00273 TABLE 243 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 1 257
[1531] Segment cluster HSENA78_node.sub.--2 (SEQ ID NO:1193)
according to the present invention is supported by 22 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSENA78_T5 (SEQ ID NO:31). Table 244 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00274 TABLE 244 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 258 390
[1532] Segment cluster HSENA78_node.sub.--6 (SEQ ID NO:1194)
according to the present invention is supported by 68 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSENA78_T5 (SEQ ID NO:31). Table 245 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00275 TABLE 245 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 585 2370
[1533] Segment cluster HSENA78_node.sub.--9 (SEQ ID NO:1195)
according to the present invention is supported by 28 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSENA78_T5 (SEQ ID NO:31). Table 246 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00276 TABLE 246 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 2394 2546
[1534] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1535] Segment cluster HSENA78_node.sub.--3 (SEQ ID NO:1196)
according to the present invention is supported by 1 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HSENA78_T5
(SEQ ID NO:31). Table 247 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00277 TABLE 247 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 391 500
[1536] Segment cluster HSENA78_node.sub.--4 (SEQ ID NO:1197)
according to the present invention is supported by 17 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSENA78_T5 (SEQ ID NO:31). Table 248 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00278 TABLE 248 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 501 584
[1537] Segment cluster HSENA78_node.sub.--8 (SEQ ID NO:1198)
according to the present invention can be found in the following
transcript(s): HSENA78_T5 (SEQ ID NO:31). Table 249 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00279 TABLE 249 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSENA78_T5 (SEQ ID NO: 31) 2371 2393
[1538] Variant protein alignment to the previously known
protein:
TABLE-US-00280 Sequence name: /tmp/5kiQY6MxWx/pLnTrxsCqk:SZ05_HUMAN
(SEQ ID NO: 1425) Sequence documentation: Alignment of: HSENA78_P2
(SEQ ID NO: 1309) .times. SZ05_HUMAN (SEQ ID NO: 1425) Alignment
segment 1/1: Quality: 767.00 Escore: 0 Matching length: 81 Total
length: 81 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00188## ##STR00189##
Description for Cluster HUMODCA
[1539] Cluster HUMODCA features 1 transcript(s) and 17 segment(s)
of interest, the names for which are given in Tables 250 and 251,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
252.
TABLE-US-00281 TABLE 250 Transcripts of interest Transcript name
Sequence ID No. HUMODCA_T17 32
TABLE-US-00282 TABLE 251 Segments of interest Segment Name Sequence
ID No. HUMODCA_node_1 405 HUMODCA_node_25 406 HUMODCA_node_32 407
HUMODCA_node_36 408 HUMODCA_node_39 409 HUMODCA_node_41 410
HUMODCA_node_0 411 HUMODCA_node_10 412 HUMODCA_node_12 413
HUMODCA_node_13 414 HUMODCA_node_2 415 HUMODCA_node_27 416
HUMODCA_node_3 417 HUMODCA_node_30 418 HUMODCA_node_34 419
HUMODCA_node_38 420 HUMODCA_node_40 421
TABLE-US-00283 TABLE 252 Proteins of interest Protein Name Sequence
ID No. HUMODCA_P9 1310
[1540] These sequences are variants of the known protein Ornithine
decarboxylase (SwissProt accession identifier DCOR_HUMAN; known
also according to the synonyms EC 4.1.1.17; ODC), SEQ ID NO: 1426,
referred to herein as the previously known protein.
[1541] Protein Ornithine decarboxylase (SEQ ID NO:1426) is known or
believed to have the following function(s): Polyamine biosynthesis;
first (rate-limiting) step. The sequence for protein Ornithine
decarboxylase (SEQ ID NO:1426) is given at the end of the
application, as "Ornithine decarboxylase (SEQ ID NO:1426) amino
acid sequence". Known polymorphisms for this sequence are as shown
in Table 253.
TABLE-US-00284 TABLE 253 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 415 Q -> E
[1542] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: polyamine
biosynthesis, which are annotation(s) related to Biological
Process; and ornithine decarboxylase; lyase, which are
annotation(s) related to Molecular Function.
[1543] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1544] Cluster HUMODCA can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 25 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1545] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 25 and Table 254. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: brain malignant tumors, colorectal cancer,
epithelial malignant tumors and a mixture of malignant tumors from
different tissues.
TABLE-US-00285 TABLE 254 Normal tissue distribution Name of Tissue
Number adrenal 120 bladder 82 bone 161 brain 53 colon 0 epithelial
107 general 94 head and neck 10 kidney 114 liver 107 lung 120 lymph
nodes 165 breast 61 bone marrow 156 muscle 55 ovary 36 pancreas 102
prostate 140 skin 188 stomach 109 T cells 278 Thyroid 128 uterus
118
TABLE-US-00286 TABLE 255 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 8.3e-01
7.8e-01 1 0.2 8.5e-01 0.7 bladder 5.4e-01 5.1e-01 6.2e-01 1.1
5.0e-01 1.1 bone 8.3e-01 3.2e-01 1 0.2 8.4e-01 0.7 brain 2.6e-01
3.8e-02 6.5e-04 2.8 8.7e-10 3.6 colon 2.2e-02 5.8e-03 1.5e-03 6.9
6.7e-05 9.9 epithelial 6.4e-02 2.7e-03 1.4e-03 1.5 1.6e-12 2.1
general 1.3e-03 5.4e-08 1.9e-08 1.7 1.4e-39 2.6 head and neck
1.7e-01 1.7e-01 1 1.2 7.5e-01 1.3 kidney 7.7e-01 7.6e-01 7.1e-01
0.8 6.6e-01 0.9 liver 7.3e-01 5.7e-01 1 0.3 2.4e-01 1.2 lung
7.8e-01 5.8e-01 7.6e-01 0.6 7.3e-04 1.7 lymph nodes 3.9e-01 2.5e-01
1.8e-01 1.1 1.4e-04 2.1 breast 7.8e-01 4.7e-01 7.7e-01 0.8 6.4e-01
1.0 bone marrow 3.4e-01 2.6e-01 2.8e-01 2.1 1.6e-01 1.2 muscle
8.5e-01 6.1e-01 1 0.2 7.1e-05 1.0 ovary 1.7e-01 9.3e-02 3.8e-01 1.7
2.2e-02 2.6 pancreas 2.2e-01 3.2e-01 5.7e-02 1.6 6.6e-03 1.5
prostate 5.0e-01 4.9e-01 3.8e-02 1.9 4.5e-02 1.7 skin 6.2e-01
5.8e-01 5.4e-02 0.9 1.5e-02 0.5 stomach 4.2e-01 2.6e-01 3.7e-01 0.7
7.3e-03 2.3 T cells 1 1 5.5e-01 1.5 8.1e-01 0.9 Thyroid 8.3e-02
8.3e-02 5.9e-01 1.3 5.9e-01 1.3 uterus 4.2e-01 2.4e-01 1.6e-01 1.2
4.9e-02 1.7
[1546] As noted above, cluster HUMODCA features 1 transcript(s),
which were listed in Table 250 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Ornithine
decarboxylase (SEQ ID NO:1426). A description of each variant
protein according to the present invention is now provided.
[1547] Variant protein HUMODCA_P9 (SEQ ID NO:1310) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcripts) HUMODCA_T17 (SEQ ID
NO:32). An alignment is given to the known protein (Ornithine
decarboxylase (SEQ ID NO:1426)) at the end of the application. One
or more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1548] Comparison report between HUMODCA_P9 (SEQ ID NO:1310) and
DCOR HUMAN (SEQ ID NO:1426):
[1549] 1. An isolated chimeric polypeptide encoding for HUMODCA_P9
(SEQ ID NO:1310), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL
(SEQ ID NO: 1768) corresponding to amino acids 1-29 of HUMODCA_P9
(SEQ ID NO:1310), and a second amino acid sequence being at least
90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVLPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 151-461
of DCOR_HUMAN (SEQ ID NO:1426), which also corresponds to amino
acids 30-340 of HUMODCA_P9 (SEQ ID NO:1310), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1550] 2. An isolated polypeptide encoding for a head of HUMODCA_P9
(SEQ ID NO:1310), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ
ID NO: 1768) of HUMODCA_P9 (SEQ ID NO:1310).
[1551] Comparison report between HUMODCA_P9 (SEQ ID NO:1310) and
AAA59968 (SEQ ID NO:1702):
[1552] 1. An isolated chimeric polypeptide encoding for HUMODCA_P9
(SEQ ID NO:1310), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL
(SEQ ID NO: 1768) corresponding to amino acids 1-29 of HUMODCA_P9
(SEQ ID NO:1310), and a second amino acid sequence being at least
90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 40-350
of AAA59968, which also corresponds to amino acids 30-340 of
HUMODCA_P9 (SEQ ID NO:1310), wherein said first and second amino
acid sequences are contiguous and in a sequential order.
[1553] 2. An isolated polypeptide encoding for a head of HUMODCA_P9
(SEQ ID NO:1310), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ
ID NO: 1768) of HUMODCA_P9 (SEQ ID NO:1310).
[1554] Comparison report between HUMODCA_P9 (SEQ ID NO:1310) and
AAH14562 (SEQ ID NO:1703):
[1555] 1. An isolated chimeric polypeptide encoding for HUMODCA_P9
(SEQ ID NO:1310), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL
(SEQ ID NO: 1768) corresponding to amino acids 1-29 of HUMODCA_P9
(SEQ ID NO:1310), and a second amino acid sequence being at least
90% homologous to
LVLRIATDDSKAVCRLSVKFGATLRTSRLLLERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDM
GAEVGFSMYLLDIGGGFPGSEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKK
IVLKEQTGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTCDGLD
RIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQFQNPDFPPEVEEQ
DASTLPVSCAWESGMKRHRAACASASINV corresponding to amino acids 86-396
of AAH14562 (SEQ ID NO:1703), which also corresponds to amino acids
30-340 of HUMODCA_P9 (SEQ ID NO:1310), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[1556] 2. An isolated polypeptide encoding for a head of HUMODCA_P9
(SEQ ID NO:1310), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence MKSLTATSSMKVLLPRTFWTRKLMKFLLL (SEQ
ID NO: 1768) of HUMODCA_P9 (SEQ ID NO:1310).
[1557] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1558] Variant protein HUMODCA_P9 (SEQ ID NO:1310) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 256, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMODCA_P9 (SEQ ID NO:1310)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00287 TABLE 256 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
150 I -> S No 150 I -> V No 262 F -> L No 263 E -> No
263 E -> G No 30 L -> No 301 N -> No 301 N -> K No 309
E -> K No 312 D -> N No 323 E -> K No 329 H -> P No 174
I -> No 34 I -> No 59 L -> No 70 V -> No 86 T -> No
86 T -> N No 90 A -> No 94 A -> No 97 V -> No 97 V
-> G No 198 N -> D No 200 G -> No 3 S -> No 207 C ->
G No 207 C -> R No 223 P -> No 262 F -> No
[1559] Variant protein HUMODCA_P9 (SEQ ID NO:1310) is encoded by
the following transcript(s): HUMODCA_T17 (SEQ ID NO:32), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript HUMODCA_T17 (SEQ ID NO:32) is shown in
bold; this coding portion starts at position 528 and ends at
position 1547. The transcript also has the following SNPs as listed
in Table 257 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMODCA_P9 (SEQ ID NO:1310) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00288 TABLE 257 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
28 C -> G Yes 210 C -> No 536 T -> No 615 T -> No 628 T
-> No 703 T -> No 736 T -> No 784 C -> No 784 C -> A
No 797 A -> No 797 A -> T No 808 C -> No 217 C -> No
817 T -> No 817 T -> G No 869 C -> T Yes 975 A -> G No
976 T -> G No 1048 T -> No 1119 A -> G No 1127 C -> No
1127 C -> G No 1146 T -> C No 366 G -> C No 1146 T -> G
No 1194 C -> No 1283 T -> C Yes 1311 T -> No 1311 T ->
C No 1315 A -> No 1315 A -> G No 1430 C -> No 1430 C ->
A No 1433 C -> G No 366 G -> T No 1433 C -> T Yes 1452 G
-> A No 1461 G -> A No 1494 G -> A No 1513 A -> C No
1632 T -> No 1673 C -> No 1739 T -> No 1739 T -> G No
1742 T -> C No 447 G -> A Yes 1786 C -> No 1786 C -> G
No 1832 T -> C Yes 1877 C -> T No 464 T -> G Yes 473 A
-> G Yes 506 G -> A Yes 521 T -> No
[1560] As noted above, cluster HUMODCA features 17 segment(s),
which were listed in Table 251 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[1561] Segment cluster HUMODCA_node.sub.--1 (SEQ ID NO:1199)
according to the present invention is supported by 76 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 258 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00289 TABLE 258 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 118 256
[1562] Segment cluster HUMODCA_node.sub.--25 (SEQ ID NO:1200)
according to the present invention is supported by 190 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 259 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00290 TABLE 259 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 614 748
[1563] Segment cluster HUMODCA_node.sub.--32 (SEQ ID NO:1201)
according to the present invention is supported by 249 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 260 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00291 TABLE 260 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 915 1077
[1564] Segment cluster HUMODCA_node.sub.--36 (SEQ ID NO:1202)
according to the present invention is supported by 348 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 261 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00292 TABLE 261 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1191 1405
[1565] Segment cluster HUMODCA_node.sub.--39 (SEQ ID NO:1203)
according to the present invention is supported by 297 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 262 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00293 TABLE 262 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1461 1633
[1566] Segment cluster HUMODCA_node.sub.--41 (SEQ ID NO:1204)
according to the present invention is supported by 230 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 263 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00294 TABLE 263 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1728 1893
[1567] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1568] Segment cluster HUMODCA_node.sub.--0 (SEQ ID NO:1205)
according to the present invention is supported by 9 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMODCA_T17
(SEQ ID NO:32). Table 264 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00295 TABLE 264 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1 117
[1569] Segment cluster HUMODCA_node.sub.--10 (SEQ ID NO:1206)
according to the present invention is support by 107 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMODCA_T17
(SEQ ID NO:32). Table 265 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00296 TABLE 265 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 385 494
[1570] Segment cluster HUMODCA_node.sub.--12 (SEQ ID NO:1207)
according to the present invention is supported by 132 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 266 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00297 TABLE 266 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 495 586
[1571] Segment cluster HUMODCA_node.sub.--13 (SEQ ID NO:1208)
according to the present invention is supported by 126 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 267 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00298 TABLE 267 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 587 613
[1572] Segment cluster HUMODCA_node.sub.--2 (SEQ ID NO:1209)
according to the present invention is supported by 81 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 268 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00299 TABLE 268 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 257 328
[1573] Segment cluster HUMODCA_node.sub.--27 (SEQ ID NO:1210)
according to the present invention is supported by 185 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 269 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00300 TABLE 269 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 749 830
[1574] Segment cluster HUMODCA_node.sub.--3 (SEQ ID NO:1211)
according to the present invention is supported by 85 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 270 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00301 TABLE 270 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 329 384
[1575] Segment cluster HUMODCA_node.sub.--30 (SEQ ID NO:1212)
according to the present invention is supported by 196 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): HUMODCA
T17 (SEQ ID NO:32). Table 271 below describes the starting and
ending position of this segment on each transcript.
TABLE-US-00302 TABLE 271 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 831 914
[1576] Segment cluster HUMODCA_node.sub.--34 (SEQ ID NO:1213)
according to the present invention is supported by 259 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 272 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00303 TABLE 272 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1078 1190
[1577] Segment cluster HUMODCA_node.sub.--38 (SEQ ID NO:1214)
according to the present invention is supported by 272 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 273 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00304 TABLE 273 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1406 1460
[1578] Segment cluster HUMODCA_node.sub.--40 (SEQ ID NO:1215)
according to the present invention is supported by 239 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMODCA_T17 (SEQ ID NO:32). Table 274 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00305 TABLE 274 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMODCA_T17 (SEQ ID NO: 32) 1634 1727
[1579] Variant protein alignment to the previously known
protein:
TABLE-US-00306 Sequence name: /tmp/y03EwE6iOl/dRQ5l2K6e2:DCOR_HUMAN
(SEQ ID NO: 1426) Sequence documentation: Alignment of: HUMODCA_P9
(SEQ ID NO: 1310) .times. DCOR_HUMAN (SEQ ID NO: 1426) Alignment
segment 1/1: Quality: 3056.00 Escore: 0 Matching length: 311 Total
length: 311 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00190## ##STR00191##
##STR00192## ##STR00193## ##STR00194## ##STR00195## ##STR00196##
Sequence name: /tmp/y03EwE6i01/dRQ5l2K6e2:AAA59968 Sequence
documentation: Alignment of: HUMODCA_P9 (SEQ ID NO: 1310) .times.
AAA59968 . . . Alignment segment 1/1: Quality: 3056.00 Escore: 0
Matching length: 311 Total length: 311 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00197## ##STR00198## ##STR00199## ##STR00200## ##STR00201##
##STR00202## ##STR00203## Sequence name:
/tmp/y03EwE6i01/dRQ5l2K6e2:AAH14562 (SEQ ID NO: 1703) Sequence
documentation: Alignment of: HUMODCA_P9 (SEQ ID NO: 1310) .times.
AAH14562 (SEQ ID NO: 1703) . . . Alignment segment 1/1: Quality:
3056.00 Escore: 0 Matching length: 311 Total length: 311 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00204## ##STR00205## ##STR00206## ##STR00207##
##STR00208## ##STR00209## ##STR00210##
Description for Cluster R00299
[1580] Cluster R00299 features 1 transcript(s) and 12 segment(s) of
interest, the names for which are given in
[1581] Tables 275 and 276, respectively, the sequences themselves
are given at the end of the application. The selected protein
variants are given in table 277.
TABLE-US-00307 TABLE 275 Transcripts of interest Transcript name
Sequence ID No. R00299_T2 33
TABLE-US-00308 TABLE 276 Segments of interest Segment Name Sequence
ID No. R00299_node_2 422 R00299_node_30 423 R00299_node_10 424
R00299_node_14 425 R00299_node_15 426 R00299_node_20 427
R00299_node_23 428 R00299_node_25 429 R00299_node_28 430
R00299_node_31 431 R00299_node_5 432 R00299_node_9 433
TABLE-US-00309 TABLE 277 Proteins of interest Protein Name Sequence
ID No. R00299_P3 1311
[1582] These sequences are variants of the known protein Tescalcin
(SwissProt accession identifier TESC_HUMAN; known also according to
the synonyms TSC), SEQ ID NO: 1427, referred to herein as the
previously known protein.
[1583] Protein Tescalcin (SEQ ID NO:1427) is known or believed to
have the following function(s): Binds calcium. The sequence for
protein Tescalcin is given at the end of the application, as
"Tescalcin amino acid sequence".
[1584] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: calcium binding,
which are annotation(s) related to Molecular Function.
[1585] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nim dot nih dot gov/projects/LocusLink/>.
[1586] Cluster R00299 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 26 below refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[1587] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 26 and Table 278. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: lung malignant tumors.
TABLE-US-00310 TABLE 278 Normal tissue distribution Name of Tissue
Number bone 0 colon 0 epithelial 11 general 11 liver 0 lung 10
lymph nodes 22 bone marrow 31 ovary 0 pancreas 14 prostate 16
stomach 76 T cells 0 Thyroid 0
TABLE-US-00311 TABLE 279 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bone 1 6.7e-01
1 1.0 7.0e-01 1.4 colon 5.0e-02 5.3e-02 2.4e-01 2.8 2.1e-01 2.8
epithelial 7.7e-02 9.5e-02 4.0e-01 1.3 6.1e-03 1.9 general 2.3e-01
2.6e-01 5.3e-01 1.0 2.6e-04 1.9 liver 1 4.5e-01 1 1.0 6.9e-01 1.5
lung 4.9e-01 2.7e-01 6.5e-01 1.7 5.6e-04 3.8 lymph nodes 8.5e-01
8.7e-01 1 0.5 2.0e-01 1.1 bone marrow 8.6e-01 8.5e-01 1 0.5 2.3e-01
1.4 ovary 4.0e-01 4.4e-01 1 1.1 1 1.1 pancreas 7.2e-01 6.9e-01
6.7e-01 1.0 3.5e-01 1.5 prostate 8.7e-01 9.1e-01 6.7e-01 1.0
7.5e-01 0.9 stomach 6.6e-01 7.5e-01 1 0.4 6.7e-01 0.7 T cells 1
6.7e-01 1 1.0 5.2e-01 1.8 Thyroid 1.8e-01 1.8e-01 6.7e-01 1.6
6.7e-01 1.6
[1588] As noted above, cluster R00299 features 1 transcript(s),
which were listed in Table 275 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Tescalcin (SEQ ID
NO:1427). A description of each variant protein according to the
present invention is now provided.
[1589] Variant protein R00299_P3 (SEQ ID NO:1311) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) R00299_T2 (SEQ ID
NO:33). An alignment is given to the known protein (Tescalcin (SEQ
ID NO:1427)) at the end of the application. One or more alignments
to one or more previously published protein sequences are given at
the end of the application. A brief description of the relationship
of the variant protein according to the present invention to each
such aligned protein is as follows:
[1590] Comparison report between R00299_P3 (SEQ ID NO:1311) and
Q9NWT9 (SEQ ID NO:1704):
[1591] 1. An isolated chimeric polypeptide encoding for R00299_P3
(SEQ ID NO:1311), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769)
corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:1311),
second amino acid sequence being at least 90% homologous to
SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLTIMS
YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNV corresponding to
amino acids 74-191 of Q9NWT9 (SEQ ID NO:1704), which also
corresponds to amino acids 45-162 of R00299_P3 (SEQ ID , and a
third amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNME
TMALCH (SEQ ID NO: 1770) corresponding to amino acids 163-238 of
R00299_P3 (SEQ ID NO:1311), wherein said first, second and third
amino acid sequences are contiguous and in a sequential order.
[1592] 2. An isolated polypeptide encoding for a head of R00299_P3
(SEQ ID NO:1311), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769) of
R00299_P3 (SEQ ID NO:1311).
[1593] 3. An isolated polypeptide encoding for a tail of R00299_P3
(SEQ ID NO:1311), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence
VEELLSGNPHIEKESARSIADGAMMEAASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHV-
RFLNME TMALCH (SEQ ID NO: 1770) in R00299_p3 (SEQ ID NO:1311).
[1594] Comparison report between R00299_P3 (SEQ ID NO:1311) and
TESCHUMAN (SEQ ID NO:1427):
[1595] 1. An isolated chimeric polypeptide encoding for R00299_P3
(SEQ ID NO:1311), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769)
corresponding to amino acids 1-44 of R00299_P3 (SEQ ID NO:1311),
and a second amino acid sequence being at least 90% homologous to
SSDQIEQLHRRFKQLSGDQPTIRKENFNNVPDLELNPIRSKIVRAFFDNRNLRKGPSGLADEINFEDFLT-
IMS
YFRPIDTTMDEEQVELSRKEKLRFLFHMYDSDSDGRITLEEYRNVVEELLSGNPHIEKESARSIADGAMM-
E AASVCMGQMEPDQVYEGITFEDFLKIWQGIDIETKMHVRFLNMETMALCH (SEQ ID NO:
1770) corresponding to amino acids 21-214 of TESC_HUMAN (SEQ ID
NO:1427), which also corresponds to amino acids 45-238 of R00299_P3
(SEQ ID NO:1311), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[1596] 2. An isolated polypeptide encoding for a head of R00299_P3
(SEQ ID NO:1311), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence
MAEKALLCPSSAGLGTWPWVLNSAWPVLPLAVDQGVDWRPRGPV (SEQ ID NO: 1769) of
R00299_P3 (SEQ ID NO:1311).
[1597] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Signal peptide,NN:NO) predicts that this
protein has a signal peptide.
[1598] Variant protein R00299_P3 (SEQ ID NO:1311) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 280, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein R00299_P3 (SEQ ID NO:1311)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00312 TABLE 280 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 120 R -> G No 120 R -> W No
[1599] Variant protein R00299_P3 (SEQ ID NO:1311) is encoded by the
following transcript(s): R00299_T2 (SEQ ID NO:33), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R00299_T2 (SEQ ID NO:33) is shown in bold;
this coding portion starts at position 142 and ends at position
855. The transcript also has the following SNPs as listed in Table
281 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R00299_P3 (SEQ ID NO:1311) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00313 TABLE 281 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 177 C
-> A Yes 499 C -> G No 499 C -> T No 900 G -> T Yes 916
G -> No 969 G -> No 969 G -> A No 987 A -> C No
[1600] As noted above, cluster K00299 features 12 segment(s), which
were listed in Table 276 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1601] Segment cluster R00299_node.sub.--2 (SEQ ID NO:1216)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): R00299_T2 (SEQ
ID NO:33). Table 282 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00314 TABLE 282 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 1 271
[1602] Segment cluster R00299_node.sub.--30 (SEQ ID NO:1217)
according to the present invention is supported by 75 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 283 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00315 TABLE 283 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 790 961
[1603] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description. Segment cluster
R00299_node_node.sub.--10 (SEQ ID NO:1218) according to the present
invention is supported by 46 libraries. The number of libraries was
determined as previously described. This segment can be found in
the following transcript(s): R00299_T2 (SEQ ID NO:33). Table 284
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00316 TABLE 284 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 346 422
[1604] Segment cluster R00299_node.sub.--14 (SEQ ID NO:1219)
according to the present invention is supported by 61 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 285 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00317 TABLE 285 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 423 537
[1605] Segment cluster R00299_node.sub.--15 (SEQ ID NO:1220)
according to the present invention can be found in the following
transcript(s): R00299_T2 (SEQ ID NO:33). Table 286 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00318 TABLE 286 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 538 562
[1606] Segment cluster R00299_node.sub.--20 (SEQ ID NO:1221)
according to the present invention is supported by 66 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33) Table 287 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00319 TABLE 287 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 563 624
[1607] Segment cluster R00299_node.sub.--23 (SEQ ID NO:1222)
according to the present invention is supported by 71 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 288 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00320 TABLE 288 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 625 732
[1608] Segment cluster R00299_node.sub.--25 (SEQ ID NO:1223)
according to the present invention is supported by 62 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 289 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00321 TABLE 289 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 733 780
[1609] Segment cluster R00299_node.sub.--28 (SEQ ID NO:1224)
according to the present invention can be found in the following
transcript(s): R00299_T2 (SEQ ID NO:33). Table 290 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00322 TABLE 290 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 781 789
[1610] Segment cluster R00299_node.sub.--31 (SEQ ID NO:1225)
according to the present invention is supported by 48 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 291 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00323 TABLE 291 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 962 1069
[1611] Segment cluster R00299_node.sub.--5 (SEQ ID NO:1226)
according to the present invention is supported by 45 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R00299_T2
(SEQ ID NO:33). Table 292 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00324 TABLE 292 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 272 341
[1612] Segment cluster R00299_node.sub.--9 (SEQ ID NO:1227)
according to the present invention can be found in the following
transcript(s): R00299_T2 (SEQ ID NO:33). Table 293 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00325 TABLE 293 Segment location on transcripts Segment
Segment starting ending Transcript name position position R00299_T2
(SEQ ID NO: 33) 342 345
[1613] Microarray (chip) data is also available for this gene as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotide was found to hit this segment (with
regard to lung cancer), shown in Table 294.
TABLE-US-00326 TABLE 294 Oligonucleotide related to this gene
Overexpressed Chip Oligonucleotide name in cancers reference
R00299_0_8_0 (SEQ ID NO: 217) lung cancer Lung
[1614] Variant protein alignment to the previously known
protein:
TABLE-US-00327 Sequence name: /tmp/OleVDhrKQ0/EjblgLomjM:Q9NWT9
(SEQ ID NO: 1704) Sequence documentation: Alignment of: R00299_P3
(SEQ ID NO: 1311) .times. Q9NWT9 (SEQ ID NO: 1704) . . . Alignment
segment 1/1: Quality: 1162.00 Escore: 0 Matching length: 118 Total
length: 118 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00211## ##STR00212##
##STR00213## Sequence name: /tmp/OleVDhrKQ0/EjblgLomjM:TESC_HUMAN
(SEQ ID NO: 1427) Sequence documentation: Alignment of: R00299_P3
(SEQ ID NO: 1311) .times. TESC_HUMAN (SEQ ID NO: 1427) . . .
Alignment segment 1/1: Quality: 1920.00 Escore: 0 Matching length:
194 Total length: 194 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00214##
##STR00215## ##STR00216## ##STR00217##
Description for Cluster W60282
[1615] Cluster W60282 features 1 transcript(s) and 6 segment(s) of
interest, the names for which are given in Tables 295 and 296,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
297.
TABLE-US-00328 TABLE 295 Transcripts of interest Transcript Name
Sequence ID No. W60282_PEA_1_T11 34
TABLE-US-00329 TABLE 296 Segments of interest Segment Name Sequence
ID No. W60282_PEA_1_node_10 434 W60282_PEA_1_node_18 435
W60282_PEA_1_node_22 436 W60282_PEA_1_node_5 437
W60282_PEA_1_node_21 438 W60282_PEA_1_node_8 439
TABLE-US-00330 TABLE 297 Proteins of interest Protein Name Sequence
ID No. W60282_PEA_1_P14 1312
[1616] These sequences are variants of the known protein Kallikrein
11 precursor (SwissProt accession identifier KLKB_HUMAN; known also
according to the synonyms EC 3.4.21.-; Hippostasin; Trypsin-like
protease), SEQ ID NO: 1428, referred to herein as the previously
known protein.
[1617] Protein Kallikrein 11 precursor (SEQ ID NO:1428) is known or
believed to have the following function(s): Possible
multifunctional protease. Efficiently cleaves
bz-Phe-Arg-4-methylcoumaryl-7-amide, a kallikrein substrate, and
weakly cleaves other substrates for kallikrein and trypsin. The
sequence for protein Kallikrein 11 precursor is given at the end of
the application, as "Kallikrein 11 precursor amino acid sequence".
Protein Kallikrein 11 precursor localization is believed to be
Secreted.
[1618] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: proteolysis and
peptidolysis, which are annotation(s) related to Biological
Process; and chymotrypsin; trypsin; serine-type peptidase;
hydrolase, which are annotation(s) related to Molecular
Function.
[1619] The GO assignment relies on information from one or more of
the SwissProt/TremB1Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1620] As noted above, cluster W60282 features 1 transcript(s),
which were listed in Table 295 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Kallikrein 11
precursor (SEQ ID NO:1428). A description of each variant protein
according to the present invention is now provided.
[1621] Variant protein W60282_PEA.sub.--1_P14 (SEQ ID NO:1312)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
W60282_PEA.sub.--1_T11 (SEQ ID NO:34). An alignment is given to the
known protein (Kallikrein 11 precursor (SEQ ID NO:1428)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1622] Comparison report between W60282_PEA.sub.--1_P14 (SEQ ID
NO:1312) and Q8IXD7 (SEQ ID NO:1705):
[1623] 1. An isolated chimeric polypeptide encoding for
W60282_PEA.sub.--1_P14 (SEQ ID NO:1312), comprising a first amino
acid sequence being at least 90% homologous to
MRILQLILLALATGLVGGETRIIKGFECKPHSQPWQAALFEKTRLLCGATLIAPRWLLTAAHCLKP
corresponding to amino acids 1-66 of Q8IXD7 (SEQ ID NO:1705), which
also corresponds to amino acids 1-66 of W60282_PEA.sub.--1_P14 (SEQ
ID NO:1312), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence TPASHLAMRQHHHH (SEQ ID NO: 1771)
corresponding to amino acids 67-80 of W60282 _PEA.sub.--1 _P14 (SEQ
ID NO:1312), wherein said first and second amino acid sequences and
in a sequential order.
[1624] 2. An isolated polypeptide encoding for a tail of
W60282_PEA.sub.--1_P14 (SEQ ID NO:1312), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
TPASHLAMRQHHHH (SEQ ID NO: 1771) in W60282_PEA.sub.--1_P14 (SEQ ID
NO:1312).
[1625] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1626] Variant protein W60282_PEA.sub.--1_P14 (SEQ ID NO:1312) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 298, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein W60282_PEA.sub.--1_P14
(SEQ ID NO:1312) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00331 TABLE 298 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 17 G -> E Yes 41 E -> K No
[1627] Variant protein W60282_PEA.sub.--1_P14 (SEQ ID NO:1312) is
encoded by the following transcript(s): W60282_PEA.sub.--1_T11 (SEQ
ID NO:34), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
W60282_PEA.sub.--1_T11 (SEQ ID NO:34) is shown in bold; this coding
portion starts at position 705 and ends at position 944. The
transcript also has the following SNPs as listed in Table 299
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein W60282_PEA.sub.--1_P14 (SEQ ID NO:1312) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00332 TABLE 299 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 219 A
-> G Yes 702 G -> A Yes 754 G -> A Yes 825 G -> A No
1289 A -> G Yes
[1628] As noted above, cluster W60282 features 6 segment(s), which
were listed in Table 296 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1629] Segment cluster W60282_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:1228) according to the present invention is supported by 45
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 300
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00333 TABLE 300 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 745 901
[1630] Segment cluster W60282_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:1229) according to the present invention is supported by 49
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 301
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00334 TABLE 301 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 902 1038
[1631] Segment cluster W60282_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:1230) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 302
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00335 TABLE 302 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 1072 1507
[1632] Segment cluster W60282_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1231) according to the present invention is supported by 20
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 303
below describeds the starting and ending position of this segment
on each transcript.
TABLE-US-00336 TABLE 303 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 1 669
[1633] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1634] Segment cluster W60282_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:1232) according to the present invention is supported by 48
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 304
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00337 TABLE 304 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 1039 1071
[1635] Segment cluster W60282_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1233) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): W60282_PEA.sub.--1_T11 (SEQ ID NO:34). Table 305
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00338 TABLE 305 Segment location on transcripts Segment
Segment starting ending Transcript name position position
W60282_PEA_1_T11 (SEQ ID NO: 34) 670 744
[1636] Variant protein alignment to the previously known
protein:
TABLE-US-00339 Sequence name: /tmp/rL7Wdc5hYg/eLOAfKIgqD:KLKB_HUMAN
(SEQ ID NO: 1428) Sequence documentation: Alignment of:
W60282_PEA_1_P14 (SEQ ID NO: 1312) .times. KLKB_HUMAN (SEQ ID NO:
1428) . . . Alignment segment 1/1: Quality: 645.00 Escore: 0
Matching length: 72 Total length: 72 Matching Percent Similarity:
94.44 Matching Percent Identity: 94.44 Total Percent Similarity:
94.44 Total Percent Identity: 94.44 Gaps: 0 Alignment: ##STR00218##
##STR00219## Sequence name: /tmp/rL7Wdc5hYg/eLOAfKIgqD:Q8IXD7 (SEQ
ID NO: 1705) Sequence documentation: Alignment of: W60282_PEA_1_P14
(SEQ ID NO: 1312) .times. Q8IXD7 (SEQ ID NO: 1705) Alignment
segment 1/1: Quality: 642.00 Escore: 0 Matching length: 66 Total
length: 66 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00220## ##STR00221##
Description for Cluster Z41644
[1637] Cluster Z41644 features 1 transcript(s) and 21 segment(s) of
interest, the names for which are given in
[1638] Tables 306 and 307, respectively, the sequences themselves
are given at the end of the application. The selected protein
variants are given in table 308.
TABLE-US-00340 TABLE 306 Transcripts of interest Transcript Name
Sequence ID No. Z41644_PEA_1_T5 35
TABLE-US-00341 TABLE 307 Segments of interest Segment Name Sequence
ID No. Z41644_PEA_1_node_0 440 Z41644_PEA_1_node_11 441
Z41644_PEA_1_node_12 442 Z41644_PEA_1_node_15 443
Z41644_PEA_1_node_20 444 Z41644_PEA_1_node_24 445
Z41644_PEA_1_node_1 446 Z41644_PEA_1_node_10 447
Z41644_PEA_1_node_13 448 Z41644_PEA_1_node_16 449
Z41644_PEA_1_node_17 450 Z41644_PEA_1_node_19 451
Z41644_PEA_1_node_2 452 Z41644_PEA_1_node_21 453
Z41644_PEA_1_node_22 454 Z41644_PEA_1_node_23 455
Z41644_PEA_1_node_25 456 Z41644_PEA_1_node_3 457
Z41644_PEA_1_node_4 458 Z41644_PEA_1_node_6 459 Z41644_PEA_1_node_9
460
TABLE-US-00342 TABLE 308 Proteins of interest Protein Name Sequence
ID No. Z41644_PEA_1_P10 1313
[1639] These sequences are variants of the known protein Small
inducible cytokine B14 precursor (SwissProt accession identifier
SZ14_HUMAN; known also according to the synonyms CXCL14; Chemokine
BRAK), SEQ ID NO:1429, referred to herein as the previously known
protein.
[1640] The sequence for protein Small inducible cytokine B14
precursor (SEQ ID NO:1429) is given at the end of the application,
as "Small inducible cytokine B14 precursor amino acid sequence".
Protein Small inducible cytokine B14 precursor localization is
believed to be Secreted.
[1641] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: chemotaxis; signal
transduction; cell-cell signaling, which are annotation(s) related
to Biological Process; and chemokine, which are annotation(s)
related to Molecular Function.
[1642] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1643] Cluster Z41644 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 27 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1644] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 27 and Table 309. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: lung malignant tumors, breast malignant
tumors and pancreas carcinoma.
TABLE-US-00343 TABLE 309 Normal tissue distribution Name of Tissue
Number bone 45 brain 62 colon 327 epithelial 179 general 104 head
and neck 10 kidney 219 lung 6 lymph nodes 37 breast 87 bone marrow
0 muscle 20 ovary 36 pancreas 0 prostate 78 skin 591 stomach 109
Thyroid 386 uterus 218
TABLE-US-00344 TABLE 310 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bone 4.9e-01
8.5e-01 1.8e-01 1.9 5.3e-01 1.0 brain 6.7e-01 8.0e-01 9.1e-01 0.6
9.9e-01 0.4 colon 6.4e-01 7.7e-01 9.7e-01 0.4 1 0.3 epithelial
4.1e-01 9.4e-01 9.6e-01 0.7 1 0.4 general 1.5e-01 9.4e-01 1.8e-01
1.0 1 0.5 head and neck 1.9e-01 3.3e-01 4.6e-01 2.8 7.5e-01 1.5
kidney 7.7e-01 8.2e-01 7.0e-01 0.7 9.5e-01 0.5 lung 2.2e-01 5.0e-01
1.3e-04 8.7 8.1e-03 4.1 lymph nodes 6.3e-01 8.7e-01 6.3e-01 1.2
9.2e-01 0.6 breast 4.0e-01 6.5e-01 3.9e-04 3.5 2.9e-02 1.9 bone
marrow 1 6.7e-01 1 1.0 5.3e-01 1.9 muscle 5.2e-01 6.1e-01 2.7e-01
3.2 6.3e-01 1.2 ovary 6.7e-01 7.1e-01 7.6e-01 1.0 8.6e-01 0.8
pancreas 2.2e-02 2.3e-02 5.7e-03 7.8 1.6e-03 8.2 prostate 8.8e-01
9.0e-01 8.3e-01 0.6 9.3e-01 0.5 skin 5.9e-01 6.9e-01 2.3e-01 0.3 1
0.0 stomach 6.1e-01 8.9e-01 8.1e-01 0.7 9.9e-01 0.4 Thyroid 7.0e-01
7.0e-01 9.9e-01 0.4 9.9e-01 0.4 uterus 5.3e-01 8.2e-01 9.5e-01 0.5
1 0.3
[1645] As noted above, cluster Z41644 features 1 transcript(s),
which were listed in Table 306 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Small inducible
cytokine B14 precursor (SEQ ID NO:1429). A description of each
variant protein according to the present invention is now
provided.
[1646] Variant protein Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). An alignment is given to the
known protein (Small inducible cytokine B14 precursor (SEQ ID
NO:1429)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1647] Comparison report between Z41644_PEA.sub.--1_P10 (SEQ ID
NO:1313) and SZ14_HUMAN (SEQ ID NO:1429):
[1648] 1. An isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 1-95 of
SZ14_HUMAN (SEQ ID NO:1429), which also corresponds to amino acids
1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772)
corresponding to amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ
ID NO:1313), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1649] 2. An isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313).
[1650] Comparison report between Z41644_PEA.sub.--1_P10 (SEQ ID
NO:1313) and Q9NS21 (SEQ ID NO: 1706):
[1651] 1. An isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of
Q9NS21 (SEQ ID NO:1706), which also corresponds to amino acids 1-95
of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) corresponding to
amino acids 96-123 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[1652] 2. An isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313).
[1653] Comparison report between Z41644_PEA.sub.--1_P10 (SEQ ID
NO:1313) and AAQ89265 (SEQ ID NO:781):
[1654] 1. An isolated chimeric polypeptide encoding for
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a first amino
acid sequence being at least 90% homologous to
MRLLAAALLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQE
HCLHPKLQSTKRFIKWYNAWNEKRR corresponding to amino acids 13-107 of
AAQ89265 (SEQ ID NO:781) , which also corresponds to amino acids
1-95 of Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772)
corresponding to amino acids 96-123 of Z41644_PEA.sub.--1 P10 (SEQ
ID NO:1313), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1655] 2. An isolated polypeptide encoding for a tail of
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
YAPPLLTFLPTRPSCGSQDGKGPPHQVI (SEQ ID NO: 1772) in
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313).
[1656] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1657] Variant protein Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 311, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z41644_PEA.sub.--1_P10
(SEQ ID NO:1313) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00345 TABLE 311 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
32 P -> H Yes 64 S -> No 80 T -> A No 80 T -> P No
[1658] Variant protein Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313) is
encoded by the following transcript(s): Z41644_PEA.sub.--1_T5 (SEQ
ID NO:35), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z41644_PEA.sub.--1_T5
(SEQ ID NO:35) is shown in bold; this coding portion starts at
position 744 and ends at position 1112. The transcript also has the
following SNPs as listed in Table 312 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
Z41644_PEA.sub.--1_P10 (SEQ ID NO:1313) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00346 TABLE 312 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
102 A -> G Yes 572 C -> No 3707 C -> T Yes 3735 C -> T
Yes 4079 G -> A No 4123 G -> A Yes 4233 A -> G Yes 4328 C
-> No 4350 A -> G Yes 4376 G -> A Yes 4390 A -> G Yes
4619 G -> T Yes 838 C -> A Yes 4754 C -> T No 4757 C ->
A No 4794 T -> G No 4827 G -> No 934 C -> No 981 A -> C
No 981 A -> G No 1817 A -> C Yes 2546 T -> No 2684 T ->
A No 2885 T -> C Yes
[1659] As noted above, cluster Z41644 features 21 segment(s), which
were listed in Table 307 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1660] Segment cluster Z41644_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1234) according to the present invention is supported by 53
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 313
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00347 TABLE 313 Segment location on transcripts Segment
Segment Transcript name starting position ending position
Z41644_PEA_1_T5 (SEQ ID 1 616 NO: 35)
[1661] Segment cluster Z41644_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:1235) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 314
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00348 TABLE 314 Segment location on transcripts Segment
starting Segment ending Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 1028 2089 NO: 35)
[1662] Segment cluster Z41644_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:1236) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 315
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00349 TABLE 315 Segment location on transcripts Segment
Segment Transcript name starting position ending position
Z41644_PEA_1_T5 2090 2350 (SEQ ID NO: 35)
[1663] Segment cluster Z41644_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:1237) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 316
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00350 TABLE 316 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z41644_PEA_1_T5 (SEQ ID 2368 3728 NO: 35)
[1664] Segment cluster Z41644_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:1238) according to the present invention is supported by 260
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 317
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00351 TABLE 317 Segment location on transcripts Segment
Transcript name starting position Segment ending position
Z41644_PEA_1_T5 3938 4506 (SEQ ID NO: 35)
[1665] Segment cluster Z41644_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1239) according to the present invention is supported by 185
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 318
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00352 TABLE 318 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 4637 4799 ID NO: 35)
[1666] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1667] Segment cluster Z41644_PEA.sub.--1_node.sub.--1 (SEQ ID
NO:1240) according to the present invention is supported by 53
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 39 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00353 TABLE 319 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 617 697 ID NO: 35)
[1668] Segment cluster Z41644_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:1241) according to the present invention is supported by 138
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 320
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00354 TABLE 320 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 972 1027 ID NO: 35)
[1669] Segment cluster Z41644_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:1242) according to the present invention can be found in the
following transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35).
Table 321 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00355 TABLE 321 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 2351 2367 ID NO: 35)
[1670] Segment cluster Z41644_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:1243) according to the present invention is supported by 152
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 322
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00356 TABLE 322 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 3729 3809 ID NO: 35)
[1671] Segment cluster Z41644_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:1244) according to the present invention can be found in the
following transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35).
Table 323 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00357 TABLE 323 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 3810 3829 ID NO: 35)
[1672] Segment cluster Z41644_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:1245) according to the present invention is supported by 112
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 324
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00358 TABLE 324 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 3830 3937 ID NO: 35)
[1673] Segment cluster Z41644_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1246) according to the present invention is supported by 58
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 325
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00359 TABLE 325 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 698 737 ID NO: 35)
[1674] Segment cluster Z41644_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:1247) according to the present invention can be found in the
following transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35).
Table 326 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00360 TABLE 326 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 4507 4529 ID NO: 35)
[1675] Segment cluster Z41644_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:1248) according to the present invention is supported by 164
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 327
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00361 TABLE 327 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 4530 4582 ID NO: 35)
[1676] Segment cluster Z41644_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:1249) according to the present invention is supported by 169
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 328
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00362 TABLE 328 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 4583 4636 ID NO: 35)
[1677] Segment cluster Z41644_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:1250) according to the present invention is supported by 138
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 329
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00363 TABLE 329 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 4800 4902 ID NO: 35)
[1678] Segment cluster Z41644_PEA.sub.--1_node.sub.--3 (SEQ IL)
NO:1251) according to the present invention is supported by 75
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 330
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00364 TABLE 330 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 738 773 ID NO: 35)
[1679] Segment cluster Z41644_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1252) according to the present invention is supported by 61
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 331
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00365 TABLE 331 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 774 807 ID NO: 35)
[1680] Segment cluster Z41644_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1253) according to the present invention is supported by 101
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644PEA.sub.--1_T5 (SEQ ID NO:35). Table 332 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00366 TABLE 332 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 808 913 ID NO: 35)
[1681] Segment cluster Z41644_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:1254) according to the present invention is supported by 134
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z41644_PEA.sub.--1_T5 (SEQ ID NO:35). Table 333
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00367 TABLE 333 Segment location on transcripts Segment
Transcript name Segment starting position ending position
Z41644_PEA_1_T5 (SEQ 914 971 ID NO: 35)
[1682] Variant protein alignment to the previously known
protein:
TABLE-US-00368 Sequence name: /tmp/p5SSvhT9Xp/HQeIMsUrfm:SZ14_HUMAN
(SEQ ID NO: 1429) Sequence documentation: Alignment of:
Z41644_PEA_1_P10 (SEQ ID NO: 1313) .times. SZ14_HUMAN (SEQ ID NO:
1429) . . . Alignment segment 1/1: Quality: 953.00 Escore: 0
Matching length: 95 Total length: 95 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00222## ##STR00223## Sequence name:
/tmp/p5SSvhT9Xp/HQeIMsUrfm:Q9NS21 (SEQ ID NO: 1706) Sequence
documentation: Alignment of: Z41644_PEA_1_P10 (SEQ ID NO: 1313)
.times. Q9NS21 (SEQ ID NO: 1706) Alignment segment 1/1: Quality:
957.00 Escore: 0 Matching length: 96 Total length: 96 Matching
Percent Similarity: 100.00 Matching Percent Identity: 98.96 Total
Percent Similarity: 100.00 Total Percent Identity: 98.96 Gaps: 0
Alignment: ##STR00224## ##STR00225## Sequence name:
/tmp/p5SSvhT9Xp/HQeIMsUrfm:AAQ89265 (SEQ ID NO: 781) Sequence
documentation: Alignment of: Z41644_PEA_1_P10 (SEQ ID NO: 1313)
.times. AAQ89265 (SEQ ID NO: 781) Alignment segment 1/1: Quality:
953.00 Escore: 0 Matching length: 95 Total length: 95 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00226## ##STR00227##
Description for Cluster Z44808
[1683] Cluster Z44808 features 5 transcript(s) and 21 segment(s) of
interest, the names for which are given in Tables 334 and 335,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
336.
TABLE-US-00369 TABLE 334 Transcripts of interest Transcript Name
Sequence ID No. Z44808_PEA_1_T11 36 Z44808_PEA_1_T4 37
Z44808_PEA_1_T5 38 Z44808_PEA_1_T8 39 Z44808_PEA_1_T9 40
TABLE-US-00370 TABLE 335 Segments of interest Segment Name Sequence
ID No. Z44808_PEA_1_node_0 461 Z44808_PEA_1_node_16 462
Z44808_PEA_1_node_2 463 Z44808_PEA_1_node_24 464
Z44808_PEA_1_node_32 465 Z44808_PEA_1_node_33 466
Z44808_PEA_1_node_36 467 Z44808_PEA_1_node_37 468
Z44808_PEA_1_node_41 469 Z44808_PEA_1_node_11 470
Z44808_PEA_1_node_13 471 Z44808_PEA_1_node_18 472
Z44808_PEA_1_node_22 473 Z44808_PEA_1_node_26 474
Z44808_PEA_1_node_30 475 Z44808_PEA_1_node_34 476
Z44808_PEA_1_node_35 477 Z44808_PEA_1_node_39 478
Z44808_PEA_1_node_4 479 Z44808_PEA_1_node_6 480 Z44808_PEA_1_node_8
481
TABLE-US-00371 TABLE 336 Proteins of interest Protein Name Sequence
ID No. Z44808_PEA_1_P5 1314 Z44808_PEA_1_P6 1315 Z44808_PEA_1_P7
1316 Z44808_PEA_1_P11 1317
[1684] These sequences are variants of the known protein SPARC
related modular calcium-binding protein 2 precursor (SwissProt
accession identifier SMO2_HUMAN; known also according to the
synonyms Secreted modular calcium-binding protein 2; SMOC-2; Smooth
muscle-associated protein 2; SMAP-2; MSTP 117), SEQ ID NO: 1430,
referred to herein as the previously known protein.
[1685] Protein SPARC related modular calcium-binding protein 2
precursor (SEQ ID NO:1430) is known or believed to have the
following function(s): calcium binding. The sequence for protein
SPARC related modular calcium-binding protein 2 precursor is given
at the end of the application, as "SPARC related modular
calcium-binding protein 2 precursor amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 337.
TABLE-US-00372 TABLE 337 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequene Comment 169-170 KT -> TR 212 S
-> P 429-446 TPRGHAESTSNRQPRXQG -> RSKRNL 434 A -> V 439 N
-> Y
[1686] Protein SPARC related modular calcium-binding protein 2
precursor (SEQ ID NO:1430) localization is believed to be
Secreted.
[1687] Cluster Z44808 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 28 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[1688] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 28 and Table 338. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: colorectal cancer, lung cancer and
pancreas carcinoma.
TABLE-US-00373 TABLE 338 Normal tissue distribution Name of Tissue
Number bladder 123 bone 304 brain 18 colon 0 epithelial 40 general
37 kidney 2 lung 0 breast 61 ovary 116 pancreas 0 prostate 128
stomach 36 uterus 195
TABLE-US-00374 TABLE 339 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 6.8e-01
7.6e-01 7.7e-01 0.8 9.1e-01 0.6 bone 7.0e-01 8.8e-01 9.9e-01 0.3 1
0.2 brain 6.8e-01 7.2e-01 3.0e-02 2.6 1.7e-01 1.6 colon 9.2e-03
1.3e-02 1.2e-01 3.6 1.6e-01 3.1 epithelial 2.1e-02 4.0e-01 1.0e-04
1.9 2.7e-01 1.0 general 2.6e-02 7.2e-01 4.9e-07 1.9 3.0e-01 1.0
kidney 7.3e-01 8.1e-01 1 1.0 1 1.0 lung 4.0e-03 1.8e-02 8.0e-04
12.2 2.1e-02 6.0 breast 4.8e-01 6.1e-01 9.8e-02 2.0 3.9e-01 1.2
ovary 8.1e-01 8.3e-01 9.1e-01 0.6 9.7e-01 0.5 pancreas 1.2e-01
2.1e-01 1.0e-03 6.5 5.9e-03 4.6 prostate 8.4e-01 8.9e-01 9.0e-01
0.6 9.8e-01 0.4 stomach 5.0e-01 8.7e-01 9.6e-04 1.5 1.9e-01 0.8
uterus 6.7e-01 7.9e-01 9.2e-01 0.5 1 0.3
[1689] As noted above, cluster Z44808 features 5 transcript(s),
which were listed in Table 334 above. These transcript(s) encode
for protein(s) which are variant(s) of protein SPARC related
modular calcium-binding protein 2 precursor (SEQ ID NO:1430). A
description of each variant protein according to the present
invention is now provided.
[1690] Variant protein Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37). An alignment is given to the
known protein (SPARC related modular calcium-binding protein 2
precursor (SEQ ID NO:1430)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1691] Comparison report between Z44808_PEA.sub.--1_P5 (SEQ ID
NO:1314) and SMO2_HUMAN (SEQ ID NO:1430):
[1692] 1. An isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKLLDKNSSGDIGKKEIKPFKFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of
SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino acids
1-441 of Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO: 1751) corresponding to
amino acids 442-464 of
[1693] Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), wherein said first
and second amino acid sequences are contiguous and in a sequential
order.
[1694] 2. An isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DAMVVSSRPKATTHRKSRTLSRR (SEQ ID NO: 1751) in Z44808_PEA.sub.--1_P5
(SEQ ID NO:1314).
[1695] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1696] Variant protein Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314) is
encoded by the following transcript(s): Z44808_PEA.sub.--1_T4 (SEQ
ID NO:37), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z44808_PEA.sub.--1_T4
(SEQ ID NO:37) is shown in bold; this coding portion starts at
position 586 and ends at position 1977. The transcript also has the
following SNPs as listed in Table 340 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
Z44808_PEA.sub.--1_P5 (SEQ ID NO:1314) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00375 TABLE 340 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
549 A -> G No 648 T -> G No 4403 G -> T No 4456 G -> A
Yes 4964 G -> C Yes 1025 C -> No 1677 T -> C No 2691 C
-> T Yes 3900 T -> C No 3929 G -> A Yes 4099 G -> T Yes
4281 T -> C No 4319 G -> C Yes
[1697] Variant protein Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z44808_PEA.sub.--1_T5 (SEQ ID NO:38). An alignment is given to the
known protein (SPARC related modular calcium-binding protein 2
precursor (SEQ ID NO:1430)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1698] Comparison report between Z44808_PEA.sub.--1_P6 (SEQ ID
NO:1315) and SMO2_HUMAN (SEQ ID NO:1430):
[1699] 1. An isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKCLLDKNSSGDIGKKEIKPFKRFLRKKSPKKCVKCKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRH corresponding to amino acids 1-428 of SMO2_HUMAN (SEQ ID
NO:1430), which also corresponds to amino acids 1-428 of
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), and a second being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence RSKRNL (SEQ ID NO: 1752)
corresponding to amino acids 429-434 of Z44808_PEA.sub.--1_P6 (SEQ
ID NO:1315), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1700] 2. An isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence RSKRNL
(SEQ ID NO: 1752) in Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315).
[1701] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1702] Variant protein Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 341, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z44808_PEA.sub.--1_P6
(SEQ ID NO:1315) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00376 TABLE 341 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
147 A -> No
[1703] Variant protein Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315) is
encoded by the following transcript(s): Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z44808_PEA.sub.--1_T5
(SEQ ID NO:38) is shown in bold; this coding portion starts at
position 586 and ends at position 1887. The transcript also has the
following SNPs as listed in Table 342 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
Z44808_PEA.sub.--1_P6 (SEQ ID NO:1315) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00377 TABLE 342 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
549 A -> G No 648 T -> G No 2866 G -> A Yes 3374 G -> C
Yes 1025 C -> No 1677 T -> C No 2310 T -> C No 2339 G
-> A Yes 2509 G -> T Yes 2691 T -> C No 2729 G -> C Yes
2813 G -> T No
[1704] Variant protein Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). An alignment is given to the
known protein (SPARC related modular calcium-binding protein 2
precursor (SEQ ID NO:1430)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[1705] Comparison report between Z44808_PEA.sub.--1_P7 (SEQ ID
NO:1316) and SMO2_HUMAN (SEQ ID NO:1430):
[1706] 1. An isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKTDDAAAPALETQPQGDEEDIASRYPTLWTEQVKSRQNKTN
KNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGYCWCVLVDTGRPIPGTSTRYEQP
KCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVHAASDPSSSSGRLSEPDPSHTLEE
RVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCDVNNDKSISVQELMGCLGVAKE
DGKADTKKRHTPRGHAESTSNRQ corresponding to amino acids 1-441 of
SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino acids
1-441 of Z44808_PEA.sub.--1_P7 (SEQ ID NO: 1316), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence LLWLRGKVSFYCF (SEQ ID NO: 1753) corresponding to amino
acids 442-454 of Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), wherein
said first and second amino acid sequences are contiguous and in a
sequential order.
[1707] 2. An isolated polypeptide encoding for a tail of
Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LLWLRGKVSFYCF (SEQ ID NO: 1753) in Z44808_PEA.sub.--1_P7 (SEQ ID
NO:1316).
[1708] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1709] Variant protein Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 343, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z44808_PEA.sub.--1_P7
(SEQ ID NO:1316) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00378 TABLE 343 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
147 A -> No
[1710] Variant protein Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316) is
encoded by the following transcript(s): Z44808_PEA.sub.--1_T9 (SEQ
ID NO:40), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z44808_PEA.sub.--1_T9
(SEQ ID NO:40) is shown in bold; this coding portion starts at
position 586 and ends at position 1947. The transcript also has the
following SNPs as listed in Table 344 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
Z44808_PEA.sub.--1_P7 (SEQ ID NO:1316) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00379 TABLE 344 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
549 A -> G No 648 T -> G No 1025 C -> No 1677 T -> C No
2169 C -> A Yes
[1711] Variant protein Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z44808_PEA.sub.--1_T11 (SEQ ID NO:36). The identification of this
transcript was performed using a non-EST based method for
identification of alternative splicing, described in the following
reference: "Sorek Ret al., Genome Res. (2004) 14:1617-23." An
alignment is given to the known protein (SPARC related modular
calcium-binding protein 2 precursor (SEQ ID NO:1430)) at the end of
the application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1712] Comparison report between Z44808_PEA.sub.--1_P11 (SEQ ID
NO:1317) and SMO2_HUMAN (SEQ ID NO:1430):
[1713] 1. An isolated chimeric polypeptide encoding for
Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), comprising a first amino
acid sequence being at least 90% homologous to
MLLPQLCWLPLLAGLLPPVPAQKFSALTFLRVDQDKDKDCSLDCAGSPQKPLCASDGRTFLSRCEFQRAK
CKDPQLEIAYRGNCKDVSRCVAERKYTQEQARKEFQQVFIPECNDDGTYSQVQCHSYTGYCWCVTPNGR
PISGTAVAHKTPRCPGSVNEKLPQREGTGKT corresponding to amino acids 1-170
of SMO2_HUMAN (SEQ ID NO:1430), which also corresponds to amino
acids 1-170 of Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), and a
second amino acid sequence being at least 90% homologous to
DIASRYPTLWTEQVKSRQNKTNKNSVSSCDQEHQSALEEAKQPKNDNVVIPECAHGGLYKPVQCHPSTGY
CWCVLVDTGRPIPGTSTRYEQPKCDNTARAHPAKARDLYKGRQLQGCPGAKKHEFLTSVLDALSTDMVH
AASDPSSSSGRLSEPDPSHTLEERVVHWYFKLLDKNSSGDIGKKEIKPFKRFLRKKSKPKKCVKKFVEYCD
VNNDKSISVQELMGCLGVAKEDGKADTKKRHTPRGHAESTSNRQPRKQG corresponding to
amino acids 188-446 of SMO2_HUMAN (SEQ ID NO:1430), which also
corresponds to amino acids 171-429 of Z44808_PEA.sub.--1_P11 (SEQ
ID NO:1317), wherein said first and second amino acid sequences are
contiguous and in a sequential order.
[1714] 2. An isolated chimeric polypeptide encoding for an edge
portion of Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise TD, having a structure as follows: a
sequence starting from any of amino acid numbers 170-x to -170; and
ending at any of amino acid numbers 171+((n-2)-x), in which x
varies from 0 to n-2.
[1715] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1716] Variant protein Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 345, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z44808_PEA.sub.--1_P11
(SEQ ID NO:1317) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00380 TABLE 345 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
147 A -> No
[1717] Variant protein Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317) is
encoded by the following transcript(s): Z44808_PEA.sub.--1_T11 (SEQ
ID NO:36), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript Z44808PEA.sub.--1_T11
(SEQ ID NO:36) is shown in bold; this coding portion starts at
position 586 and ends at position 1872. The transcript also has the
following SNPs as listed in Table 346 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
Z44808_PEA.sub.--1_P11 (SEQ ID NO:1317) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00381 TABLE 346 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
549 A -> G No 648 T -> G No 2720 G -> A Yes 3228 G -> C
Yes 1025 C -> No 1626 T -> C No 2164 T -> C No 2193 G
-> A Yes 2363 G -> T Yes 2545 T -> C No 2583 G -> C Yes
2667 G -> T No
[1718] As noted above, cluster Z44808 features 21 segment(s), which
were listed in Table 335 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1719] Segment cluster Z44808_PEA.sub.--1_node_O (SEQ ID NO:1255)
according to the present invention is supported by 29 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
Z44808_PEA.sub.--1_T11 (SEQ ID NO:36), Z44808_PEA.sub.--1_T4 (SEQ
ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ ID NO:38),
Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and Z44808_PEA.sub.--1_T9 (SEQ
ID NO:40). Table 347 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00382 TABLE 347 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1 669 Z44808_PEA_1_T4 (SEQ ID NO:
37) 1 669 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1 669 Z44808_PEA_1_T8
(SEQ ID NO: 39) 1 669 Z44808_PEA_1_T9 (SEQ ID NO: 40) 1 669
[1720] Segment cluster Z44808_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:1256) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 348 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00383 TABLE 348 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1172 1358 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1223 1409 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1223 1409
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1223 1409 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1223 1409
[1721] Segment cluster Z44808_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1257) according to the present invention is supported by 34
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 349 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00384 TABLE 349 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 670 841 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 670 841 Z44808_PEA_1_T5 (SEQ ID NO: 38) 670 841
Z44808_PEA_1_T8 (SEQ ID NO: 39) 670 841 Z44808_PEA_1_T9 (SEQ ID NO:
40) 670 841
[1722] Segment cluster Z44808_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1258) according to the present invention is supported by 52
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1 T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 350 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00385 TABLE 350 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1545 1819 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1596 1870 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1596 1870
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1596 1870 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1596 1870
[1723] Segment cluster Z44808_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:1259) according to the present invention supported by 17
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) and
Z44808_PEA.sub.--1_T8 (SEQ ID NO:39). Table 351 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00386 TABLE 351 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T4 (SEQ ID NO: 37) 1909 3593 Z44808_PEA_1_T8 (SEQ ID
NO: 39) 1909 2397
[1724] Segment cluster Z44808_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:1260) according to the present invention is supported by 133
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1 T4 (SEQ ID NO:37) and Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38). Table 352 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00387 TABLE 352 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1858 2734 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 3594 4470 Z44808_PEA_1_T5 (SEQ ID NO: 38) 2004 2880
[1725] Segment cluster Z44808_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:1261) according to the present invention is supported by 117
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) and Z44808 _PEA.sub.--1 _T5
(SEQ ID NO:38). Table 353 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00388 TABLE 353 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 2829 3080 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 4565 4816 Z44808_PEA_1_T5 (SEQ ID NO: 38) 2975 3226
[1726] Segment cluster Z44808_PEA.sub.--1_node.sub.--37 (SEQ ID
NO:1262) according to the present invention is supported by 120
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) and Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38). Table 354 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00389 TABLE 354 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 3081 3429 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 4817 5165 Z44808_PEA_1_T5 (SEQ ID NO: 38) 3227 3575
[1727] Segment cluster Z44808_PEA.sub.--1_node.sub.--41 (SEQ ID
NO:1263) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 355
below describeds the starting and ending position of this segment
on each transcript.
TABLE-US-00390 TABLE 355 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z44808_PEA_1_T9 (SEQ ID NO: 40) 1974 2206
[1728] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description. Segment cluster
Z44808_PEA.sub.--1_node_l 1 (SEQ ID NO:1264) according to the
present invention is supported by 25 libraries. The number of
libraries was determined as previously described. This segment can
be found in the following transcript(s): Z44808_PEA.sub.--1_T4 (SEQ
ID NO:37), Z44808_PEA.sub.--1 T5 (SEQ ID NO:38),
Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and Z44808_PEA.sub.--1_T9 (SEQ
ID NO:40). Table 365 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00391 TABLE 356 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z44808_PEA_1_T4 (SEQ ID NO: 37) 1097 1147 Z44808_PEA_1_T5 (SEQ ID
NO: 38) 1097 1147 Z44808_PEA_1_T8 (SEQ ID NO: 39) 1097 1147
Z44808_PEA_1_T9 (SEQ ID NO: 40) 1097 1147
[1729] Segment cluster Z44808_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:1265) according to the present invention is supported by 28
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1 T4 (SEQ ID NO:37) , Z44808PEA.sub.--1_T5 (SEQ ID
NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 357 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00392 TABLE 357 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1097 1171 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1148 1222 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1148 1222
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1148 1222 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1148 1222
[1730] Segment cluster Z44808_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:1266) according to the present invention is supported by 27
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1 T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 358 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00393 TABLE 358 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1359 1441 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1410 1492 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1410 1492
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1410 1492 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1410 1492
[1731] Segment cluster Z44808_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:1267) according to the present invention is supported by 33
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 359 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00394 TABLE 359 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1442 1544 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1493 1595 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1493 1595
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1493 1595 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1493 1595
[1732] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (with
regard to lung cancer), shown in Table 360.
TABLE-US-00395 TABLE 360 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
Z44808_0_8_0 Lung squamous cell LUN (SEQ ID NO: 218) carcinoma
[1733] Segment cluster Z44808_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:1268) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T5 (SEQ ID NO:38). Table 361
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00396 TABLE 361 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z44808_PEA_1_T5 (SEQ ID NO: 38) 1871 1965
[1734] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (with
regard to lung cancer), shown in Table 362.
TABLE-US-00397 TABLE 362 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
Z44808_0_0_72347 Lung small cell cancer LUN (SEQ ID NO: 219)
[1735] Segment cluster Z44808_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:1269) according to the present invention is supported by 44
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 363 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00398 TABLE 363 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1820 1857 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1871 1908 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1966 2003
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1871 1908 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1871 1908
[1736] Segment cluster Z44808_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:1270) according to the present invention is supported by 70
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) and Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38). Table 364 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00399 TABLE 364 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 2735 2809 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 4471 4545 Z44808_PEA_1_T5 (SEQ ID NO: 38) 2881 2955
[1737] Segment cluster Z44808_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:1271) according to the present invention can be found in the
following transcript(s): Z44808PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) and Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38). Table 365 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00400 TABLE 365 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 2810 2828 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 4546 4564 Z44808_PEA_1_T5 (SEQ ID NO: 38) 2956 2974
[1738] Segment cluster Z44808_PEA.sub.--1_node.sub.--39 (SEQ ID
NO:1272) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 366
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00401 TABLE 366 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z44808_PEA_1_T9 (SEQ ID NO: 40) 1909 1973
[1739] Segment cluster Z44808_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1273) according to the present invention is supported by 33
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808PEA.sub.--1_T5 (SEQ ID
NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 367 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00402 TABLE 367 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 842 948 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 842 948 Z44808_PEA_1_T5 (SEQ ID NO: 38) 842 948
Z44808_PEA_1_T8 (SEQ ID NO: 39) 842 948 Z44808_PEA_1_T9 (SEQ ID NO:
40) 842 948
[1740] Segment cluster Z44808_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1274) according to the present invention is supported by 30
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 368 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00403 TABLE 368 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 949 1048 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 949 1048 Z44808_PEA_1_T5 (SEQ ID NO: 38) 949 1048
Z44808_PEA_1_T8 (SEQ ID NO: 39) 949 1048 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 949 1048
[1741] Segment cluster Z44808_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1275) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z44808_PEA.sub.--1_T11 (SEQ ID NO:36),
Z44808_PEA.sub.--1_T4 (SEQ ID NO:37) , Z44808_PEA.sub.--1_T5 (SEQ
ID NO:38), Z44808_PEA.sub.--1_T8 (SEQ ID NO:39) and
Z44808_PEA.sub.--1_T9 (SEQ ID NO:40). Table 369 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00404 TABLE 369 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z44808_PEA_1_T11 (SEQ ID NO: 36) 1049 1096 Z44808_PEA_1_T4 (SEQ ID
NO: 37) 1049 1096 Z44808_PEA_1_T5 (SEQ ID NO: 38) 1049 1096
Z44808_PEA_1_T8 (SEQ ID NO: 39) 1049 1096 Z44808_PEA_1_T9 (SEQ ID
NO: 40) 1049 1096
[1742] Variant protein alignment to the previously known
protein:
TABLE-US-00405 Sequence name: /tmp/vUqLu6eAVZ/K3JDuPvaLo:SMO2_HUMAN
(SEQ ID NO: 1430) Sequence documentation: Alignment of:
Z44808_PEA_1_P5 (SEQ ID NO: 1314) .times. SMO2_HUMAN (SEQ ID NO:
1430) Alignment segment 1/1: Quality: 4440.00 Escore: 0 Matching
length: 441 Total length: 441 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00228##
##STR00229## ##STR00230## ##STR00231## ##STR00232## ##STR00233##
##STR00234## ##STR00235## ##STR00236## Sequence name:
/tmp/QSUNfTsJ5y/kLOw5Vb6SD:SMO2_HUMAN (SEQ ID NO: 1430) Sequence
documentation: Alignment of: Z44808_PEA_1_P6 (SEQ ID NO: 1315)
.times. SMO2_HUMAN (SEQ ID NO: 1430) Alignment segment 1/1:
Quality: 4310.00 Escore: 0 Matching length: 428 Total length: 428
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00237## ##STR00238## ##STR00239##
##STR00240## ##STR00241## ##STR00242## ##STR00243## ##STR00244##
##STR00245## Sequence name: /tmp/MZVdR4PVdM/5uN8RwViJ1:SMO2_HUMAN
(SEQ ID NO: 1430) Sequence documentation: Alignment of:
Z44808_PEA_1_P7 (SEQ ID NO: 1316) .times. SMO2_HUMAN (SEQ ID NO:
1430) Alignment segment 1/1: Quality: 4440.00 Escore: 0 Matching
length: 441 Total length: 441 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00246##
##STR00247## ##STR00248## ##STR00249## ##STR00250## ##STR00251##
##STR00252## ##STR00253## ##STR00254## Sequence name:
/tmp/3fGVxqLloe/J5mQduAd0F:SMO2_HUMAN (SEQ ID NO: 1430) Sequence
documentation: Alignment of: Z44808_PEA_1_P11 (SEQ ID NO: 1317)
.times. SMO2_HUMAN (SEQ ID NO: 1430) . . . Alignment segment 1/1:
Quality: 4228.00 Escore: 0 Matching length: 429 Total length: 446
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 96.19 Total Percent Identity:
96.19 Gaps: 1 Alignment: ##STR00255## ##STR00256## ##STR00257##
##STR00258## ##STR00259## ##STR00260## ##STR00261## ##STR00262##
##STR00263##
[1743] Expression of SMO2_HUMAN SPARC related modular
calcium-binding protein 2 precursor Z44808 transcripts which are
detectable by amplicon as depicted in sequence name Z44808junc8-11
(SEQ ID NO: 1651) in normal and cancerous lung tissues
[1744] Expression of SMO2_HUMAN SPARC related modular
calcium-binding protein 2 precursor (Secreted modular
calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated
protein 2) transcripts detectable by or according to junc8-11,
Z44808 junc8-11 amplicon (SEQ ID NO: 1651) and Z44808junc8-11F (SEQ
ID NO: 1649) and Z44808junc8-11R (SEQ ID NO: 1650) primers was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[1745] FIG. 29 is a histogram showing over expression of the
above-indicated SMO2_HUMAN SPARC related modular calcium-binding
protein 2 precursor transcripts in cancerous lung samples relative
to the normal samples.
[1746] As is evident from FIG. 29, the expression of SMO2_HUMAN
SPARC related modular calcium-binding protein 2 precursor
transcripts detectable by the above amplicon in several cancer
samples was significantly higher than in the non-cancerous samples
(Sample Nos. 47-50, 90-93, 96-99 Table 2, "Tissue samples in
testing panel").
[1747] Notably an over-expression of at least 5 fold was found in 2
out of 15 adenocarcinoma samples and in 3 out of 8 small cells
carcinoma samples.
[1748] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair:
Z44808junc8-11F forward primer (SEQ ID NO: 1649); and
Z44808junc8-11 R reverse primer (SEQ ID NO: 1650).
[1749] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z44808junc8-11(SEQ ID NO: 1651)
TABLE-US-00406 Forward primer (SEQ ID NO: 1649):
GAAGGCACAGGAAAAACAGATATTG Reverse primer (SEQ ID NO: 1650):
TGGTGCTCTTGGTCACAGGAT Amplicon (SEQ ID NO: 1651):
GAAGGCACAGGAAAAACAGATATTGCATCACGTTACCCTACCCTTTGGAC
TGAACAGGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTCAT
CCTGTGACCAAGAGCACCA
[1750] Expression of SMO2_HUMAN SPARC related modular
calcium-binding protein 2 precursor (Secreted modular
calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated
protein 2) Z44808 transcripts which are detectable by amplicon as
depicted in sequence name Z44808 junc8-11(SEQ ID NO: 1651) in
different normal tissues
[1751] Expression of SMO2_HUMAN SPARC related modular
calcium-binding protein 2 precursor (Secreted modular
calcium-binding protein 2) (SMOC-2) (Smooth muscle-associated
protein 2) transcripts detectable by or according to Z44808
junc8-11 amplicon (SEQ ID NO: 1651) and primers: Z44808
junc8-11F(SEQ ID NO: 1649) and Z44808 junc8-11R (SEQ ID NO: 1650)
was measured by real time PCR. In parallel the expression of four
housekeeping genes--RPL19 (GenBank Accession No. NM.sub.--000981
(SEQ ID NO:1715); RPL19 amplicon, SEQ ID NO:1630), TATA box
(GenBank Accession No. NM.sub.--003194 (SEQ ID NO:1716); TATA
amplicon, SEQ ID NO:1633), Ubiquitin (GenBank Accession No.
BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the ovary samples
(Sample Nos. 18-20, Table 3), to obtain a value of relative
expression of each sample relative to median of the ovary
samples.
TABLE-US-00407 Primers: Forward primer (SEQ ID NO: 1649):
GAAGGCACAGGAAAAACAGATATTG Reverse primer (SEQ ID NO: 1650):
TGGTGCTCTTGGTCACAGGAT Amplicon (SEQ ID NO: 1651):
GAAGGCACAGGAAAAACAGATATTGCATCACGTTACCCTACCCTTTGGAC
TGAACAGGTTAAAAGTCGGCAGAACAAAACCAATAAGAATTCAGTGTCAT
CCTGTGACCAAGAGCACCA
[1752] The results are demonstrated in FIG. 18, showing the
expression of SMO2_HUMAN SPARC related modular calcium-binding
protein 2 precursor (Secreted modular calcium-binding protein 2)
(SMOC-2) (Smooth muscle-associated protein 2) Z44808 transcripts
which are detectable by amplicon as depicted in sequence name
Z44808 junc8-11 (SEQ ID NO: 1651) in different normal tissues.
Description for Cluster AA161187
[1753] Cluster AA161187 features 7 transcript(s) and 20 segment(s)
of interest, the names for which are given in Tables 370 and 371,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
372.
TABLE-US-00408 TABLE 370 Transcripts of interest Transcript Name
Sequence ID No. AA161187_T0 41 AA161187_T7 42 AA161187_T15 43
AA161187_T16 44 AA161187_T20 45 AA161187_T21 46 AA161187_T22 47
TABLE-US-00409 TABLE 371 Segments of interest Segment Name Sequence
ID No. AA161187_node_0 482 AA161187_node_6 483 AA161187_node_14 484
AA161187_node_16 485 AA161187_node_25 486 AA161187_node_26 487
AA161187_node_28 488 AA161187_node_4 489 AA161187_node_7 490
AA161187_node_8 491 AA161187_node_9 492 AA161187_node_10 493
AA161187_node_12 494 AA161187_node_13 495 AA161187_node_19 496
AA161187_node_20 497 AA161187_node_21 498 AA161187_node_22 499
AA161187_node_23 500 AA161187_node_24 501
TABLE-US-00410 TABLE 372 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) AA161187_P1 1318 AA161187_T0
(SEQ ID NO: 41) AA161187_P6 1319 AA161187_T7 (SEQ ID NO: 42)
AA161187_P13 1320 AA161187_T15 (SEQ ID NO: 43) AA161187_P14 1321
AA161187_T16 (SEQ ID NO: 44) AA161187_P18 1322 AA161187_T20 (SEQ ID
NO: 45) AA161187_P19 1323 AA161187_T21 (SEQ ID NO: 46)
[1754] These sequences are variants of the known protein Testisin
precursor (SwissProt accession identifier TEST_HUMAN; known also
according to the synonyms EC 3.4.21.-; Eosinophil serine protease
1; ESP-1; UNQ266/PRO303), SEQ ID NO: 1431, referred to herein as
the previously known protein.
[1755] Protein Testisin precursor (SEQ ID NO:1431) is known or
believed to have the following function(s): Could regulate
proteolytic events associated with testicular germ cell maturation.
The sequence for protein Testisin precursor is given at the end of
the application, as "Testisin precursor amino acid sequence".
Protein Testisin precursor localization is believed to be attached
to the membrane by a GPI-anchor.
[1756] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: serine-type
peptidase, which are annotation(s) related to Molecular Function;
and membrane fraction; cytoplasm; plasma membrane, which are
annotation(s) related to Cellular Component.
[1757] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1758] Cluster AA 161187 can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the left hand column of the table and the numbers on
the y-axis of FIG. 30 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million). Overall, the following
results were obtained as shown with regard to the histograms in
FIG. 30 and Table 373. This cluster is overexpressed (at least at a
minimum level) in the following pathological conditions: brain
malignant tumors, epithelial malignant tumors and a mixture of
malignant tumors from different tissues.
TABLE-US-00411 TABLE 373 Normal tissue distribution Name of Tissue
Number bone 0 brain 1 colon 0 epithelial 0 general 0 lung 0 breast
0 bone marrow 0 ovary 0 pancreas 0 prostate 4 stomach 0 uterus
0
TABLE-US-00412 TABLE 374 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bone 1 6.7e-01
1 1.0 3.4e-01 1.9 brain 9.8e-01 6.0e-01 1 0.7 3.8e-03 3.6 colon
4.4e-01 5.0e-01 7.0e-01 1.5 7.7e-01 1.3 epithelial 1.3e-02 2.6e-03
1.7e-03 8.4 2.4e-04 7.9 general 1.6e-03 1.9e-05 1.9e-05 12.1
2.9e-10 15.6 lung 5.0e-01 6.3e-01 1.7e-01 3.9 3.8e-01 2.2 breast 1
6.7e-01 1 1.0 8.2e-01 1.2 bone marrow 1 4.2e-01 1 1.0 1.5e-01 2.9
ovary 6.2e-01 6.5e-01 4.7e-01 1.9 5.9e-01 1.6 pancreas 1 4.4e-01 1
1.0 2.8e-01 2.8 prostate 5.9e-01 5.9e-01 1.4e-01 2.9 2.4e-01 2.3
stomach 1 4.7e-01 1 1.0 6.4e-01 1.5 uterus 1 2.4e-01 1 1.0 1.7e-01
2.0
[1759] As noted above, cluster AA161187 features transcript(s),
which were listed in Table 370 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Testisin precursor
(SEQ ID NO:1431). A description of each variant protein according
to the present invention is now provided.
[1760] Variant protein AA161187_P1 (SEQ ID NO:1318) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T0
(SEQ ID NO:41). The location of the variant protein was determined
according to results from a number of different software programs
and analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide.
[1761] Variant protein AA161187_P1 (SEQ ID NO:1318) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 375, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AA161187_P1 (SEQ ID NO:1318)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00413 TABLE 375 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
1 M -> No 16 A -> No 226 N -> No 253 I -> V No 255 V
-> I No 264 R -> No 264 R -> P No 264 R -> Q Yes
[1762] Variant protein AA161187_P1 (SEQ ID NO:1318) is encoded by
the following transcript(s): AA161187_T0 (SEQ ID NO:41), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AA161187_T0 (SEQ ID NO:41) is shown in
bold; this coding portion starts at position 107 and ends at
position 1048. The transcript also has the following SNPs as listed
in Table 376 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AA161187_P1 (SEQ ID NO:1318) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00414 TABLE 376 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
66 T -> A No 67 T -> G No 105 C -> T No 108 T -> No 154
T -> No 190 C -> G No 469 A -> G Yes 571 C -> T Yes 782
A -> No 859 T -> C Yes 863 A -> G No 869 G -> A No 897
G -> No 897 G -> A Yes 897 G -> C No 1000 A -> G Yes
1068 G -> No 1068 G -> A No 1069 C -> A No 1168 A -> G
Yes
[1763] Variant protein AA161187_P6 (SEQ ID NO:1319) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T7
(SEQ ID NO:42). An alignment is given to the known protein
(Testisin precursor (SEQ ID NO:1431)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1764] Comparison report between AA161187_P6 (SEQ ID NO:1319) and
TEST_HUMAN (SEQ ID NO:1431):
[1765] 1. An isolated chimeric polypeptide encoding for AA161187_P6
(SEQ ID NO:1319), comprising a first amino acid sequence being at
least 70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273)
corresponding to amino acids 1-42 of AA161187_P6 (SEQ ID NO:1319),
and a second amino acid sequence being at least 90% homologous to
GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFETYSDLSDPSGWMVQ
FGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDC
WVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGG
PLACNKNGLWYQIGVVSWGVGCGRPNRPGVYTNISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALP
LLGPV corresponding to amino acids 31-314 of TEST_HUMAN (SEQ ID
NO:1431), which also corresponds to amino acids 43-326 of
AA161187_P6 (SEQ ID NO:1319), wherein said first amino acid
sequence and second amino acid sequence are contiguous and in a
sequential order.
[1766] 2. An isolated polypeptide encoding for a head of
AA161187_P6 (SEQ ID NO:1319), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273) of
AA161187_P6 (SEQ ID NO:1319).
[1767] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although it is a partial protein,
because both trans-membrane region prediction programs predict that
this protein has a trans-membrane region.
[1768] Variant protein AA161187_P6 (SEQ ID NO:1319) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 377, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AA161187_P6 (SEQ ID NO:1319)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00415 TABLE 377 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
238 N -> No 265 I -> V No 267 V -> I No 276 R -> No 276
R -> P No 276 R -> Q Yes
[1769] The glycosylation sites of variant protein AA161187_P6 (SEQ
ID NO:1319), as compared to the known protein Testisin precursor
(SEQ ID NO:1431), are described in Table 378 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00416 TABLE 378 Glycosylation site(s) Position(s) on known
amino Present in acid sequence variant protein? Position in variant
protein? 200 yes 212 167 yes 179 273 yes 285
[1770] Variant protein AA161187_P6 (SEQ ID NO:1319) is encoded by
the following transcript(s): AA161187_T7 (SEQ ID NO:42), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AA161187_T7 (SEQ ID NO:42) is shown in
bold; this coding portion starts at position 1 and ends at position
979. The transcript also has the following SNPs as listed in Table
379 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein AA161187_P6 (SEQ ID NO:1319) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00417 TABLE 379 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
400 A -> G Yes 502 C -> T Yes 713 A -> No 790 T -> C
Yes 794 A -> G No 800 G -> A No 828 G -> No 828 G -> A
Yes 828 G -> C No 931 A -> G Yes 999 G -> No 999 G -> A
No 1000 C -> A No 1099 A -> G Yes
[1771] Variant protein AA161187_P13 (SEQ ID NO:1320) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T15
(SEQ ID NO:43). An alignment is given to the known protein
(Testisin precursor (SEQ ID NO:1431)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1772] Comparison report between AA161187_P13 (SEQ ID NO:1320) and
TEST_HUMAN (SEQ ID NO:1431):
[1773] 1. An isolated chimeric polypeptide encoding for
AA161187_P13 (SEQ ID NO:1320), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of TEST_HUMAN (SEQ ID NO:1431), which also corresponds
to amino acids 1-183 of AA161187_P13 (SEQ ID NO:1320), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG (SEQ ID NO: 274)
corresponding to amino acids 184-213 of AA161187_P13 (SEQ ID
NO:1320), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[1774] 2. An isolated polypeptide encoding for a tail of
AA161187_P13 (SEQ ID NO:1320), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
GSSGRHHKQLYVQPPLPQVQFPQGHLWRHG (SEQ ID NO: 274) in AA161187_P13
(SEQ ID NO:1320).
[1775] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region. Variant protein AA161187_P13
(SEQ ID NO:1320) also has the following non-silent SNPs (Single
Nucleotide Polymorphisms) as listed in Table 380, (given according
to their position(s) on the amino acid sequence, with the
alternative amino acid(s) listed; the last column indicates whether
the SNP is known or not; the presence of known SNPs in variant
protein AA161187_P13 (SEQ ID NO:1320) sequence provides support for
the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00418 TABLE 380 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
1 M -> No 16 A -> No
[1776] The glycosylation sites of variant protein AA161187_P13 (SEQ
ID NO:1320), as compared to the known protein Testisin precursor
(SEQ ID NO:1431), are described in Table 381 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00419 TABLE 381 Glycosylation site(s) Position(s) on known
amino Present in acid sequence variant protein? Position in variant
protein? 200 no 167 yes 167 273 no
[1777] Variant protein AA161187_P13 (SEQ ID NO:1320) is encoded by
the following transcript(s): AA161187_T15 (SEQ ID NO:43), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AA161187_T15 (SEQ ID NO:43) is shown
in bold; this coding portion starts at position 107 and ends at
position 745. The transcript also has the following SNPs as listed
in Table 382 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AA161187P13 (SEQ ID NO:1320) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00420 TABLE 382 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
66 T -> A No 67 T -> G No 105 C -> T No 108 T -> No 154
T -> No 190 C -> G No 469 A -> G Yes 571 C -> T Yes 791
T -> C Yes 795 A -> G No 801 G -> A No 829 G -> No 829
G -> A Yes 829 G -> C No 932 A -> G Yes 1000 G -> No
1000 G -> A No 1001 C -> A No 1100 A -> G Yes
[1778] Variant protein AA161187_P14 (SEQ ID NO:1321) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T16
(SEQ ID NO:44). An alignment is given to the known protein
(Testisin precursor (SEQ ID NO:1431)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1779] Comparison report between AA161187_P14 (SEQ ID NO:1321) and
TEST_HUMAN (SEQ ID NO:1431):
[1780] 1. An isolated chimeric polypeptide encoding for
AA161187_P14 (SEQ ID NO:1321), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of
[1781] TEST_HUMAN (SEQ ID NO:1431), which also corresponds to amino
acids 1-183 of AA161187_P14 (SEQ ID NO:1321), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
GCCLSPSHYRPHSTAISPHPPGSSGRHHKQLYVQPPLPQVQFPQGHLWRHGLCWQCPRREGCLLRECPCH
HSQPRKASCVPVPYLTLMPTPGGGDCCPTLQMQKRRLGCCQGEEEDVHPVYPAP (SEQ ID NO:
275) corresponding to amino acids 184-307 of AA161187_P14 (SEQ ID
NO:1321), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[1782] 2. An isolated polypeptide encoding for a tail of
AA161187_P14 (SEQ ID NO:1321), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
GCCLSPSHYRPHSTAISPHPPGSSGRHHKQLYVQPPLPQVQFPQGHLWRHGLCWQCPRREGCLL-
RECPCH HSQPRKASCVPVPYLTLJMPTPGGGDCCPTLQMQKRRLGCCQGEEEDVHPVYPAP (SEQ
ID NO: 275) in AA161187_P14 (SEQ ID NO:1321).
[1783] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1784] Variant protein AA161187_P14 (SEQ ID NO:1321) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 383, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AA161187_P14 (SEQ ID NO:1321)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00421 TABLE 383 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
1 M -> No 16 A -> No 238 Q -> No
[1785] The glycosylation sites of variant protein AA161187_P14 (SEQ
ID NO:1321), as compared to the known protein Testisin precursor
(SEQ ID NO:1431), are described in Table 384 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00422 TABLE 384 Glycosylation site(s) Position(s) on known
amino Present in acid sequence variant protein? Position in variant
protein? 200 no 167 yes 167 273 no
[1786] Variant protein AA161187_P14 (SEQ ID NO:1321) is encoded by
the following transcript(s): AA161187_T16 (SEQ ID NO:44), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AA161187_T16 (SEQ ID NO:44) is shown
in bold; this coding portion starts at position 107 and ends at
position 1027. The transcript also has the following SNPs as listed
in Table 385 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AA161187_P14 (SEQ ID NO:1321) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00423 TABLE 385 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
66 T -> A No 67 T -> G No 105 C -> T No 108 T -> No 154
T -> No 190 C -> G No 469 A -> G Yes 571 C -> T Yes 819
A -> No 859 C -> T Yes 1152 T -> C Yes 1156 A -> G No
1162 G -> A No 1190 G -> No 1190 G -> A Yes 1190 G -> C
No 1293 A -> G Yes 1361 G -> No 1361 G -> A No 1362 C
-> A No 1461 A -> G Yes
[1787] Variant protein AA161187_P18 (SEQ ID NO:1322) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T20
(SEQ ID NO:45). An alignment is given to the known protein
(Testisin precursor (SEQ ID NO:1431)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1788] Comparison report between AA161187_P18 (SEQ ID NO:1322) and
TEST_HUMAN (SEQ ID NO:1431):
[1789] 1. An isolated chimeric polypeptide encoding for
AA161187_P18 (SEQ ID NO:1322), comprising a first amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273)
corresponding to amino acids 1-42 of AA161187_P18 (SEQ ID NO:1322),
a second amino acid sequence being at least 90% homologous to
GPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGVSLLSHRWALTAAHCFET
corresponding to amino acids 31-86 of TEST_HUMAN (SEQ ID NO:1431),
which also corresponds to amino acids 43-98 of AA161187_P18 (SEQ ID
NO:1322), a third amino acid sequence being at least 90% homologous
to
DLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIALVKLSAPVTYTKHIQPICLQ
ASTFEFENRTDCWVTGWGYIKEDEALPSPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQG
GKDACF corresponding to amino acids 89-235 of TEST_HUMAN (SEQ ID
NO:1431), which also corresponds to amino acids 99-245 of
AA161187_P18 (SEQ ID NO:1322), and a fourth amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
VSVPATTPSPGKHPVSLCLI (SEQ ID NO: 277) corresponding to amino acids
246-265 of AA161187_P18 (SEQ ID NO:1322), wherein said first amino
acid sequence, second amino acid sequence, third amino acid
sequence and fourth amino acid sequence are contiguous and in a
sequential order.
[1790] 2. An isolated polypeptide encoding for a head of
AA161187_P18 (SEQ ID NO:1322), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
HTREGTLGGQKRAFPDGVEGEKGRGRAWGAASRGSAVPLTIR (SEQ ID NO: 273) of
AA161187_P18 (SEQ ID NO:1322).
[1791] 3. An isolated chimeric polypeptide encoding for an edge
portion of AA161187_P18 (SEQ ID NO:1322), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise TD, having a structure as follows: a sequence
starting from any of amino acid numbers 98-x to 98; and ending at
any of amino acid numbers 99+((n-2)-x), in which x varies from 0 to
n-2.
[1792] 4. An isolated polypeptide encoding for a tail of
AA161187_P18 (SEQ ID NO:1322), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VSVPATTPSPGKHPVSLCLI
(SEQ ID NO: 277) in AA161187_P18 (SEQ ID NO:1322).
[1793] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although it is a partial protein,
because both trans-membrane region prediction programs predict that
this protein has a trans-membrane region.
[1794] Variant protein AA161187_P18 (SEQ ID NO:1322) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 386, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AA161187_P18 (SEQ ID NO:1322)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00424 TABLE 386 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
236 N -> No 249 P -> L Yes
[1795] The glycosylation sites of variant protein AA161187_P18 (SEQ
ID NO:1322), as compared to the known protein Testisin precursor
(SEQ ID NO:1431), are described in Table 387 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00425 TABLE 387 Glycosylation site(s) Position(s) on known
amino Present in acid sequence variant protein? Position in variant
protein? 200 yes 210 167 yes 177 273 no
[1796] Variant protein AA161187_P18 (SEQ ID NO:1322) is encoded by
the following transcript(s): AA 161187_T20 (SEQ ID NO:45), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript AA161187_T20 (SEQ ID NO:45) is
shown in bold; this coding portion starts at position 1 and ends at
position 796. The transcript also has the following SNPs as listed
in Table 388 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AA161187_P18 (SEQ ID NO:1322) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00426 TABLE 388 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
394 A -> G Yes 496 C -> T Yes 707 A -> No 747 C -> T
Yes 1040 T -> C Yes 1044 A -> G No 1050 G -> A No 1078 G
-> No 1078 G -> A Yes 1078 G -> C No 1181 A -> G Yes
1249 G -> No 1249 G -> A No 1250 C -> A No 1349 A -> G
Yes
[1797] Variant protein AA161187_P19 (SEQ ID NO:1323) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AA161187_T21
(SEQ ID NO:46). An alignment is given to the known protein
(Testisin precursor (SEQ ID NO:1431)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1798] Comparison report between AA161187_P19 (SEQ ID NO:1323) and
TEST_HUMAN (SEQ ID NO:1431):
[1799] 1. An isolated chimeric polypeptide encoding for
AA161187_P19 (SEQ ID NO:1323), comprising a first amino acid
sequence being at least 90% homologous to
MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVCGV
SLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNSPYDIA
LVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDE corresponding to amino
acids 1-183 of TEST_HUMAN (SEQ ID NO:1431), which also corresponds
to amino acids 1-183 of AA161187_P19 NO:1323), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence DKRTQ (SEQ ID NO: 278) corresponding to amino acids
184-188 of AA161187_P19 (SEQ ID NO:1323), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[1800] 2. An isolated polypeptide encoding for a tail of
AA161187_P19 (SEQ ID NO:1323), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence DKRTQ (SEQ ID NO: 278)
in AA161187_P19 (SEQ ID NO:1323).
[1801] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1802] Variant protein AA161187_P19 (SEQ ID NO:1323) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 389, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AA161187_P19 (SEQ ID NO:1323)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00427 TABLE 389 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
1 M -> No 16 A -> No
[1803] The glycosylation sites of variant protein AA161187_P19 (SEQ
ID NO:1323), as Compared to the known protein Testisin precursor
(SEQ ID NO:1431), are described in Table 390 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00428 TABLE 390 Glycosylation site(s) Position(s) on known
amino Present in acid sequence variant protein? Position in variant
protein? 200 no 167 yes 167 273 no
[1804] Variant protein AA161187_P19 (SEQ lD NO:1323) is encoded by
the following transcript(s): AA161187_T21 (SEQ ID NO:46), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AA161187_T21 (SEQ ID NO:46) is shown
in bold; this coding portion starts at position 107 and ends at
position 670. The transcript also has the following SNPs as listed
in Table 391 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AA161187_P19 (SEQ ID NO:1323) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00429 TABLE 391 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
66 T -> A No 67 T -> G No 105 C -> T No 108 T -> No 154
T -> No 190 C -> G No 469 A -> G Yes 571 C -> T Yes 719
G -> T Yes
[1805] As noted above, cluster AA161187 features 20 segment(s),
which were listed in Table 371 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[1806] Segment cluster AA161187_node_O (SEQ ID NO:482) according to
the present invention is supported by 21 libraries. The number of
libraries was determined as previously described. This segment can
be found in the following transcript(s): AA161187_T0 (SEQ ID
NO:41), AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T21 (SEQ ID NO:46) and AA161187_T22 (SEQ ID NO:47). Table
392 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00430 TABLE 392 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 1 170 AA161187_T15 (SEQ ID NO: 43) 1
170 AA161187_T16 (SEQ ID NO: 44) 1 170 AA161187_T21 (SEQ ID NO: 46)
1 170 AA161187_T22 (SEQ ID NO: 47) 1 170
[1807] Segment cluster AA161187_node.sub.--6 (SEQ ID NO:483)
according to the present invention is support by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): AA161187_T7
(SEQ ID NO:42) and AA161187_T20 (SEQ ID NO:45). Table 393 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00431 TABLE 393 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T7 (SEQ ID NO: 42) 1 120 AA161187_T20 (SEQ ID NO: 45) 1
120
[1808] Segment cluster AA161187_node.sub.--14 (SEQ ID NO:484)
according to the present invention is supported by 35 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T20 (SEQ ID NO:45), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 394 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00432 TABLE 394 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 446 656 AA161187_T7 (SEQ ID NO: 42) 377
587 AA161187_T15 (SEQ ID NO: 43) 446 656 AA161187_T16 (SEQ ID NO:
44) 446 656 AA161187_T20 (SEQ ID NO: 45) 371 581 AA161187_T21 (SEQ
ID NO: 46) 446 656 AA161187_T22 (SEQ ID NO: 47) 446 656
[1809] Segment cluster AA161187_node.sub.--16 (SEQ ID NO:485)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): AA161187_T22
(SEQ ID NO:47). Table 395 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00433 TABLE 395 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T22 (SEQ ID NO: 47) 657 953
[1810] Segment cluster AA161187_node.sub.--25 (SEQ ID NO:486)
according to the present invention is supported by 13 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T16 (SEQ ID NO:44) and AA161187_T20 (SEQ ID NO:45). Table
396 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00434 TABLE 396 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T16 (SEQ ID NO: 44) 880 1104 AA161187_T20 (SEQ ID NO: 45)
768 992
[1811] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 397.
TABLE-US-00435 TABLE 397 Oligonucleotides related to this segment
Overexpressed Oligonucleotide name in cancers Chip reference
AA161187_0_0_430 lung malignant tumors LUN (SEQ ID NO: 222)
[1812] Segment cluster AA161187_node.sub.--26 (SEQ ID NO:487)
according to the present invention is supported by 39 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44) and
AA161187_T20 (SEQ ID NO:45). Table 398 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00436 TABLE 398 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 812 1173 AA161187_T7 (SEQ ID NO: 42)
743 1104 AA161187_T15 (SEQ ID NO: 43) 744 1105 AA161187_T16 (SEQ ID
NO: 44) 1105 1466 AA161187_T20 (SEQ ID NO: 45) 993 1354
[1813] Segment cluster AA161187_node.sub.--28 (SEQ ID NO:488)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): AA161187_T21
(SEQ ID NO:46). Table 399 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00437 TABLE 399 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T21 (SEQ ID NO: 46) 657 1171
[1814] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1815] Segment cluster AA161187_node.sub.--4 (SEQ ID NO:489)
according to the present invention is supported by 22 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T15 (SEQ ID NO:43),
AA161187_T16 (SEQ ID NO:44), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 400 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00438 TABLE 400 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 171 197 AA161187_T15 (SEQ ID NO: 43)
171 197 AA161187_T16 (SEQ ID NO: 44) 171 197 AA161187_T21 (SEQ ID
NO: 46) 171 197 AA161187_T22 (SEQ ID NO: 47) 171 197
[1816] Segment cluster AA161187_node.sub.--7 (SEQ ID NO:490)
according to the present invention can be found in the following
transcript(s): AA161187_T7 (SEQ ID NO:42) and AA161187_T20 (SEQ ID
NO:45). Table 401 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00439 TABLE 401 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T7 (SEQ ID NO: 42) 121 128 AA161187_T20 (SEQ ID NO: 45)
121 128
[1817] Segment cluster AA161187_node.sub.--8 (SEQ ID NO:491)
according to the present invention is supported by 23 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T20 (SEQ ID NO:45), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 402 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00440 TABLE 402 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 198 256 AA161187_T7 (SEQ ID NO: 42) 129
187 AA161187_T15 (SEQ ID NO: 43) 198 256 AA161187_T16 (SEQ ID NO:
44) 198 256 AA161187_T20 (SEQ ID NO: 45) 129 187 AA161187_T21 (SEQ
ID NO: 46) 198 256 AA161187_T22 (SEQ ID NO: 47) 198 256
[1818] Segment cluster AA161187_node.sub.--9 (SEQ ID NO:492)
according to the present invention is supported by 24 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T20 (SEQ ID NO:45), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 403 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00441 TABLE 403 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 257 298 AA161187_T7 (SEQ ID NO: 42) 188
229 AA161187_T15 (SEQ ID NO: 43) 257 298 AA161187_T16 (SEQ ID NO:
44) 257 298 AA161187_T20 (SEQ ID NO: 45) 188 229 AA161187_T21 (SEQ
ID NO: 46) 257 298 AA161187_T22 (SEQ ID NO: 47) 257 298
[1819] Segment cluster AA161187_node.sub.--10 (SEQ ID NO:493)
according to the present invention is supported by 25 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T20 (SEQ ID NO:45), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 404 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00442 TABLE 404 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 299 363 AA161187_T7 (SEQ ID NO: 42) 230
294 AA161187_T15 (SEQ ID NO: 43) 299 363 AA161187_T16 (SEQ ID NO:
44) 299 363 AA161187_T20 (SEQ ID NO: 45) 230 294 AA161187_T21 (SEQ
ID NO: 46) 299 363 AA161187_T22 (SEQ ID NO: 47) 299 363
[1820] Segment cluster AA161187_node.sub.--12 (SEQ ID NO:494)
according to the present invention can be found in the following
transcript(s): AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID
NO:42), AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T21 (SEQ ID NO:46) and AA161187_T22 (SEQ ID NO:47). Table
405 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00443 TABLE 405 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 364 369 AA161187_T7 (SEQ ID NO: 42) 295
300 AA161187_T15 (SEQ ID NO: 43) 364 369 AA161187_T16 (SEQ ID NO:
44) 364 369 AA161187_T21 (SEQ ID NO: 46) 364 369 AA161187_T22 (SEQ
ID NO: 47) 364 369
[1821] Segment cluster AA161187_node.sub.--13 (SEQ ID NO:495)
according to the present invention is supported by 25 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44),
AA161187_T20 (SEQ ID NO:45), AA161187_T21 (SEQ ID NO:46) and
AA161187_T22 (SEQ ID NO:47). Table 406 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00444 TABLE 406 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 370 445 AA161187_T7 (SEQ ID NO: 42) 301
376 AA161187_T15 (SEQ ID NO: 43) 370 445 AA161187_T16 (SEQ ID NO:
44) 370 445 AA161187_T20 (SEQ ID NO: 45) 295 370 AA161187_T21 (SEQ
ID NO: 46) 370 445 AA161187_T22 (SEQ ID NO: 47) 370 445
[1822] Segment cluster AA161187_node.sub.--19 (SEQ ID NO:496)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): AA161187_T16
(SEQ ID NO:44). Table 407 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00445 TABLE 407 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T16 (SEQ ID NO: 44) 657 693
[1823] Segment cluster AA161187_node.sub.--20 (SEQ ID NO:497)
according to the present invention is supported by 28 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T16 (SEQ ID NO:44) and AA161187_T20 (SEQ ID NO:45). Table
408 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00446 TABLE 408 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 657 682 AA161187_T7 (SEQ ID NO: 42) 588
613 AA161187_T16 (SEQ ID NO: 44) 694 719 AA161187_T20 (SEQ ID NO:
45) 582 607
[1824] Segment cluster AA161187_node.sub.--21 (SEQ ID NO:498)
according to the present invention is supported by 31 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID'NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44) and
AA161187_T20 (SEQ ID NO:45). Table 409 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00447 TABLE 409 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 683 741 AA161187_T7 (SEQ ID NO: 42) 614
672 AA161187_T15 (SEQ ID NO: 43) 657 715 AA161187_T16 (SEQ ID NO:
44) 720 778 AA161187_T20 (SEQ ID NO: 45) 608 666
[1825] Segment cluster AA161187_node.sub.--22 (SEQ ID NO:499)
according to the present invention is supported by 34 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T15 (SEQ ID NO:43), AA161187_T16 (SEQ ID NO:44) and
AA161187_T20 (SEQ ID NO:45). Table 410 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00448 TABLE 410 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 742 769 AA161187_T7 (SEQ ID NO: 42) 673
700 AA161187_T15 (SEQ ID NO: 43) 716 743 AA161187_T16 (SEQ ID NO:
44) 779 806 AA161187_T20 (SEQ ID NO: 45) 667 694
[1826] Segment cluster AA161187_node.sub.--23 (SEQ ID NO:500)
according to the present invention is supported by 31 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T0 (SEQ ID NO:41), AA161187_T7 (SEQ ID NO:42),
AA161187_T16 (SEQ ID NO:44) and AA161187_T20 (SEQ ID NO:45). Table
411 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00449 TABLE 411 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T0 (SEQ ID NO: 41) 770 811 AA161187_T7 (SEQ ID NO: 42) 701
742 AA161187_T16 (SEQ ID NO: 44) 807 848 AA161187_T20 (SEQ ID NO:
45) 695 736
[1827] Segment cluster AA161187_node.sub.--24 (SEQ ID NO:501)
according to the present invention is supported by 12 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AA161187_T16 (SEQ ID NO:44) and AA161187_T20 (SEQ ID NO:45). Table
412 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00450 TABLE 412 Segment location on transcripts Segment
Segment Transcript name starting position ending position
AA161187_T16 (SEQ ID NO: 44) 849 879 AA161187_T20 (SEQ ID NO: 45)
737 767
Variant protein alignment to the previously known protein:
TABLE-US-00451 Sequence name: TEST_HUMAN (SEQ ID NO: 1431) Sequence
documentation: Alignment of: AA161187_P6 (SEQ ID NO: 1319) .times.
TEST_HUMAN (SEQ ID NO: 1431) Alignment segment 1/1: Quality:
2894.00 Escore: 0 Matching length: 284 Total length: 284 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00264## ##STR00265## ##STR00266## ##STR00267##
##STR00268## ##STR00269## Sequence name: TEST_HUMAN (SEQ ID NO:
1431) Sequence documentation: Alignment of: AA161187_P13 (SEQ ID
NO: 1320) .times. TEST_HUMAN (SEQ ID NO: 1431) Alignment segment
1/1: Quality: 1829.00 Escore: 0 Matching length: 183 Total length:
183 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00270## ##STR00271## ##STR00272##
##STR00273## Sequence name: TEST_HUMAN (SEQ ID NO: 1431) Sequence
documentation: Alignment of: AA161187_P14 (SEQ ID NO: 1321) .times.
TEST_HUMAN (SEQ ID NO: 1431) Alignment segment 1/1: Quality:
1829.00 Escore: 0 Matching length: 183 Total length: 183 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00274## ##STR00275## ##STR00276## ##STR00277##
Sequence name: TEST_HUMAN (SEQ ID NO: 1431) Sequence documentation:
Alignment of: AA161187_P18 (SEQ ID NO: 1322) .times. TEST_HUMAN
(SEQ ID NO: 1431) Alignment segment 1/1: Quality: 1957.00 Escore: 0
Matching length: 203 Total length: 205 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
99.02 Total Percent Identity: 99.02 Gaps: 1 Alignment: ##STR00278##
##STR00279## ##STR00280## ##STR00281## ##STR00282## Sequence name:
TEST_HUMAN (SEQ ID NO: 1431) Sequence documentation: Alignment of:
AA161187_P19 (SEQ ID NO: 1323) .times. TEST_HUMAN (SEQ ID NO: 1431)
Alignment segment 1/1: Quality: 1829.00 Escore: 0 Matching length:
183 Total length: 183 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00283##
##STR00284## ##STR00285## ##STR00286##
Expression of Homo sapiens protease, serine, 21 (testisin) (PRSS21)
AA161187 transcripts which are detectable by amplicon as depicted
in sequence name AA161187 seg25 (SEQ ID NO:1654) in normal and
cancerous lung tissues
[1828] Expression of Homo sapiens protease, serine, 21 (testisin)
(PRSS21) transcripts detectable by or according to seg25, AA161187
seg25 amplicon (SEQ ID NO:1654) and primers AA161187 seg17F2 (SEQ
ID NO:1652) and AA161187 seg17R2 (SEQ ID NO:1653) was measured by
real time PCR. In parallel the expression of four housekeeping
genes-PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon-PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO:1714); amplicon-HPRT1-amplicon, SEQ
ID NO:1297), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO:1711); amplicon-Ubiquitin-amplicon, SEQ ID NO:328) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon-SDHA-amplicon, SEQ ID NO:331), was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, above), to obtain a
value of fold up-regulation for each sample relative to median of
the normal PM samples.
[1829] FIG. 64 is a histogram showing over expression of the
above-indicated Homo sapiens protease, serine, 21 (testisin)
(PRSS21) transcripts in cancerous lung samples relative to the
normal samples.
[1830] As is evident from FIG. 64, the expression of Homo sapiens
protease, serine, 21 (testisin) (PRSS21) transcripts detectable by
the above amplicon(s) was higher in a few cancer samples than in
the non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99 Table
2). Notably an over-expression of at least 6 fold was found in 1
out of 15 adenocarcinoma samples, 3 out of 16 squamous cell
carcinoma samples, 1 out of 4 large cell carcinoma samples.
[1831] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: AA161187
seg17F2 forward primer (SEQ ID NO:1652); and AA161187 seg17R2
reverse primer (SEQ ID NO:1653).
[1832] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: AA161187 seg25 (SEQ ID NO:1654).
TABLE-US-00452 Forward primer AA161187 seg17F2 (SEQ ID NO:1652):
CCCTGTGCCTTATTTGACCCT Reverse primer AA161187 seg17R2 (SEQ ID NO:
1653): GCTGGGTAGACTGGGTGCA Amplicon AA161187 seg25 (SEQ ID NO:
1654): CCTGTGCCTTATTTGACCCTCATGCCAACCCCGGGAGGTGGAGACTGTTG
CCCCACTCTGCAGATGCAGAAACGGAGGCTTGGCTGCTGCCAGGGGGAGG A
Description for Cluster R66178
[1833] Cluster R66178 features 3 transcript(s) and 16 segment(s) of
interest, the names for which are given in Tables 413 and 414,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
415.
TABLE-US-00453 TABLE 413 Transcripts of interest Transcript Name
Sequence ID No. R66178_T2 48 R66178_T3 49 R66178_T7 50
TABLE-US-00454 TABLE 414 Segments of interest Segment Name Sequence
ID No. R66178_node_0 502 R66178_node_6 503 R66178_node_8 504
R66178_node_15 505 R66178_node_24 506 R66178_node_26 507
R66178_node_27 508 R66178_node_4 509 R66178_node_5 510
R66178_node_9 511 R66178_node_11 512 R66178_node_16 513
R66178_node_18 514 R66178_node_19 515 R66178_node_20 516
R66178_node_21 517
TABLE-US-00455 TABLE 415 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) R66178_P3 1324 R66178_T2 (SEQ ID
NO: 48) R66178_P4 1325 R66178_T3 (SEQ ID NO: 49) R66178_P8 1326
R66178_T7 (SEQ ID NO: 50)
[1834] These sequences are variants of the known protein Poliovirus
receptor related protein 1 precursor (SwissProt accession
identifier PVR1_HUMAN; known also according to the synonyms Herpes
virus entry mediator C; HveC; Nectin 1; Herpesvirus Ig-like
receptor; HIgR; CD111 antigen), SEQ ID NO: 1432, referred to herein
as the previously known protein.
[1835] Protein Poliovirus receptor related protein 1 precursor (SEQ
ID NO:1432) is known or believed to have the following function(s):
probably involved in cell adhesion; receptor for alphaherpesvirus
(HSV-1, HSV-2 and Pseudorabies virus) entry into cells. The
sequence for protein Poliovirus receptor related protein 1
precursor is given at the end of the application, as "Poliovirus
receptor related protein 1 precursor amino acid sequence". Protein
Poliovirus receptor related protein 1 precursor localization is
believed to be Type I membrane protein (isoforms alpha and delta).
Secreted (isoform gamma).
[1836] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: immune response;
cell-cell adhesion, which are annotation(s) related to Biological
Process; cell adhesion receptor; protein binding; coreceptor, which
are annotation(s) related to Molecular Function; and adherens
junction; integral membrane protein, which are annotation(s)
related to Cellular Component.
[1837] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[1838] As noted above, cluster R66178 features 3 transcript(s),
which were listed in Table 413 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Poliovirus receptor
related protein 1 precursor (SEQ ID NO:1432). A description of each
variant protein according to the present invention is now
provided.
[1839] Variant protein R66178_P3 (SEQ ID NO:1324) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) R66178_T2 (SEQ ID
NO:48). An alignment is given to the known protein (Poliovirus
receptor related protein 1 precursor (SEQ ID NO:1432)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1840] Comparison report between R66178_P3 (SEQ ID NO:1324) and
PVR1_HUMAN (SEQ ID NO:1432):
[1841] 1. An isolated chimeric polypeptide encoding for R66178_P3
(SEQ ID NO:1324), comprising a first amino acid sequence being at
least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVEVNIT
corresponding to amino acids 1-334 of PVR1_HUMAN (SEQ ID NO:1432),
which also corresponds to amino acids 1-334 of R66178_P3 (SEQ ID
NO:1324), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence GEGHSLPISPGVLQTQNCGP (SEQ ID NO:
694) corresponding to amino acids 335-354 of R66178_P3 (SEQ ID
NO:1324), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[1842] 2. An isolated polypeptide encoding for a tail of R66178_P3
(SEQ ID NO:1324), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence GEGHSLPISPGVLQTQNCGP (SEQ ID NO:
694) in R66178_P3 (SEQ ID NO:1324).
[1843] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1844] Variant protein R66178_P3 (SEQ ID NO:1324) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 416, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein R66178_P3 (SEQ ID NO:1324)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00456 TABLE 416 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
77 N -> S No
[1845] The glycosylation sites of variant protein R66178_P3 (SEQ ID
NO:1324), as compared to the known protein Poliovirus receptor
related protein 1 precursor (SEQ ID NO:1432), are described in
Table 417 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00457 TABLE 417 Glycosylation site(s) Position(s) on known
amino acid Present Position sequence in variant protein? in variant
protein? 72 yes 72 297 yes 297 202 yes 202 307 yes 307 332 yes 332
139 yes 139 36 yes 36 286 yes 286
[1846] Variant protein R66178_P3 (SEQ ID NO:1324) is encoded by the
following transcript(s): R66178_T2 (SEQ ID NO:48), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R66178_T2 (SEQ ID NO:48) is shown in bold;
this coding portion starts at position 634 and ends at position
1695. The transcript also has the following SNPs as listed in Table
418 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R66178_P3 (SEQ ID NO:1324) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00458 TABLE 418 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
474 -> T No 476 -> C No 632 -> T No 633 G -> T No 863 A
-> G No 897 C -> T Yes 2178 A -> G No 2465 G -> A Yes
2687 G -> A Yes
[1847] Variant protein R66178_P4 (SEQ ID NO:1325) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) R66178_T3 (SEQ ID
NO:49). An alignment is given to the known protein (Poliovirus
receptor related protein 1 precursor (SEQ ID NO:1432)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1848] Comparison report between R66178_P4 (SEQ ID NO:1325) and
PVR1_HUMAN (SEQ ID NO:1432):
[1849] 1. An isolated chimeric polypeptide encoding for R66178_P4
(SEQ ID NO:1325), comprising a first amino acid sequence being at
least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVEVNIT
corresponding to amino acids 1-334 of PVR1_HUMAN (SEQ ID NO:1432),
which also corresponds to amino acids 1-334 of R66178_P4 (SEQ ID
NO:1325), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence AFCQLIYPGKGRTRARMF (SEQ ID NO:
1702) corresponding to amino acids 335-352 of R66178_P4 (SEQ ID
NO:1325), wherein said first amino acid sequence and second amino
acid sequence are contiguous and in a sequential order.
[1850] 2. An isolated polypeptide encoding for a tail of R66178_P4
(SEQ ID NO:1325), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence AFCQLIYPGKGRTRARMF (SEQ ID NO: 1702)
in R66178_P4 (SEQ ID NO:1325).
[1851] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1852] Variant protein R66178_P4 (SEQ ID NO:1325) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 419, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein R66178_P4 (SEQ ID NO:1325)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00459 TABLE 419 Amino acid mutations SNP position(s) on
Alternative amino acid sequence amino acid(s) Previously known SNP?
77 N -> S No
[1853] The glycosylation sites of variant protein R66178_P4 (SEQ ID
NO:1325), as compared to the known protein Poliovirus receptor
related protein 1 precursor (SEQ ID NO:1432), are described in
Table 420 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00460 TABLE 420 Glycosylation site(s) Position(s) on known
amino acid Present Position sequence in variant protein? in variant
protein? 72 yes 72 297 yes 297 202 yes 202 307 yes 307 332 yes 332
139 yes 139 36 yes 36 286 yes 286
[1854] Variant protein R66178_P4 (SEQ ID NO:1325) is encoded by the
following transcript(s): R66178_T3 (SEQ ID NO:49), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R66178_T3 (SEQ ID NO:49) is shown in bold;
this coding portion starts at position 634 and ends at position
1689. The transcript also has the following SNPs as listed in Table
421 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R66178_P4 (SEQ ID NO:1325) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00461 TABLE 421 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
474 -> T No 476 -> C No 632 -> T No 633 G -> T No 863 A
-> G No 897 C -> T Yes 1762 C -> Yes
[1855] Variant protein R66178_P8 (SEQ ID NO:1326) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) R66178_T7 (SEQ ID
NO:50). An alignment is given to the known protein (Poliovirus
receptor related protein 1 precursor (SEQ ID NO:1432)) at the end
of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[1856] Comparison report between R66178_P8 (SEQ ID NO:1326) and
PVR1_HUMAN (SEQ ID NO:1432):
[1857] 1. An isolated chimeric polypeptide encoding for R66178_P8
(SEQ ID NO:1326), comprising a first amino acid sequence being at
least 90% homologous to
MARMGLAGAAGRWWGLALGLTAFFLPGVHSQVVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTWQ
KSTNGSKQNVAIYNPSMGVSVLAPYRERVEFLRPSFTDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNL
TVMAKPTNWIEGTQAVLRAKKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVIS
RYRLVPSREAHQQSLACIVNYHMDRFKESLTLNVQYEPEVTIEGFDGNWYLQRMDVKLTCKADANPPAT
EYHWTTLNGSLPKGVEAQNRTLFFKGPINYSLAGTYICEATNPIGTRSGQVE corresponding
to amino acids 1-330 of PVR1_HUMAN (SEQ ID NO:1432), which also
corresponds to amino acids 1-330 of R66178_P8 (SEQ ID NO:1326), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC (SEQ ID NO: 1717)
corresponding to amino acids 331-363 of R66178_P8 (SEQ ID NO:1326),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[1858] 2. An isolated polypeptide encoding for a tail of R66178_P8
(SEQ ID NO:1326), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence NSPTPRLLPNMGGAPGRCPRPSLGAWRGASCWC
(SEQ ID NO: 1717) in R66178_P8 (SEQ ID NO:1326).
[1859] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1860] Variant protein R66178_P8 (SEQ ID NO:1326) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 422, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein R66178_P8 (SEQ ID NO:1326)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00462 TABLE 422 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
77 N -> S No
[1861] The glycosylation sites of variant protein R66178_P8 (SEQ ID
NO:1326), as compared to the known protein Poliovirus receptor
related protein 1 precursor (SEQ ID NO:1432), are described in
Table 423 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00463 TABLE 423 Glycosylation site(s) Position(s) on known
amino acid Present Position sequence in variant protein? in variant
protein? 72 yes 72 297 yes 297 202 yes 202 307 yes 307 332 no 139
yes 139 36 yes 36 286 yes 286
[1862] Variant protein R66178_P8 (SEQ ID NO:1326) is encoded by the
following transcript(s): R66178_T7 (SEQ ID NO:50), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R66178_T7 (SEQ ID NO:50) is shown in bold;
this coding portion starts at position 634 and ends at position
1722. The transcript also has the following SNPs as listed in Table
424 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R66178_P8 (SEQ ID NO:1326) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00464 TABLE 424 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
474 -> T No 476 -> C No 632 -> T No 633 G -> T No 863 A
-> G No 897 C -> T Yes 2210 A -> C No 2211 A -> C
No
[1863] As noted above, cluster R66178 features 16 segment(s), which
were listed in Table 414 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[1864] Segment cluster R66178_node.sub.--0 (SEQ ID NO:502)
according to the present invention is supported by 19 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 425 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00465 TABLE 425 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1 712 R66178_T3 (SEQ ID NO: 49) 1 712 R66178_T7
(SEQ ID NO: 50) 1 712
[1865] Segment cluster R66178_node.sub.--6 (SEQ ID NO:503)
according to the present invention is supported by 39 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 426 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00466 TABLE 426 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 762 1063 R66178_T3 (SEQ ID NO: 49) 762 1063
R66178_T7 (SEQ ID NO: 50) 762 1063
[1866] Segment cluster R66178_node.sub.--8 (SEQ ID NO:504)
according to the present invention is supported by 39 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 427 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00467 TABLE 427 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1064 1269 R66178_T3 (SEQ ID NO: 49) 1064 1269
R66178_T7 (SEQ ID NO: 50) 1064 1269
[1867] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 428.
TABLE-US-00468 TABLE 428 Oligonucleotides related to this segment
Overexpressed Chip Oligonucleotide name in cancers reference
R66178_0_7_0 (SEQ ID NO: 223) lung malignant tumors LUN
[1868] Segment cluster R66178_node.sub.--15 (SEQ ID NO:505)
according to the present invention is supported by 40 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 429 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00469 TABLE 429 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1485 1623 R66178_T3 (SEQ ID NO: 49) 1485 1623
R66178_T7 (SEQ ID NO: 50) 1485 1623
[1869] Segment cluster R66178_node.sub.--24 (SEQ ID NO:506)
according to the present invention is supported by 10 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48). Table 430 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00470 TABLE 430 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1637 3110
[1870] Segment cluster R66178_node.sub.--26 (SEQ ID NO:507)
according to the present invention is supported by 24 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T7
(SEQ ID NO:50). Table 431 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00471 TABLE 431 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T7
(SEQ ID NO: 50) 1624 2087
[1871] Segment cluster R66178_node.sub.--27 (SEQ ID NO:508)
according to the present invention is supported by 12 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T7
(SEQ ID NO:50). Table 432 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00472 TABLE 432 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T7
(SEQ ID NO: 50) 2088 2364
[1872] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1873] Segment cluster R66178_node.sub.--4 (SEQ ID NO:509)
according to the present invention is supported by 21 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 433 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00473 TABLE 433 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 713 749 R66178_T3 (SEQ ID NO: 49) 713 749 R66178_T7
(SEQ ID NO: 50) 713 749
[1874] Segment cluster R66178_node.sub.--5 (SEQ ID NO:510)
according to the present invention can be found in the following
transcript(s): R66178_T2 (SEQ ID NO:48), R66178_T3 (SEQ ID NO:49)
and R66178_T7 (SEQ ID NO:50). Table 434 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00474 TABLE 434 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 750 761 R66178_T3 (SEQ ID NO: 49) 750 761 R66178_T7
(SEQ ID NO: 50) 750 761
[1875] Segment cluster R66178_node.sub.--9 (SEQ NO:511) according
to the present invention is supported by 44 libraries. The number
of libraries was determined as previously described. This segment
can be found in the following transcript(s): R66178 T2 (SEQ ID
NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID NO:50).
Table 435 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00475 TABLE 435 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1270 1366 R66178_T3 (SEQ ID NO: 49) 1270 1366
R66178_T7 (SEQ ID NO: 50) 1270 1366
[1876] Segment cluster R66178_node.sub.--11 (SEQ ID NO:512)
according to the present invention is supported by 44 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T2
(SEQ ID NO:48), R66178_T3 (SEQ ID NO:49) and R66178_T7 (SEQ ID
NO:50). Table 436 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00476 TABLE 436 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1367 1484 R66178_T3 (SEQ ID NO: 49) 1367 1484
R66178_T7 (SEQ ID NO: 50) 1367 1484
[1877] Segment cluster R66178_node.sub.--16 (SEQ ID NO:513)
according to the present invention can be found in the following
transcript(s): R66178_T2 (SEQ ID NO:48) and R66178_T3 (SEQ ID
NO:49). Table 437 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-00477 TABLE 437 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T2
(SEQ ID NO: 48) 1624 1636 R66178_T3 (SEQ ID NO: 49) 1624 1636
[1878] Segment cluster R66178_node.sub.--18 (SEQ ID NO:514)
according to the present invention is supported by 13 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T3
(SEQ ID NO:49). Table 438 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00478 TABLE 438 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T3
(SEQ ID NO: 49) 1637 1743
[1879] Segment cluster R66178_node.sub.--19 (SEQ ID NO:515)
according to the present invention can be found in the following
transcript(s): R66178_T3 (SEQ ID NO:49). Table 439 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00479 TABLE 439 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T3
(SEQ ID NO: 49) 1744 1763
[1880] Segment cluster R66178_node.sub.--20 (SEQ ID NO:516)
according to the present invention is supported by 12 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T3
(SEQ ID NO:49). Table 440 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00480 TABLE 440 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T3
(SEQ ID NO: 49) 1764 1791
[1881] Segment cluster R66178_node.sub.--21 (SEQ ID NO:517)
according to the present invention is supported by 11 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R66178_T3
(SEQ ID NO:49). Table 441 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00481 TABLE 441 Segment location on transcripts Segment
Segment Transcript name starting position ending position R66178_T3
(SEQ ID NO: 49) 1792 1903
Variant protein alignment to the previously known protein:
TABLE-US-00482 Sequence name: PVR1_HUMAN (SEQ ID NO: 1432) Sequence
documentation: Alignment of: R66178_P3 (SEQ ID NO: 1324) .times.
PVR1_HUMAN (SEQ ID NO: 1432) . . . Alignment segment 1/1: Quality:
3826.00 Escore: 0 Matching length: 334 Total length: 334 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00287## ##STR00288## ##STR00289## ##STR00290##
##STR00291## ##STR00292## ##STR00293## Sequence name: PVR1_HUMAN
(SEQ ID NO: 1432) Sequence documentation: Alignment of: R66178_P4
(SEQ ID NO: 1325) .times. PVR1_HUMAN (SEQ ID NO: 1432) . . .
Alignment segment 1/1: Quality: 3294.00 Escore: 0 Matching length:
336 Total length: 336 Matching Percent Similarity: 99.70 Matching
Percent Identity: 99.70 Total Percent Similarity: 99.70 Total
Percent Identity: 99.70 Gaps: 0 Alignment: ##STR00294##
##STR00295## ##STR00296## ##STR00297## ##STR00298## ##STR00299##
##STR00300## Sequence name: PVR1_HUMAN (SEQ ID NO: 1432) Sequence
documentation: Alignment of: R66178_P8 (SEQ ID NO: 1326) .times.
PVR1_HUMAN (SEQ ID NO: 1432) . . . Alignment segment 1/1: Quality:
3250.00 Escore: 0 Matching length: 330 Total length: 330 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00301## ##STR00302## ##STR00303## ##STR00304##
##STR00305## ##STR00306## ##STR00307##
Description for Cluster HUMPHOSLIP
[1882] Cluster HUMPHOSLIP features 7 transcript(s) and 53
segment(s) of interest, the names for which are given in Tables 442
and 443, respectively, the sequences themselves are given at the
end of the application. The selected protein variants are given in
table 444.
TABLE-US-00483 TABLE 442 Transcripts of interest Transcript Name
Sequence ID No. HUMPHOSLIP_PEA_2_T6 51 HUMPHOSLIP_PEA_2_T7 52
HUMPHOSLIP_PEA_2_T14 53 HUMPHOSLIP_PEA_2_T16 54
HUMPHOSLIP_PEA_2_T17 55 HUMPHOSLIP_PEA_2_T18 56
HUMPHOSLIP_PEA_2_T19 57
TABLE-US-00484 TABLE 443 Segments of interest Segment Name Sequence
ID No. HUMPHOSLIP_PEA_2_node_0 518 HUMPHOSLIP_PEA_2_node_19 519
HUMPHOSLIP_PEA_2_node_34 520 HUMPHOSLIP_PEA_2_node_68 521
HUMPHOSLIP_PEA_2_node_70 522 HUMPHOSLIP_PEA_2_node_75 523
HUMPHOSLIP_PEA_2_node_2 524 HUMPHOSLIP_PEA_2_node_3 525
HUMPHOSLIP_PEA_2_node_4 526 HUMPHOSLIP_PEA_2_node_6 527
HUMPHOSLIP_PEA_2_node_7 528 HUMPHOSLIP_PEA_2_node_8 529
HUMPHOSLIP_PEA_2_node_9 530 HUMPHOSLIP_PEA_2_node_14 531
HUMPHOSLIP_PEA_2_node_15 532 HUMPHOSLIP_PEA_2_node_16 533
HUMPHOSLIP_PEA_2_node_17 534 HUMPHOSLIP_PEA_2_node_23 535
HUMPHOSLIP_PEA_2_node_24 536 HUMPHOSLIP_PEA_2_node_25 537
HUMPHOSLIP_PEA_2_node_26 538 HUMPHOSLIP_PEA_2_node_29 539
HUMPHOSLIP_PEA_2_node_30 540 HUMPHOSLIP_PEA_2_node_33 541
HUMPHOSLIP_PEA_2_node_36 542 HUMPHOSLIP_PEA_2_node_37 543
HUMPHOSLIP_PEA_2_node_39 544 HUMPHOSLIP_PEA_2_node_40 545
HUMPHOSLIP_PEA_2_node_41 546 HUMPHOSLIP_PEA_2_node_42 547
HUMPHOSLIP_PEA_2_node_44 548 HUMPHOSLIP_PEA_2_node_45 549
HUMPHOSLIP_PEA_2_node_47 550 HUMPHOSLIP_PEA_2_node_51 551
HUMPHOSLIP_PEA_2_node_52 552 HUMPHOSLIP_PEA_2_node_53 553
HUMPHOSLIP_PEA_2_node_54 554 HUMPHOSLIP_PEA_2_node_55 555
HUMPHOSLIP_PEA_2_node_58 556 HUMPHOSLIP_PEA_2_node_59 557
HUMPHOSLIP_PEA_2_node_60 558 HUMPHOSLIP_PEA_2_node_61 559
HUMPHOSLIP_PEA_2_node_62 560 HUMPHOSLIP_PEA_2_node_63 562
HUMPHOSLIP_PEA_2_node_64 562 HUMPHOSLIP_PEA_2_node_65 563
HUMPHOSLIP_PEA_2_node_66 564 HUMPHOSLIP_PEA_2_node_67 565
HUMPHOSLIP_PEA_2_node_69 566 HUMPHOSLIP_PEA_2_node_71 567
HUMPHOSLIP_PEA_2_node_72 568 HUMPHOSLIP_PEA_2_node_73 569
HUMPHOSLIP_PEA_2_node_74 570
TABLE-US-00485 TABLE 444 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) HUMPHOSLIP_PEA_2_P10 1327
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_P12 1328
HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) HUMPHOSLIP_PEA_2_P30 1329
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_P31 1330
HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_P33 1331
HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) HUMPHOSLIP_PEA_2_P34 1332
HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) HUMPHOSLIP_PEA_2_P35 1333
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56)
[1883] These sequences are variants of the known protein
Phospholipid transfer protein precursor (SwissProt accession
identifier PLTP_HUMAN; known also according to the synonyms Lipid
transfer protein II), SEQ ID NO: 1433, referred to herein as the
previously known protein.
[1884] Protein Phospholipid transfer protein precursor (SEQ ID
NO:1433) is known or believed to have the following function(s):
Converts HDL into larger and smaller particles. May play a key role
in extracellular phospholipid transport and modulation of HDL
particles. The sequence for protein Phospholipid transfer protein
precursor is given at the end of the application, as "Phospholipid
transfer protein precursor amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 445.
TABLE-US-00486 TABLE 445 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 282 R -> Q. /FTId =
VAR_017020. 372 R -> H. /FTId = VAR_017021. 380 R -> W (in
dbSNP: 6065903). /FTId = VAR_017022. 444 F -> L (in dbSNP:
1804161). /FTId = VAR_012073. 487 T -> K (in dbSNP: 1056929).
/FTId = VAR_012074. 18 E -> V
[1885] Protein Phospholipid transfer protein precursor (SEQ ID
NO:1433) localization is believed to be Secreted.
[1886] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: lipid metabolism;
lipid transport, which are annotation(s) related to Biological
Process; lipid binding, which are annotation(s) related to
Molecular Function; and extracellular, which are annotation(s)
related to Cellular Component.
[1887] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from
<expasy dot ch/sprot/>; or Locuslink, available from <dot
ncbi dot nlm dot nih dot gov/projects/LocusLink/>.
[1888] For this cluster, at least one oligonucleotide was found to
demonstrate overexpression of the cluster, although not of at least
one transcript/segment as listed below. Microarray (chip) data is
also available for this cluster as follows. Various
oligonucleotides were tested for being differentially expressed in
various disease conditions, particularly cancer, as previously
described. The following oligonucleotides were found to hit this
cluster but not other segments/transcripts below, shown in Table
446, with regard to lung cancer.
TABLE-US-00487 TABLE 446 Oligonucleotides related to this cluster
Oligonucleotide name Overexpressed in cancers Chip reference
HUMPHOSLIP_0_0_18458 lung malignant tumors LUN (SEQ ID NO: 224)
[1889] As noted above, cluster HUMPHOSLIP features 7 transcript(s),
which were listed in Table 1 above. These transcript(s) encode for
protein(s) which are variant(s) of protein Phospholipid transfer
protein precursor (SEQ ID NO:1433). A description of each variant
protein according to the present invention is now provided.
[1890] Variant protein HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1891] Comparison report between HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID
NO:1327) and PLTP_HUMAN (SEQ ID NO:1433):
[1892] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISE
corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-67 of
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), and a second amino
acid sequence being at least 90% homologous to
KVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVGIDYSLMKDPVASTSNLDMD
FRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAGALQLLLVGDKVPHDLDMLL
RATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPPDQPEVQLSSMTMDARLSAK
MALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLNERTWRGVQIPLPEGINFVHE
VVTNHAGFLTIGADLHFAKGLREVIEKNRPADVRASTAPTPSTAAV corresponding to
amino acids 163-493 of PLTP_HUMAN (SEQ ID NO:1433), which also
corresponds to amino acids 68-398 of HUMPHOSLIP_PEA.sub.--2_P10
(SEQ ID NO:1327), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[1893] 2. An isolated chimeric polypeptide encoding for an edge
portion of HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), comprising
a polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EK, having a structure as follows: a
sequence starting from any of amino acid numbers 67-x to 67; and
ending at any of amino acid numbers 68+((n-2)-x), in which x varies
from 0 to n-2.
[1894] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1895] Variant protein HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 447, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00488 TABLE 447 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 113 S -> F Yes 118 V -> No
140 R -> No 140 R -> P No 150 N -> No 160 P -> No 201 P
-> No 274 M -> No 285 R -> W Yes 292 Q -> No 315 L
-> * No 330 M -> I Yes 349 F -> L Yes 392 T -> K
Yes
[1896] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 448 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00489 TABLE 448 Glycosylation site(s) Position(s) on known
Present Position amino acid sequence in variant protein? in variant
protein? 94 no 143 no 64 yes 64 245 yes 150 398 yes 303 117 no
[1897] Variant protein HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID NO:1327)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55) is
shown in bold; this coding portion starts at position 276 and ends
at position 1469. The transcript also has the following SNPs as
listed in Table 449 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P10 (SEQ ID
NO:1327) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00490 TABLE 449 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 431 G -> A Yes 551 C -> T Yes 613 C -> T Yes 628 T
-> No 694 G -> No 694 G -> C No 723 A -> No 753 C ->
No 876 C -> No 1037 C -> T Yes 1097 G -> No 1128 C -> T
Yes 1149 C -> No 1219 T -> A No 1230 C -> T Yes 1265 G
-> C Yes 1322 T -> A Yes 1450 C -> A Yes 1469 C -> T No
1549 C -> T Yes 1565 A -> G No 1565 A -> T No 1630 A ->
G Yes 1654 T -> A No 1731 G -> T Yes 1864 G -> A Yes 1893
G -> T Yes 2073 G -> A Yes 2269 C -> T Yes 2325 G -> T
Yes 2465 C -> T Yes 2566 C -> T Yes 2881 A -> G No
[1898] Variant protein HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1899] Comparison report between HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID
NO:1328) and PLTP_HUMAN (SEQ ID NO:1433):
[1900] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPVRSSVDELVG
IDYSLMKDPVASTSNLDMDFRGAFFPLTERNWSLPNRAVEPQLQEEERMVYVAFSEFFFDSAMESYFRAG
ALQLLLVGDKVPHDLDMLLRATYFGSIVLLSPAVIDSPLKLELRVLAPPRCTIKPSGTTISVTASVTIALVPP
DQPEVQLSSMTMDARLSAKMALRGKALRTQLDLRRFRIYSNHSALESLALIPLQAPLKTMLQIGVMPMLN
corresponding to amino acids 1-427 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-427 of
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GKAGV (SEQ ID NO: 263) corresponding to amino acids
428-432 of HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[1901] 2. An isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
GKAGV (SEQ ID NO: 263) in HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID
NO:1328).
[1902] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1903] Variant protein HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 450, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00491 TABLE 450 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 81 D -> H Yes 124 S -> Y
Yes 160 T -> No 160 T -> N No 208 S -> F Yes 213 V ->
No 235 R -> P No 235 R -> No 245 N -> No 255 P -> No
296 P -> No 369 M -> No 380 R -> W Yes 387 Q -> No 410
L -> * No 425 M -> I Yes
[1904] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 451 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00492 TABLE 451 Glycosylation site(s) Position(s) on known
Present Position amino acid sequence in variant protein? in variant
protein? 94 yes 94 143 yes 143 64 yes 64 245 yes 245 398 yes 398
117 yes 117
[1905] Variant protein HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID NO:1328)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57) is
shown in bold; this coding portion starts at position 276 and ends
at position 1571. The transcript also has the following SNPs as
listed in Table 452 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P12 (SEQ ID
NO:1328) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00493 TABLE 452 Nucleic acid SNPs SNP position(s) on
nucleotide sequence Alternative nucleic acid Previously known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 431 G -> A Yes 516 G -> C Yes 644 G -> A Yes 646 C
-> A Yes 754 C -> No 754 C -> A No 836 C -> T Yes 898 C
-> T Yes 913 T -> No 979 G -> No 979 G -> C No 1008 A
-> No 1038 C -> No 1161 C -> No 1322 C -> T Yes 1382 G
-> No 1413 C -> T Yes 1434 C -> No 1504 T -> A No 1515
C -> T Yes 1550 G -> C Yes 1690 T -> A Yes 1818 C -> A
Yes 1837 C -> T No 1917 C -> T Yes 1933 A -> G No 1933 A
-> T No 1998 A -> G Yes 2022 T -> A No 2099 G -> T Yes
2232 G -> A Yes 2261 G -> T Yes 2441 G -> A Yes 2637 C
-> T Yes 2693 G -> T Yes 2833 C -> T Yes 2934 C -> T
Yes 3249 A -> G No
[1906] Variant protein HUMPHOSLIP_PEA.sub.--2_P30 (SEQ ID NO:1329)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51). The location of the
variant protein was determined according to results from a number
of different software programs and analyses, including analyses
from SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[1907] Variant protein HUMPHOSLIP_PEA.sub.--2_P30 (SEQ ID NO:1329)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 453, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P30 (SEQ ID NO:1329) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00494 TABLE 453 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 37 R -> Q Yes
[1908] Variant protein HUMPHOSLIP_PEA.sub.--2_P30 (SEQ ID NO:1329)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51), for which the sequence(s)
is/are given at the end of the application. The coding portion of
transcript HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51) is shown in
bold; this coding portion starts at position 276 and ends at
position 431. The transcript also has the following SNPs as listed
in Table 454 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P30 (SEQ ID NO:1329)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00495 TABLE 454 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 385 G -> A Yes 470 G -> C Yes 598 G -> A Yes 600 C
-> A Yes 708 C -> No 708 C -> A No 790 C -> T Yes 852 C
-> T Yes 867 T -> No 933 G -> No 933 G -> C No 962 A
-> No 992 C -> No 1115 C -> No 1276 C -> T Yes 1336 G
-> No 1367 C -> T Yes 1388 C -> No 1458 T -> A No 1469
C -> T Yes 1504 G -> C Yes 1561 T -> A Yes 1689 C -> A
Yes 1708 C -> T No 1788 C -> T Yes 1804 A -> G No 1804 A
-> T No 1869 A -> G Yes 1893 T -> A No 1970 G -> T Yes
2103 G -> A Yes 2132 G -> T Yes 2312 G -> A Yes 2508 C
-> T Yes 2564 G -> T Yes 2704 C -> T Yes 2805 C -> T
Yes 3120 A -> G No
[1909] Variant protein HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1910] Comparison report between HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID
NO:1330) and PLTP_HUMAN (SEQ ID NO:1433):
[1911] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISE
corresponding to amino acids 1-67 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-67 of
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), and a second amino
acid sequence 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO: 264) corresponding to
amino acids 68-98 of HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[1912] 2. An isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
PGLERGADKFPVVGGSSLFLALDLTLRPPVG (SEQ ID NO: 264) in
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330).
[1913] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1914] Variant protein HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 455, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00496 TABLE 455 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes
[1915] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 456 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00497 TABLE 456 Glycosylation site(s) Position(s) on known
Present Position in amino acid sequence in variant protein? variant
protein? 94 no 143 no 64 yes 64 245 no 398 no 117 no
[1916] Variant protein HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52), for which the sequence(s)
is/are given at the end of the application. The coding portion of
transcript HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52) is shown in
bold; this coding portion starts at position 276 and ends at
position 569. The transcript also has the following SNPs as listed
in Table 457 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P31 (SEQ ID NO:1330)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00498 TABLE 457 Nucleic acid SNPs SNP position nucleotide
sequence Alternative nucleic acid Previously known SNP? 174 G ->
T No 175 A -> T No 322 A -> G Yes 328 A -> T Yes 431 G
-> A Yes 608 G -> C Yes 736 G -> A Yes 738 C -> A Yes
846 C -> No 846 C -> A No 928 C -> T Yes 990 C -> T Yes
1005 T -> No 1071 G -> No 1071 G -> C No 1100 A -> No
1130 C -> No 1253 C -> No 1414 C -> T Yes 1474 G -> No
1505 C -> T Yes 1526 C -> No 1596 T -> A No 1607 C -> T
Yes 1642 G -> C Yes 1699 T -> A Yes 1827 C -> A Yes 1846 C
-> T No 1926 C -> T Yes 1942 A -> G No 1942 A -> T No
2007 A -> G Yes 2031 T -> A No 2108 G -> T Yes 2241 G
-> A Yes 2270 G -> T Yes 2450 G -> A Yes 2646 C -> T
Yes 2702 G -> T Yes 2842 C -> T Yes 2943 C -> T Yes 3258 A
-> G No
[1917] Variant protein HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1918] Comparison report between HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID
NO:1331) and PLTP_HUMAN (SEQ ID NO:1433):
[1919] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQ corresponding to amino
acids 1-183 of PLTP_HUMAN (SEQ ID NO:1433), which also corresponds
to amino acids 1-183 of HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID
NO:1331), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VWAATGRRVARVGMLSL (SEQ ID NO: 265)
corresponding to amino acids 184-200 of HUMPHOSLIP_PEA.sub.--2_P33
(SEQ ID NO:1331), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[1920] 2. An isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VWAATGRRVARVGMLSL (SEQ ID NO: 265) in HUMPHOSLIP_PEA.sub.--2_P33
(SEQ ID NO:1331).
[1921] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1922] Variant protein HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 458, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00499 TABLE 458 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 81 D -> H Yes 124 S -> Y
Yes 160 T -> No 160 T -> N No
[1923] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 459 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00500 TABLE 459 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 94 yes 94 143 yes 143 64 yes 64 245 no 398 no 117 yes
117
[1924] Variant protein HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID NO:1331)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53) is
shown in bold; this coding portion starts at position 276 and ends
at position 875. The transcript also has the following SNPs as
listed in Table 460 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P33 (SEQ ID
NO:1331) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00501 TABLE 460 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 431 G -> A Yes 516 G -> C Yes 644 G -> A Yes 646 C
-> A Yes 754 C -> No 754 C -> A No 921 C -> T Yes 983 C
-> T Yes 998 T -> No 1064 G -> No 1064 G -> C No 1093 A
-> No 1123 C -> No 1246 C -> No 1407 C -> T Yes 1467 G
-> No 1498 C -> T Yes 1519 C -> No 1589 T -> A No 1600
C -> T Yes 1635 G -> C Yes 1692 T -> A Yes 1820 C -> A
Yes 1839 C -> T No 1919 C -> T Yes 1935 A -> G No 1935 A
-> T No 2000 A -> G Yes 2024 T -> A No 2101 G -> T Yes
2234 G -> A Yes 2263 G -> T Yes 2443 G -> A Yes 2639 C
-> T Yes 2695 G -> T Yes 2835 C -> T Yes 2936 C -> T
Yes 3251 A -> G No
[1925] Variant protein HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1926] Comparison report between HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID
NO:1332) and PLTP_HUMAN (SEQ ID NO:1433):
[1927] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWFFYDGGYINASAEGVSIRTGLELSRDPAGRMKVSN
VSCQASVSRMHAAFGGTFKKVYDFLSTFITSGMRFLLNQQICPVLYHAGTVLLNSLLDTVPV
corresponding to amino acids 1-205 of PLTP_HUMAN (SEQ ID NO:1433),
which also corresponds to amino acids 1-205 of
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence LWTSLLALTIPS (SEQ ID NO: 266) corresponding to amino acids
206-217 of HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[1928] 2. An isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
LWTSLLALTIPS (SEQ ID NO: 266) in HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID
NO:1332).
[1929] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1930] Variant protein HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332)
also has the following non-silent SNPs
[1931] (Single Nucleotide Polymorphisms) as listed in Table 461,
(given according to their position(s) on the amino acid sequence,
with the alternative amino acid(s) listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00502 TABLE 461 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 81 D -> H Yes 124 S -> Y
Yes 160 T -> No 160 T -> N No 211 L -> No
[1932] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 462 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00503 TABLE 462 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 94 yes 94 143 yes 143 64 yes 64 245 no 398 no 117 yes
117
[1933] Variant protein HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID NO:1332)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54) is
shown in bold; this coding portion starts at position 276 and ends
at position 926. The transcript also has the following SNPs as
listed in Table 463 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P34 (SEQ ID
NO:1332) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00504 TABLE 463 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 431 G -> A Yes 516 G -> C Yes 644 G -> A Yes 646 C
-> A Yes 754 C -> No 754 C -> A No 836 C -> T Yes 891 C
-> T Yes 906 T -> No 972 G -> No 972 G -> C No 1001 A
-> No 1031 C -> No 1154 C -> No 1315 C -> T Yes 1375 G
-> No 1406 C -> T Yes 1427 C -> No 1497 T -> A No 1508
C -> T Yes 1543 G -> C Yes 1600 T -> A Yes 1728 C -> A
Yes 1747 C -> T No 1827 C -> T Yes 1843 A -> G No 1843 A
-> T No 1908 A -> G Yes 1932 T -> A No 2009 G -> T Yes
2142 G -> A Yes 2171 G -> T Yes 2351 G -> A Yes 2547 C
-> T Yes 2603 G -> T Yes 2743 C -> T Yes 2844 C -> T
Yes 3159 A -> G No
[1934] Variant protein HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56). An alignment is given to
the known protein (Phospholipid transfer protein precursor (SEQ ID
NO:1433)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[1935] Comparison report between HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID
NO:1333) and PLTP_HUMAN (SEQ ID NO:1433):
[1936] 1. An isolated chimeric polypeptide encoding for
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising a first
amino acid sequence being at least 90% homologous to
MALFGALFLALLAGAHAEFPGCKIRVTSKALELVKQEGLRFLEQELETITIPDLRGKEGHFYYNISEVKVTE
LQLTSSELDFQPQQELMLQITNASLGLRFRRQLLYWF corresponding to amino acids
1-109 of PLTP_HUMAN (SEQ ID NO:1433), which also corresponds to
amino acids 1-109 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), a
second amino acid sequence bridging amino acid sequence comprising
of L, a third amino acid sequence being at least 90% homologous to
KVYDFLSTFITSGMRFLLNQQ corresponding to amino acids 163-183 of
PLTP_HUMAN (SEQ ID NO:1433), which also corresponds to amino acids
111-131 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), and a
fourth amino acid sequen least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VWAATGRRVARVGMLSL (SEQ ID NO: 265) corresponding to amino
acids 132-148 of HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333),
wherein said first amino acid sequence, second amino acid sequence,
third amino acid sequence and fourth amino acid sequence are
contiguous and in a sequential order.
[1937] 2. An isolated polypeptide encoding for an edge portion of
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise FLK having a structure as follows
(numbering according to HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID
NO:1333)): a sequence starting from any of amino acid numbers 109-x
to 109; and ending at any of amino acid numbers 111+((n-2)-x), in
which x varies from 0 to n-2.
[1938] 3. An isolated polypeptide encoding for a tail of
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VWAATGRRVARVGMLSL (SEQ ID NO: 265) in HUMPHOSLIP_PEA.sub.--2_P35
(SEQ ID NO:1333).
[1939] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[1940] Variant protein HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 464, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00505 TABLE 464 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 H -> R Yes 18 E -> V Yes 81 D -> H Yes
[1941] The glycosylation sites of variant protein
HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333), as compared to the
known protein Phospholipid transfer protein precursor (SEQ ID
NO:1433), are described in Table 465 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-00506 TABLE 465 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 94 yes 94 143 no 64 yes 64 245 no 398 no 117 no
[1942] Variant protein HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID NO:1333)
is encoded by the following transcript(s):
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) is
shown in bold; this coding portion starts at position 276 and ends
at position 719. The transcript also has the following SNPs as
listed in Table 466 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMPHOSLIP_PEA.sub.--2_P35 (SEQ ID
NO:1333) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00507 TABLE 466 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
174 G -> T No 175 A -> T No 322 A -> G Yes 328 A -> T
Yes 431 G -> A Yes 516 G -> C Yes 765 C -> T Yes 827 C
-> T Yes 842 T -> No 908 G -> No 908 G -> C No 937 A
-> No 967 C -> No 1090 C -> No 1251 C -> T Yes 1311 G
-> No 1342 C -> T Yes 1363 C -> No 1433 T -> A No 1444
C -> T Yes 1479 G -> C Yes 1536 T -> A Yes 1664 C -> A
Yes 1683 C -> T No 1763 C -> T Yes 1779 A -> G No 1779 A
-> T No 1844 A -> G Yes 1868 T -> A No 1945 G -> T Yes
2078 G -> A Yes 2107 G -> T Yes 2287 G -> A Yes 2483 C
-> T Yes 2539 G -> T Yes 2679 C -> T Yes 2780 C -> T
Yes 3095 A -> G No
[1943] As noted above, cluster HUMPHOSLIP features 53 segment(s),
which were listed in Table 443 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[1944] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--0 (SEQ ID
NO:518) according to the present invention is supported by 150
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 467 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00508 TABLE 467 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 1 264 HUMPHOSLIP_PEA_2_T7 (SEQ
ID NO: 52) 1 264 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 1 264
HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 1 264 HUMPHOSLIP_PEA_2_T17
(SEQ ID NO: 55) 1 264 HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 1 264
HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 1 264
[1945] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--19 (SEQ ID
NO:519) according to the present invention is supported by 186
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53), HUMPHOSLIP_PEA2_T16 (SEQ
ID NO:54) and HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 468
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00509 TABLE 468 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 559 714 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 697 852 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 605
760 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 605 760
HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 605 760
[1946] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--34 (SEQ ID
NO:520) according to the present invention is supported by 191
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54), HUMPHOSLIP_PEA2_T17 (SEQ
ID NO:55), HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 469 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00510 TABLE 469 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 971 1111 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 1109 1249 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 1102
1242 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 1010 1150
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 732 872 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 946 1086 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 1017
1157
[1947] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--68 (SEQ ID
NO:521) according to the present invention is supported by 131
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 470 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00511 TABLE 470 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 1867 2285 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 2005 2423 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 1998
2416 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 1906 2324
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 1628 2046 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 1842 2260 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 1996
2414
[1948] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--70 (SEQ ID
NO:522) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 471 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00512 TABLE 471 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 2298 2529 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 2436 2667 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 2429
2660 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 2337 2568
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 2059 2290 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 2273 2504 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 2427
2658
[1949] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--75 (SEQ ID
NO:523) according to the present invention is supported by 14
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53), HUMPHOSLIP_PEA2_T16 (SEQ
ID NO:54), HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 472 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00513 TABLE 472 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 2846 3125 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 2984 3263 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 2977
3256 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 2885 3164
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 2607 2886 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 2821 3100 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 2975
3254
[1950] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[1951] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--2 (SEQ ID
NO:524) according to the present invention is supported by 159
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 473 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00514 TABLE 473 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 265 337 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 265 337 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 265
337 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 265 337
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 265 337 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 265 337 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 265
337
[1952] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--3 (SEQ ID
NO:525) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 474 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00515 TABLE 474 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 52) 338 355 HUMPHOSLIP_PEA_2_T14
(SEQ ID NO: 53) 338 355 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 338
355 HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 338 355
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 338 355 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 338 355
[1953] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--4 (SEQ ID
NO:526) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 475 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00516 TABLE 475 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 52) 356 375 HUMPHOSLIP_PEA_2_T14
(SEQ ID NO: 53) 356 375 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 356
375 HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 356 375
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 356 375 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 356 375
[1954] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--6 (SEQ ID
NO:527) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP _PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 476 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00517 TABLE 476 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 52) 376 383 HUMPHOSLIP_PEA_2_T14
(SEQ ID NO: 53) 376 383 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 376
383 HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 376 383
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 376 383 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 376 383
[1955] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--7 (SEQ ID
NO:528) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 477 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00518 TABLE 477 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 338 343 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 384 389 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 384
389 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 384 389
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 384 389 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 384 389 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 384
389
[1956] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--8 (SEQ ID
NO:529) according to the present invention is supported by 171
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 478 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00519 TABLE 478 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 344 378 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 390 424 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 390
424 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 390 424
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 390 424 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 390 424 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 390
424
[1957] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--9 (SEQ ID
NO:530) according to the present invention is supported by 168
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56 and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 479 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00520 TABLE 479 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 379 429 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 425 475 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 425
475 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 425 475
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 425 475 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 425 475 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 425
475
[1958] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--14 (SEQ ID
NO:531) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52). Table 480
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00521 TABLE 480 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T7 (SEQ ID NO: 52) 476 567
[1959] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--15 (SEQ ID
NU:532) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 481 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00522 TABLE 481 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 430 445 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 568 583 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 476
491 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 476 491
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 476 491 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 476 491
[1960] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--16 (SEQ ID
NO:533) according to the present invention is supported by 179
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 482 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00523 TABLE 482 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 446 534 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 584 672 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 492
580 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 492 580
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 492 580 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 492 580
[1961] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--17 (SEQ ID
NO:534) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 483 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00524 TABLE 483 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 535 558 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 673 696 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 581
604 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 581 604
HUMPHOSLIP_PEA_2_T18 (SEQ ID NO: 56) 581 604 HUMPHOSLIP_PEA_2_T19
(SEQ ID NO: 57) 581 604
[1962] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--23 (SEQ ID
NO:535) according to the present invention is supported by 168
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 484 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00525 TABLE 484 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 715 766 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 853 904 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 761
812 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 761 812
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 476 527 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 605 656 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 761
812
[1963] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--24 (SEQ ID
NO:536) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 485 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00526 TABLE 485 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 767 778 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 905 916 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 813
824 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 813 824
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 528 539 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 657 668 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 813
824
[1964] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--25 (SEQ ID
NO:537) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53) and
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56). Table 486 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00527 TABLE 486 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 825 909 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 669 753
[1965] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--26 (SEQ ID
NO:538) according to the present invention is supported by 163
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53), HUMPHOSLIP_PEA2_T16 (SEQ
ID NO:54), HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 487 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00528 TABLE 487 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 779 842 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 917 980 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 910
973 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 825 888
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 540 603 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 754 817 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 825
888
[1966] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--29 (SEQ ID
NO:539) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53) ,
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 488 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00529 TABLE 488 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 843 849 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7 981
987 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 974 980 (SEQ ID NO: 53)
HUMPHOSLIP_PEA_2_T17 604 610 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
818 824 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 889 895 (SEQ ID NO:
57)
[1967] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--30 (SEQ ID
NO:540) according to the present invention is supported by 181
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 489 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00530 TABLE 489 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 850 934 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7 988
1072 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 981 1065 (SEQ ID NO: 53)
HUMPHOSLIP_PEA_2_T16 889 973 (SEQ ID NO: 54) HUMPHOSLIP_PEA_2_T17
611 695 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18 825 909 (SEQ ID NO:
56) HUMPHOSLIP_PEA_2_T19 896 980 (SEQ ID NO: 57)
[1968] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--33 (SEQ ID
NO:541) according to the present invention is supported by 173
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 490 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00531 TABLE 490 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 935 970 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1073 1108 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1066 1101 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 974 1009 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 696 731 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
910 945 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 981 1016 (SEQ ID NO:
57)
[1969] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--36 (SEQ ID
NO:542) according to the present invention is supported by 163
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55), HUMPHOSLIP_PEA2_T18 (SEQ
ID NO:56) and HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 491
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00532 TABLE 491 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1112 1156 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1250 1294 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1243 1287 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1151 1195 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 873 917 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1087 1131 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1158 1202 (SEQ ID
NO: 57)
[1970] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--37 (SEQ ID
NO:543) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 492 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00533 TABLE 492 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1157 1171 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1295 1309 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1288 1302 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1196 1210 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 918 932 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1132 1146 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1203 1217 (SEQ ID
NO: 57)
[1971] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--39 (SEQ ID
NO:544) according to the present invention is supported by 166
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 493 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00534 TABLE 493 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1172 1201 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1310 1339 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1303 1332 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1211 1240 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 933 962 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1147 1176 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1218 1247 (SEQ ID
NO: 57)
[1972] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--40 (SEQ ID
NO:545) according to the present invention is supported by 199
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table. 494 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00535 TABLE 494 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1202 1288 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1340 1426 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1333 1419 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1241 1327 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 963 1049 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1177 1263 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1248 1334 (SEQ ID
NO: 57)
[1973] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--41 (SEQ ID
NO:546) according to the present invention is supported by 186
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 495 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00536 TABLE 495 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1289 1318 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1427 1456 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1420 1449 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1328 1357 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1050 1079 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1264 1293 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1335 1364 (SEQ ID
NO: 57)
[1974] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--42 (SEQ ID
NO:547) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 496 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00537 TABLE 496 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1319 1336 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1457 1474 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1450 1467 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1358 1375 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1080 1097 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1294 1311 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1365 1382 (SEQ ID
NO: 57)
[1975] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--44 (SEQ ID
NO:548) according to the present invention is supported by 185
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 497 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00538 TABLE 497 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1337 1363 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1475 1501 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1468 1494 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1376 1402 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1098 1124 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1312 1338 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1383 1409 (SEQ ID
NO: 57)
[1976] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--45 (SEQ ID
NO:549) according to the present invention is supported by 197
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2.sub.--T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 498 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00539 TABLE 498 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1364 1404 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1502 1542 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1495 1535 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1403 1443 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1125 1165 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1339 1379 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1410 1450 (SEQ ID
NO: 57)
[1977] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--47 (SEQ ID
NO:550) according to the present invention is supported by 223
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 499 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00540 TABLE 499 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1405 1447 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1543 1585 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1536 1578 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1444 1486 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1166 1208 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1380 1422 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1451 1493 (SEQ ID
NO: 57)
[1978] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--51 (SEQ ID
NO:551) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and HUMPHOSLIP_PEA2_T19
(SEQ ID NO:57). Table 500 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00541 TABLE 500 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1448 1462 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1586 1600 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1579 1593 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1487 1501 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1209 1223 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1423 1437 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1494 1508 (SEQ ID
NO: 57)
[1979] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--52 (SEQ ID
NO:552) according to the present invention is supported by 235
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA2_T7 (SEQ ID NO:52), HUMPHOSLIP_PEA.sub.--2_T14 (SEQ
ID NO:53), HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 501 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00542 TABLE 501 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1463 1511 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1601 1649 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1594 1642 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1502 1550 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1224 1272 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1438 1486 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1509 1557 (SEQ ID
NO: 57)
[1980] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--53 (SEQ ID
NO:553) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 502
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00543 TABLE 502 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T19 1558 1640 (SEQ ID NO: 57)
[1981] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--54 (SEQ ID
NO:554) according to the present invention is supported by 236
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 503 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00544 TABLE 503 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1512 1552 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1650 1690 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1643 1683 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1551 1591 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1273 1313 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1487 1527 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1641 1681 (SEQ ID
NO: 57)
[1982] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--55 (SEQ ID
NO:555) according to the present invention is supported by 232
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53), HUMPHOSLIP_PEA2_T16 (SEQ
ID NO:54), HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 504 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00545 TABLE 504 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1553 1588 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1691 1726 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1684 1719 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1592 1627 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1314 1349 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1528 1563 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1682 1717 (SEQ ID
NO: 57)
[1983] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--58 (SEQ ID
NO:556) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 505 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00546 TABLE 505 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1589 1612 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1727 1750 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1720 1743 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1628 1651 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1350 1373 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1564 1587 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1718 1741 (SEQ ID
NO: 57)
[1984] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--59 (SEQ ID
NO:557) according to the present invention is supported by 230
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 506 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00547 TABLE 506 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1613 1648 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1751 1786 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1744 1779 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1652 1687 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1374 1409 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1588 1623 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1742 1777 (SEQ ID
NO: 57)
[1985] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--60 (SEQ ID
NO:558) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 507 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00548 TABLE 507 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1649 1671 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1787 1809 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1780 1802 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1688 1710 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1410 1432 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1624 1646 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1778 1800 (SEQ ID
NO: 57)
[1986] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--61 (SEQ ID
NO:559) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 508 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00549 TABLE 508 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1672 1680 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1810 1818 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1803 1811 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1711 1719 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1433 1441 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1647 1655 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1801 1809 (SEQ ID
NO: 57)
[1987] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--62 (SEQ ID
NO:560) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 509 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00550 TABLE 509 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1681 1703 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1819 1841 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1812 1834 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1720 1742 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1442 1464 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1656 1678 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1810 1832 (SEQ ID
NO: 57)
[1988] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--63 (SEQ ID
NO:561) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 510 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00551 TABLE 510 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1704 1727 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1842 1865 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1835 1858 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1743 1766 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1465 1488 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1679 1702 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1833 1856 (SEQ ID
NO: 57)
[1989] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--64 (SEQ ID
NO:562) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 511 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00552 TABLE 511 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1728 1734 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1866 1872 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1859 1865 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1767 1773 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1489 1495 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1703 1709 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1857 1863 (SEQ ID
NO: 57)
[1990] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--65 (SEQ ID
NO:563) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 512 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00553 TABLE 512 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1735 1754 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1873 1892 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1866 1885 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1774 1793 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1496 1515 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1710 1729 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1864 1883 (SEQ ID
NO: 57)
[1991] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--66 (SEQ ID
NU:564) according to the present invention is supported by 180
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55), HUMPHOSLIP_PEA2_T18 (SEQ
ID NO:56) and HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 513
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00554 TABLE 513 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1755 1844 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1893 1982 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1886 1975 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1794 1883 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1516 1605 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1730 1819 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1884 1973 (SEQ ID
NO: 57)
[1992] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--67 (SEQ ID
NO:565) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 514 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00555 TABLE 514 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 1845 1866 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
1983 2004 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 1976 1997 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 1884 1905 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 1606 1627 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
1820 1841 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 1974 1995 (SEQ ID
NO: 57)
[1993] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--69 (SEQ ID
NO:566) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 515 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00556 TABLE 515 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 2286 2297 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
2424 2435 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 2417 2428 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 2325 2336 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 2047 2058 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
2261 2272 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 2415 2426 (SEQ ID
NO: 57)
[1994] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--71 (SEQ ID
NO:567) according to the present invention can be found in the
following transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 516 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00557 TABLE 516 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 2530 2542 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
2668 2680 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 2661 2673 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 2569 2581 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 2291 2303 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
2505 2517 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 2659 2671 (SEQ ID
NO: 57)
[1995] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--72 (SEQ ID
NO:568) according to the present invention is supported by 7
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 517 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00558 TABLE 517 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HUMPHOSLIP_PEA_2_T6 2543 2647 (SEQ ID NO: 51) HUMPHOSLIP_PEA_2_T7
2681 2785 (SEQ ID NO: 52) HUMPHOSLIP_PEA_2_T14 2674 2778 (SEQ ID
NO: 53) HUMPHOSLIP_PEA_2_T16 2582 2686 (SEQ ID NO: 54)
HUMPHOSLIP_PEA_2_T17 2304 2408 (SEQ ID NO: 55) HUMPHOSLIP_PEA_2_T18
2518 2622 (SEQ ID NO: 56) HUMPHOSLIP_PEA_2_T19 2672 2776 (SEQ ID
NO: 57)
[1996] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--73 (SEQ ID
NO:569) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 518 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00559 TABLE 518 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 2648 2755 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 2786 2893 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 2779
2886 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 2687 2794
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 2409 2516 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 2623 2730 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 2777
2884
[1997] Segment cluster HUMPHOSLIP_PEA.sub.--2_node.sub.--74 (SEQ ID
NO:570) according to the present invention is supported by 10
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMPHOSLIP_PEA.sub.--2_T6 (SEQ ID NO:51),
HUMPHOSLIP_PEA.sub.--2_T7 (SEQ ID NO:52),
HUMPHOSLIP_PEA.sub.--2_T14 (SEQ ID NO:53),
HUMPHOSLIP_PEA.sub.--2_T16 (SEQ ID NO:54),
HUMPHOSLIP_PEA.sub.--2_T17 (SEQ ID NO:55),
HUMPHOSLIP_PEA.sub.--2_T18 (SEQ ID NO:56) and
HUMPHOSLIP_PEA.sub.--2_T19 (SEQ ID NO:57). Table 519 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00560 TABLE 519 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMPHOSLIP_PEA_2_T6 (SEQ ID NO: 51) 2756 2845 HUMPHOSLIP_PEA_2_T7
(SEQ ID NO: 52) 2894 2983 HUMPHOSLIP_PEA_2_T14 (SEQ ID NO: 53) 2887
2976 HUMPHOSLIP_PEA_2_T16 (SEQ ID NO: 54) 2795 2884
HUMPHOSLIP_PEA_2_T17 (SEQ ID NO: 55) 2517 2606 HUMPHOSLIP_PEA_2_T18
(SEQ ID NO: 56) 2731 2820 HUMPHOSLIP_PEA_2_T19 (SEQ ID NO: 57) 2885
2974
Variant protein alignment to the previously known protein:
TABLE-US-00561 Sequence name: PLTP_HUMAN (SEQ ID NO: 1433) Sequence
documentation: Alignment of: HUMPHOSLIP_PEA_2_P10 (SEQ ID NO: 1327)
.times. PLTP_HUMAN (SEQ ID NO: 1433) . . . Alignment segment 1/1:
Quality: 3716.00 Escore: 0 Matching length: 398 Total length: 493
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 80.73 Total Percent Identity:
80.73 Gaps: 1 Alignment: ##STR00308## ##STR00309## ##STR00310##
##STR00311## ##STR00312## ##STR00313## ##STR00314## ##STR00315##
##STR00316## Sequence name: PLTP_HUMAN (SEQ ID NO: 1433) Sequence
documentation: Alignment of: HUMPHOSLIP_PEA_2_P12 (SEQ ID NO: 1328)
.times. PLTP_HUMAN (SEQ ID NO: 1433) . . . Alignment segment 1/1:
Quality: 4101.00 Escore: 0 Matching length: 427 Total length: 427
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00317## ##STR00318## ##STR00319##
##STR00320## ##STR00321## ##STR00322## ##STR00323## ##STR00324##
##STR00325## Sequence name: PLTP_HUMAN (SEQ ID NO: 1433) Sequence
documentation: Alignment of: HUMPHOSLIP_PEA_2_P31 (SEQ ID NO: 1330)
.times. PLTP_HUMAN (SEQ ID NO : 1433) . . . Alignment segment 1/1:
Quality: 639.00 Escore: 0 Matching length: 67 Total length: 67
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00326## ##STR00327## Sequence name:
PLTP_HUMAN (SEQ ID NO: 1433) Sequence documentation: Alignment of:
HUMPHOSLIP_PEA_2_P33 (SEQ ID NO: 1331) .times. PLTP_HUMAN (SEQ ID
NO: 1433) Alignment segment 1/1: Quality: 1767.00 Escore: 0
Matching length: 184 Total length: 184 Matching Percent Similarity:
100.00 Matching Percent Identity: 99.46 Total Percent Similarity:
100.00 Total Percent Identity: 99.46 Gaps: 0 Alignment:
##STR00328## ##STR00329## ##STR00330## ##STR00331## Sequence name:
PLTP_HUMAN (SEQ ID NO: 1433) Sequence documentation: Alignment of:
HUMPHOSLIP_PEA_2_P34 (SEQ ID NO: 1332) .times. PLTP_HUMAN (SEQ ID
NO: 1433) . . . Alignment segment 1/1: Quality: 1971.00 Escore: 0
Matching length: 205 Total length: 205 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00332## ##STR00333## ##STR00334## ##STR00335## ##STR00336##
Sequence name: PLTP_HUMAN (SEQ ID NO: 1433) Sequence documentation:
Alignment of: HUMPHOSLIP_PEA_2_P35 (SEQ ID NO: 1333) .times.
PLTP_HUMAN (SEQ ID NO: 1433) . . . Alignment segment 1/1: Quality:
1158.00 Escore: 0 Matching length: 132 Total length: 184 Matching
Percent Similarity: 100.00 Matching Percent Identity: 98.48 Total
Percent Similarity: 71.74 Total Percent Identity: 70.65 Gaps: 1
Alignment: ##STR00337## ##STR00338## ##STR00339## ##STR00340##
Description for Cluster AI076020
[1998] Cluster AI076020 features 1 transcript(s) and 8 segment(s)
of interest, the names for which are given in Tables 520 and 521,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
522.
TABLE-US-00562 TABLE 520 Transcripts of interest Transcript Name
Sequence ID No. AI076020_T0 58
TABLE-US-00563 TABLE 521 Segments of interest Segment Name Sequence
ID No. AI076020_node_0 571 AI076020_node_3 572 AI076020_node_8 573
AI076020_node_1 574 AI076020_node_4 575 AI076020_node_5 576
AI076020_node_6 577 AI076020_node_7 578
TABLE-US-00564 TABLE 522 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) AI076020_P1 1334 AI076020_T0
(SEQ ID NO: 58)
[1999] These sequences are variants of the known protein
C1q-related factor precursor (SwissProt accession identifier
C1RF_HUMAN), SEQ ID NO: 1434, referred to herein as the previously
known protein.
[2000] The sequence for protein C1q-related factor precursor (SEQ
ID NO:1434) is given at the end of the application, as "C1q-related
factor precursor amino acid sequence".
[2001] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: locomotory
behavior, which are annotation(s) related to Biological
Process.
[2002] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2003] Cluster AI076020 can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the right hand column of the table and the numbers on
the y-axis of FIG. 31 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[2004] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 31 and Table 523. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: brain malignant tumors and a mixture of
malignant tumors from different tissues.
TABLE-US-00565 TABLE 523 Normal tissue distribution Name of Tissue
Number bone 0 brain 9 epithelial 0 general 4 kidney 2 lung 0 ovary
0 pancreas 30 uterus 0
TABLE-US-00566 TABLE 524 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bone 3.3e-01
5.9e-02 4.0e-01 2.5 2.4e-01 3.0 brain 8.8e-04 2.2e-03 5.5e-11 14.2
4.6e-08 8.7 epithelial 2.6e-01 8.6e-02 2.8e-01 2.4 1.8e-02 4.5
general 2.1e-03 3.0e-04 2.0e-06 4.3 8.4e-06 3.5 kidney 5.5e-01
3.3e-01 3.4e-01 2.3 8.2e-02 3.3 lung 1 6.3e-01 1 1.0 3.8e-01 2.2
ovary 4.2e-01 4.5e-01 0.0e+00 0.0 0.0e+00 0.0 pancreas 6.0e-01
7.1e-01 8.9e-01 0.6 9.5e-01 0.5 uterus 1 4.0e-01 1 1.0 6.4e-01
1.5
[2005] As noted above, cluster AI076020 features 1 transcript(s),
which were listed in Table 520 above. These transcript(s) encode
for protein(s) which are variant(s) of protein C1q-related factor
precursor (SEQ ID NO:1434). A description of each variant protein
according to the present invention is now provided.
[2006] Variant protein AI076020_P1 (SEQ ID NO:1334) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) AI076020_T0
(SEQ ID NO:58). The location of the variant protein was determined
according to results from a number of different software programs
and analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2007] Variant protein AI076020_P1 (SEQ ID NO:1334) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 525, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein AI076020_P1 (SEQ ID NO:1334)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00567 TABLE 525 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 36 P -> R Yes 66 Q -> R Yes 165 K -> R Yes
[2008] Variant protein AI076020_P1 (SEQ ID NO:1334) is encoded by
the following transcript(s): AI076020_T0 (SEQ ID NO:58), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript AI076020_T0 (SEQ ID NO:58) is shown in
bold; this coding portion starts at position 261 and ends at
position 1034. The transcript also has the following SNPs as listed
in Table 526 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein AI076020_P1 (SEQ ID NO:1334) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00568 TABLE 526 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 367 C
-> G Yes 457 A -> G Yes 464 C -> A Yes 754 A -> G Yes
1265 C -> T Yes 1384 C -> T Yes 1402 G -> C Yes 1452 T
-> C Yes
[2009] As noted above, cluster AI076020 features 8 segment(s),
which were listed in Table 521 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[2010] Segment cluster AI076020_node.sub.--0 (SEQ ID NO:571)
according to the present invention is supported by 28 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 527 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00569 TABLE 527 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1 774
[2011] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 528.
TABLE-US-00570 TABLE 528 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
AI076020_0_3_0 lung malignant tumors LUN (SEQ ID NO: 226)
[2012] Segment cluster AI076020_node.sub.--3 (SEQ ID NO:572)
according to the present invention is supported by 30 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 529 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00571 TABLE 529 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 858 1027
[2013] Segment cluster AI076020_node.sub.--8 (SEQ ID NO:573)
according to the present invention is supported by 35 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 530 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00572 TABLE 530 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1359 1533
[2014] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2015] Segment cluster AI076020_node.sub.--1 (SEQ ID NO:574)
according to the present invention is supported by 19 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 531 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00573 TABLE 531 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 775 857
[2016] Segment cluster AI076020_node.sub.--4 (SEQ ID NO:575)
according to the present invention is supported by 28 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 532 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00574 TABLE 532 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1028 1129
[2017] Segment cluster AI076020_node.sub.--5 (SEQ ID NO:576)
according to the present invention is supported by 31 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): A1076020
T0 (SEQ ID NO:58). Table 533 below describes the starting and
ending position of this segment on each transcript.
TABLE-US-00575 TABLE 533 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1130 1244
[2018] Segment cluster AI076020_node.sub.--6 (SEQ ID NO:577)
according to the present invention is supported by 32 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 534 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00576 TABLE 534 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1245 1320
[2019] Segment cluster AI076020_node.sub.--7 (SEQ ID NO:578)
according to the present invention is supported by 33 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
AI076020_T0 (SEQ ID NO:58). Table 535 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00577 TABLE 535 Segment location on transcripts Segment
Segment starting ending Transcript name position position
AI076020_T0 (SEQ ID NO: 58) 1321 1358
Description for Cluster T23580
[2020] Cluster T23580 features 1 transcript(s) and 5 segment(s) of
interest, the names for which are given in Tables 536 and 537,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
538.
TABLE-US-00578 TABLE 536 Transcripts of interest Transcript Name
Sequence ID No. T23580_T10 1626
TABLE-US-00579 TABLE 537 Segments of interest Segment Name Sequence
ID No. T23580_node_17 579 T23580_node_18 580 T23580_node_21 581
T23580_node_19 582 T23580_node_20 583
TABLE-US-00580 TABLE 538 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) T23580_P5 1335 T23580_T10 (SEQ
ID NO: 1626)
[2021] These sequences are variants of the known protein Neuronal
protein NP25 (SwissProt accession identifier TAG3_HUMAN; known also
according to the synonyms Neuronal protein 22; NP22; Transgelin-3),
SEQ ID NO: 1435, referred to herein as the previously known protein
and also as NP25_HUMAN, which is the former SwissProt accession
identifier.
[2022] The sequence for protein Neuronal protein NP25 (SEQ ID
NO:1435) is given at the end of the application, as "Neuronal
protein NP25 amino acid sequence".
[2023] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: central nervous
system development, which are annotation(s) related to Biological
Process.
[2024] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2025] For this cluster, at least one oligonucleotide was found to
demonstrate overexpression of the cluster, although not of at least
one transcript/segment as listed below. Microarray (chip) data is
also available for this cluster as follows. Various
oligonucleotides were tested for being differentially expressed in
various disease conditions, particularly cancer, as previously
described. The following oligonucleotides were found to hit this
cluster but not other segments/transcripts below, shown in Table
539, with regard to lung cancer.
TABLE-US-00581 TABLE 539 Oligonucleotides related to this cluster
Oligonucleotide name Overexpressed in cancers Chip reference
T23580_0_0_902 lung malignant tumors LUN (SEQ ID NO: 227)
[2026] As noted above, cluster T23580 features 1 transcript(s),
which were listed in Table 536 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Neuronal protein
NP25 (SEQ ID NO:1435). A description of each variant protein
according to the present invention is now provided.
[2027] Variant protein T23580_P5 (SEQ ID NO:1335) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) T23580_T10 (SEQ ID
NO:1626). The location of the variant protein was determined
according to results from a number of different software programs
and analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Signal peptide,NN:NO) predicts that this
protein has a signal peptide.
[2028] Variant protein T23580_P5 (SEQ ID NO:1335) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 540, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein T23580_P5 (SEQ ID NO:1335)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00582 TABLE 540 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 129 V -> I Yes
[2029] Variant protein T23580_P5 (SEQ ID NO:1335) is encoded by the
following transcript(s): T23580_T10 (SEQ ID NO:1626), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript T23580_T10 (SEQ ID NO:1626) is shown in bold;
this coding portion starts at position 1066 and ends at position
1485. The transcript also has the following SNPs as listed in Table
541 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T23580_P5 (SEQ ID NO:1335) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-00583 TABLE 541 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 37 A
-> C Yes 320 G -> A Yes 371 G -> T Yes 372 G -> A Yes
441 A -> G Yes 699 G -> C Yes 744 C -> G Yes 862 G -> T
Yes 1450 G -> A Yes
[2030] As noted above, cluster T23580 features 5 segment(s), which
were listed in Table 537 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2031] Segment cluster T23580_node.sub.--17 (SEQ ID NO:579)
according to the present invention is supported by 10 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T23580_T10 (SEQ ID NO:1626). Table 542 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00584 TABLE 542 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T23580_T10 (SEQ ID NO: 1626) 1 1098
[2032] Segment cluster T23580_node.sub.--18 (SEQ ID NO:580)
according to the present invention is supported by 102 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T23580_T10 (SEQ ID NO:1626). Table 543 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00585 TABLE 543 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T23580_T10 (SEQ ID NO: 1626) 1099 1357
[2033] Segment cluster T23580_node.sub.--21 (SEQ ID NO:581)
according to the present invention is supported by 79 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T23580_T10 (SEQ ID NO:1626). Table 544 below describes the starting
and ending position of this segment on each transcript.
TABLE-US-00586 TABLE 544 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T23580_T10 (SEQ ID NO: 1626) 1382 1582
[2034] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2035] Segment cluster T23580_node.sub.--19 (SEQ ID NO:582)
according to the present invention can be found in the following
transcript(s): T23580_T10 (SEQ ID NO:1626). Table 545 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00587 TABLE 545 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T23580_T10 (SEQ ID NO: 1626) 1358 1370
[2036] Segment cluster T23580_node.sub.--20 (SEQ ID NO:583)
according to the present invention can be found in the following
transcript(s): T23580_T10 (SEQ ID NO:1626). Table 546 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00588 TABLE 546 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T23580_T10 (SEQ ID NO: 1626) 1371 1381
Description for Cluster M79217
[2037] Cluster M79217 features 6 transcript(s) and 32 segment(s) of
interest, the names for which are given in Tables 547 and 548,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
549.
TABLE-US-00589 TABLE 547 Transcripts of interest Transcript Name
Sequence ID No. M79217_PEA_1_T1 59 M79217_PEA_1_T3 60
M79217_PEA_1_T8 61 M79217_PEA_1_T10 62 M79217_PEA_1_T15 63
M79217_PEA_1_T18 64
TABLE-US-00590 TABLE 548 Segments of interest Segment Name Sequence
ID No. M79217_PEA_1_node_2 584 M79217_PEA_1_node_4 585
M79217_PEA_1_node_9 586 M79217_PEA_1_node_10 587
M79217_PEA_1_node_11 588 M79217_PEA_1_node_13 589
M79217_PEA_1_node_14 590 M79217_PEA_1_node_16 591
M79217_PEA_1_node_23 592 M79217_PEA_1_node_24 593
M79217_PEA_1_node_31 594 M79217_PEA_1_node_33 595
M79217_PEA_1_node_34 596 M79217_PEA_1_node_35 597
M79217_PEA_1_node_37 598 M79217_PEA_1_node_38 599
M79217_PEA_1_node_41 600 M79217_PEA_1_node_44 601
M79217_PEA_1_node_0 602 M79217_PEA_1_node_7 603
M79217_PEA_1_node_12 604 M79217_PEA_1_node_19 605
M79217_PEA_1_node_21 606 M79217_PEA_1_node_26 607
M79217_PEA_1_node_27 608 M79217_PEA_1_node_30 609
M79217_PEA_1_node_32 610 M79217_PEA_1_node_36 611
M79217_PEA_1_node_39 612 M79217_PEA_1_node_40 613
M79217_PEA_1_node_42 614 M79217_PEA_1_node_43 615
TABLE-US-00591 TABLE 549 Proteins of interest Sequence ID Protein
Name No. Corresponding Transcript(s) M79217_PEA_1_P1 1336
M79217_PEA_1_T1 (SEQ ID NO: 59); M79217_PEA_1_T3 (SEQ ID NO: 60)
M79217_PEA_1_P2 1337 M79217_PEA_1_T8 (SEQ ID NO: 61)
M79217_PEA_1_P4 1338 M79217_PEA_1_T10 (SEQ ID NO: 62)
M79217_PEA_1_P8 1339 M79217_PEA_1_T15 (SEQ ID NO: 63)
M79217_PEA_1_P11 1340 M79217_PEA_1_T18 (SEQ ID NO: 64)
[2038] These sequences are variants of the known protein
Exostosin-like 3 (SwissProt accession identifier EXL3_HUMAN; known
also according to the synonyms EC 2.4.1.223;
Glucuronyl-galactosyl-proteoglycan
4-alpha-N-acetylglucosaminyltransferase; Putative tumor suppressor
protein EXTL3; Multiple exostosis-like protein 3; Hereditary
multiple exostoses gene isolog; EXT-related protein 1), SEQ ID NO:
1436, referred to herein as the previously known protein.
[2039] Protein Exostosin-like 3 (SEQ ID NO:1436) is known or
believed to have the following function(s): Probable
glycosyltransferase (By similarity). The sequence for protein
Exostosin-like 3 is given at the end of the application, as
"Exostosin-like 3 amino acid sequence". Protein Exostosin-like 3
localization is believed to be Type II membrane protein.
Endoplasmic reticulum.
[2040] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: cell growth and/or
maintenance, which are annotation(s) related to Biological Process;
transferase, transferring glycosyl groups, which are annotation(s)
related to Molecular Function; and endoplasmic reticulum; integral
membrane protein, which are annotation(s) related to Cellular
Component.
[2041] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2042] As noted above, cluster M79217 features 6 transcript(s),
which were listed in Table 547 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Exostosin-like 3
(SEQ ID NO:1436). A 20. description of each variant protein
according to the present invention is now provided.
[2043] Variant protein M79217_PEA.sub.--1_P1 (SEQ ID NO:1336)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M79217_PEA.sub.--1_T1 (SEQ ID NO:59). An alignment is given to the
known protein (Exostosin-like 3 (SEQ ID NO:1436)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2044] Comparison report between M79217_PEA.sub.--1_P1 (SEQ ID
NO:1336) and BAA25445 (SEQ ID NO: 1437):
[2045] 1. An isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P1 (SEQ ID NO:1336), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVDEYINCEDIAMNFLVSHITRKPPIK
VTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFRVDSVLFKTRLPHDKTKCFKFI
corresponding to amino acids 13-931 of BAA25445 (SEQ ID NO:1437),
which also corresponds to amino acids 1-919 of
M79217_PEA.sub.--1_P1 (SEQ ID NO:1336).
[2046] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because the Signalp_hmm software predicts
that this protein has a signal anchor region.
[2047] Variant protein M79217_PEA.sub.--1_P1 (SEQ ID NO:1336) is
encoded by the following transcript(s): M79217_PEA.sub.--1_T1 (SEQ
ID NO:59), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M79217_PEA.sub.--1_T1
(SEQ ID NO:59) is shown in bold; this coding portion starts at
position 1074 and ends at position 3830. The transcript also has
the following SNPs as listed in Table 550 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M79217_PEA.sub.--1_P1 (SEQ ID NO:1336) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00592 TABLE 550 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
1014 C -> T No 1015 T -> No 1072 T -> C No 1232 T -> A
No 1383 A -> G No 1440 A -> G No 1544 C -> No 1546 G ->
A No 1685 T -> G No 2215 C -> No 2300 A -> G Yes 2483 T
-> C No 2518 C -> No 2632 T -> G No 3190 T -> C Yes
3352 T -> C No 3373 G -> T No 3386 C -> No 3449 C -> T
Yes 3618 A -> G No 3733 A -> G No 4021 C -> No 4021 C
-> T No 4086 G -> A No 4087 G -> A No 4416 T -> A No
4586 G -> A Yes 4772 C -> T No 5110 C -> T Yes 5219 C
-> T Yes 5437 G -> A No 5645 G -> A No 5743 G -> A Yes
5887 G -> T Yes 6143 A -> C No 6277 G -> No 6277 G -> C
No 6295 C -> G Yes 6308 T -> A No 6403 G -> A Yes 6442 G
-> No 6495 C -> T No
[2048] Variant protein M79217_PEA.sub.--1_P2 (SEQ ID NO:1337)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M79217_PEA.sub.--1_T8 (SEQ ID NO:61). An alignment is given to the
known protein (Exostosin-like 3 (SEQ ID NO:1436)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2049] Comparison report between M79217_PEA.sub.--1_P2 (SEQ ID
NO:1337) and EXL3_HUMAN (SEQ ID NO:1436):
[2050] 1. An isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHK corresponding to amino acids 1-807 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
1-807 of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), and a second amino
acid sequence being at least 90% homologous to
AIRDMVDEYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYM
PLLYTQFRVDSVLFKTRLPHDKTKCFKFI corresponding to amino acids 820-919
of EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino
acids 808-907 of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2051] 2. An isolated chimeric polypeptide encoding for an edge
portion of M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise KA, having a structure as follows: a
sequence starting from any of amino acid numbers 807-x to 807; and
ending at any of amino acid numbers 808+((n-2)-x), in which x
varies from 0 to n-2.
[2052] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because the Signalp_hmm software predicts
that this protein has a signal anchor region.
[2053] Variant protein M79217_PEA.sub.--1_P2 (SEQ ID NO:1337) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 551, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M79217_PEA.sub.--1_P2
(SEQ ID NO:1337) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00593 TABLE 551 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
104 N -> D No 123 N -> D No 157 I -> No 158 R -> Q No
204 F -> L No 381 A -> No 482 A -> No 520 F -> C No 706
L -> P Yes 760 V -> A No 767 R -> L No 771 F -> No 837
I -> V No 875 Y -> C No
[2054] The glycosylation sites of variant protein
M79217_PEA.sub.--1_P2 (SEQ ID NO:1337), as compared to the known
protein Exostosin-like 3 (SEQ ID NO:1436), are described in Table
552 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00594 TABLE 552 Glycosylation site(s) Position(s) on known
amino acid Present in sequence variant protein? Position in variant
protein? 290 yes 290 592 yes 592 790 yes 790 277 yes 277
[2055] Variant protein M79217_PEA.sub.--1_P2 (SEQ ID NO:1337) is
encoded by the following transcript(s): M79217_PEA.sub.--1_T8 (SEQ
ID NO:61), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M79217_PEA.sub.--1_T8
(SEQ ID NO:61) is shown in bold; this coding portion starts at
position 748 and ends at position 3468. The transcript also has the
following SNPs as listed in Table 553 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M79217_PEA.sub.--1_P2 (SEQ ID NO:1337) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00595 TABLE 553 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
688 C -> T No 689 T -> No 746 T -> C No 906 T -> A No
1057 A -> G No 1114 A -> G No 1218 C -> No 1220 G -> A
No 1359 T -> G No 1889 C -> No 1974 A -> G Yes 2157 T
-> C No 2192 C -> No 2306 T -> G No 2864 T -> C Yes
3026 T -> C No 3047 G -> T No 3060 C -> No 3123 C -> T
Yes 3256 A -> G No 3371 A -> G No 3659 C -> No 3659 C
-> T No 3724 G -> A No 3725 G -> A No 4054 T -> A No
4224 G -> A Yes 4410 C -> T No 4748 C -> T Yes 4857 C
-> T Yes 5075 G -> A No 5283 G -> A No 5381 G -> A Yes
5525 G -> T Yes 5781 A -> C No 5915 G -> No 5915 G -> C
No 5933 C -> G Yes 5946 T -> A No 6041 G -> A Yes 6080 G
-> No 6133 C -> T No
[2056] Variant protein M79217_PEA.sub.--1_P4 (SEQ ID NO:1338)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M79217_PEA.sub.--1_T10 (SEQ ID NO:62). An alignment is given to the
known protein (Exostosin-like 3 (SEQ ID NO:1436)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2057] Comparison report between M79217_PEA.sub.--1_P4 (SEQ ID
NO:1338) and EXL3_HUMAN (SEQ ID NO:1436):
[2058] 1. An isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence PELRQPARLGLPECWDYRHEPRCPAQMGSHFIVQAGLKLLASSKPPKCWDY (SEQ
ID NO: 1724) corresponding to amino acids 1-51 of
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), and a second amino acid
sequence being at least 90% homologous to
RVWREARDRIVGFPGRYHAWDIPHQSWLYNSNYSCELSMVLTGAAFFHKYYAYLYSYVMPQAIRDMVD
EYINCEDIAMNFLVSHITRKPPIKVTSRWTFRCPGCPQALSHDDSHFHERHKCINFFVKVYGYMPLLYTQFR
VDSVLFKTRLPHDKTKCFKFI corresponding to amino acids 759-919 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
52-212 of M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2059] 2. An isolated polypeptide encoding for a head of
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PELRQPARLGLPECWDYRHEPRCPAQMGSHFIVQAGLKLLASSKPPKCWDY (Seq id no:
1724) of M79217PEA.sub.--1_P4 (SEQ ID NO:1338).
[2060] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although it is a partial protein,
because both trans-membrane region prediction programs predict that
this protein has a trans-membrane region.
[2061] Variant protein M79217_PEA.sub.--1_P4 (SEQ ID NO:1338) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 554, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M79217_PEA.sub.--1_P4
(SEQ ID NO:1338) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00596 TABLE 554 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
53 V -> A No 60 R -> L No 64 F -> No 142 I -> V No 180
Y -> C No
[2062] The glycosylation sites of variant protein
M79217_PEA.sub.--1_P4 (SEQ ID NO:1338), as compared to the known
protein Exostosin-like 3 (SEQ ID NO:1436), are described in Table
555 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00597 TABLE 555 Glycosylation site(s) Position(s) on known
amino acid Present in sequence variant protein? Position in variant
protein? 290 no 592 no 790 yes 83 277 no
[2063] Variant protein M79217_PEA.sub.--1_P4 (SEQ ID NO:1338) is
encoded by the following transcript(s): M79217_PEA.sub.--1_T10 (SEQ
ID NO:62), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M79217_PEA.sub.--1_T10 (SEQ ID NO:62) is shown in bold; this coding
portion starts at position 1 and ends at position 637. The
transcript also has the following SNPs as listed in Table 556
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M79217_PEA.sub.--1_P4 (SEQ ID NO:1338) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00598 TABLE 556 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
159 T -> C No 180 G -> T No 193 C -> No 256 C -> T Yes
425 A -> G No 540 A -> G No 828 C -> No 828 C -> T No
893 G -> A No 894 G -> A No 1223 T -> A No 1393 G -> A
Yes 1579 C -> T No 1917 C -> T Yes 2026 C -> T Yes 2244 G
-> A No 2452 G -> A No 2550 G -> A Yes 2694 G -> T Yes
2950 A -> C No 3084 G -> No 3084 G -> C No 3102 C -> G
Yes 3115 T -> A No 3210 G -> A Yes 3249 G -> No 3302 C
-> T No
[2064] Variant protein M79217_PEA.sub.--1_P8 (SEQ ID NO:1339)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M79217_PEA.sub.--1_T15 (SEQ ID NO:63). An alignment is given to the
known protein (Exostosin-like 3 (SEQ ID NO:1436)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2065] Comparison report between M79217_PEA.sub.--1_P8 (SEQ ID
NO:1339) and EXL3_HUMAN (SEQ ID NO:1436):
[2066] 1. An isolated chimeric polypeptide encoding for
M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), comprising a first amino
acid sequence being at least 90% homologous to
MTGYTMLRNGGAGNGGQTCMLRWSNRIRLTWLSFTLFVILVFFPLIAHYYLTTLDEADEAGKRIFGPRVG
NELCEVKHVLDLCRIRESVSEELLQLEAKRQELNSEIAKLNLKIEACKKSIENAKQDLLQLKNVISQTEHSY
KELMAQNQPKLSLPIRLLPEKDDAGLPPPKATRGCRLHNCFDYSRCPLTSGFPVYVYDSDQFVFGSYLDPL
VKQAFQATARANVYVTENADIACLYVILVGEMQEPVVLRPAELEKQLYSLPHWRTDGHNHVIINLSRKSD
TQNLLYNVSTGRAMVAQSTFYTVQYRPGFDLVVSPLVHAMSEPNFMEIPPQVPVKRKYLFTFQGEKIESLR
SSLQEARSFEEEMEGDPPADYDDRIIATLKAVQDSKLDQVLVEFTCKNQPKPSLPTEWALCGEREDRLELL
KLSTFALIITPGDPRLVISSGCATRLFEALEVGAVPVVLGEQVQLPYQDMLQWNEAALVVPKPRVTEVHFL
LRSLSDSDLLAMRRQGRFLWETYFSTADSIFNTVLAMIRTRIQIPAAPIREEAAAEIPHRSGKAAGTDPNMA
DNGDLDLGPVETEPPYASPRYLRNFTLTVTDFYRSWNCAPGPFHLFPHTPFDPVLPSEAKFLGSGTGFRPIG
GGAGGSGKEFQAALGGNVPREQFTVVMLTYEREEVLMNSLERLNGLPYLNKVVVVWNSPKLPSEDLLW
PDIGVPIMVVRTEKNSLNNRFLPWNEIETEAILSIDDDAHLRHDEIMFGFRVWREARDRIVGFPGRYHAWDI
PHQSWLYNSNYSCELSMVLTGAAFFHK corresponding to amino acids 1-807 of
EXL3_HUMAN (SEQ ID NO:1436), which also corresponds to amino acids
1-807 of M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VRKSW (SEQ ID NO: 1725) corresponding to amino acids
808-812 of M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2067] 2. An isolated polypeptide encoding for a tail of
M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence VRKSW (SEQ
ID NO: 1725) in M79217PEA.sub.--1_P8 (SEQ ID NO:1339).
[2068] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because the Signalp_hmm software predicts
that this protein has a signal anchor region.
[2069] Variant protein M79217_PEA.sub.--1_P8 (SEQ ID NO:1339) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 557, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M79217_PEA.sub.--1_P8
(SEQ ID NO:1339) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00599 TABLE 557 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
104 N -> D No 123 N -> D No 157 I -> No 158 R -> Q No
204 F -> L No 381 A -> No 482 A -> No 520 F -> C No 706
L -> P Yes 760 V -> A No 767 R -> L No 771 F -> No
[2070] The glycosylation sites of variant protein
M79217_PEA.sub.--1_P8 (SEQ ID NO:1339), as compared to the known
protein Exostosin-like 3 (SEQ ID NO:1436), are described in Table
558 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-00600 TABLE 558 Glycosylation site(s) Position(s) on known
amino acid Present in sequence variant protein? Position in variant
protein? 290 yes 290 592 yes 592 790 yes 790 277 yes 277
[2071] Variant protein M79217_PEA.sub.--1_P8 (SEQ ID NO:1339) is
encoded by the following transcript(s): M79217_PEA.sub.--1_T15 (SEQ
ED NO:63), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M79217_PEA.sub.--1_T15 (SEQ ID NO:63) is shown in bold; this coding
portion starts at position 748 and ends at position 3183. The
transcript also has the following SNPs as listed in Table 559
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M79217_PEA.sub.--1_P8 (SEQ ID NO:1339) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00601 TABLE 559 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
688 C -> T No 689 T -> No 746 T -> C No 906 T -> A No
1057 A -> G No 1114 A -> G No 1218 C -> No 1220 G -> A
No 1359 T -> G No 1889 C -> No 1974 A -> G Yes 2157 T
-> C No 2192 C -> No 2306 T -> G No 2864 T -> C Yes
3026 T -> C No 3047 G -> T No 3060 C -> No 3123 C -> T
Yes 3391 C -> T No 3560 T -> C No
[2072] Variant protein M79217_PEA.sub.--1_P11 (SEQ ID NO:1340)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because one of the two signal-peptide prediction programs
(HMM:Signal peptide,NN:NO) predicts that this protein has a signal
peptide.
[2073] Variant protein M79217_PEA.sub.--1_P11 (SEQ ID NO:1340) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 560, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M79217_PEA.sub.--1_P11
(SEQ ID NO:1340) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00602 TABLE 560 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
17 P -> No 28 C -> S No 72 V -> No 90 S -> F No
[2074] Variant protein M79217_PEA.sub.--1_P11 (SEQ ID NO:1340) is
encoded by the following transcript(s): M79217_PEA.sub.--1_T18 (SEQ
ID NO:64), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M79217_PEA.sub.--1_T18 (SEQ ID NO:64) is shown in bold; this coding
portion starts at position 1354 and ends at position 1674. The
transcript also has the following SNPs as listed in Table 561
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M79217_PEA.sub.--1_P11 (SEQ ID NO:1340) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00603 TABLE 561 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
688 C -> T No 689 T -> No 746 T -> C No 772 G -> A No
870 G -> A Yes 1014 G -> T Yes 1270 A -> C No 1404 G ->
No 1404 G -> C No 1422 C -> G Yes 1435 T -> A No 1530 G
-> A Yes 1569 G -> No 1622 C -> T No
[2075] As noted above, cluster M79217 features 32 segment(s), which
were listed in Table 548 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2076] Segment cluster M79217_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:584) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T3 (SEQ ID NO:60). Table 562
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00604 TABLE 562 Segment location on transcripts Segment
Segment Transcript name starting position ending position
M79217_PEA_1_T3 50 177 (SEQ ID NO: 60)
[2077] Segment cluster M79217_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:585) according to the present invention is supported by 8
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T8 (SEQ ID NO:61),
M79217_PEA.sub.--1_T15 (SEQ ID NO:63) and M79217_PEA.sub.--1_T18
(SEQ ID NO:64). Table 563 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00605 TABLE 563 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T8 (SEQ ID NO: 61) 1 177 M79217_PEA_1_T15 (SEQ ID NO:
63) 1 177 M79217_PEA_1_T18 (SEQ ID NO: 64) 1 177
[2078] Segment cluster M79217_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:586) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59). Table 564
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00606 TABLE 564 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 1 597
[2079] Segment cluster M79217_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:587) according to the present invention is supported by 33
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T15 (SEQ ID NO:63) and
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 565 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00607 TABLE 565 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 598 1080 M79217_PEA_1_T3 (SEQ ID
NO: 60) 272 754 M79217_PEA_1_T8 (SEQ ID NO: 61) 272 754
M79217_PEA_1_T15 (SEQ ID NO: 63) 272 754 M79217_PEA_1_T18 (SEQ ID
NO: 64) 272 754
[2080] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 566.
TABLE-US-00608 TABLE 566 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
M79217_0_9_0 lung malignant tumors LUN (SEQ ID NO: 229)
[2081] Segment cluster M79217_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:588) according to the present invention is supported by 42
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T15 (SEQ ID NO:63). Table 567 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00609 TABLE 567 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 1081 1523 M79217_PEA_1_T3 (SEQ ID
NO: 60) 755 1197 M79217_PEA_1_T8 (SEQ ID NO: 61) 755 1197
M79217_PEA_1_T15 (SEQ ID NO: 63) 755 1197
[2082] Segment cluster M79217_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:589) according to the present invention is supported by 35
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1T15 (SEQ ID NO:63). Table 568 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00610 TABLE 568 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 1548 2075 M79217_PEA_1_T3 (SEQ ID
NO: 60) 1222 1749 M79217_PEA_1_T8 (SEQ ID NO: 61) 1222 1749
M79217_PEA_1_T15 (SEQ ID NO: 63) 1222 1749
[2083] Segment cluster M79217_PEA.sub.--1_node.sub.--14 (SEQ ID
NO:590) according to the present invention is supported by 65
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T15 (SEQ ID NO: 63). Table 569 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00611 TABLE 569 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 2076 3221 M79217_PEA_1_T3 (SEQ ID
NO: 60) 1750 2895 M79217_PEA_1_T8 (SEQ ID NO: 61) 1750 2895
M79217_PEA_1_T15 (SEQ ID NO: 63) 1750 2895
[2084] Segment cluster M79217_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:591) according to the present invention is supported by 51
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T15 (SEQ ID NO:63). Table 570 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00612 TABLE 570 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3222 3349 M79217_PEA_1_T3 (SEQ ID
NO: 60) 2896 3023 M79217_PEA_1_T8 (SEQ ID NO: 61) 2896 3023
M79217_PEA_1_T15 (SEQ ID NO: 63) 2896 3023
[2085] Segment cluster M79217_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:592) according to the present invention is supported by 50
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T10 (SEQ ID NO:62) and
M79217_PEA.sub.--1_T15 (SEQ ID NO:63). Table 571 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00613 TABLE 571 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3350 3494 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3024 3168 M79217_PEA_1_T8 (SEQ ID NO: 61) 3024 3168
M79217_PEA_1_T10 (SEQ ID NO: 62) 157 301 M79217_PEA_1_T15 (SEQ ID
NO: 63) 3024 3168
[2086] Segment cluster M79217_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:593) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T15 (SEQ ID NO:63). Table 572
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00614 TABLE 572 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T15 (SEQ ID NO: 63) 3169 3580
[2087] Segment cluster M79217_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:594) according to the present invention is supported by 50
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217PEA1_T8 (SEQ ID NO:61)
and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 573 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00615 TABLE 573 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3716 3960 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3390 3634 M79217_PEA_1_T8 (SEQ ID NO: 61) 3354 3598
M79217_PEA_1_T10 (SEQ ID NO: 62) 523 767
[2088] Segment cluster M79217_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:595) according to the present invention is supported by 71
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 574 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00616 TABLE 574 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 4015 4631 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3689 4305 M79217_PEA_1_T8 (SEQ ID NO: 61) 3653 4269
M79217_PEA_1_T10 (SEQ ID NO: 62) 822 1438
[2089] Segment cluster M79217_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:596) according to the present invention is supported by 51
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 575 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00617 TABLE 575 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 4632 4869 M79217_PEA_1_T3 (SEQ ID
NO: 60) 4306 4543 M79217_PEA_1_T8 (SEQ ID NO: 61) 4270 4507
M79217_PEA_1_T10 (SEQ ID NO: 62) 1439 1676
[2090] Segment cluster M79217_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:597) according to the present invention is supported by 53
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 576 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00618 TABLE 576 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 4870 4997 M79217_PEA_1_T3 (SEQ ID
NO: 60) 4544 4671 M79217_PEA_1_T8 (SEQ ID NO: 61) 4508 4635
M79217_PEA_1_T10 (SEQ ID NO: 62) 1677 1804
[2091] Segment cluster M79217_PEA.sub.--1_node.sub.--37 (SEQ ID
NO:598) according to the present invention is supported by 58
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 577 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00619 TABLE 577 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 5039 5280 M79217_PEA_1_T3 (SEQ ID
NO: 60) 4713 4954 M79217_PEA_1_T8 (SEQ ID NO: 61) 4677 4918
M79217_PEA_1_T10 (SEQ ID NO: 62) 1846 2087
[2092] Segment cluster M79217_PEA.sub.--1_node.sub.--38 (SEQ ID
NO:599) according to me present invention is supported by 62
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 578 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00620 TABLE 578 Segment location on transcripts Segment
starting Segment Transcript name position ending position
M79217_PEA_1_T1 (SEQ ID NO: 59) 5281 5436 M79217_PEA_1_T3 (SEQ ID
NO: 60) 4955 5110 M79217_PEA_1_T8 (SEQ ID NO: 61) 4919 5074
M79217_PEA_1_T10 (SEQ ID NO: 62) 2088 2243
[2093] Segment cluster M79217_PEA.sub.--1_node.sub.--41 (SEQ ID
NO:600) according to the present invention is supported by 171
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T10 (SEQ ID NO:62) and
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 579 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00621 TABLE 579 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 5628 6357 M79217_PEA_1_T3 (SEQ ID
NO: 60) 5302 6031 M79217_PEA_1_T8 (SEQ ID NO: 61) 5266 5995
M79217_PEA_1_T10 (SEQ ID NO: 62) 2435 3164 M79217_PEA_1_T18 (SEQ ID
NO: 64) 755 1484
[2094] Segment cluster M79217_PEA.sub.--1_node.sub.--44 (SEQ ID
NO:601) according to the present invention is supported by 89
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T10 (SEQ ID NO:62) and
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 580 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00622 TABLE 580 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 6472 6659 M79217_PEA_1_T3 (SEQ ID
NO: 60) 6146 6333 M79217_PEA_1_T8 (SEQ ID NO: 61) 6110 6297
M79217_PEA_1_T10 (SEQ ID NO: 62) 3279 3466 M79217_PEA_1_T18 (SEQ ID
NO: 64) 1599 1786
[2095] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 bp in length, and so
are included in a separate description.
[2096] Segment cluster M79217_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:602) according to the present invention is supported by 4
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T3 (SEQ ID NO:60). Table 581
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00623 TABLE 581 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T3 (SEQ ID NO: 60) 1 49
[2097] Segment cluster M79217_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:603) according to the present invention is supported by 11
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T3 (SEQ ID NO:60),
M79217_PEA.sub.--1_T8 (SEQ ID NO:61), M79217_PEA.sub.--1_T15 (SEQ
ID NO:63) and M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 582
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00624 TABLE 582 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T3 (SEQ ID NO: 60) 178 271 M79217_PEA_1_T8 (SEQ ID NO:
61) 178 271 M79217_PEA_1_T15 (SEQ ID NO: 63) 178 271
M79217_PEA_1_T18 (SEQ ID NO: 64) 178 271
[2098] Segment cluster M79217_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:604) according to the present invention can be found in the
following transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T15 (SEQ ID NO:63). Table 583 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00625 TABLE 583 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 1524 1547 M79217_PEA_1_T3 (SEQ ID
NO: 60) 1198 1221 M79217_PEA_1_T8 (SEQ ID NO: 61) 1198 1221
M79217_PEA_1_T15 (SEQ ID NO: 63) 1198 1221
[2099] Segment cluster M79217_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:605) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 584
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00626 TABLE 584 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T10 (SEQ ID NO: 62) 1 79
[2100] Segment cluster M79217_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:606) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA_l_T10 (SEQ ID NO:62). Table 585 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00627 TABLE 585 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T10 (SEQ ID NO: 62) 80 156
[2101] Segment cluster M79217_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:607) according to the present invention is supported by 40
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60) and M79217_PEA.sub.--1_T10
(SEQ ID NO:62). Table 586 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00628 TABLE 586 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3495 3530 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3169 3204 M79217_PEA_1_T10 (SEQ ID NO: 62) 302 337
[2102] Segment cluster M79217_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:608) according to the present invention is supported by 46
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217PEA.sub.--1_T10 (SEQ ID NO:62). Table 587 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00629 TABLE 587 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3531 3623 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3205 3297 M79217_PEA_1_T8 (SEQ ID NO: 61) 3169 3261
M79217_PEA_1_T10 (SEQ ID NO: 62) 338 430
[2103] Segment cluster M79217_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:609) according to the present invention is supported by 47
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 588 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00630 TABLE 588 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3624 3715 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3298 3389 M79217_PEA_1_T8 (SEQ ID NO: 61) 3262 3353
M79217_PEA_1_T10 (SEQ ID NO: 62) 431 522
[2104] Segment cluster M79217_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:610) according to the present invention is supported by 40
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 589 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00631 TABLE 589 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 3961 4014 M79217_PEA_1_T3 (SEQ ID
NO: 60) 3635 3688 M79217_PEA_1_T8 (SEQ ID NO: 61) 3599 3652
M79217_PEA_1_T10 (SEQ ID NO: 62) 768 821
[2105] Segment cluster M79217_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:611) according to the present invention is supported by 42
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 590 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00632 TABLE 590 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 4998 5038 M79217_PEA_1_T3 (SEQ ID
NO: 60) 4672 4712 M79217_PEA_1_T8 (SEQ ID NO: 61) 4636 4676
M79217_PEA_1_T10 (SEQ ID NO: 62) 1805 1845
[2106] Segment cluster M79217_PEA.sub.--1_node.sub.--39 (SEQ ID
NO:612) according to the present invention is supported by 57
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 591 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00633 TABLE 591 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 5437 5520 M79217_PEA_1_T3 (SEQ ID
NO: 60) 5111 5194 M79217_PEA_1_T8 (SEQ ID NO: 61) 5075 5158
M79217_PEA_1_T10 (SEQ ID NO: 62) 2244 2327
[2107] Segment cluster M79217_PEA.sub.--1_node.sub.--40 (SEQ ID
NO:613) according to the present invention is supported by 59
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61) and M79217_PEA.sub.--1_T10 (SEQ ID NO:62). Table 592 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00634 TABLE 592 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 5521 5627 M79217_PEA_1_T3 (SEQ ID
NO: 60) 5195 5301 M79217_PEA_1_T8 (SEQ ID NO: 61) 5159 5265
M79217_PEA_1_T10 (SEQ ID NO: 62) 2328 2434
[2108] Segment cluster M79217_PEA.sub.--1_node.sub.--42 (SEQ ID
NO:614) according to the present invention is supported by 99
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T10 (SEQ ID NO:62) and
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 593 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00635 TABLE 593 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO. 59) 6358 6443 M79217_PEA_1_T3 (SEQ ID
NO: 60) 6032 6117 M79217_PEA_1_T8 (SEQ ID NO: 61) 5996 6081
M79217_PEA_1_T10 (SEQ ID NO: 62) 3165 3250 M79217_PEA_1_T18 (SEQ ID
NO: 64) 1485 1570
[2109] Segment cluster M79217_PEA.sub.--1_node.sub.--43 (SEQ ID
NO:615) according to the present invention is supported by 90
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M79217_PEA.sub.--1_T1 (SEQ ID NO:59),
M79217_PEA.sub.--1_T3 (SEQ ID NO:60), M79217_PEA.sub.--1_T8 (SEQ ID
NO:61), M79217_PEA.sub.--1_T10 (SEQ ID NO:62) and
M79217_PEA.sub.--1_T18 (SEQ ID NO:64). Table 594 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00636 TABLE 594 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M79217_PEA_1_T1 (SEQ ID NO: 59) 6444 6471 M79217_PEA_1_T3 (SEQ ID
NO: 60) 6118 6145 M79217_PEA_1_T8 (SEQ ID NO: 61) 6082 6109
M79217_PEA_1_T10 (SEQ ID NO: 62) 3251 3278 M79217_PEA_1_T18 (SEQ ID
NO: 64) 1571 1598
Variant protein alignment to the previously known protein:
TABLE-US-00637 Sequence name: BAA25445 (SEQ ID NO: 1437) Sequence
documentation: Alignment of: M79217_PEA_1_P1 (SEQ ID NO: 1336)
.times. BAA25445 (SEQ ID NO: 1437) Alignment segment 1/1: Quality:
9101.00 Escore: 0 Matching length: 919 Total length: 919 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00341## ##STR00342## ##STR00343## ##STR00344##
##STR00345## ##STR00346## ##STR00347## ##STR00348## ##STR00349##
##STR00350## ##STR00351## ##STR00352## ##STR00353## ##STR00354##
##STR00355## ##STR00356## ##STR00357## ##STR00358## ##STR00359##
Sequence name: EXL3_HUMAN (SEQ ID NO: 1436) Sequence documentation:
Alignment of: M79217_PEA_1_P2 (SEQ ID NO: 1337) .times. EXL3_HUMAN
(SEQ ID NO: 1436) Alignment segment 1/1: Quality: 8873.00 Escore: 0
Matching length: 907 Total length: 919 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
98.69 Total Percent Identity: 98.69 Gaps: 1 Alignment: ##STR00360##
##STR00361## ##STR00362## ##STR00363## ##STR00364## ##STR00365##
##STR00366## ##STR00367## ##STR00368## ##STR00369## ##STR00370##
##STR00371## ##STR00372## ##STR00373## ##STR00374## ##STR00375##
##STR00376## ##STR00377## ##STR00378## Sequence name: EXL3_HUMAN
(SEQ ID NO: 1436) Sequence documentation: Alignment of:
M79217_PEA_1_P4 (SEQ ID NO: 1338) .times. EXL3_HUMAN (SEQ ID NO:
1436) Alignment segment 1/1: Quality: 1668.00 Escore: 0 Matching
length: 162 Total length: 162 Matching Percent Similarity: 100.00
Matching Percent Identity: 99.38 Total Percent Similarity: 100.00
Total Percent Identity: 99.38 Gaps: 0 Alignment: ##STR00379##
##STR00380## ##STR00381## ##STR00382## Sequence name: EXL3_HUMAN
(SEQ ID NO: 1436) Sequence documentation: Alignment of:
M79217_PEA_1_P8 (SEQ ID NO: 1339) .times. EXL3_HUMAN (SEQ ID NO:
1436) Alignment segment 1/1: Quality: 7947.00 Escore: 0 Matching
length: 807 Total length: 807 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00383##
##STR00384## ##STR00385## ##STR00386## ##STR00387## ##STR00388##
##STR00389## ##STR00390## ##STR00391## ##STR00392## ##STR00393##
##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398##
##STR00399##
Description for Cluster M62096
[2110] Cluster M62096 features 9 transcript(s) and 42 segment(s) of
interest, the names for which are given in Tables 595 and 596,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
597.
TABLE-US-00638 TABLE 595 Transcripts of interest Transcript name
Sequence ID No. M62096_PEA_1_T4 65 M62096_PEA_1_T5 66
M62096_PEA_1_T6 67 M62096_PEA_1_T7 68 M62096_PEA_1_T9 69
M62096_PEA_1_T11 70 M62096_PEA_1_T13 71 M62096_PEA_1_T14 72
M62096_PEA_1_T15 73
TABLE-US-00639 TABLE 596 Segments of interest Segment Name Sequence
ID No. M62096_PEA_1_node_0 616 M62096_PEA_1_node_2 617
M62096_PEA_1_node_15 618 M62096_PEA_1_node_17 619
M62096_PEA_1_node_19 620 M62096_PEA_1_node_23 621
M62096_PEA_1_node_27 623 M62096_PEA_1_node_29 624
M62096_PEA_1_node_31 625 M62096_PEA_1_node_34 626
M62096_PEA_1_node_36 627 M62096_PEA_1_node_38 628
M62096_PEA_1_node_40 629 M62096_PEA_1_node_48 630
M62096_PEA_1_node_50 631 M62096_PEA_1_node_56 632
M62096_PEA_1_node_60 633 M62096_PEA_1_node_65 634
M62096_PEA_1_node_69 635 M62096_PEA_1_node_71 636
M62096_PEA_1_node_1 637 M62096_PEA_1_node_4 638 M62096_PEA_1_node_6
639 M62096_PEA_1_node_7 640 M62096_PEA_1_node_9 641
M62096_PEA_1_node_11 642 M62096_PEA_1_node_13 643
M62096_PEA_1_node_21 644 M62096_PEA_1_node_25 645
M62096_PEA_1_node_33 646 M62096_PEA_1_node_42 647
M62096_PEA_1_node_44 648 M62096_PEA_1_node_47 649
M62096_PEA_1_node_51 650 M62096_PEA_1_node_53 651
M62096_PEA_1_node_55 652 M62096_PEA_1_node_58 653
M62096_PEA_1_node_62 654 M62096_PEA_1_node_66 655
M62096_PEA_1_node_67 656 M62096_PEA_1_node_68 657
M62096_PEA_1_node_70 658
TABLE-US-00640 TABLE 597 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) M62096_PEA_1_P4 1341
M62096_PEA_1_T6 (SEQ ID NO: 67) M62096_PEA_1_P5 1342
M62096_PEA_1_T7 (SEQ ID NO: 68) M62096_PEA_1_P3 1343
M62096_PEA_1_T9 (SEQ ID NO: 69) M62096_PEA_1_P7 1344
M62096_PEA_1_T11 (SEQ ID NO: 70) M62096_PEA_1_P8 1345
M62096_PEA_1_T13 (SEQ ID NO: 71) M62096_PEA_1_P9 1346
M62096_PEA_1_T14 (SEQ ID NO: 72) M62096_PEA_1_P10 1347
M62096_PEA_1_T15 (SEQ ID NO: 73) M62096_PEA_1_P11 1348
M62096_PEA_1_T4 (SEQ ID NO: 65) M62096_PEA_1_P12 1349
M62096_PEA_1_T5 (SEQ ID NO: 66)
[2111] These sequences are variants of the known protein Kinesin
heavy chain isoform 5C (SwissProt accession identifier KF5C_HUMAN;
known also according to the synonyms Kinesin heavy chain
neuron-specific 2), SEQ ID NO: 1438, referred to herein as the
previously known protein.
[2112] Protein Kinesin heavy chain isoform 5C (SEQ ID NO:1438) is
known or believed to have the following function(s): Kinesin is a
microtubule-associated force-producing protein that may play a role
in organelle transport. The sequence for protein Kinesin heavy
chain isoform 5C is given at the end of the application, as
"Kinesin heavy chain isoform 5C amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 598.
TABLE-US-00641 TABLE 598 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 355-360 TLKNVI ->
STHASV 583-585 EFT -> DRV
[2113] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: organelle
organization and biogenesis, which are annotation(s) related to
Biological Process; microtubule motor; ATP binding, which are
annotation(s) related to Molecular Function; and kinesin, which are
annotation(s) related to Cellular Component.
[2114] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2115] As noted above, cluster M62096 features 9 transcript(s),
which were listed in Table 595 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Kinesin heavy chain
isoform 5C (SEQ ID NO:1438). A description of each variant protein
according to the present invention is now provided.
[2116] Variant protein M62096_PEA.sub.--1_P4 (SEQ ID NO:1341)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T6 (SEQ ID NO:67). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2117] Comparison report between M62096_PEA.sub.--1_P4 (SEQ ID
NO:1341) and KF5C_HUMAN (SEQ ID NO:1438):
[2118] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MATYIH (SEQ ID NO: 1726) corresponding to amino acids 1-6
of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), and a second amino acid
sequence being at least 90% homologous to
VSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKMTRILQDSLGGNCRTTIVICCSPSV-
FN
EAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKTLKNVIQHLEMELNRWRNGEAVPED
EQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEINQQSQLAEKLKQQMLD
QDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEVEDKTRANEQLTDELAQ
KTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADVNGVIEEEFTMARLYISK
MKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEAKIKSLTDYMQNMEQKRRQLEESQD
SLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAHQKQLSRLRDEIEEKQKII
DEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLR
KLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRA
TAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVH
AIRGGGGSSSNSTHYQK corresponding to amino acids 239-957 of
KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino acids
7-725 of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), wherein said first
amino acid sequence and second amino acid sequence are contiguous
and in a sequential order.
[2119] 2.An isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P4 (SEQ ID NO:1341), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MATYIH
(SEQ ID NO: 1726) of M62096_PEA.sub.--1_P4 (SEQ ID NO:1341).
[2120] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2121] Variant protein M62096_PEA.sub.--1_P4 (SEQ ID NO:1341) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T6 (SEQ
ID NO:67), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M62096_PEA.sub.--1_T6
(SEQ ID NO:67) is shown in bold; this coding portion starts at
position 108 and ends at position 2282. The transcript also has the
following SNPs as listed in Table 599 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M62096_PEA.sub.--1_P4 (SEQ ID NO:1341) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00642 TABLE 599 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
5757 G -> T No
[2122] Variant protein M62096_PEA.sub.--1_P5 (SEQ ID NO:1342)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T7 (SEQ ID NO:68). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2123] Comparison report between M62096_PEA.sub.--1_P5 (SEQ ID
NO:1342) and KF5C_HUMAN (SEQ ID NO:1438):
[2124] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P5 (SEQ ID NO:1342), comprising a first amino
acid sequence being at least 90% homologous to
MTRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNK
TLKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYR
QLDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAV
NYDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGT
NDVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHE
AKIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQ
MESHREAHQKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKR
EQAREDLKGLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKV
HKQLVRDNADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMAR
RAHSAQIAKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK corresponding to amino
acids 284-957 of KF5C_HUMAN (SEQ ID NO:1438), which also
corresponds to amino acids 1-674 of M62096_PEA.sub.--1_P5 (SEQ ID
NO:1342).
[2125] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2126] Variant protein M62096_PEA.sub.--1_P5 (SEQ ID NO:1342) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T7 (SEQ
ID NO:68), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M62096_PEA.sub.--1_T7
(SEQ ID NO:68) is shown in bold; this coding portion starts at
position 283 and ends at position 2304. The transcript also has the
following SNPs as listed in Table 600 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M62096_PEA.sub.--1_P5 (SEQ ID NO:1342) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00643 TABLE 600 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
5779 G -> T No
[2127] Variant protein M62096_PEA.sub.--1_P3 (SEQ ID NO:1343)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T9 (SEQ ID NO:69). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2128] Comparison report between M62096_PEA.sub.--1_P3 (SEQ ID
NO:1343) and KF5C_HUMAN (SEQ ID NO:1438):
[2129] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P3 (SEQ ID NO:1343), comprising a first amino
acid sequence being at least 90% homologous to
MELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQLDDKDDEIN
QQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVNYDQKSQEV
EDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTNDVKTLADV
NGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRICMNASERELAACQLLISQHEAKIKSLTDY
MQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQMESHREAH
QKQLSRLRDEIEEKQKIIDEIRDLNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLK
GLEETVSRELQTLHNLRKLFVQDLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRD
NADLRCELPKLEKRLRATAERVKALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQI
AKPIRPGHYPASSPTAVHAIRGGGGSSSNSTHYQK corresponding to amino acids
365-957 of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to
amino acids 1-593 of M62096_PEA.sub.--1_P3 (SEQ ID NO:1343).
[2130] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2131] Variant protein M62096_PEA.sub.--1_P3 (SEQ ID NO:1343) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T9 (SEQ
ID NO:69), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M62096_PEA.sub.--1_T9
(SEQ ID NO:69) is shown in bold; this coding portion start at
position 565 and ends at position 2343. The transcript also has the
following SNPs as listed in Table 601 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M62096_PEA.sub.--1_P3 (SEQ ID NO:1343) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00644 TABLE 601 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
5818 G -> T No
[2132] Variant protein M62096_PEA.sub.--1_P7 (SEQ ID NO:1344)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T11 (SEQ ID NO:70). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2133] Comparison report between M62096_PEA.sub.--1_P7 (SEQ ID
NO:1344) and KF5C_HUMAN (SEQ ID NO:1438):
[2134] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) corresponding to
amino acids 1-19 of M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), and a
second amino acid sequence being at least 90% homologous to
LNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQ
DLTTRVKKSVELDNDDGGGSAAQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERV
KALESALKEAKENAMRDRKRYQQEVDRIKEAVRAKNMARRAHSAQIAKPIRPGHYPASSPTAVHAIRGG
GGSSSNSTHYQK corresponding to amino acids 738-957 of KF5C_HUMAN
(SEQ ID NO:1438), which also corresponds to amino acids 20-239 of
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2135] 2.An isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P7 (SEQ ID NO:1344), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) of M62096_PEA.sub.--1_P7 (SEQ
ID NO:1344).
[2136] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Non-secretory protein,NN:YES) predicts
that this protein has a signal peptide.
[2137] Variant protein M62096_PEA.sub.--1_P7 (SEQ ID NO:1344) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T11 (SEQ
ID NO:70), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M62096_PEA.sub.--1_T11 (SEQ ID NO:70) is shown in bold; this coding
portion starts at position 633 and ends at position 1349. The
transcript also has the following SNPs as listed in Table 602
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M62096_PEA.sub.--1_P7 (SEQ ID NO:1344) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00645 TABLE 602 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
4824 G -> T No
[2138] Variant protein M62096_PEA.sub.--1_P8 (SEQ ID NO:1345)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T13 (SEQ ID NO:71). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2139] Comparison report between M62096_PEA.sub.--1_P8 (SEQ ID
NO:1345) and KF5C_HUMAN (SEQ ID NO:1438):
[2140] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDINFDHIYSMDENLEFHIKVSYFEIYLDKI-
R
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQ
LDDKDDEINQQSQLAEKLKQQMLDQDELLASTRRDYEKIQEELTRLQIENEAAKDEVKEVLQALEELAVN
YDQKSQEVEDKTRANEQLTDELAQKTTTLTTTQRELSQLQELSNHQKKRATEILNLLLKDLGEIGGIIGTN
DVKTLADVNGVIEEEFTMARLYISKMKSEVKSLVNRSKQLESAQMDSNRKMNASERELAACQLLISQHEA
KIKSLTDYMQNMEQKRRQLEESQDSLSEELAKLRAQEKMHEVSFQDKEKEHLTRLQDAEEMKKALEQQ
MESHREAHQKQLSRLRDEIEEKQKIIDEIR corresponding to amino acids 1-736
of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino
acids 1-736 of M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence E corresponding to amino acids 737-737 of
M62096_PEA.sub.--1_P8 (SEQ ID NO:1345), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2141] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2142] Variant protein M62096_PEA.sub.--1_P8 (SEQ ID NO:1345) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 603, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M62096_PEA.sub.--1_P8
(SEQ ID NO:1345) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00646 TABLE 603 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
5 A -> T Yes
[2143] Variant protein M62096_PEA.sub.--1_P8 (SEQ ID NO:1345) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T13 (SEQ
ID NO:71), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M62096_PEA.sub.--1_T13 (SEQ ID NO:71) is shown in bold; this coding
portion starts at position 396 and ends at position 2606. The
transcript also has the following SNPs as listed in Table 604
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M62096_PEA.sub.--1_P8 (SEQ ID NO:1345) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00647 TABLE 604 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
92 C -> A Yes 408 G -> A Yes
[2144] Variant protein M62096_PEA.sub.--1_P9 (SEQ ID NO:1346)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T14 (SEQ ID NO:72). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2145] Comparison report between M62096_PEA.sub.--1_P9 (SEQ ID
NO:1346) and KF5C_HUMAN (SEQ ID NO:1438):
[2146] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRNGEAVPEDEQISAKDQKNLEPCDNTPIIDNIAPVVAGISTEEKEKYDEEISSLYRQ
LDDKDDEINQQSQLAEKLKQQMLDQDE corresponding to amino acids 1-454 of
KF5C_HUMAN (SEQ ID NO:1438), which also corresponds to amino acids
1-454 of M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRCPFTASYKIITEFRK (SEQ ID
NO: 1728) corresponding to amino acids 455-514 of
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2147] 2.An isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P9 (SEQ ID NO:1346), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VKNAIYFFFHKVLLLLFVVDVCSRNLIGIEAFHNYRIMWKFLGRCPFTASYKLIITEFRK (SEQ
ID NO: 1728) in M62096_PEA.sub.--1_P9 (SEQ ID NO:1346).
[2148] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2149] Variant protein M62096_PEA.sub.--1_P9 (SEQ ID NO:1346) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 605, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M62096_PEA.sub.--1_P9
(SEQ ID NO:1346) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00648 TABLE 605 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
5 A -> T Yes
[2150] Variant protein M62096_PEA.sub.--1_P9 (SEQ ID NO:1346) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T14 (SEQ
ID NO:72), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M62096_PEA.sub.--1_T14 (SEQ ID NO:72) is shown in bold; this coding
portion starts at position 396 and ends at position 1937. The
transcript also has the following SNPs as listed in Table 606
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M62096_PEA.sub.--1_P9 (SEQ ID NO:1346) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00649 TABLE 606 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
92 C -> A Yes 408 G -> A Yes
[2151] Variant protein M62096_PEA.sub.--1_P10 (SEQ ID NO:1347)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T15 (SEQ ID NO:73). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2152] Comparison report between M62096_PEA.sub.--1_P10 (SEQ ID
NO:1347) and KF5C_HUMAN (SEQ ID NO:1438):
[2153] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) corresponding to
amino acids 1-19 of M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), a
second amino acid sequence being at least 90% homologous to
LNQKLQLEQEKLSSDYNKLKIEDQEREMKLEKLLLLNDKREQAREDLKGLEETVSRELQTLHNLRKLFVQ
DLTTRVKK corresponding to amino acids 738-815 of KF5C_HUMAN (SEQ ID
NO:1438), which also corresponds to amino acids 20-97 of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), and a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
VSSLCLNGTEKKIKDGREESFSVEISLA (SEQ ID NO: 1730) corresponding to
amino acids 98-125 of M62096_PEA.sub.--1_P10 (SEQ ID NO:1347),
wherein said first amino acid sequence, second amino acid sequence
and third amino acid sequence are contiguous and in a sequential
order.
[2154] 2.An isolated polypeptide encoding for a head of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MTQNFRLMWNILLFPLNFS (SEQ ID NO: 1727) of M62096_PEA.sub.--1_P10
(SEQ ID NO:1347).
[2155] 3.An isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VSSLCLNGTEKKIKDGREESFSVEISLA (SEQ ID NO: 1730) in
M62096_PEA.sub.--1_P10 (SEQ ID NO:1347).
[2156] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because one of the two signal-peptide
prediction programs (HMM:Non-secretory protein,NN:YES) predicts
that this protein has a signal peptide.
[2157] Variant protein M62096_PEA.sub.--1_P10 (SEQ ID NO:1347) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T15 (SEQ
ID NO:73), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M62096_PEA.sub.--1_T15 (SEQ ID NO:73) is shown in bold; this coding
portion starts at position 633 and ends at position 1007.
[2158] Variant protein M62096_PEA.sub.--1P11 (SEQ ID NO:1348)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T4 (SEQ ID NO:65). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2159] Comparison report between M62096_PEA.sub.--1_P11 (SEQ ID
NO:1348) and KF5C_HUMAN (SEQ ID NO:1438):
[2160] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQRAKTIKNTVSVNLELTAEEWKKKYEKEKEKNKT
LKNVIQHLEMELNRWRN corresponding to amino acids 1-372 of KFSC_HUMAN
(SEQ ID NO:1438), which also corresponds to amino acids 1-372 of
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
DFLAAHVFGKLLE (SEQ ID NO: 1731) corresponding to amino acids
373-385 of M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), which amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2161] 2.An isolated polypeptide encoding for a tail of
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DFLAAHVFGKLLE (SEQ ID NO: 1731) in M62096_PEA.sub.--1_P11 (SEQ ID
NO:1348).
[2162] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2163] Variant protein M62096_PEA.sub.--1_P11 (SEQ ID NO:1348) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 607, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M62096_PEA.sub.--1_P11
(SEQ ID NO:1348) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00650 TABLE 607 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
5 A -> T Yes
[2164] Variant protein M62096_PEA.sub.--1_P11 (SEQ ID NO:1348) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T4 (SEQ
ID NO:65), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M62096_PEA.sub.--1_T4
(SEQ ID NO:65) is shown in bold; this coding portion starts at
position 396 and ends at position 1550. The transcript also has the
following SNPs as listed in Table 608 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M62096_PEA.sub.--1_P11 (SEQ ID NO:1348) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00651 TABLE 608 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
92 C -> A Yes 408 G -> A Yes 6908 G -> T No
[2165] Variant protein M62096_PEA.sub.--1_P12 (SEQ ID NO:1349)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M62096_PEA.sub.--1_T5 (SEQ ID NO:66). An alignment is given to the
known protein (Kinesin heavy chain isoform 5C (SEQ ID NO:1438)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2166] Comparison report between M62096_PEA.sub.--1_P12 (SEQ ID
NO:1349) and KF5C_HUMAN (SEQ ID NO:1438):
[2167] 1.An isolated chimeric polypeptide encoding for
M62096_PEA.sub.--1_P12 (SEQ ID NO:1349), comprising a first amino
acid sequence being at least 90% homologous to
MADPAECSIKVMCRFRPLNEAEILRGDKFIPKFKGDETVVIGQGKPYVFDRVLPPNTTQEQVYNACAKQIV
KDVLEGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIAHDIFDHIYSMDENLEFHIKVSYFEIYLDKIR
DLLDVSKTNLAVHEDKNRVPYVKGCTERFVSSPEEVMDVIDEGKANRHVAVTNMNEHSSRSHSIFLINIK
QENVETEKKLSGKLYLVDLAGSEKVSKTGAEGAVLDEAKNINKSLSALGNVISALAEGTKTHVPYRDSKM
TRILQDSLGGNCRTTIVICCSPSVFNEAETKSTLMFGQR corresponding to amino
acids 1-323 of KF5C_HUMAN (SEQ ID NO:1438), which also corresponds
to amino acids 1-323 of M62096_PEA.sub.--1_P12 (SEQ ID NO:1349),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence V corresponding to amino acids 324-324 of
M62096_PEA.sub.--1_P12 (SEQ ID NO:1349), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2168] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2169] Variant protein M62096_PEA.sub.--1_P12 (SEQ ID NO:1349) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 609, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M62096_PEA.sub.--1_P12
(SEQ ID NO:1349) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00652 TABLE 609 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
5 A -> T Yes
[2170] Variant protein M62096_PEA.sub.--1_P12 (SEQ ID NO:1349) is
encoded by the following transcript(s): M62096_PEA.sub.--1_T5 (SEQ
ID NO:66), for which the sequence(s) is/are given at the end of the
application coding portion of transcript M62096_PEA.sub.--1_T5 (SEQ
ID NO:66) is shown in bold; this coding portion starts at position
378 and ends at position 1349. The transcript also has the
following SNPs as listed in Table 610 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M62096_PEA.sub.--1_P12 (SEQ ID NO:1349) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00653 TABLE 610 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
92 C -> A Yes 390 G -> A Yes 6784 G -> T No
[2171] As noted above, cluster M62096 features 42 segment(s), which
were listed in Table 596 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2172] Segment cluster M62096_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:616) according to the present invention is supported by 14
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 611
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00654 TABLE 611 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1 355 M62096_PEA_1_T5 (SEQ ID NO:
66) 1 355 M62096_PEA_1_T13 (SEQ ID NO: 71) 1 355 M62096_PEA_1_T14
(SEQ ID NO: 72) 1 355
[2173] Segment cluster M62096_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:617) according to the present invention is supported by 12
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 612
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00655 TABLE 612 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 374 521 M62096_PEA_1_T5 (SEQ ID NO:
66) 356 503 M62096_PEA_1_T13 (SEQ ID NO: 71) 374 521
M62096_PEA_1_T14 (SEQ ID NO: 72) 374 521
[2174] Segment cluster M62096_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:618) according to the present invention is supported by 28
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 613
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00656 TABLE 613 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 985 1109 M62096_PEA_1_T5 (SEQ ID
NO: 66) 967 1091 M62096_PEA_1_T13 (SEQ ID NO: 71) 985 1109
M62096_PEA_1_T14 (SEQ ID NO: 72) 985 1109
[2175] Segment cluster M62096_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:619) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T7 (SEQ ID NO:68). Table 614
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00657 TABLE 614 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T7 (SEQ ID NO: 68) 1 147
[2176] Segment cluster M62096_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:620) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T6 (SEQ ID NO:67) and
M62096_PEA.sub.--1_T9 (SEQ ID NO:69). Table 615 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00658 TABLE 615 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T6 (SEQ ID NO: 67) 1 125 M62096_PEA_1_T9 (SEQ ID NO:
69) 1 125
[2177] Segment cluster M62096_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:621) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096_PEA.sub.--1_T13 (SEQ ID NO:71) and
M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 616 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00659 TABLE 616 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1215 1363 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1197 1345 M62096_PEA_1_T6 (SEQ ID NO: 67) 231 379
M62096_PEA_1_T7 (SEQ ID NO: 68) 253 401 M62096_PEA_1_T9 (SEQ ID NO:
69) 231 379 M62096_PEA_1_T13 (SEQ ID NO: 71) 1215 1363
M62096_PEA_1_T14 (SEQ ID NO: 72) 1215 1363
[2178] Segment cluster M62096_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:623) according to the present invention is supported by 35
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1 T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096_PEA.sub.--1_T13 (SEQ ID NO:71) and
M62096PEA.sub.--1_T14 (SEQ ID NO:72). Table 617 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00660 TABLE 617 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1364 1512 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1407 1555 M62096_PEA_1_T6 (SEQ ID NO: 67) 380 528
M62096_PEA_1_T7 (SEQ ID NO: 68) 402 550 M62096_PEA_1_T9 (SEQ ID NO:
69) 441 589 M62096_PEA_1_T13 (SEQ ID NO: 71) 1364 1512
M62096_PEA_1_T14 (SEQ ID NO: 72) 1364 1512
[2179] Segment cluster M62096_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:624) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65). Table 618
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00661 TABLE 618 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1513 1679
[2180] Segment cluster M62096_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:625) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096_PEA.sub.--1.sub.--113 (SEQ ID NO:71) and
M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 619 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00662 TABLE 619 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1680 1855 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1556 1731 M62096_PEA_1_T6 (SEQ ID NO: 67) 529 704
M62096_PEA_1_T7 (SEQ ID NO: 68) 551 726 M62096_PEA_1_T9 (SEQ ID NO:
69) 590 765 M62096_PEA_1_T13 (SEQ ID NO: 71) 1513 1688
M62096_PEA_1_T14 (SEQ ID NO: 72) 1513 1688
[2181] Segment cluster M62096_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:626) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 620
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00663 TABLE 620 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T14 (SEQ ID NO: 72) 1758 2261
[2182] Segment cluster M62096_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:627) according to the present invention is supported by 26
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 621
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00664 TABLE 621 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1925 2131 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1801 2007 M62096_PEA_1_T6 (SEQ ID NO: 67) 774 980
M62096_PEA_1_T7 (SEQ ID NO: 68) 796 1002 M62096_PEA_1_T9 (SEQ ID
NO: 69) 835 1041 M62096_PEA_1_T13 (SEQ ID NO: 71) 1758 1964
[2183] Segment cluster M62096_PEA.sub.--1_node.sub.--38 (SEQ ID
NO:628) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1.sub.--17 (SEQ ID NO:68),
M62096_PEA.sub.--1_T9 (SEQ ID NO:69) and M62096_PEA.sub.--1_T13
(SEQ ID NO:71). Table 622 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00665 TABLE 622 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2132 2278 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2008 2154 M62096_PEA_1_T6 (SEQ ID NO: 67) 981 1127
M62096_PEA_1_T7 (SEQ ID NO: 68) 1003 1149 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1042 1188 M62096_PEA_1_T13 (SEQ ID NO: 71) 1965 2111
[2184] Segment cluster M62096_PEA.sub.--1_node.sub.--40 (SEQ ID
NO:629) according to the present invention is supported by 21
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 623
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00666 TABLE 623 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2279 2467 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2155 2343 M62096_PEA_1_T6 (SEQ ID NO: 67) 1128 1316
M62096_PEA_1_T7 (SEQ ID NO: 68) 1150 1338 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1189 1377 M62096_PEA_1_T13 (SEQ ID NO: 71) 2112 2300
[2185] Segment cluster M62096_PEA.sub.--1_node.sub.--48 (SEQ ID
NO:630) according to the present invention is supported by 7
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 624
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00667 TABLE 624 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T13 (SEQ ID NO: 71) 2606 2945
[2186] Segment cluster M62096_PEA.sub.--1_node.sub.--50 (SEQ ID
NO:631) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T11 (SEQ ID NO:70) and
M62096_PEA.sub.--1_T15 (SEQ ID NO:73). Table 625 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00668 TABLE 625 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T11 (SEQ ID NO: 70) 1 688 M62096_PEA_1_T15 (SEQ ID NO:
73) 1 688
[2187] Segment cluster M62096_PEA.sub.--1_node.sub.--56 (SEQ ID
NO:632) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1.sub.--115 (SEQ ID NO:73). Table
626 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00669 TABLE 626 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T15 (SEQ ID NO: 73) 924 1059
[2188] Segment cluster M62096_PEA.sub.--1_node.sub.--60 (SEQ ID
NO:633) according to the present invention is supported by 13
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T11 (SEQ
ID NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68),
M62095_PEA.sub.--1_T9 (SEQ ID NO:69) and M62096_PEA.sub.--1_T11
(SEQ ID NO:70). Table 627 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00670 TABLE 627 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 3113 3329 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2989 3205 M62096_PEA_1_T6 (SEQ ID NO: 67) 1962 2178
M62096_PEA_1_T7 (SEQ ID NO: 68) 1984 2200 M62096_PEA_1_T9 (SEQ ID
NO: 69) 2023 2239 M62096_PEA_1_T11 (SEQ ID NO: 70) 1029 1245
[2189] Segment cluster M62096_PEA.sub.--1_node.sub.--65 (SEQ ID
NO:634) according to the present invention is supported by 51
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA1.sub.--16 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 628
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00671 TABLE 628 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 3444 4763 M62096_PEA_1_T5 (SEQ ID
NO: 66) 3320 4639 M62096_PEA_1_T6 (SEQ ID NO: 67) 2293 3612
M62096_PEA_1_T7 (SEQ ID NO: 68) 2315 3634 M62096_PEA_1_T9 (SEQ ID
NO: 69) 2354 3673 M62096_PEA_1_T11 (SEQ ID NO: 70) 1360 2679
[2190] Segment cluster M62096_PEA.sub.--1_node.sub.--69 (SEQ ID
NO:635) according to the present invention is supported by 85
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 629
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00672 TABLE 629 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 4894 5826 M62096_PEA_1_T5 (SEQ ID
NO: 66) 4770 5702 M62096_PEA_1_T6 (SEQ ID NO: 67) 3743 4675
M62096_PEA_1_T7 (SEQ ID NO: 68) 3765 4697 M62096_PEA_1_T9 (SEQ ID
NO: 69) 3804 4736 M62096_PEA_1_T11 (SEQ ID NO: 70) 2810 3742
[2191] Segment cluster M62096_PEA.sub.--1_node.sub.--71 (SEQ ID
NO:636) according to me present invention is supported by 178
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 630
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00673 TABLE 630 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 5882 7128 M62096_PEA_1_T5 (SEQ ID
NO: 66) 5758 7004 M62096_PEA_1_T6 (SEQ ID NO: 67) 4731 5977
M62096_PEA_1_T7 (SEQ ID NO: 68) 4753 5999 M62096_PEA_1_T9 (SEQ ID
NO: 69) 4792 6038 M62096_PEA_1_T11 (SEQ ID NO: 70) 3798 5044
[2192] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 bp in length, and so
are included in a separate description.
[2193] Segment cluster M62096_PEA.sub.--1_node.sub.--1 (SEQ ID
NO:637) according to the present invention can be found in the
following transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T13 (SEQ ID NO:71) and M62096_PEA.sub.--1_T14
(SEQ ID NO:72). Table 631 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00674 TABLE 631 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 356 373 M62096_PEA_1_T13 (SEQ ID
NO: 71) 356 373 M62096_PEA_1_T14 (SEQ ID NO: 72) 356 373
[2194] Segment cluster M62096_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:638) according to the present invention is supported by 12
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 632
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00675 TABLE 632 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 522 612 M62096_PEA_1_T5 (SEQ ID NO:
66) 504 594 M62096_PEA_1_T13 (SEQ ID NO: 71) 522 612
M62096_PEA_1_T14 (SEQ ID NO: 72) 522 612
[2195] Segment cluster M62096_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:639) according to the present invention is supported by 13
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 633
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00676 TABLE 633 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 613 686 M62096_PEA_1_T5 (SEQ ID NO:
66) 595 668 M62096_PEA_1_T13 (SEQ ID NO: 71) 613 686
M62096_PEA_1_T14 (SEQ ID NO: 72) 613 686
[2196] Segment cluster M62096_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:640) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 634
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00677 TABLE 634 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 687 791 M62096_PEA_1_T5 (SEQ ID NO:
66) 669 773 M62096_PEA_1_T13 (SEQ ID NO: 71) 687 791
M62096_PEA_1_T14 (SEQ ID NO: 72) 687 791
[2197] Segment cluster M62096_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:641) according to the present invention is supported by 18
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 635
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00678 TABLE 635 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 792 840 M62096_PEA_1_T5 (SEQ ID NO:
66) 774 822 M62096_PEA_1_T13 (SEQ ID NO: 71) 792 840
M62096_PEA_1_T14 (SEQ ID NO: 72) 792 840
[2198] Segment cluster M62096_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:642) according to the present invention is supported by 22
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 636
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00679 TABLE 636 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 841 896 M62096_PEA_1_T5 (SEQ ID NO:
66) 823 878 M62096_PEA_1_T13 (SEQ ID NO: 71) 841 896
M62096_PEA_1_T14 (SEQ ID NO: 72) 841 896
[2199] Segment cluster M62096_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:643) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T13 (SEQ
ID NO:71) and M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 637
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00680 TABLE 637 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 897 984 M62096_PEA_1_T5 (SEQ ID NO:
66) 879 966 M62096_PEA_1_T13 (SEQ ID NO: 71) 897 984
M62096_PEA_1_T14 (SEQ ID NO: 72) 897 984
[2200] Segment cluster M62096_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:644) according to the present invention is supported by 33
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096_PEA.sub.--1_T13 (SEQ ID NO:71) and
M62096_PEA.sub.--1_T14 (SEQ ID NO:72). Table 638 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00681 TABLE 638 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1110 1214 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1092 1196 M62096_PEA_1_T6 (SEQ ID NO: 67) 126 230
M62096_PEA_1_T7 (SEQ ID NO: 68) 148 252 M62096_PEA_1_T9 (SEQ ID NO:
69) 126 230 M62096_PEA_1_T13 (SEQ ID NO: 71) 1110 1214
M62096_PEA_1_T14 (SEQ ID NO: 72) 1110 1214
[2201] Segment cluster M62096_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:645) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T5 (SEQ ID NO:66) and
M62096_PEA.sub.--1_T9 (SEQ ID NO:69). Table 639 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00682 TABLE 639 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T5 (SEQ ID NO: 66) 1346 1406 M62096_PEA_1_T9 (SEQ ID
NO: 69) 380 440
[2202] Segment cluster M62096_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:645) according to the present invention is supported by 20
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T9 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096_PEA.sub.--1_T13 (SEQ ID NO:71) and
M62096_PEA1_T14 (SEQ ID NO:72). Table 640 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00683 TABLE 640 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 1856 1924 M62096_PEA_1_T5 (SEQ ID
NO: 66) 1732 1800 M62096_PEA_1_T6 (SEQ ID NO: 67) 705 773
M62096_PEA_1_T7 (SEQ ID NO: 68) 727 795 M62096_PEA_1_T9 (SEQ ID NO:
69) 766 834 M62096_PEA_1_T13 (SEQ ID NO: 71) 1689 1757
M62096_PEA_1_T14 (SEQ ID NO: 72) 1689 1757
[2203] Segment cluster M62096_PEA.sub.--1_node.sub.--42 (SEQ ID
NO:647) according to the present invention is supported by 17
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID 68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 641
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00684 TABLE 641 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2468 2585 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2344 2461 M62096_PEA_1_T6 (SEQ ID NO: 67) 1317 1434
M62096_PEA_1_T7 (SEQ ID NO: 68) 1339 1456 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1378 1495 M62096_PEA_1_T13 (SEQ ID NO: 71) 2301 2418
[2204] Segment cluster M62096_PEA.sub.--1_node.sub.--44 (SEQ ID
NO:648) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 642
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00685 TABLE 642 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2586 2662 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2462 2538 M62096_PEA_1_T6 (SEQ ID NO: 67) 1435 1511
M62096_PEA_1_T7 (SEQ ID NO: 68) 1457 1533 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1496 1572 M62096_PEA_1_T13 (SEQ ID NO: 71) 2419 2495
[2205] Segment cluster M62096_PEA.sub.--1_node.sub.--47 (SEQ ID
NO:649) according to the present invention is supported by 21
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T13 (SEQ ID NO:71). Table 643
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00686 TABLE 643 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2663 2772 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2539 2648 M62096_PEA_1_T6 (SEQ ID NO: 67) 1512 1621
M62096_PEA_1_T7 (SEQ ID NO: 68) 1534 1643 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1573 1682 M62096_PEA_1_T13 (SEQ ID NO: 71) 2496 2605
[2206] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 644.
TABLE-US-00687 TABLE 644 Oligonucleotides related to this segment
Overexpressed Chip Oligonucleotide name in cancers reference
M62096_0_7_0 (SEQ ID NO: 231) lung malignant tumors LUN
[2207] Segment cluster M62096_PEA.sub.--1_node.sub.--51 (SEQ ID
NO:650) according to the present invention is supported by 11
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9 (SEQ
ID NO:69), M62096_PEA.sub.--1_T11 (SEQ ID NO:70) and
M62096_PEA.sub.--1_T15 (SEQ ID NO:73). Table 645 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00688 TABLE 645 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2773 2874 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2649 2750 M62096_PEA_1_T6 (SEQ ID NO: 67) 1622 1723
M62096_PEA_1_T7 (SEQ ID NO: 68) 1644 1745 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1683 1784 M62096_PEA_1_T11 (SEQ ID NO: 70) 689 790
M62096_PEA_1_T15 (SEQ ID NO: 73) 689 790
[2208] Segment cluster M62096_PEA.sub.--1_node.sub.--53 (SEQ ID
NO:651) according to the present invention is supported by 10
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69), M62096PEA.sub.--1_T11 (SEQ ID NO:70) and
M62096PEA.sub.--1_T15 (SEQ ID NO:73). Table 646 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00689 TABLE 646 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2875 2935 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2751 2811 M62096_PEA_1_T6 (SEQ ID NO: 67) 1724 1784
M62096_PEA_1_T7 (SEQ ID NO: 68) 1746 1806 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1785 1845 M62096_PEA_1_T11 (SEQ ID NO: 70) 791 851
M62096_PEA_1_T15 (SEQ ID NO: 73) 791 851
[2209] Segment cluster M62096_PEA.sub.--1_node.sub.--55 (SEQ ID
NO:652) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T9 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA .sub.--1_T7 (SEQ ID NO:68),
M62096_PEA.sub.--1_T9 (SEQ ID NO:69), M62096_PEA.sub.--1_T11 (SEQ
ID NO:70) and M62096PEA.sub.--1_T15 (SEQ ID NO:73). Table 647 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00690 TABLE 647 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 2936 3007 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2812 2883 M62096_PEA_1_T6 (SEQ ID NO: 67) 1785 1856
M62096_PEA_1_T7 (SEQ ID NO: 68) 1807 1878 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1846 1917 M62096_PEA_1_T11 (SEQ ID NO: 70) 852 923
M62096_PEA_1_T15 (SEQ ID NO: 73) 852 923
[2210] Segment cluster M62096_PEA.sub.--1_node.sub.--58 (SEQ ID
NO:653) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 648
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00691 TABLE 648 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 3008 3112 M62096_PEA_1_T5 (SEQ ID
NO: 66) 2884 2988 M62096_PEA_1_T6 (SEQ ID NO: 67) 1857 1961
M62096_PEA_1_T7 (SEQ ID NO: 68) 1879 1983 M62096_PEA_1_T9 (SEQ ID
NO: 69) 1918 2022 M62096_PEA_1_T11 (SEQ ID NO: 70) 924 1028
[2211] Segment cluster M62096_PEA.sub.--1_node.sub.--62 (SEQ ID
NO:654) according to the present invention is supported by 14
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 649
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00692 TABLE 649 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 3330 3443 M62096_PEA_1_T5 (SEQ ID
NO: 66) 3206 3319 M62096_PEA_1_T6 (SEQ ID NO: 67) 2179 2292
M62096_PEA_1_T7 (SEQ ID NO: 68) 2201 2314 M62096_PEA_1_T9 (SEQ ID
NO: 69) 2240 2353 M62096_PEA_1_T11 (SEQ ID NO: 70) 1246 1359
[2212] Segment cluster M62096_PEA.sub.--1_node.sub.--66 (SEQ ID
NO:655) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 650
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00693 TABLE 650 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 4764 4881 M62096_PEA_1_T5 (SEQ ID
NO: 66) 4640 4757 M62096_PEA_1_T6 (SEQ ID NO: 67) 3613 3730
M62096_PEA_1_T7 (SEQ ID NO: 68) 3635 3752 M62096_PEA_1_T9 (SEQ ID
NO: 69) 3674 3791 M62096_PEA_1_T11 (SEQ ID NO: 70) 2680 2797
[2213] Segment cluster M62096_PEA.sub.--1_node.sub.--67 (SEQ ID
NO:656) according to the present invention can be found in the
following transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 651
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00694 TABLE 651 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 4882 4887 M62096_PEA_1_T5 (SEQ ID
NO: 66) 4758 4763 M62096_PEA_1_T6 (SEQ ID NO: 67) 3731 3736
M62096_PEA_1_T7 (SEQ ID NO: 68) 3753 3758 M62096_PEA_1_T9 (SEQ ID
NO: 69) 3792 3797 M62096_PEA_1_T11 (SEQ ID NO: 70) 2798 2803
[2214] Segment cluster M62096_PEA.sub.--1_node.sub.--68 (SEQ ID
NO:657) according to the present invention can be found in the
following transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1_T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 652
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00695 TABLE 652 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 4888 4893 M62096_PEA_1_T5 (SEQ ID
NO: 66) 4764 4769 M62096_PEA_1_T6 (SEQ ID NO: 67) 3737 3742
M62096_PEA_1_T7 (SEQ ID NO: 68) 3759 3764 M62096_PEA_1_T9 (SEQ ID
NO: 69) 3798 3803 M62096_PEA_1_T11 (SEQ ID NO: 70) 2804 2809
[2215] Segment cluster M62096_PEA.sub.--1_node.sub.--70 (SEQ ID
NO:658) according to the present invention is supported by 55
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M62096_PEA.sub.--1_T4 (SEQ ID NO:65),
M62096_PEA.sub.--1_T5 (SEQ ID NO:66), M62096_PEA.sub.--1_T6 (SEQ ID
NO:67), M62096_PEA.sub.--1T7 (SEQ ID NO:68), M62096_PEA.sub.--1_T9
(SEQ ID NO:69) and M62096_PEA.sub.--1_T11 (SEQ ID NO:70). Table 653
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00696 TABLE 653 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M62096_PEA_1_T4 (SEQ ID NO: 65) 5827 5881 M62096_PEA_1_T5 (SEQ ID
NO: 66) 5703 5757 M62096_PEA_1_T6 (SEQ ID NO: 67) 4676 4730
M62096_PEA_1_T7 (SEQ ID NO: 68) 4698 4752 M62096_PEA_1_T9 (SEQ ID
NO: 69) 4737 4791 M62096_PEA_1_T11 (SEQ ID NO: 70) 3743 3797
Variant protein alignment to the previously known protein:
TABLE-US-00697 Sequence name: KF5C_HUMAN (SEQ ID NO: 1438) Sequence
documentation: Alignment of: M62096_PEA_1_P4 (SEQ ID NO: 1341)
.times. KF5C_HUMAN (SEQ ID NO: 1438) Alignment segment 1/1:
Quality: 6936.00 Escore: 0 Matching length: 719 Total length: 719
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00400## ##STR00401## ##STR00402##
##STR00403## ##STR00404## ##STR00405## ##STR00406## ##STR00407##
##STR00408## ##STR00409## ##STR00410## ##STR00411## ##STR00412##
##STR00413## ##STR00414## Sequence name: KF5C_HUMAN (SEQ ID NO:
1438) Sequence documentation: Alignment of: M62096_PEA_1_P5 (SEQ ID
NO: 1342) .times. KF5C_HUMAN (SEQ ID NO: 1438) Alignment segment
1/1: Quality: 6520.00 Escore: 0 Matching length: 674 Total length:
674 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00415## ##STR00416## ##STR00417##
##STR00418## ##STR00419## ##STR00420## ##STR00421## ##STR00422##
##STR00423## ##STR00424## ##STR00425## ##STR00426## ##STR00427##
##STR00428## Sequence name: KF5C_HUMAN (SEQ ID NO: 1438) Sequence
documentation: Alignment of: M62096_PEA_1_P3 (SEQ ID NO: 1343)
.times. KF5C_HUMAN (SEQ ID NO: 1438) Alignment segment 1/1:
Quality: 5726.00 Escore: 0 Matching length: 593 Total length: 593
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00429## ##STR00430## ##STR00431##
##STR00432## ##STR00433## ##STR00434## ##STR00435## ##STR00436##
##STR00437## ##STR00438## ##STR00439## ##STR00440## Sequence name:
KF5C_HUMAN (SEQ ID NO: 1438) Sequence documentation: Alignment of:
M62096_PEA_1_P7 (SEQ ID NO: 1344) .times. KF5C_HUMAN (SEQ ID NO:
1438) Alignment segment 1/1: Quality: 2117.00 Escore: 0 Matching
length: 220 Total length: 220 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00441##
##STR00442## ##STR00443## ##STR00444## ##STR00445## Sequence name:
KF5C_HUMAN (SEQ ID NO: 1438) Sequence documentation: Alignment of:
M62096_PEA_1_P8 (SEQ ID NO: 1345) .times. KF5C_HUMAN (SEQ ID NO:
1438) Alignment segment 1/1: Quality: 7146.00 Escore: 0 Matching
length: 737 Total length: 737 Matching Percent Similarity: 100.00
Matching Percent Identity: 99.86 Total Percent Similarity: 100.00
Total Percent Identity: 99.86 Gaps: 0 Alignment: ##STR00446##
##STR00447## ##STR00448## ##STR00449## ##STR00450## ##STR00451##
##STR00452## ##STR00453## ##STR00454## ##STR00455## ##STR00456##
##STR00457## ##STR00458## ##STR00459## ##STR00460## Sequence name:
KF5C_HUMAN (SEQ ID NO: 1438) Sequence documentation: Alignment of:
M62096_PEA_1_P9 (SEQ ID NO: 1346) .times. KF5C_HUMAN (SEQ ID NO:
1438) Alignment segment 1/1: Quality: 4434.00 Escore: 0 Matching
length: 454 Total length: 454 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00461##
##STR00462## ##STR00463## ##STR00464## ##STR00465## ##STR00466##
##STR00467## ##STR00468## ##STR00469## ##STR00470## Sequence name:
KF5C_HUMAN (SEQ ID NO: 1438) Sequence documentation: Alignment of:
M62096_PEA_1_P10 (SEQ ID NO: 1347) .times. KF5C_HUMAN (SEQ ID NO:
1438) Alignment segment 1/1: Quality: 747.00 Escore: 0 Matching
length: 78 Total length: 78 Matching Percent Similarity: 100.00
Matching Percent Identity: 100.00 Total Percent Similarity: 100.00
Total Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00471##
##STR00472## Sequence name: KF5C_HUMAN (SEQ ID NO: 1438) Sequence
documentation: Alignment of: M62096_PEA_1_P11 (SEQ ID NO: 1348)
.times. KF5C_HUMAN (SEQ ID NO: 1438) . . . Alignment segment 1/1:
Quality: 3634.00 Escore: 0 Matching length: 372 Total length: 372
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00473## ##STR00474##
##STR00475##
##STR00476## ##STR00477## ##STR00478## ##STR00479## ##STR00480##
Sequence name: KF5C_HUMAN (SEQ ID NO: 1438) Sequence documentation:
Alignment of: M62096_PEA_1_P12 (SEQ ID NO: 1349) .times. KF5C_HUMAN
(SEQ ID NO: 1438) . . . Alignment segment 1/1: Quality: 3145.00
Escore: 0 Matching length: 323 Total length: 323 Matching Percent
Similarity: 100.00 Matching Percent Identity: 100.00 Total Percent
Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00481## ##STR00482## ##STR00483## ##STR00484##
##STR00485## ##STR00486## ##STR00487##
Expression of Homo sapiens Protein Tyrosine Phosphatase, Receptor
Type, S (PTPRS) M62069 Transcripts Which are Detectable by Amplicon
as Depicted in Sequence Name M62069 seg19 (SEQ ID NO: 1657) in
Normal and Cancerous Lung Tissues
[2216] Expression of Homo sapiens protein tyrosine phosphatase,
receptor type, S (PTPRS) transcripts detectable by or according to
seg19, M62069 seg19 amplicon (SEQ ID NO: 1657) and M62069 seg19F
(SEQ ID NO: 1655) and M62069 seg19R (SEQ ID NO: 1656) primers was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[2217] FIG. 65 is a histogram showing over expression of the
above-indicated Homo sapiens protein tyrosine phosphatase, receptor
type, S (PTPRS) transcripts in cancerous lung samples relative to
the normal samples. Values represent the average of duplicate
experiments. Error bars indicate the minimal and maximal values
obtained.
[2218] As is evident from FIG. 65, the expression of Homo sapiens
protein tyrosine phosphatase, receptor type, S (PTPRS) transcripts
detectable by the above amplicon(s) in cancer samples was
significantly higher than in the non-cancerous samples (Sample Nos.
47-50, 90-93, 96-99 Table 2). Notably an over-expression of at
least 5 fold was found in 2 out of 15 adenocarcinoma samples, and
in 8 out of 8 small cells carcinoma samples.
[2219] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: M62069 seg19F
forward primer (SEQ ID NO: 1655); and M62069 seg19R reverse primer
(SEQ ID NO: 1656).
[2220] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: M62069 seg19 (SEQ ID NO: 1657).
TABLE-US-00698 Forward primer- M62069 seg19F (SEQ ID NO: 1655):
GCTGATTGTCCCCATGAAGG Reverse primer- M62069 seg19 (SEQ ID NO:
1656): TGGCATACGGGAACTCAGTG Amplicon (SEQ ID NO: 1657):
GCTGATTGTCCCCATGAAGGGCAGCCTTGAAGCTTGGTCAGTCTCCCTAA
CTGTATGATTGATCCCCACTTATTGCACTACATCACTGAGTTCCCGTATGC
Expression of Homo sapiens Protein Tyrosine Phosphatase, Receptor
Type, S (PTPRS) M62069 Transcripts Which are Detectable by Amplicon
as Depicted in Sequence Name M62069 seg29 (SEQ ID NO: 1660) in
Normal and Cancerous Lung Tissues
[2221] Expression of Homo sapiens protein tyrosine phosphatase,
receptor type, S (PTPRS) transcripts detectable by or according to
seg29, M62069 seg29 amplicon (SEQ ID NO: 1660) and M62069 seg29F
(SEQ ID NO: 1658) and M62069 seg29R (SEQ ID NO: 1659) primers was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[2222] FIG. 66 is a histogram showing over expression of the
above-indicated Homo sapiens protein tyrosine phosphatase, receptor
type, S (PTPRS) transcripts in cancerous lung samples relative to
the normal samples. Values represent the average of duplicate
experiments. Error bars indicate the minimal and maximal values
obtained.
[2223] As is evident from FIG. 66, the expression of Homo sapiens
protein tyrosine phosphatase, receptor type, S (PTPRS) transcripts
detectable by the above amplicon(s) in cancer samples was
significantly higher than in the non-cancerous samples (Sample Nos.
47-50, 90-93, 96-99 Table 2). Notably an over-expression of at
least 5 fold was found in 2 out of 15 adenocarcinoma samples, and
in 7 out of 8 small cells carcinoma samples.
[2224] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: M62069 seg29F
forward primer (SEQ ID NO: 1658); and M62069 seg29R reverse primer
(SEQ ID NO: 1659).
[2225] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: M62069 seg29 (SEQ ID NO: 1660).
TABLE-US-00699 Forward primer- M62069 seg29F:
ATTGAATAATTCAGCACCTGAGGC Reverse primer- M62069 seg29R:
TTCATATGGCTACTCCCCACCT Amplicon:
ATTGAATAATTCAGCACCTGAGGCTGGTGGATGATTCTTTGCAATTTGGC
AGGAATGGGAGAGTCGGGAGCAGTAGTTGGCAAGGTGGGGAGTAGCCATA TGAA
Description for Cluster M78076
[2226] Cluster M78076 features 9 transcript(s) and 35 segment(s) of
interest, the names for which are given in Tables 654 and 655,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
656.
TABLE-US-00700 TABLE 654 Transcripts of interest Transcript Name
Sequence ID No. M78076_PEA_1_T2 74 M78076_PEA_1_T3 75
M78076_PEA_1_T5 76 M78076_PEA_1_T13 77 M78076_PEA_1_T15 78
M78076_PEA_1_T23 79 M78076_PEA_1_T26 80 M78076_PEA_1_T27 81
M78076_PEA_1_T28 82
TABLE-US-00701 TABLE 655 Segments of interest Segment Name Sequence
ID No. M78076_PEA_1_node_0 659 M78076_PEA_1_node_10 660
M78076_PEA_1_node_15 661 M78076_PEA_1_node_18 662
M78076_PEA_1_node_20 663 M78076_PEA_1_node_24 664
M78076_PEA_1_node_26 665 M78076_PEA_1_node_29 666
M78076_PEA_1_node_32 667 M78076_PEA_1_node_35 668
M78076_PEA_1_node_37 669 M78076_PEA_1_node_46 670
M78076_PEA_1_node_47 671 M78076_PEA_1_node_54 672
M78076_PEA_1_node_1 673 M78076_PEA_1_node_2 674 M78076_PEA_1_node_3
675 M78076_PEA_1_node_6 676 M78076_PEA_1_node_7 677
M78076_PEA_1_node_12 678 M78076_PEA_1_node_22 679
M78076_PEA_1_node_27 680 M78076_PEA_1_node_30 681
M78076_PEA_1_node_31 682 M78076_PEA_1_node_34 683
M78076_PEA_1_node_36 684 M78076_PEA_1_node_41 685
M78076_PEA_1_node_42 686 M78076_PEA_1_node_43 687
M78076_PEA_1_node_45 688 M78076_PEA_1_node_49 689
M78076_PEA_1_node_50 690 M78076_PEA_1_node_51 691
M78076_PEA_1_node_52 692 M78076_PEA_1_node_53 693
TABLE-US-00702 TABLE 656 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) M78076_PEA_1_P3 1350
M78076_PEA_1_T2 (SEQ ID NO: 74); M78076_PEA_1_T5 (SEQ ID NO: 76)
M78076_PEA_1_P4 1351 M78076_PEA_1_T3 (SEQ ID NO: 75)
M78076_PEA_1_P12 1352 M78076_PEA_1_T13 (SEQ ID NO: 77)
M78076_PEA_1_P14 1353 M78076_PEA_1_T15 (SEQ ID NO: 78)
M78076_PEA_1_P21 1354 M78076_PEA_1_T23 (SEQ ID NO: 79)
M78076_PEA_1_P24 1355 M78076_PEA_1_T26 (SEQ ID NO: 80)
M78076_PEA_1_P2 1356 M78076_PEA_1_T27 (SEQ ID NO: 81)
M78076_PEA_1_P25 1357 M78076_PEA_1_T28 (SEQ ID NO: 82)
[2227] These sequences are variants of the known protein
Amyloid-like protein 1 precursor (SwissProt accession identifier
APP1_HUMAN; known also according to the synonyms APLP; APLP-1), SEQ
ID NO: 1439, referred to herein as the previously known
protein.
[2228] Protein Amyloid-like protein 1 precursor (SEQ ID NO:1439) is
known or believed to have the following function(s): May play a
role in postsynaptic function. The C-terminal gamma-secretase
processed fragment, ALID1, activates transcription activation
through APBB1 (Fe65) binding (By similarity). Couples to JIP signal
transduction through C-terminal binding. May interact with cellular
G-protein signaling pathways. Can regulate neurite outgrowth
through binding to components of the extracellular matrix such as
heparin and collagen I. The gamma-CTF peptide, C30, is a potent
enhancer of neuronal apoptosis (By similarity). The sequence for
protein Amyloid-like protein 1 precursor is given at the end of the
application, as "Amyloid-like protein 1 precursor amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 657.
TABLE-US-00703 TABLE 657 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 48 A -> P
[2229] Protein Amyloid-like protein 1 precursor (SEQ ID NO:1439)
localization is believed to be Type I membrane protein.
C-terminally processed in the Golgi complex.
[2230] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: endocytosis;
apoptosis; cell adhesion; neurogenesis; cell death, which are
annotation(s) related to Biological Process; protein binding;
heparin binding, which are annotation(s) related to Molecular
Function; and basement membrane; coated pit; integral membrane
protein, which are annotation(s) related to Cellular Component.
[2231] The GO assignment relies on information from one or more of
the SwissProt/TremB1Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2232] As noted above, cluster M78076 features 9 transcript(s),
which were listed in Table 654 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Amyloid-like protein
1 precursor (SEQ ID NO:1439). A description of each variant protein
according to the present invention is now provided.
[2233] Variant protein M78076_PEA.sub.--1_P3 (SEQ ID NO:1350)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T2 (SEQ ID NO:74). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2234] Comparison report between M78076_PEA.sub.--1_P3 (SEQ ID
NO:1350) and APP1_HUMAN (SEQ ID NO:1439):
[2235] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKD corresponding to amino acids 1-517 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-517 of M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GE corresponding to amino acids 518-519 of
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2236] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2237] Variant protein M78076_PEA.sub.--1_P3 (SEQ ID NO:1350) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 658, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P3
(SEQ ID NO:1350) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00704 TABLE 658 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No 38 G
-> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No 145 F
-> S No 214 G -> R No 214 G -> No 262 Q -> No 270 V
-> No 309 G -> E Yes 370 Q -> No
[2238] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 659(given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00705 TABLE 659 Glycosylation site(s) Position(s) on known
amino acid Present in Position in sequence variant protein? variant
protein? 337 yes 337 461 yes 461 551 no
[2239] Variant protein M78076_PEA.sub.--1_P3 (SEQ ID NO:1350) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T2 (SEQ
ID NO:74), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M78076_PEA.sub.--1_T2
(SEQ ID NO:74) is shown in bold; this coding portion starts at
position 142 and ends at position 1698. The transcript also has the
following SNPs as listed in Table 660 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M78076_PEA.sub.--1_P3 (SEQ ID NO:1350) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00706 TABLE 660 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
114 G -> No 151 G -> C Yes 158 C -> A Yes 179 G -> A
Yes 219 A -> G Yes 243 G -> No 253 G -> A Yes 315 A ->
G Yes 366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C
-> No 522 C -> T No 575 T -> C No 781 G -> No 781 G
-> A No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G
-> A Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes
2146 G -> A Yes 2224 C -> T No 2362 C -> T Yes 2513 A
-> G No 2656 C -> T Yes
[2240] Variant protein M78076_PEA.sub.--1_P4 (SEQ ID NO:1351)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T3 (SEQ ID NO:75). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2241] Comparison report between M78076_PEA.sub.--1_P4 (SEQ ID
NO:1351) and APP1_HUMAN (SEQ ID NO:1439):
[2242] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids
1-526 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 1-526 of M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence ECLTVNPSLQIPLNP (SEQ ID NO: 1718) corresponding to amino
acids 527-541 of M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2243] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ECLTVNPSLQIPLNP (SEQ ID NO: 1718) in M78076_PEA.sub.--1_P4 (SEQ ID
NO:1351).
[2244] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2245] Variant protein M78076_PEA.sub.--1_P4 (SEQ ID NO:1351) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 661, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P4
(SEQ ID NO:1351) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00707 TABLE 661 Amino acid mutations SNP position(s)
Previously on amino acid Alternative known sequence amino acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No
[2246] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 662 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00708 TABLE 662 Glycosylation site(s) Position(s) Position
on known in amino acid Present in variant sequence variant protein?
protein? 337 yes 337 461 yes 461 551 no
[2247] Variant protein M78076_PEA.sub.--1_P4 (SEQ ID NO:1351) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T3 (SEQ
ID NO:75), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript M78076_PEA.sub.--1_T3
(SEQ ID NO:75) is shown in bold; this coding portion starts at
position 142 and ends at position 1764. The transcript also has the
following SNPs as listed in Table 663 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
M78076_PEA.sub.--1_P4 (SEQ ID NO:1351) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00709 TABLE 663 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
114 G -> No 151 G -> C Yes 158 C -> A Yes 179 G -> A
Yes 219 A -> G Yes 243 G -> No 253 G -> A Yes 315 A ->
G Yes 366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C
-> No 522 C -> T No 575 T -> C No 781 G -> No 781 G
-> A No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G
-> A Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes
1817 G -> A Yes 2362 G -> A Yes 2440 C -> T No 2578 C
-> T Yes 2729 A -> G No 2872 C -> T Yes
[2248] Variant protein M78076_PEA.sub.--1_P12 (SEQ ID NO:1352)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T13 (SEQ ID NO:77). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2249] Comparison report between M78076_PEA.sub.--1_P12 (SEQ ID
NO:1352) and APP1_HUMAN (SEQ ID NO:1439):
[2250] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKG corresponding to amino acids
1-526 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 1-526 of M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence ECVCSKGFPFPLIGDSEG (SEQ ID NO: 1719) corresponding to
amino acids 527-544 of M78076_PEA.sub.--1_P12 (SEQ ID NO:1352),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2251] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
ECVCSKGFPFPLIGDSEG (SEQ ID NO: 1719) in M78076_PEA.sub.--1_P12 (SEQ
ID NO:1352).
[2252] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2253] Variant protein M78076_PEA.sub.--1_P12 (SEQ ID NO:1352) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 664, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P12
(SEQ ID NO:1352) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00710 TABLE 664 Amino acid mutations SNP position(s)
Previously on amino acid Alternative known sequence amino acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No
[2254] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P12 (SEQ ID NO:1352), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 665 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00711 TABLE 665 Glycosylation site(s) Position(s) on known
amino acid Present in Position in sequence variant protein? variant
protein? 337 yes 337 461 yes 461 551 no
[2255] Variant protein M78076_PEA.sub.--1_P12 (SEQ ID NO:1352) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T13 (SEQ
ID NO:77), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T13 (SEQ ID NO:77) is shown in bold; this coding
portion starts at position 142 and ends at position 1773. The
transcript also has the following SNPs as listed in Table 666
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P12 (SEQ ID NO:1352) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00712 TABLE 666 Nucleic acid SNPs SNP position on
nucleotide Previously sequence Alternative nucleic acid known SNP?
114 G -> No 151 G -> C Yes 158 C -> A Yes 179 G -> A
Yes 219 A -> G Yes 243 G -> No 253 G -> A Yes 315 A ->
G Yes 366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C
-> No 522 C -> T No 575 T -> C No 781 G -> No 781 G
-> A No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G
-> A Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes
1816 G -> A Yes 1894 C -> T No 2032 C -> T Yes 2183 A
-> G No 2326 C -> T Yes
[2256] Variant protein M78076_PEA.sub.--1_P14 (SEQ ID NO:1353)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T15 (SEQ ID NO:78). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2257] Comparison report between M78076_PEA.sub.--1_P14 (SEQ ID
NO:1353) and APP1_HUMAN (SEQ ID NO:1439):
[2258] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQIQELLHSEHLGPS
ELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLEQYERKVNASVPRGFPFHSSE
IQRDEL corresponding to amino acids 1-570 of APP1_HUMAN (SEQ ID
NO:1439), which also corresponds to amino acids 1-570 of
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO: 1720)
corresponding to amino acids 571-619 of M78076_PEA.sub.--1_P14 (SEQ
ID NO:1353), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[2259] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
VRGGTAGYLGEETRGQRPGCDSQSHTGPSKKPSAPSPLPAGTSWDRGVP (SEQ ID NO: 1720)
in M78076_PEA.sub.--1_P14 (SEQ ID NO:1353).
[2260] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2261] Variant protein M78076_PEA.sub.--1_P14 (SEQ ID NO:1353) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 667, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P14
(SEQ ID NO:1353) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00713 TABLE 667 Amino acid mutations SNP position(s)
Previously on amino acid Alternative known sequence amino acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No
[2262] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P14 (SEQ ID NO:1353), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 668 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00714 TABLE 668 Glycosylation site(s) Position(s) on known
Present Position amino acid in variant in variant sequence protein?
protein? 337 yes 337 461 yes 461 551 yes 551
[2263] Variant protein M78076_PEA.sub.--1_P14 (SEQ ID NO:1353) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T15 (SEQ
ID NO:78), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) is shown in bold; this coding
portion starts at position 142 and ends at position 1998. The
transcript also has the following SNPs as listed in Table 669
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P14 (SEQ ID NO:1353) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00715 TABLE 669 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 114 G
-> No 151 G -> C Yes 158 C -> A Yes 179 G -> A Yes 219
A -> G Yes 243 G -> No 253 G -> A Yes 315 A -> G Yes
366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C ->
No 522 C -> T No 575 T -> C No 781 G -> No 781 G -> A
No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G -> A
Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes 2008 G
-> A Yes 2086 C -> T No 2224 C -> T Yes 2375 A -> G No
2518 C -> T Yes
[2264] Variant protein M78076_PEA.sub.--1_P21 (SEQ ID NO:1354)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T23 (SEQ ID NO:79). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2265] Comparison report between M78076_PEA.sub.--1_P21 (SEQ ID
NO:1354) and APP1_HUMAN (SEQ ID NO:1439):
[2266] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
corresponding to amino acids 1-352 of APP1_HUMAN (SEQ ID NO:1439),
which also corresponds to amino acids 1-352 of
M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), and a second amino acid
sequence being at least 90% homologous to
AERVLLALRRYLRAEQKEQRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHL
AQELRPQIQELLHSEHLGPSELEAPAPGGSSEDKGGLQPPDSKDDTPMTLPKGSTEQDAASPEKEKMNPLE
QYERKVNASVPRGFPFHSSEIQRDELAPAGTGVSREAVSGLLIMGAGGGSLIVLSMLLLRRKKPYGAISHG
VVEVDPMLTLEEQQLRELQRHGYENPTYRFLEERP corresponding to amino acids
406-650 of APP1_HUMAN (SEQ ID NO:1439), which also corresponds to
amino acids 353-597 of M78076_PEA.sub.--1_P21 (SEQ ID NO:1354),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2267] 2.An isolated chimeric polypeptide encoding for an edge
portion of M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EA, having a structure as follows: a
sequence starting from any of amino acid numbers 352-x to 352; and
ending at any of amino acid numbers 353+((n-2)-x), in which x
varies from 0 to n-2.
[2268] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although both signal-peptide
prediction programs agree that this protein has a signal peptide,
both trans-membrane region prediction programs predict that this
protein has a trans-membrane region downstream of this signal
peptide.
[2269] Variant protein M78076_PEA.sub.--1_P21 (SEQ ID NO:1354) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 670, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P21
(SEQ ID NO:1354) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00716 TABLE 670 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes
[2270] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P21 (SEQ ID NO:1354), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 671 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00717 TABLE 671 Glycosylation site(s) Position(s) on known
Present Position amino acid in variant in variant sequence protein?
protein? 337 yes 337 461 yes 408 551 yes 498
[2271] Variant protein M78076_PEA.sub.--1_P21 (SEQ ID NO:1354) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T23 (SEQ ID NO:79) is shown in bold; this coding
portion starts at position 142 and ends at position 1932. The
transcript also has the following SNPs as listed in Table 672
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P21 (SEQ ID NO:1354) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00718 TABLE 672 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 114 G
-> No 151 G -> C Yes 158 C -> A Yes 179 G -> A Yes 219
A -> G Yes 243 G -> No 253 G -> A Yes 315 A -> G Yes
366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C ->
No 522 C -> T No 575 T -> C No 781 G -> No 781 G -> A
No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G -> A
Yes 1239 G -> T Yes 1264 C -> T Yes 1728 G -> A Yes 1806 C
-> T No 1944 C -> T Yes 2095 A -> G No 2238 C -> T
Yes
[2272] Variant protein M78076_PEA.sub.--1_P24 (SEQ ID NO:1355)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T26 (SEQ ID NO:80). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2273] Comparison report between M78076_PEA.sub.--1_P24 (SEQ ID
NO:1355) and APP1_HUMAN (SEQ ID NO:1439):
[2274] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQVHTHLQVIEERVNQSLGLLDQNPHLAQELRPQI
corresponding to amino acids 1-481 of APP1_HUMAN (SEQ ID NO:1439),
which also corresponds to amino acids 1-481 of
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
RECLLPWLPLQISEGRS (SEQ ID NO: 1721) corresponding to amino acids
482-498 of M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2275] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
RECLLPWLPLQISEGRS (SEQ ID NO: 1721) in M78076_PEA.sub.--1_P24 (SEQ
ID NO:1355).
[2276] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2277] Variant protein M78076_PEA.sub.--1_P24 (SEQ ID NO:1355) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 673, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P24
(SEQ ID NO:1355) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00719 TABLE 673 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No
[2278] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P24 (SEQ ID NO:1355), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 674 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00720 TABLE 674 Glycosylation site(s) Position(s) on known
Present Position amino acid in variant in variant sequence protein?
protein? 337 yes 337 461 yes 461 551 no
[2279] Variant protein M78076_PEA.sub.--1_P24 (SEQ ID NO:1355) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T26 (SEQ
ID NO:80), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T26 (SEQ ID NO:80) is shown in bold; this coding
portion starts at position 142 and ends at position 1635. The
transcript also has the following SNPs as listed in Table 675
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P24 (SEQ ID NO:1355) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00721 TABLE 675 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 114 G
-> No 151 G -> C Yes 158 C -> A Yes 179 G -> A Yes 219
A -> G Yes 243 G -> No 253 G -> A Yes 315 A -> G Yes
366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C ->
No 522 C -> T No 575 T -> C No 781 G -> No 781 G -> A
No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G -> A
Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes 2184 G
-> A Yes
[2280] Variant protein M78076_PEA.sub.--1_P2 (SEQ ID NO:1356)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T27 (SEQ ID NO:81). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2281] Comparison report between M78076_PEA.sub.--1_P2 (SEQ ID
NO:1356) and APP1_HUMAN (SEQ ID NO:1439):
[2282] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQV corresponding to amino acids 1-449 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-449 of M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLTCCVFDPCFLALG
FLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIATSTSWVQAILLPQPLE
(SEQ ID NO:1722) corresponding to amino acids 450-588 of
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2283] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LTSFQLPNAPLFLRRPRLRLFSCPLDPLSVSWTPSYPLNTASLPLPSLSAQLPDPETWTLTCCVFDPCFLALG
FLLPPPSILCSVPWIFTAFPRIVFFFFFFLRQVLALSPRQESSVRSWLIATSTSWVQAILLPQPLE
(SEQ ID NO: 1722) in M78076_PEA.sub.--1_P2 (SEQ ID NO:1356).
[2284] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although both signal-peptide
prediction programs agree that this protein has a signal peptide,
both trans-membrane region prediction programs predict that this
protein has a trans-membrane region downstream of this signal
peptide.
[2285] Variant protein M78076_PEA.sub.--1_P2 (SEQ ID NO:1356) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 676, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P2
(SEQ ID NO:1356) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00722 TABLE 676 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No 520 A -> S Yes 546 F
-> Yes 564 S -> C Yes
[2286] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P2 (SEQ ID NO:1356), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 677 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00723 TABLE 677 Glycosylation site(s) Position(s) on known
Present Position amino acid in variant in variant sequence protein?
protein? 337 yes 337 461 no 551 no
[2287] Variant protein M78076_PEA.sub.--1_P2 (SEQ ID NO:1356) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T27 (SEQ
ID NO:81), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) is shown in bold; this coding
portion starts at position 142 and ends at position 1905. The
transcript also has the following SNPs as listed in Table 678
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P2 (SEQ ID NO:1356) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00724 TABLE 678 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 114 G
-> No 151 G -> C Yes 158 C -> A Yes 179 G -> A Yes 219
A -> G Yes 243 G -> No 253 G -> A Yes 315 A -> G Yes
366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C ->
No 522 C -> T No 575 T -> C No 781 G -> No 781 G -> A
No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G -> A
Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes 1500 C
-> T Yes 1699 G -> T Yes 1725 G -> A Yes 1777 T -> Yes
1831 A -> T Yes 2274 A -> G Yes 2525 A -> G Yes 2681 G
-> A Yes 3831 G -> A Yes
[2288] Variant protein M78076_PEA.sub.--1_P25 (SEQ ID NO:1357)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
M78076_PEA.sub.--1_T28 (SEQ ID NO:82). An alignment is given to the
known protein (Amyloid-like protein 1 precursor (SEQ ID NO:1439))
at the end of the application. One or more alignments to one or
more previously published protein sequences are given at the end of
the application. A brief description of the relationship of the
variant protein according to the present invention to each such
aligned protein is as follows:
[2289] Comparison report between M78076_PEA.sub.--1_P25 (SEQ ID
NO:1357) and APP1_HUMAN (SEQ ID NO:1439):
[2290] 1.An isolated chimeric polypeptide encoding for
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), comprising a first amino
acid sequence being at least 90% homologous to
MGPASPAARGLSRRPGQPPLPLLLPLLLLLLRAQPAIGSLAGGSPGAAEAPGSAQVAGLCGRLTLHRDLRT
GRWEPDPQRSRRCLRDPQRVLEYCRQMYPELQIARVEQATQAIPMERWCGGSRSGSCAHPHHQVVPFRC
LPGEFVSEALLVPEGCRFLHQERMDQCESSTRRHQEAQEACSSQGLILHGSGMLLPCGSDRFRGVEYVCCP
PPGTPDPSGTAVGDPSTRSWPPGSRVEGAEDEEEEESFPQPVDDYFVEPPQAEEEEETVPPPSSHTLAVVGK
VTPTPRPTDGVDIYFGMPGEISEHEGFLRAKMDLEERRMRQINEVMREWAMADNQSKNLPKADRQALNE
HFQSILQTLEEQVSGERQRLVETHATRVIALINDQRRAALEGFLAALQADPPQAERVLLALRRYLRAEQKE
QRHTLRHYQHVAAVDPEKAQQMRFQ corresponding to amino acids 1-448 of
APP1_HUMAN (SEQ ID NO:1439), which also corresponds to amino acids
1-448 of M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP
(SEQ ID NO: 1723) corresponding to amino acids 449-505 of
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2291] 2.An isolated polypeptide encoding for a tail of
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
PQNPNSQPRAAGSLEVIISHPFVRRLEILISPFQFQNSIPKNSQIVPAASPRGTSSP (SEQ ID
NO: 1723) in M78076_PEA.sub.--1_P25 (SEQ ID NO:1357).
[2292] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2293] Variant protein M78076_PEA.sub.--1_P25 (SEQ ID NO:1357) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 679, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein M78076_PEA.sub.--1_P25
(SEQ ID NO:1357) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00725 TABLE 679 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 4 A -> P Yes 6 P -> H Yes 13 R -> H Yes 34 Q -> No
38 G -> R Yes 88 P -> R Yes 124 R -> Q Yes 127 S -> No
145 F -> S No 214 G -> R No 214 G -> No 262 Q -> No 270
V -> No 309 G -> E Yes 370 Q -> No
[2294] The glycosylation sites of variant protein
M78076_PEA.sub.--1_P25 (SEQ ID NO:1357), as compared to the known
protein Amyloid-like protein 1 precursor (SEQ ID NO:1439), are
described in Table 680 (given according to their position(s) on the
amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-00726 TABLE 680 Glycosylation site(s) Position(s) on known
Present Position amino acid in variant in variant sequence protein?
protein? 337 yes 337 461 no 551 no
[2295] Variant protein M78076_PEA.sub.--1_P25 (SEQ ID NO:1357) is
encoded by the following transcript(s): M78076_PEA.sub.--1_T28 (SEQ
ID NO:82), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
M78076_PEA.sub.--1_T28 (SEQ ID NO:82) is shown in bold; this coding
portion starts at position 142 and ends at position 1656. The
transcript also has the following SNPs as listed in Table 681
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein M78076_PEA.sub.--1_P25 (SEQ ID NO:1357) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00727 TABLE 681 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 114 G
-> No 151 G -> C Yes 158 C -> A Yes 179 G -> A Yes 219
A -> G Yes 243 G -> No 253 G -> A Yes 315 A -> G Yes
366 A -> G Yes 404 C -> G Yes 512 G -> A Yes 522 C ->
No 522 C -> T No 575 T -> C No 781 G -> No 781 G -> A
No 927 G -> No 951 C -> No 1067 G -> A Yes 1077 G -> A
Yes 1251 G -> No 1398 G -> T Yes 1423 C -> T Yes 1593 A
-> G No 1736 C -> T Yes
[2296] As noted above, cluster M78076 features 35 segment(s), which
were listed in Table 655 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2297] Segment cluster M78076_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:659) according to the present invention is supported by 47
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 682 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00728 TABLE 682 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1 160 M78076_PEA_1_T3 (SEQ ID NO:
75) 1 160 M78076_PEA_1_T5 (SEQ ID NO: 76) 1 160 M78076_PEA_1_T13
(SEQ ID NO: 77) 1 160 M78076_PEA_1_T15 (SEQ ID NO: 78) 1 160
M78076_PEA_1_T23 (SEQ ID NO: 79) 1 160 M78076_PEA_1_T26 (SEQ ID NO:
80) 1 160 M78076_PEA_1_T27 (SEQ ID NO: 81) 1 160 M78076_PEA_1_T28
(SEQ ID NO: 82) 1 160
[2298] Segment cluster M78076_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:660) according to the present invention is supported by 70
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 683 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00729 TABLE 683 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 433 565 M78076_PEA_1_T3 (SEQ ID NO:
75) 433 565 M78076_PEA_1_T5 (SEQ ID NO: 76) 433 565
M78076_PEA_1_T13 (SEQ ID NO: 77) 433 565 M78076_PEA_1_T15 (SEQ ID
NO: 78) 433 565 M78076_PEA_1_T23 (SEQ ID NO: 79) 433 565
M78076_PEA_1_T26 (SEQ ID NO: 80) 433 565 M78076_PEA_1_T27 (SEQ ID
NO: 81) 433 565 M78076_PEA_1_T28 (SEQ ID NO: 82) 433 565
[2299] Segment cluster M78076_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:661) according to the present invention is supported by 74
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T15 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ
ID NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 684 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00730 TABLE 684 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 679 812 M78076_PEA_1_T3 (SEQ ID NO:
75) 679 812 M78076_PEA_1_T5 (SEQ ID NO: 76) 679 812
M78076_PEA_1_T13 (SEQ ID NO: 77) 679 812 M78076_PEA_1_T15 (SEQ ID
NO: 78) 679 812 M78076_PEA_1_T23 (SEQ ID NO: 79) 679 812
M78076_PEA_1_T26 (SEQ ID NO: 80) 679 812 M78076_PEA_1_T27 (SEQ ID
NO: 81) 679 812 M78076_PEA_1_T28 (SEQ ID NO: 82) 679 812
[2300] Segment cluster M78076_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:662) according to me present invention is supported by 95
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 685 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00731 TABLE 685 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 813 991 M78076_PEA_1_T3 (SEQ ID NO:
75) 813 991 M78076_PEA_1_T5 (SEQ ID NO: 76) 813 991
M78076_PEA_1_T13 (SEQ ID NO: 77) 813 991 M78076_PEA_1_T15 (SEQ ID
NO: 78) 813 991 M78076_PEA_1_T23 (SEQ ID NO: 79) 813 991
M78076_PEA_1_T26 (SEQ ID NO: 80) 813 991 M78076_PEA_1_T27 (SEQ ID
NO: 81) 813 991 M78076_PEA_1_T28 (SEQ ID NO: 82) 813 991
[2301] Segment cluster M78076_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:663) according to the present invention is supported by 99
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 686 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00732 TABLE 686 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 992 1122 M78076_PEA_1_T3 (SEQ ID
NO: 75) 992 1122 M78076_PEA_1_T5 (SEQ ID NO: 76) 992 1122
M78076_PEA_1_T13 (SEQ ID NO: 77) 992 1122 M78076_PEA_1_T15 (SEQ ID
NO: 78) 992 1122 M78076_PEA_1_T23 (SEQ ID NO: 79) 992 1122
M78076_PEA_1_T26 (SEQ ID NO: 80) 992 1122 M78076_PEA_1_T27 (SEQ ID
NO: 81) 992 1122 M78076_PEA_1_T28 (SEQ ID NO: 82) 992 1122
[2302] Segment cluster M78076_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:664) according to the present invention is supported by 105
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T26 (SEQ
ID NO:80), M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and
M78076_PEA.sub.--1_T28 (SEQ ID NO:82). Table 687 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00733 TABLE 687 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1198 1356 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1198 1356 M78076_PEA_1_T5 (SEQ ID NO: 76) 1198 1356
M78076_PEA_1_T13 (SEQ ID NO: 77) 1198 1356 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1198 1356 M78076_PEA_1_T26 (SEQ ID NO: 80) 1198 1356
M78076_PEA_1_T27 (SEQ ID NO: 81) 1198 1356 M78076_PEA_1_T28 (SEQ ID
NO: 82) 1198 1356
[2303] Segment cluster M78076_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:665) according to the present invention is supported by 99
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 688 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00734 TABLE 688 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1357 1485 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1357 1485 M78076_PEA_1_T5 (SEQ ID NO: 76) 1357 1485
M78076_PEA_1_T13 (SEQ ID NO: 77) 1357 1485 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1357 1485 M78076_PEA_1_T23 (SEQ ID NO: 79) 1198 1326
M78076_PEA_1_T26 (SEQ ID NO: 80) 1357 1485 M78076_PEA_1_T27 (SEQ ID
NO: 81) 1357 1485 M78076_PEA_1_T28 (SEQ ID NO: 82) 1357 1485
[2304] Segment cluster M78076_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:666) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T27 (SEQ ID NO:81). Table 689
below described the starting and ending position of this segment on
each transcript.
TABLE-US-00735 TABLE 689 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T27 (SEQ ID NO: 81) 1490 3132
[2305] Segment cluster M78076_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:667) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T26 (SEQ ID NO:80) and
M78076_PEA.sub.--1_T27 (SEQ ID NO:81). Table 690 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00736 TABLE 690 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T26 (SEQ ID NO: 80) 1586 2457 M78076_PEA_1_T27 (SEQ ID
NO: 81) 3233 4104
[2306] Segment cluster M78076_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:668) according to the present invention is supported by 4
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74) and
M78076_PEA.sub.--1_T5 (SEQ ID NO:76). Table 691 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00737 TABLE 691 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1694 1952 M78076_PEA_1_T5 (SEQ ID
NO: 76) 1694 1952
[2307] Segment cluster M78076_PEA.sub.--1_node.sub.--37 (SEQ ID
NO:669) according to the present invention is supported by 11
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T3 (SEQ ID NO:75) and
M78076_PEA.sub.--1_T5 (SEQ ID NO:76). Table 692 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00738 TABLE 692 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T3 (SEQ ID NO: 75) 1718 2180 M78076_PEA_1_T5 (SEQ ID
NO: 76) 1977 2439
[2308] Segment cluster M78076_PEA.sub.--1_node.sub.--46 (SEQ ID
NO:670) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T15 (SEQ ID NO:78). Table 693
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00739 TABLE 693 Segment location on transcripts Segment
Segment starting ending Transcript name position position
M78076_PEA_1_T15 (SEQ ID NO: 78) 1852 1972
[2309] Segment cluster M78076_PEA.sub.--1_node.sub.--47 (SEQ ID
NO:671) according to the present invention is supported by 155
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 694 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00740 TABLE 694 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2111 2254 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2327 2470 M78076_PEA_1_T5 (SEQ ID NO: 76) 2586 2729
M78076_PEA_1_T13 (SEQ ID NO: 77) 1781 1924 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1973 2116 M78076_PEA_1_T23 (SEQ ID NO: 79) 1693 1836
[2310] Segment cluster M78076_PEA.sub.--1_node.sub.--54 (SEQ ID
NO:672) according to the present invention is supported by 133
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79) and M78076_PEA.sub.--1_T28 (SEQ ID NO:82). Table 695
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00741 TABLE 695 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2412 2715 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2628 2931 M78076_PEA_1_T5 (SEQ ID NO: 76) 2887 3190
M78076_PEA_1_T13 (SEQ ID NO: 77) 2082 2385 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2274 2577 M78076_PEA_1_T23 (SEQ ID NO: 79) 1994 2297
M78076_PEA_1_T28 (SEQ ID NO: 82) 1492 1795
[2311] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 bp in length, and so
are included in a separate description.
[2312] Segment cluster M78076_PEA.sub.--1_node.sub.--1 (SEQ ID
NO:673) according to the present invention is supported by 47
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 696 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00742 TABLE 696 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 161 204 M78076_PEA_1_T3 (SEQ ID NO:
75) 161 204 M78076_PEA_1_T5 (SEQ ID NO: 76) 161 204
M78076_PEA_1_T13 (SEQ ID NO: 77) 161 204 M78076_PEA_1_T15 (SEQ ID
NO: 78) 161 204 M78076_PEA_1_T23 (SEQ ID NO: 79) 161 204
M78076_PEA_1_T26 (SEQ ID NO: 80) 161 204 M78076_PEA_1_T27 (SEQ ID
NO: 81) 161 204 M78076_PEA_1_T28 (SEQ ID NO: 82) 161 204
[2313] Segment cluster M78076_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:674) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 697 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00743 TABLE 697 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 205 224 M78076_PEA_1_T3 (SEQ ID NO:
75) 205 224 M78076_PEA_1_T5 (SEQ ID NO: 76) 205 224
M78076_PEA_1_T13 (SEQ ID NO: 77) 205 224 M78076_PEA_1_T15 (SEQ ID
NO: 78) 205 224 M78076_PEA_1_T23 (SEQ ID NO: 79) 205 224
M78076_PEA_1_T26 (SEQ ID NO: 80) 205 224 M78076_PEA_1_T27 (SEQ ID
NO: 81) 205 224 M78076_PEA_1_T28 (SEQ ID NO: 82) 205 224
[2314] Segment cluster M78076_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:675) according to the present invention is supported by 52
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 698 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00744 TABLE 698 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 225 288 M78076_PEA_1_T3 (SEQ ID NO:
75) 225 288 M78076_PEA_1_T5 (SEQ ID NO: 76) 225 288
M78076_PEA_1_T13 (SEQ ID NO: 77) 225 288 M78076_PEA_1_T15 (SEQ ID
NO: 78) 225 288 M78076_PEA_1_T23 (SEQ ID NO: 79) 225 288
M78076_PEA_1_T26 (SEQ ID NO: 80) 225 288 M78076_PEA_1_T27 (SEQ ID
NO: 81) 225 288 M78076_PEA_1_T28 (SEQ ID NO: 82) 225 288
[2315] Segment cluster M78076_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:676) according to the present invention is supported by 59
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 699 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00745 TABLE 699 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 289 370 M78076_PEA_1_T3 (SEQ ID NO:
75) 289 370 M78076_PEA_1_T5 (SEQ ID NO: 76) 289 370
M78076_PEA_1_T13 (SEQ ID NO: 77) 289 370 M78076_PEA_1_T15 (SEQ ID
NO: 78) 289 370 M78076_PEA_1_T23 (SEQ ID NO: 79) 289 370
M78076_PEA_1_T26 (SEQ ID NO: 80) 289 370 M78076_PEA_1_T27 (SEQ ID
NO: 81) 289 370 M78076_PEA_1_T28 (SEQ ID NO: 82) 289 370
[2316] Segment cluster M78076_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:677) according to the present invention is supported by 64
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 700 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00746 TABLE 700 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 371 432 M78076_PEA_1_T3 (SEQ ID NO:
75) 371 432 M78076_PEA_1_T5 (SEQ ID NO: 76) 371 432
M78076_PEA_1_T13 (SEQ ID NO: 77) 371 432 M78076_PEA_1_T15 (SEQ ID
NO: 78) 371 432 M78076_PEA_1_T23 (SEQ ID NO: 79) 371 432
M78076_PEA_1_T26 (SEQ ID NO: 80) 371 432 M78076_PEA_1_T27 (SEQ ID
NO: 81) 371 432 M78076_PEA_1_T28 (SEQ ID NO: 82) 371 432
[2317] Segment cluster M78076_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:678) according to the present invention is supported by 71
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 701 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00747 TABLE 701 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 566 678 M78076_PEA_1_T3 (SEQ ID NO:
75) 566 678 M78076_PEA_1_T5 (SEQ ID NO: 76) 566 678
M78076_PEA_1_T13 (SEQ ID NO: 77) 566 678 M78076_PEA_1_T15 (SEQ ID
NO: 78) 566 678 M78076_PEA_1_T23 (SEQ ID NO: 79) 566 678
M78076_PEA_1_T26 (SEQ ID NO: 80) 566 678 M78076_PEA_1_T27 (SEQ ID
NO: 81) 566 678 M78076_PEA_1_T28 (SEQ ID NO: 82) 566 678
[2318] Segment cluster M78076_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:679) according to the present invention is supported by 92
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80),
M78076_PEA.sub.--1_T27 (SEQ ID NO:81) and M78076_PEA.sub.--1_T28
(SEQ ID NO:82). Table 702 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00748 TABLE 702 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1123 1197 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1123 1197 M78076_PEA_1_T5 (SEQ ID NO: 76) 1123 1197
M78076_PEA_1_T13 (SEQ ID NO: 77) 1123 1197 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1123 1197 M78076_PEA_1_T23 (SEQ ID NO: 79) 1123 1197
M78076_PEA_1_T26 (SEQ ID NO: 80) 1123 1197 M78076_PEA_1_T27 (SEQ ID
NO: 81) 1123 1197 M78076_PEA_1_T28 (SEQ ID NO: 82) 1123 1197
[2319] Segment cluster M78076_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:680) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T27 (SEQ ID NO:81).
Table 703 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00749 TABLE 703 Segment location on transcripts Segment
Segment Transcript name starting position ending position
M78076_PEA_1_T27 1486 1489 (SEQ ID NO: 81)
[2320] Segment cluster M78076_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:681) according to the present invention is supported by 90
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74), M78076_PEA_T3
(SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID NO:76),
M78076_PEA.sub.--1_T13 (SEQ ID NO:77), M78076_PEA.sub.--1_T15 (SEQ
ID NO:78), M78076_PEA.sub.--1_T23 (SEQ ID NO:79),
M78076_PEA.sub.--1_T26 (SEQ ID NO:80) and M78076_PEA.sub.--1_T27
(SEQ ID NO:81). Table 704 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00750 TABLE 704 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1486 1557 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1486 1557 M78076_PEA_1_T5 (SEQ ID NO: 76) 1486 1557
M78076_PEA_1_T13 (SEQ ID NO: 77) 1486 1557 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1486 1557 M78076_PEA_1_T23 (SEQ ID NO: 79) 1327 1398
M78076_PEA_1_T26 (SEQ ID NO: 80) 1486 1557 M78076_PEA_1_T27 (SEQ ID
NO: 81) 3133 3204
[2321] Segment cluster M78076_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:682) according to the present invention is supported by 89
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79), M78076_PEA.sub.--1_T26 (SEQ ID NO:80) and
M78076PEA.sub.--1_T27 (SEQ ID NO:81). Table 705 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00751 TABLE 705 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1558 1585 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1558 1585 M78076_PEA_1_T5 (SEQ ID NO: 76) 1558 1585
M78076_PEA_1_T13 (SEQ ID NO: 77) 1558 1585 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1558 1585 M78076_PEA_1_T23 (SEQ ID NO: 79) 1399 1426
M78076_PEA_1_T26 (SEQ ID NO: 80) 1558 1585 M78076_PEA_1_T27 (SEQ ID
NO: 81) 3205 3232
[2322] Segment cluster M78076_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:683) according to the present invention is supported by 103
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5
(SEQ ID NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 706 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00752 TABLE 706 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1586 1693 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1586 1693 M78076_PEA_1_T5 (SEQ ID NO: 76) 1586 1693
M78076_PEA_1_T13 (SEQ ID NO: 77) 1586 1693 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1586 1693 M78076_PEA_1_T23 (SEQ ID NO: 79) 1427 1534
[2323] Segment cluster M78076_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:684) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 707 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00753 TABLE 707 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1953 1976 M78076_PEA_1_T3 (SEQ ID
NO: 75) 1694 1717 M78076_PEA_1_T5 (SEQ ID NO: 76) 1953 1976
M78076_PEA_1_T13 (SEQ ID NO: 77) 1694 1717 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1694 1717 M78076_PEA_1_T23 (SEQ ID NO: 79) 1535 1558
[2324] Segment cluster M78076_PEA.sub.--1_node.sub.--41 (SEQ ID
NO:685) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T3 (SEQ ID NO:75) and
M78076_PEA.sub.--1_T5 (SEQ ID NO:76). Table 708 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00754 TABLE 708 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T3 (SEQ ID NO: 75) 2181 2192 M78076_PEA_1_T5 (SEQ ID
NO: 76) 2440 2451
[2325] Segment cluster M78076_PEA.sub.--1_node.sub.--42 (SEQ ID
NO:686) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and
M78076_PEA.sub.--1_T23 (SEQ ID NO:79). Table 709 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00755 TABLE 709 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1977 1985 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2193 2201 M78076_PEA_1_T5 (SEQ ID NO: 76) 2452 2460
M78076_PEA_1_T15 (SEQ ID NO: 78) 1718 1726 M78076_PEA_1_T23 (SEQ ID
NO: 79) 1559 1567
[2326] Segment cluster M78076_PEA.sub.--1_node.sub.--43 (SEQ ID
NO:687) according to the present invention is supported by 110
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and
M78076_PEA.sub.--1_T23 (SEQ ID NO:79). Table 710 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00756 TABLE 710 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 1986 2047 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2202 2263 M78076_PEA_1_T5 (SEQ ID NO: 76) 2461 2522
M78076_PEA_1_T15 (SEQ ID NO: 78) 1727 1788 M78076_PEA_1_T23 (SEQ ID
NO: 79) 1568 1629
[2327] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 711.
TABLE-US-00757 TABLE 711 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
M78076_0_7_0 lung malignant tumors LUN (SEQ ID NO: 232)
[2328] Segment cluster M78076_PEA.sub.--1_node.sub.--45 (SEQ ID
NO:688) according to the present invention is supported by 132
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 712 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00758 TABLE 712 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2048 2110 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2264 2326 M78076_PEA_1_T5 (SEQ ID NO: 76) 2523 2585
M78076_PEA_1_T13 (SEQ ID NO: 77) 1718 1780 M78076_PEA_1_T15 (SEQ ID
NO: 78) 1789 1851 M78076_PEA_1_T23 (SEQ ID NO: 79) 1630 1692
[2329] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 713.
TABLE-US-00759 TABLE 713 Oligonucleotides related to this segment
Overexpressed Chip Oligonucleotide name in cancers reference
M78076_0_7_0 (SEQ ID NO: 232) lung malignant tumors LUN
[2330] Segment cluster M78076_PEA.sub.--1_node.sub.--49 (SEQ ID
NO:689) according to the present invention is supported by 129
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 714 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00760 TABLE 714 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2255 2290 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2471 2506 M78076_PEA_1_T5 (SEQ ID NO: 76) 2730 2765
M78076_PEA_1_T13 (SEQ ID NO: 77) 1925 1960 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2117 2152 M78076_PEA_1_T23 (SEQ ID NO: 79) 1837 1872
[2331] Segment cluster M78076_PEA.sub.--1_node.sub.--50 (SEQ ID
NO:690) according to the present invention is supported by 125
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 715 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00761 TABLE 715 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2291 2329 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2507 2545 M78076_PEA_1_T5 (SEQ ID NO: 76) 2766 2804
M78076_PEA_1_T13 (SEQ ID NO: 77) 1961 1999 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2153 2191 M78076_PEA_1_T23 (SEQ ID NO: 79) 1873 1911
[2332] Segment cluster M78076_PEA.sub.--1_node.sub.--51 (SEQ ID
NO:691) according to the present invention is supported by 123
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 716 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00762 TABLE 716 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2330 2388 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2546 2604 M78076_PEA_1_T5 (SEQ ID NO: 76) 2805 2863
M78076_PEA_1_T13 (SEQ ID NO: 77) 2000 2058 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2192 2250 M78076_PEA_1_T23 (SEQ ID NO: 79) 1912 1970
[2333] Segment cluster M78076_PEA.sub.--1_node.sub.--52 (SEQ ID
NO:692) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78) and M78076_PEA.sub.--1_T23
(SEQ ID NO:79). Table 717 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00763 TABLE 717 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2389 2405 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2605 2621 M78076_PEA_1_T5 (SEQ ID NO: 76) 2864 2880
M78076_PEA_1_T13 (SEQ ID NO: 77) 2059 2075 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2251 2267 M78076_PEA_1_T23 (SEQ ID NO: 79) 1971 1987
[2334] Segment cluster M78076_PEA.sub.--1_node.sub.--53 (SEQ ID
NO:693) according to the present invention can be found in the
following transcript(s): M78076_PEA.sub.--1_T2 (SEQ ID NO:74),
M78076_PEA.sub.--1_T3 (SEQ ID NO:75), M78076_PEA.sub.--1_T5 (SEQ ID
NO:76), M78076_PEA.sub.--1_T13 (SEQ ID NO:77),
M78076_PEA.sub.--1_T15 (SEQ ID NO:78), M78076_PEA.sub.--1_T23 (SEQ
ID NO:79) and M78076_PEA.sub.--1_T28 (SEQ ID NO:82). Table 718
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00764 TABLE 718 Segment location on transcripts Segment
Segment ending Transcript name starting position position
M78076_PEA_1_T2 (SEQ ID NO: 74) 2406 2411 M78076_PEA_1_T3 (SEQ ID
NO: 75) 2622 2627 M78076_PEA_1_T5 (SEQ ID NO: 76) 2881 2886
M78076_PEA_1_T13 (SEQ ID NO: 77) 2076 2081 M78076_PEA_1_T15 (SEQ ID
NO: 78) 2268 2273 M78076_PEA_1_T23 (SEQ ID NO: 79) 1988 1993
M78076_PEA_1_T28 (SEQ ID NO: 82) 1486 1491
Variant protein alignment to the previously known protein:
TABLE-US-00765 Sequence name: APP1_HUMAN (SEQ ID NO: 1439) Sequence
documentation: Alignment of: M78076_PEA_1_P3 (SEQ ID NO: 1350)
.times. APP1_HUMAN (SEQ ID NO: 1439) Alignment segment 1/1:
Quality: 5132.00 Escore: 0 Matching length: 517 Total length: 517
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00488## ##STR00489## ##STR00490##
##STR00491## ##STR00492## ##STR00493## ##STR00494## ##STR00495##
##STR00496## ##STR00497## ##STR00498## Sequence name: APP1_HUMAN
(SEQ ID NO: 1439) Sequence documentation: Alignment of:
M78076_PEA_1_P4 (SEQ ID NO: 1351) .times. APP1_HUMAN (SEQ ID NO:
1439 1439) Alignment segment 1/1: Quality: 5223.00 Escore: 0
Matching length: 526 Total length: 526 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00499## ##STR00500## ##STR00501## ##STR00502## ##STR00503##
##STR00504## ##STR00505## ##STR00506## ##STR00507## ##STR00508##
##STR00509## Sequence name: APP1_HUMAN (SEQ ID NO: 1439) Sequence
documentation: Alignment of: M78076_PEA_1_P12 (SEQ ID NO: 1352)
.times. APP1_HUMAN (SEQ ID NO: 1439) . . . Alignment segment 1/1:
Quality: 5223.00 Escore: 0 Matching length: 526 Total length: 526
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00510## ##STR00511## ##STR00512##
##STR00513## ##STR00514## ##STR00515## ##STR00516## ##STR00517##
##STR00518## ##STR00519## ##STR00520## Sequence name: APP1_HUMAN
(SEQ ID NO: 1439) Sequence documentation: Alignment of:
M78076_PEA_1_P14 (SEQ ID NO: 1353) .times. APP1_HUMAN (SEQ ID NO:
1439) . . . Alignment segment 1/1: Quality: 5672.00 Escore: 0
Matching length: 575 Total length: 575 Matching Percent Similarity:
99.48 Matching Percent Identity: 99.48 Total Percent Similarity:
99.48 Total Percent Identity: 99.48 Gaps: 0 Alignment: ##STR00521##
##STR00522## ##STR00523## ##STR00524## ##STR00525## ##STR00526##
##STR00527## ##STR00528## ##STR00529## ##STR00530## ##STR00531##
##STR00532## Sequence name: APP1_HUMAN (SEQ ID NO: 1439) Sequence
documentation: Alignment of: M78076_PEA_1_P21 (SEQ ID NO: 1354)
.times. APP1_HUMAN (SEQ ID NO: 1439) . . . Alignment segment 1/1:
Quality: 5822.00 Escore: 0 Matching length: 597 Total length: 650
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 91.85 Total Percent Identity:
91.85 Gaps: 1 Alignment: ##STR00533## ##STR00534## ##STR00535##
##STR00536## ##STR00537## ##STR00538## ##STR00539## ##STR00540##
##STR00541## ##STR00542## ##STR00543## ##STR00544## ##STR00545##
Sequence name: APP1_HUMAN (SEQ ID NO: 1439) Sequence documentation:
Alignment of: M78076_PEA_1_P24 (SEQ ID NO: 1355) .times. APP1_HUMAN
(SEQ ID NO: 1439) . . . Alignment segment 1/1: Quality: 4791.00
Escore: 0 Matching length: 485 Total length: 485 Matching Percent
Similarity: 99.79 Matching Percent Identity: 99.59 Total Percent
Similarity: 99.79 Total Percent Identity: 99.59 Gaps: 0 Alignment:
##STR00546## ##STR00547## ##STR00548## ##STR00549## ##STR00550##
##STR00551## ##STR00552## ##STR00553## ##STR00554## ##STR00555##
Sequence name: APP1_HUMAN (SEQ ID NO: 1439) Sequence documentation:
Alignment of: M78076_PEA_1_P2 (SEQ ID NO: 1356) .times. APP1_HUMAN
(SEQ ID NO: 1439) Alignment segment 1/1: Quality: 4474.00 Escore: 0
Matching length: 454 Total length: 454 Matching Percent Similarity:
99.56 Matching Percent Identity: 99.34 Total Percent Similarity:
99.56 Total Percent Identity: 99.34 Gaps: 0 Alignment: ##STR00556##
##STR00557## ##STR00558## ##STR00559## ##STR00560## ##STR00561##
##STR00562## ##STR00563## ##STR00564## ##STR00565## Sequence name:
APP1_HUMAN (SEQ ID NO: 1439) Sequence documentation: Alignment of:
M78076_PEA_1_P25 (SEQ ID NO: 1357) .times. APP1_HUMAN (SEQ ID
NO: 1439) . . . Alignment segment 1/1: Quality: 4455.00 Escore: 0
Matching length: 448 Total length: 448 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00566## ##STR00567## ##STR00568## ##STR00569## ##STR00570##
##STR00571## ##STR00572## ##STR00573## ##STR00574##
Description for Cluster T99080
[2335] Cluster T99080 features 14 transcript(s) and 11 segment(s)
of interest, the names for which are given in Tables 719 and 720,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
721.
TABLE-US-00766 TABLE 719 Transcripts of interest Transcript Name
Sequence ID No. T99080_PEA_4_T0 83 T99080_PEA_4_T2 84
T99080_PEA_4_T4 85 T99080_PEA_4_T6 86 T99080_PEA_4_T9 87
T99080_PEA_4_T10 88 T99080_PEA_4_T11 89 T99080_PEA_4_T13 90
T99080_PEA_4_T14 91 T99080_PEA_4_T17 92 T99080_PEA_4_T18 93
T99080_PEA_4_T19 94 T99080_PEA_4_T20 95 T99080_PEA_4_T21 96
TABLE-US-00767 TABLE 720 Segments of interest Segment Name Sequence
ID No. T99080_PEA_4_node_1 695 T99080_PEA_4_node_6 696
T99080_PEA_4_node_11 697 T99080_PEA_4_node_19 698
T99080_PEA_4_node_20 699 T99080_PEA_4_node_3 700
T99080_PEA_4_node_5 701 T99080_PEA_4_node_8 702
T99080_PEA_4_node_13 703 T99080_PEA_4_node_15 704
T99080_PEA_4_node_18 705
TABLE-US-00768 TABLE 721 Proteins of interest Sequence Protein Name
ID No. Corresponding Transcript(s) T99080_PEA_4_P1 1358
T99080_PEA_4_T0 (SEQ ID NO: 83) T99080_PEA_4_P2 1359
T99080_PEA_4_T2 (SEQ ID NO: 84) T99080_PEA_4_P5 1360
T99080_PEA_4_T6 (SEQ ID NO: 86) T99080_PEA_4_P8 1361
T99080_PEA_4_T9 (SEQ ID NO: 87) T99080_PEA_4_P9 1362
T99080_PEA_4_T10 (SEQ ID NO: 88) T99080_PEA_4_P10 1363
T99080_PEA_4_T11 (SEQ ID NO: 89) T99080_PEA_4_P12 1364
T99080_PEA_4_T14 (SEQ ID NO: 91) T99080_PEA_4_P13 1365
T99080_PEA_4_T17 (SEQ ID NO: 92) T99080_PEA_4_P14 1366
T99080_PEA_4_T18 (SEQ ID NO: 93) T99080_PEA_4_P15 1367
T99080_PEA_4_T19 (SEQ ID NO: 94) T99080_PEA_4_P16 1368
T99080_PEA_4_T20 (SEQ ID NO: 95) T99080_PEA_4_P17 1369
T99080_PEA_4_T21 (SEQ ID NO: 96)
[2336] These sequences are variants of the known protein
Acylphosphatase, organ-common type isozyme (SwissProt accession
identifier ACYO_HUMAN; known also according to the synonyms EC
3.6.1.7; Acylphosphate phosphohydrolase; Acylphosphatase,
erythrocyte isozyme), SEQ ID NO: 1440, referred to herein as the
previously known protein.
[2337] The sequence for protein Acylphosphatase (SEQ ID NO:1440),
organ-common type isozyme is given at the end of the application,
as "Acylphosphatase, organ-common type isozyme amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 722.
TABLE-US-00769 TABLE 722 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 19 G -> R
[2338] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: phosphate
metabolism, which are annotation(s) related to Biological Process;
and acylphosphatase, which are annotation(s) related to Molecular
Function.
[2339] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nihdot gov/projects/LocusLink/>.
[2340] As noted above, cluster T99080 features 14 transcript(s),
which were listed in Table 719 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Acylphosphatase (SEQ
ID NO:1440), organ-common type isozyme. A description of each
variant protein according to the present invention is now
provided.
[2341] Variant protein T99080_PEA.sub.--4_P1 (SEQ ID NO:1358)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T0 (SEQ ID NO:83). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2342] Variant protein T99080_PEA.sub.--4_P1 (SEQ ID NO:1358) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 723, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P1
(SEQ ID NO:1358) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00770 TABLE 723 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
23 A -> V Yes
[2343] Variant protein T99080_PEA.sub.--4_P1 (SEQ ID NO:1358) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T0 (SEQ
ID NO:83), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript T99080_PEA.sub.--4_T0
(SEQ ID NO:83) is shown in bold; this coding portion starts at
position 226 and ends at position 411. The transcript also has the
following SNPs as listed in Table 724 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
T99080_PEA.sub.--4_P1 (SEQ ID NO:1358) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00771 TABLE 724 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes 1293 G -> C Yes 2034 A -> G Yes 2114 A
-> C Yes 2153 -> A No
[2344] Variant protein T99080_PEA.sub.--4_P2 (SEQ ID NO:1359)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T2 (SEQ ID NO:84). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
membrane. The protein localization is believed to be membrane
because although it is a partial protein, because both
trans-membrane region prediction programs predict that this protein
has a trans-membrane region.
[2345] Variant protein T99080_PEA.sub.--4_P2 (SEQ ID NO:1359) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T2 (SEQ
ID NO:84), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript T99080_PEA.sub.--4_T2
(SEQ ID NO:84) is shown in bold; this coding portion starts at
position 1 and ends at position 192. The transcript also has the
following SNPs as listed in Table 725 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
T99080_PEA.sub.--4_P2 (SEQ ID NO:1359) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00772 TABLE 725 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
1074 G -> C Yes 1815 A -> G Yes 1895 A -> C Yes 1934 ->
A No
[2346] Variant protein T99080_PEA.sub.--4_P5 (SEQ ID NO:1360)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T6 (SEQ ID NO:86). An alignment is given to the
known protein (Acylphosphatase (SEQ ID NO:1440), organ-common type
isozyme) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[2347] Comparison report between T99080_PEA.sub.--4_P5 (SEQ ID
NO:1360) and ACYO_HUMAN_V1 (SEQ ID NO: 1441):
[2348] 1. An isolated chimeric polypeptide encoding for
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MPASARLAGAGLLLAFLRALGCAGRAPGLS (SEQ ID NO: 1732)
corresponding to amino acids 1-30 of T99080_PEA.sub.--4_P5 (SEQ ID
NO:1360), and a second amino acid sequence being at least 90%
homologous to
MAEGNTLISVDYEIFGKVQGVFFRKCHTQAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLET
RGSPKSHIDKANFNNEKVILKLDYSDFQIVK corresponding to amino acids 1-99
of ACYO_HUMAN_V1 (SEQ ID NO:1441), which also corresponds to amino
acids 31-129 of T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2349] 2. An isolated polypeptide encoding for a head of
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MPASARLAGAGLLIAFLRALGCAGRAPGLS (SEQ ID NO: 1732) of
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360).
[2350] It should be noted that the known protein sequence
(ACYO_HUMAN (SEQ ID NO:1440)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ACYO_HUMAN_V1 (SEQ ID NO:1441). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-00773 TABLE 726 Changes to ACYO_HUMAN_V1 (SEQ ID NO: 1441)
SNP position(s) on amino acid sequence Type of change 1
init_met
[2351] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2352] Variant protein T99080_PEA.sub.--4_P5 (SEQ ID NO:1360) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 727, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P5
(SEQ ID NO:1360) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00774 TABLE 727 Amino acid mutations SNP position(s) on
amino acid Alternative Previously sequence amino acid(s) known SNP?
23 A -> V Yes
[2353] Variant protein T99080_PEA.sub.--4_P5 (SEQ ID NO:1360) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T6 (SEQ
ID NO:86), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript T99080_PEA.sub.--4_T6
(SEQ ID NO:86) is shown in bold; this coding portion starts at
position 226 and ends at position 612. The transcript also has the
following SNPs as listed in Table 728 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
T99080_PEA.sub.--4_P5 (SEQ ID NO:1360) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00775 TABLE 728 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes 697 A -> G Yes 777 A -> C Yes 816 -> A
No
[2354] Variant protein T99080_PEA.sub.--4_P8 (SEQ ID NO:1361)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T9 (SEQ ID NO:87). An alignment is given to the
known protein (Acylphosphatase (SEQ ID NO:1440), organ-common type
isozyme) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[2355] Comparison report between T99080_PEA.sub.--4_P8 (SEQ ID
NO:1361) and ACYO_HUMAN_V1 (SEQ ID NO:1441):
[2356] 1. An isolated chimeric polypeptide encoding for
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence M corresponding to amino acids 1-1 of
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361), and a second amino acid
sequence being at least 90% homologous to
QAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEKVILKLDYSDFQ
IVK corresponding to amino acids 28-99 of ACYO_HUMAN_V1 (SEQ ID
NO:1441), which also corresponds to amino acids 2-73 of
T99080_PEA.sub.--4 P8 (SEQ ID NO:1361), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2357] It should be noted that the known protein sequence
(ACYO_HUMAN (SEQ ID NO:1440)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ACYO_HUMAN_V1 (SEQ ID NO:1441). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-00776 TABLE 729 Changes to ACYO_HUMAN_V1 (SEQ ID NO: 1441)
SNP position(s) on amino acid sequence Type of change 1
init_met
[2358] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2359] Variant protein T99080_PEA.sub.--4_P8 (SEQ ID NO:1361) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T9 (SEQ
ID NO:87), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript T99080_PEA.sub.--4_T9
(SEQ ID NO:87) is shown in bold; this coding portion starts at
position 162 and ends at position 380. The transcript also has the
following SNPs as listed in Table 730 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
T99080_PEA.sub.--4_P8 (SEQ ID NO:1361) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00777 TABLE 730 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
465 A -> G Yes 545 A -> C Yes 584 -> A No
[2360] Variant protein T99080_PEA.sub.--4_P9 (SEQ ID NO:1362)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T10 (SEQ ID NO:88). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
membrane. The protein localization is believed to be membrane
because although it is a partial protein, because both
trans-membrane region prediction programs predict that this protein
has a trans-membrane region.
[2361] Variant protein T99080_PEA.sub.--4_P9 (SEQ ID NO:1362) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T10 (SEQ
ID NO:88), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T10 (SEQ ID NO:88) is shown in bold; this coding
portion starts at position 1 and ends at position 261. The
transcript also has the following SNPs as listed in Table 731
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P9 (SEQ ID NO:1362) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00778 TABLE 731 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
557 A -> G Yes 637 A -> C Yes 676 -> A No
[2362] Variant protein T99080_PEA.sub.--4_P10 (SEQ ID NO:1363)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T11 (SEQ ID NO:89). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
membrane. The protein localization is believed to be membrane
because although it is a partial protein, because both
trans-membrane region prediction programs predict that this protein
has a trans-membrane region.
[2363] Variant protein T99080_PEA.sub.--4_P10 (SEQ ID NO:1363) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T11 (SEQ
ID NO:89), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T11 (SEQ ID NO:89) is shown in bold; this coding
portion starts at position 1 and ends at position 240. The
transcript also has the following SNPs as listed in Table 732
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P10 (SEQ ID NO:1363) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00779 TABLE 732 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
269 G -> T Yes 592 A -> G Yes 672 A -> C Yes 711 -> A
No
[2364] Variant protein T99080_PEA.sub.--4_P 12 (SEQ ID NO:1364)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T14 (SEQ ID NO:91). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
membrane. The protein localization is believed to be membrane
because although it is a partial protein, because both
trans-membrane region prediction programs predict that this protein
has a trans-membrane region.
[2365] Variant protein T99080_PEA.sub.--4_P12 (SEQ ID NO:1364) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T14 (SEQ
ID NO:91), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T14 (SEQ ID NO:91) is shown in bold; this coding
portion starts at position 1 and ends at position 282.
[2366] Variant protein T99080_PEA.sub.--4_P13 (SEQ ID NO:1365)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T17 (SEQ ID NO:92). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
membrane. The protein localization is believed to be membrane
because although it is a partial protein, because both
trans-membrane region prediction programs predict that this protein
has a trans-membrane region.
[2367] Variant protein T99080_PEA.sub.--4_P13 (SEQ ID NO:1365) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T17 (SEQ
ID NO:92), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T17 (SEQ ID NO:92) is shown in bold; this coding
portion starts at position 1 and ends at position 207.
[2368] Variant protein T99080_PEA.sub.--4_P14 (SEQ ID NO:1366)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T18 (SEQ ID NO:93). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2369] Variant protein T99080_PEA.sub.--4_P14 (SEQ ID NO:1366) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 733, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P14
(SEQ ID NO:1366) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00780 TABLE 733 Amino acid mutations SNP position(s) on
amino acid Alternative Previously sequence amino acid(s) known SNP?
23 A -> V Yes
[2370] Variant protein T99080_PEA.sub.--4_P14 (SEQ ID NO:1366) is
encoded by the following transcript(s): T99080_PEA4_T18 (SEQ ID
NO:93), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T18 (SEQ ID NO:93) is shown in bold; this coding
portion starts at position 226 and ends at position 480. The
transcript also has the following SNPs as listed in Table 734
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P14 (SEQ ID NO:1366) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00781 TABLE 734 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes 776 A -> G Yes 856 A -> C Yes 895 -> A
No
[2371] Variant protein T99080_PEA.sub.--4_P15 (SEQ ID NO:1367)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T19 (SEQ ID NO:94). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2372] Variant protein T99080_PEA.sub.--4_P15 (SEQ ID NO:1367) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 735, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P15
(SEQ ID NO:1367) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00782 TABLE 735 Amino acid mutations SNP position(s) on
amino acid Alternative Previously sequence amino acid(s) known SNP?
23 A -> V Yes
[2373] Variant protein T99080_PEA.sub.--4_P15 (SEQ ID NO:1367) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T19 (SEQ
ID NO:94), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T19 (SEQ ID NO:94) is shown in bold; this coding
portion starts at position 226 and ends at position 459. The
transcript also has the following SNPs as listed in Table 736
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P15 (SEQ ID NO:1367) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00783 TABLE 736 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes 488 G -> T Yes 811 A -> G Yes 891 A -> C
Yes 930 -> A No
[2374] Variant protein T99080_PEA.sub.--4_P16 (SEQ ID NO:1368)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T20 (SEQ ID NO:95). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2375] Variant protein T99080_PEA.sub.--4_P16 (SEQ ID NO:1368) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 737, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P16
(SEQ ID NO:1368) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00784 TABLE 737 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
23 A -> V Yes
[2376] Variant protein T99080_PEA.sub.--4_P16 (SEQ ID NO:1368) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T20 (SEQ
ID NO:95), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T20 (SEQ ID NO:95) is shown in bold; this coding
portion starts at position 226 and ends at position 501. The
transcript also has the following SNPs as listed in Table 738
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P16 (SEQ ID NO:1368) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00785 TABLE 738 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes
[2377] Variant protein T99080_PEA.sub.--4_P17 (SEQ ID NO:1369)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T99080_PEA.sub.--4_T21 (SEQ ID NO:96). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2378] Variant protein T99080_PEA.sub.--4_P17 (SEQ ID NO:1369) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 739, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T99080_PEA.sub.--4_P17
(SEQ ID NO:1369) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00786 TABLE 739 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
23 A -> V Yes
[2379] Variant protein T99080_PEA.sub.--4_P17 (SEQ ID NO:1369) is
encoded by the following transcript(s): T99080_PEA.sub.--4_T21 (SEQ
ID NO:96), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T99080_PEA.sub.--4_T21 (SEQ ID NO:96) is shown in bold; this coding
portion starts at position 226 and ends at position 426. The
transcript also has the following SNPs as listed in Table 740
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T99080_PEA.sub.--4_P17 (SEQ ID NO:1369) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00787 TABLE 740 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
293 C -> T Yes
[2380] As noted above, cluster T99080 features 11 segment(s), which
were listed in Table 720 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2381] Segment cluster T99080_PEA.sub.--4_node.sub.--1 (SEQ ID
NO:695) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T0 (SEQ ID NO:83),
T99080_PEA.sub.--4_T6 (SEQ ID NO:86), T99080_PEA.sub.--4_T13 (SEQ
ID NO:90), T99080_PEA.sub.--4_T18 (SEQ ID NO:93),
T99080_PEA.sub.--4_T19 (SEQ ID NO:94), T99080_PEA.sub.--4_T20 (SEQ
ID NO:95) and T99080_PEA.sub.--4_T21 (SEQ ID NO:96). Table 741
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00788 TABLE 741 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T99080_PEA_4_T0 (SEQ ID NO: 83) 1 307 T99080_PEA_4_T6 (SEQ ID NO:
86) 1 307 T99080_PEA_4_T13 (SEQ ID NO: 90) 1 307 T99080_PEA_4_T18
(SEQ ID NO: 93) 1 307 T99080_PEA_4_T19 (SEQ ID NO: 94) 1 307
T99080_PEA_4_T20 (SEQ ID NO: 95) 1 307 T99080_PEA_4_T21 (SEQ ID NO:
96) 1 307
[2382] Segment cluster T99080_PEA.sub.--4_node.sub.--6 (SEQ ID
NO:696) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T17 (SEQ ID NO:92) and
T99080_PEA.sub.--4_T21 (SEQ ID NO:96). Table 742 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00789 TABLE 742 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T99080_PEA_4_T17 (SEQ ID NO: 92) 181 627 T99080_PEA_4_T21 (SEQ ID
NO: 96) 400 846
[2383] Segment cluster T99080_PEA.sub.--4_node_l 1 (SEQ ID NO:697)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s):
T99080_PEA.sub.--4_T14 (SEQ ID NO:91) and T99080_PEA.sub.--4_T20
(SEQ ID NO:95). Table 743 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00790 TABLE 743 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T99080_PEA_4_T14 (SEQ ID NO: 91) 260 782 T99080_PEA_4_T20 (SEQ ID
NO: 95) 479 1001
[2384] Segment cluster T99080_PEA.sub.--4_node.sub.--19 (SEQ ID
NO:698) according to the present invention is supported by 59
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T0 (SEQ ID NO:83), T99080_PEA_T2
(SEQ ID NO:84) and T99080_PEA.sub.--4_T4 (SEQ ID NO:85). Table 744
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00791 TABLE 744 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T0 (SEQ ID NO: 83) 449 1736 T99080_PEA_4_T2 (SEQ ID
NO: 84) 230 1517 T99080_PEA_4_T4 (SEQ ID NO: 85) 78 1365
[2385] Segment cluster T99080_PEA.sub.--4_node.sub.--20 (SEQ ID
NO:699) according to the present invention is supported by 98
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T0 (SEQ ID NO:83),
T99080_PEA.sub.--4_T2 (SEQ ID NO:84), T99080_PEA.sub.--4_T4 (SEQ ID
NO:85), T99080_PEA.sub.--4_T6 (SEQ ID NO:86), T99080_PEA.sub.--4_T9
(SEQ ID NO:87), T99080_PEA.sub.--4_T10 (SEQ ID NO:88),
T99080_PEA.sub.--4_T11 (SEQ ID NO:89), T99080_PEA.sub.--4_T13 (SEQ
ID NO:90), T99080_PEA.sub.--4_T18 (SEQ ID NO:93) and
T99080_PEA.sub.--4_T19 (SEQ ID NO:94). Table 745 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00792 TABLE 745 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T0 (SEQ ID NO: 83) 1737 2175 T99080_PEA_4_T2 (SEQ ID
NO: 84) 1518 1956 T99080_PEA_4_T4 (SEQ ID NO: 85) 1366 1804
T99080_PEA_4_T6 (SEQ ID NO: 86) 400 838 T99080_PEA_4_T9 (SEQ ID NO:
87) 168 606 T99080_PEA_4_T10 (SEQ ID NO: 88) 260 698
T99080_PEA_4_T11 (SEQ ID NO: 89) 295 733 T99080_PEA_4_T13 (SEQ ID
NO: 90) 308 746 T99080_PEA_4_T18 (SEQ ID NO: 93) 479 917
T99080_PEA_4_T19 (SEQ ID NO: 94) 514 952
[2386] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2387] Segment cluster T99080_PEA.sub.--4_node.sub.--3 (SEQ ID
NO:700) according to the present invention is supported by 40
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T2 (SEQ ID NO:84),
T99080_PEA.sub.--4_T9 (SEQ ID NO:87), T99080_PEA.sub.--4_T10 (SEQ
ID NO:88), T99080_PEA.sub.--4_T11 (SEQ ID NO:89),
T99080_PEA.sub.--4_T14 (SEQ ID NO:91) and T99080_PEA.sub.--4_T17
(SEQ ID NO:92). Table 746 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00793 TABLE 746 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T2 (SEQ ID NO: 84) 1 88 T99080_PEA_4_T9 (SEQ ID NO:
87) 1 88 T99080_PEA_4_T10 (SEQ ID NO: 88) 1 88 T99080_PEA_4_T11
(SEQ ID NO: 89) 1 88 T99080_PEA_4_T14 (SEQ ID NO: 91) 1 88
T99080_PEA_4_T17 (SEQ ID NO: 92) 1 88
[2388] Segment cluster T99080_PEA.sub.--4_node.sub.--5 (SEQ ID
NO:701) according to the present invention is supported by 57
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_TO (SEQ ID NO:83),
T99080_PEA.sub.--4_T2 (SEQ ID NO:84), T99080_PEA.sub.--4_T6 (SEQ ID
NO:86), T99080_PEA.sub.--4_T10 (SEQ ID NO:88),
T99080_PEA.sub.--4_T11 (SEQ ID NO:89), T99080_PEA.sub.--4_T14 (SEQ
ID NO:91), T99080_PEA.sub.--4_T17 (SEQ ID NO:92),
T99080_PEA.sub.--4_T18 (SEQ ID NO:93), T99080_PEA.sub.--4_T19 (SEQ
ID NO:94), T99080_PEA.sub.--4_T20 (SEQ ID NO:95) and
T99080_PEA.sub.--4_T21 (SEQ ID NO:96). Table 747 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00794 TABLE 747 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T0 (SEQ ID NO: 83) 308 399 T99080_PEA_4_T2 (SEQ ID NO:
84) 89 180 T99080_PEA_4_T6 (SEQ ID NO: 86) 308 399 T99080_PEA_4_T10
(SEQ ID NO: 88) 89 180 T99080_PEA_4_T11 (SEQ ID NO: 89) 89 180
T99080_PEA_4_T14 (SEQ ID NO: 91) 89 180 T99080_PEA_4_T17 (SEQ ID
NO: 92) 89 180 T99080_PEA_4_T18 (SEQ ID NO: 93) 308 399
T99080_PEA_4_T19 (SEQ ID NO: 94) 308 399 T99080_PEA_4_T20 (SEQ ID
NO: 95) 308 399 T99080_PEA_4_T21 (SEQ ID NO: 96) 308 399
[2389] Segment cluster T99080_PEA.sub.--4_node.sub.--8 (SEQ ID
NO:702) according to the present invention is supported by 12
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T9 (SEQ ID NO:87),
T99080_PEA.sub.--4_T10 (SEQ ID NO:88), T99080_PEA.sub.--4_T14 (SEQ
ID NO:91), T99080_PEA4_T18 (SEQ ID NO:93) and
T99080_PEA.sub.--4_T20 (SEQ ID NO:95). Table 748 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00795 TABLE 748 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T9 (SEQ ID NO: 87) 89 167 T99080_PEA_4_T10 (SEQ ID NO:
88) 181 259 T99080_PEA_4_T14 (SEQ ID NO: 91) 181 259
T99080_PEA_4_T18 (SEQ ID NO: 93) 400 478 T99080_PEA_4_T20 (SEQ ID
NO: 95) 400 478
[2390] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 749.
TABLE-US-00796 TABLE 749 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
T99080_0_0_58896 lung malignant tumors LUN (SEQ ID NO: 233)
[2391] Segment cluster T99080_PEA.sub.--4_node.sub.--13 (SEQ ID
NO:703) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T4 (SEQ ID NO:85). Table 750
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00797 TABLE 750 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T4 (SEQ ID NO: 85) 1 77
[2392] Segment cluster T99080_PEA.sub.--4_node.sub.--15 (SEQ ID
NO:704) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T99080_PEA.sub.--4_T11 (SEQ ID NO:89) and
T99080_PEA.sub.--4_T19 (SEQ ID NO:94). Table 751 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00798 TABLE 751 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T11 (SEQ ID NO: 89) 181 294 T99080_PEA_4_T19 (SEQ ID
NO: 94) 400 513
[2393] Segment cluster T99080_PEA.sub.--4_node_l 8 (SEQ ID NO:705)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s):
T99080_PEA.sub.--4_TO (SEQ ID NO:83) and T99080_PEA.sub.--4_T2 (SEQ
ID NO:84). Table 752 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00799 TABLE 752 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T99080_PEA_4_T0 (SEQ ID NO: 83) 400 448 T99080_PEA_4_T2 (SEQ ID NO:
84) 181 229
Variant protein alignment to the previously known protein:
TABLE-US-00800 Sequence name: ACYO_HUMAN_V1 (SEQ ID NO: 1441)
Sequence documentation: Alignment of: T99080_PEA_4_P5 (SEQ ID NO:
1360) .times. ACYO_HUMAN_V1 (SEQ ID NO: 1441) . . . Alignment
segment 1/1: Quality: 973.00 Escore: 0 Matching length: 99 Total
length: 99 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00575## ##STR00576##
Sequence name: ACYO_HUMAN_V1 (SEQ ID NO: 1441) Sequence
documentation: Alignment of: T99080_PEA_4_P8 (SEQ ID NO: 1361)
.times. ACYO_HUMAN_V1 (SEQ ID NO: 1441) . . . Alignment segment
1/1: Quality: 711.00 Escore: 0 Matching length: 72 Total length: 72
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00577## ##STR00578##
Description for Cluster T08446
[2394] Cluster T08446 features 2 transcript(s) and 36 segment(s) of
interest, the names for which are given in Tables 753 and 754,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
755.
TABLE-US-00801 TABLE 753 Transcripts of interest Transcript Name
Sequence ID No. T08446_PEA_1_T2 97 T08446_PEA_1_T22 98
TABLE-US-00802 TABLE 754 Segments of interest Segment Name Sequence
ID No. T08446_PEA_1_node_2 706 T08446_PEA_1_node_9 707
T08446_PEA_1_node_15 708 T08446_PEA_1_node_17 709
T08446_PEA_1_node_25 710 T08446_PEA_1_node_29 711
T08446_PEA_1_node_38 712 T08446_PEA_1_node_43 713
T08446_PEA_1_node_51 714 T08446_PEA_1_node_52 715
T08446_PEA_1_node_55 716 T08446_PEA_1_node_57 717
T08446_PEA_1_node_59 718 T08446_PEA_1_node_62 719
T08446_PEA_1_node_63 720 T08446_PEA_1_node_3 721
T08446_PEA_1_node_5 722 T08446_PEA_1_node_7 723
T08446_PEA_1_node_12 724 T08446_PEA_1_node_13 725
T08446_PEA_1_node_19 726 T08446_PEA_1_node_21 727
T08446_PEA_1_node_23 728 T08446_PEA_1_node_27 729
T08446_PEA_1_node_32 730 T08446_PEA_1_node_34 731
T08446_PEA_1_node_45 732 T08446_PEA_1_node_46 733
T08446_PEA_1_node_48 734 T08446_PEA_1_node_54 735
T08446_PEA_1_node_58 736 T08446_PEA_1_node_60 737
T08446_PEA_1_node_61 738 T08446_PEA_1_node_64 739
T08446_PEA_1_node_65 740 T08446_PEA_1_node_66 741
TABLE-US-00803 TABLE 755 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) T08446_PEA_1_P18 1370
T08446_PEA_1_T2 (SEQ ID NO: 97) T08446_PEA_1_P19 1371
T08446_PEA_1_T22 (SEQ ID NO: 98)
[2395] These sequences are variants of the known protein Sorting
nexin 26 (SwissProt accession identifier SNXQ_HUMAN), SEQ ID NO:
1442, referred to herein as the previously known protein.
[2396] Protein Sorting nexin 26 (SEQ ID NO:1442) is known or
believed to have the following function(s): May be involved in
several stages of intracellular trafficking (By similarity). The
sequence for protein Sorting nexin 26 is given at the end of the
application, as "Sorting nexin 26 amino acid sequence".
[2397] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: intracellular
protein traffic, which are annotation(s) related to Biological
Process; and protein transporter, which are annotation(s) related
to Molecular Function.
[2398] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2399] As noted above, cluster T08446 features 2 transcript(s),
which were listed in Table 753 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Sorting nexin 26
(SEQ ID NO:1442). A description of each variant protein according
to the present invention is now provided.
[2400] Variant protein T08446_PEA.sub.--1_P18 (SEQ ID NO:1370)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T08446_PEA.sub.--1_T2 (SEQ ID NO:97). An alignment is given to the
known protein (Sorting nexin 26 (SEQ ID NO:1442)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2401] Comparison report between T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370) and SNXQ_HUMAN (SEQ ID NO:1442):
[2402] 1. An isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 90% homologous to
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWME corresponding to amino
acids 1-185 of SNXQ_HUMAN (SEQ ID NO:1442), which also corresponds
to amino acids 1-185 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFF
PSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQR
VFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHS
VSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSA
NTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGR
CLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFF
ALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPV
GPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDF-
D
PLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGA-
GG
APASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPG-
G
APPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAH
PGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVP
TPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPT-
R
SWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLAL
GPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGG
ELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC (SEQ ID NO: 1733)
corresponding to amino acids 186-1305 of T08446_PEA.sub.--1_P18
(SEQ ID NO:1370), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[2403] 2. An isolated polypeptide encoding for a tail of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFF
PSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQR
VFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHS
VSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSA
NTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGR
CLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFF
ALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSEELSSQASGAGLQRLHRLRRPHSSSDAFPV
GPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDF-
D
PLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGA-
GG
APASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPG-
G
APPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAH
PGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVP
TPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPT-
R
SWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLAL
GPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGG
ELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC (SEQ ID NO: 1733) in
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[2404] Comparison report between T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370) and Q9NT23 (SEQ ID NO:1443) (SEQ ID NO: 1443):
[2405] 1. An isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A MSVPGEEERLVRV (SEQ ID NO: 1734) corresponding to amino acids
1-443 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a second amino
acid sequence being at least 90% homologous to
HDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFREVRV
QSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPTTPK
APASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSAKSE
ESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSSSESSAAGLGALSGSPS
HRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPPVTPQAISPRGP
TSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQQEMC
SKLRGAQGLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPPASQ
SPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGPAQV
SAWLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRS
SLGPPAPLDRGENLYYEIGASEGSPYSG corresponding to amino acids 1-674 of
Q9NT23 (SEQ ID NO:1443), which also corresponds to amino acids
444-1117 of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a bridging
amino acid P corresponding to amino acid 1118 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), and a third amino acid
sequence being at least 90% homologous to
TRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYV-
NL
ALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYG-
R GGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC corresponding to
amino acids 676-862 of Q9NT23 (SEQ ID NO:1443), which also
corresponds to amino acids 1119-1305 of T08446_PEA.sub.--1_P18 (SEQ
ID NO:1370), wherein said first amino acid sequence, second amino
acid sequence, bridging amino acid and third amino acid sequence
are contiguous and in a sequential order.
[2406] 2. An isolated polypeptide encoding for a head of
T08446_PEA_l_P18 (SEQ ID NO:1370), comprising a polypeptide being
at least 70%, optionally at least about 80%, preferably at least
about 85%, more preferably at least about 90% and most preferably
at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGSVKGKPGKRLSAPRGPFPRLA-
DCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFS-
CLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHV-
IK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNOLLTYQLYGKFSE-
A MSVPGEEERLVRV (SEQ ID NO: 1734) of T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370).
[2407] Comparison report between T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370) and Q96CP3 (SEQ ID NO:1444) (SEQ ID NO: 1444):
[2408] 1. An isolated chimeric polypeptide encoding for
T08446_PEA_l_P18 (SEQ ID NO:1370), comprising a first amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
MLSLSLCHLWGPLILSALQARSTDSLDPGPGEGVQPLPTAGGPSVKGKPGKRLSAPRGPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A
MSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESV
GMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQART
QGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPKKPLPWLGGTRAPPQPSG
SRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSS-
ES
SAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASA-
F
PPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLR-
GA
EAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAEQ
QSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPM
GTSRRG corresponding to amino acids 1-1010 of T08446_PEA_l_P18 (SEQ
ID NO:1370), and a second amino acid sequence being at least 90%
homologous to
LRGPAQVSAQLRAGGGGRDAPEAAAQSPCSVPSQVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQP-
SS
PAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYSGPTRSWSPFRSMPPDLNASYGMLGQSPPLHRSPDFLL
SYPPAPSCFPPDHLGYSAPQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQK-
Q
RAPWGPRTPHRVPGPWGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSE
GQTRSYC corresponding to amino acids 1-295 of Q96CP3 (SEQ ID
NO:1444), which also corresponds to amino acids 1011-1305 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), wherein said first amino
acid and second amino acid sequence are contiguous and in a
sequential order.
[2409] 2. An isolated polypeptide encoding for a head of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHIK
RYTAQAPDELSFEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIP
APQGISSLTSAVPRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEF
IEAHGVVDGIYRLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSE-
A
MSVPGEEERLVRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESV
GMGGAAAFREVRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQART
QGRLGTPTEPTTPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSG
SRPDTVTLRSAKSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSS-
ES
SAAGLGALSGSPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPASPASPAPPAPA-
SAF
PPRVTPQAISPRGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLL-
LRGA
EAPLTDACQQEMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPPKNPARLMALALAERAQQVAE-
Q
QSQQECGGTPPASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPM
GTSRRG of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[2410] Comparison report between T08446_PEA.sub.--1_P18 (SEQ ID
NO:1370) and BAC86902 (SEQ ID NO: 1445):
[2411] 1. An isolated chimeric polypeptide encoding for
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQ corresponding to amino acids 1-154 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a second amino acid
sequence being at least 90% homologous to
MLVPLLLQYLETLSGLVDSNLNCGPVLTWMELDNHGRRLLLSEEASLNIPAVAAAHVIKRYTAQAPDELS
FEVGDIVSVIDMPPTEDRSWWRGKRGFQVGFFPSECVELFTERPGPGLKADADGPPCGIPAPQGISSLTSAV
PRPRGKLAGLLRTFMRSRPSRQRLRQRGILRQRVFGCDLGEHLSNSGQDVPQVLRCCSEFIEAHGVVDGIY
RLSGVSSNIQRLRHEFDSERIPELSGPAFLQDIHSVSSLCKLYFRELPNPLLTYQLYGKFSEAMSVPGEEERL
VRVHDVIQQLPPPHYRTLEYLLRHLARMARHSANTSMHARNLAIVWAPNLLRSMELESVGMGGAAAFRE
VRVQSVVVEFLLTHVDVLFSDTFTSAGLDPAGRCLLPRPKSLAGSCPSTRLLTLEEAQARTQGRLGTPTEPT
TPKAPASPAERRKGERGEKQRKPGGSSWKTFFALGRGPSVPRKKPLPWLGGTRAPPQPSGSRPDTVTLRSA
KSEESLSSQASGAGLQRLHRLRRPHSSSDAFPVGPAPAGSCESLSSSSSSESSSSESSSSSSESSAAGLGALS-
G
SPSHRTSAWLDDGDELDFSPPRCLEGLRGLDFDPLTFRCSSPTPGDPAPPASPAPPAPASAFPPRVTPQAIS-
P
RGPTSPASPAALDISEPLAVSVPPAVLELLGAGGAPASATPTPALSPGRSLRPHLIPLLLRGAEAPLTDACQ-
Q
EMCSKLRGAQGPLGPDMESPLPPPPLSLLRPGGAPPPPKNPARLMALALAERAQQVAEQQSQQECGGTPP
ASQSPFHRSLSLEVGGEPLGTSGSGPPPNSLAHPGAWVPGPPPYLPRQQSDGSLLRSQRPMGTSRRGLRGP
A corresponding to amino acids 1-861 of BAC86902 (SEQ ID NO:1445),
which also corresponds to amino acids 155-1015 of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
QVSAQLRAGGGGRDAPEAAAQSPCSVPS corresponding to amino acids 1016-1043
of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), a fourth amino acid
sequence being at least 90% homologous to
QVPTPGFFSPAPRECLPPFLGVPKPGLYPLGPPSFQPSSPAPVWRSSLGPPAPLDRGENLYYEIGASEGSPYS
GPTRSWSPFRSMPPDRLNASYGMLGQSPPLHRSPDFLLSYPPAPSCFPPDHLGYS
corresponding to amino acids 862-989 of BAC86902 (SEQ ID NO:1445),
which also corresponds to amino acids 1044-1171 of T08446
PEA.sub.--1_P18 _P18 (SEQ ID NO:1370), and a fifth amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
APQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVPRLPQKQRAPWGPRTPHRVPGP
WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYC
corresponding to amino acids 1172-1305 of T08446_PEA.sub.--1_P18
(SEQ ID NO:1370), wherein said first amino acid sequence, second
amino acid sequence, third amino acid sequence, fourth amino acid
sequence and fifth amino acid sequence are contiguous and in a
sequential order.
[2412] 2. An isolated polypeptide encoding for a head of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MLSLSLCSHLWGPLILSALQARSTDSLDGPGEGSVQPLPTAGGPSVKGKPGKRLSAPRGPFPRLADCAHFH
YENVDFGHIQLLLSPDREGPSLSGENELVFGVQVTCQGRSWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPEL
PPPPEGARAAQ of T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[2413] 3. An isolated polypeptide encoding for an edge portion of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising an amino acid
sequence being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
encoding for QVSAQLRAGGGGRDAPEAAAQSPCSVPS, corresponding to
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[2414] 4. An isolated polypeptide encoding for a tail of
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
APQHPARRPTPPEPLYVNLALGPRGPSPASSSSSSPPAHPRSRSDPGPPVRRLPQKQRAPWGPRTPHRVPGP
WGPPEPLLLYRAAPPAYGRGGELHRGSLYRNGGQRGEGAGPPPPYPTPSWSLHSEGQTRSYS in
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370).
[2415] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2416] Variant protein T08446_PEA.sub.--1_P18 (SEQ ID NO:1370) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 756, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T08446_PEA.sub.--1_P18
(SEQ ID NO:1370) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00804 TABLE 756 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 714 S -> C Yes 1000 S -> N No 1273 R -> S No 1274 N
-> H No
[2417] Variant protein T08446_PEA.sub.--1_P18 (SEQ ID NO:1370) is
encoded by the following transcript(s): T08446_PEA.sub.--1T2 (SEQ
ID NO:97), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript T08446_PEA.sub.--1_T2
(SEQ ID NO:97) is shown in bold; this coding portion starts at
position 228 and ends at position 4142. The transcript also has the
following SNPs as listed in Table 757 (given according to their
position on the nucleotide sequence, with the alternative nucleic
acid listed; the last column indicates whether the SNP is known or
not; the presence of known SNPs in variant protein
T08446_PEA.sub.--1_P18 (SEQ ID NO:1370) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-00805 TABLE 757 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 212 G
-> A Yes 431 C -> T Yes 809 C -> T Yes 1547 G -> A Yes
2368 C -> G Yes 3226 G -> A No 3284 C -> G Yes 3377 C
-> T Yes 4046 A -> C No 4047 A -> C No
[2418] Variant protein T08446_PEA.sub.--1_P19 (SEQ ID NO:1371)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2419] Variant protein T08446_PEA.sub.--1_P19 (SEQ ID NO:1371) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 758, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T08446_PEA_l_P19 (SEQ ID
NO:1371) sequence provides support for the deduced sequence of this
variant protein according to the present invention).
TABLE-US-00806 TABLE 758 Amino acid mutations SNP position(s)
Alternative Previously on amino acid amino known sequence acid(s)
SNP? 194 D -> G Yes
[2420] Variant protein T08446_PEA.sub.--1_P19 (SEQ ID NO:1371) is
encoded by the following transcript(s): T08446_PEA.sub.--1 T22 (SEQ
ID NO:98), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
T08446_PEA.sub.--1_T22 (SEQ ID NO:98) is shown in bold; this coding
portion starts at position 228 and ends at position 965. The
transcript also has the following SNPs as listed in Table 759
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T08446_PEA.sub.--1_P19 (SEQ ID NO:1371) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00807 TABLE 759 Nucleic acid SNPs SNP position Alternative
Previously on nucleotide nucleic known sequence acid SNP? 212 G
-> A Yes 431 C -> T Yes 808 A -> G Yes
[2421] As noted above, cluster T08446 features 36 segment(s), which
were listed in Table 2 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2422] Segment cluster T08446_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:706) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEAWT2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 760 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00808 TABLE 760 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1 287 T08446_PEA_1_T22 (SEQ ID NO:
98) 1 287
[2423] Segment cluster T08446_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:707) according to the present invention is supported by 17
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 761 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00809 TABLE 761 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 552 689 T08446_PEA_1_T22 (SEQ ID
NO: 98) 552 689
[2424] Segment cluster T08446_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:708) according to the present invention is supported by 0
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 762
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00810 TABLE 762 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T22 (SEQ ID NO: 98) 829 968
[2425] Segment cluster T08446_PEA.sub.--1_node_l 7 (SEQ ID NO:709)
according to the present invention is supported by 22 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 763 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00811 TABLE 763 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 783 905
[2426] Segment cluster T08446_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:710) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 764
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00812 TABLE 764 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1111 1263
[2427] Segment cluster T08446_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:711) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 765
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00813 TABLE 765 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1367 1511
[2428] Segment cluster T08446_PEA.sub.--1_node.sub.--38 (SEQ ID
NO:712) according to the present invention is supported by 20
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 766
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00814 TABLE 766 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1703 1848
[2429] Segment cluster T08446_PEA.sub.--1_node.sub.--43 (SEQ ID
NO:713) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 767
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00815 TABLE 767 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1849 2002
[2430] Segment cluster T08446_PEA.sub.--1_node.sub.--51 (SEQ ID
NO:714) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 768
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00816 TABLE 768 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2224 2571
[2431] Segment cluster T08446_PEA.sub.--1_node.sub.--52 (SEQ ID
NO:715) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 769
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00817 TABLE 769 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2572 2694
[2432] Segment cluster T08446_PEA.sub.--1_node.sub.--55 (SEQ ID
NO:716) according to the present invention is supported by 21
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 770
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00818 TABLE 770 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2707 2883
[2433] Segment cluster T08446_PEA.sub.--1_node.sub.--57 (SEQ ID
NO:717) according to the present invention is supported by 37
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 771
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00819 TABLE 771 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2884 3275
[2434] Segment cluster T08446_PEA.sub.--1_node.sub.--59 (SEQ ID
NO:718) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 772
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00820 TABLE 772 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3360 3670
[2435] Segment cluster T08446_PEA.sub.--1_node.sub.--62 (SEQ ID
NO:719) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 773
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00821 TABLE 773 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3783 3988
[2436] Segment cluster T08446_PEA.sub.--1_node.sub.--63 (SEQ ID
NO:720) according to the present invention is supported by 64
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 774
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00822 TABLE 774 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3989 4414
[2437] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2438] Segment cluster T08446_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:721) according to the present invention is supported by 14
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 775 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00823 TABLE 775 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 288 385 T08446_PEA_1_T22 (SEQ ID
NO: 98) 288 385
[2439] Segment cluster T08446_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:722) according to the present invention is supported by 17
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 776 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00824 TABLE 776 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 386 470 T08446_PEA_1_T22 (SEQ ID
NO: 98) 386 470
[2440] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 777.
TABLE-US-00825 TABLE 777 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
T08446_0_9_0 lung malignant tumors LUN (SEQ ID NO: 234)
[2441] Segment cluster T08446_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:723) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 778 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00826 TABLE 778 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 471 551 T08446_PEA_1_T22 (SEQ ID
NO: 98) 471 551
[2442] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 779.
TABLE-US-00827 TABLE 779 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
T08446_0_9_0 lung malignant tumors LUN (SEQ ID NO: 234)
[2443] Segment cluster T08446_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:724) according to the present invention is supported by 14
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97) and
T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 780 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00828 TABLE 780 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 690 782 T08446_PEA_1_T22 (SEQ ID
NO: 98) 690 782
[2444] Segment cluster T08446_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:725) according to the present invention is supported by 0
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T22 (SEQ ID NO:98). Table 781
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00829 TABLE 781 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T22 (SEQ ID NO: 98) 783 828
[2445] Segment cluster T08446_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:726) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 782
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00830 TABLE 782 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 906 983
[2446] Segment cluster T08446_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:727) according to the present invention is supported by 21
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 783
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00831 TABLE 783 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 984 1050
[2447] Segment cluster T08446_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:728) according to the present invention is supported by 22
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 784
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00832 TABLE 784 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1051 1110
[2448] Segment cluster T08446_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:729) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 785
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00833 TABLE 785 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1264 1366
[2449] Segment cluster T08446_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:730) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 786
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00834 TABLE 786 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1512 1594
[2450] Segment cluster T08446_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:731) according to the present invention is supported by 22
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 787
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00835 TABLE 787 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 1595 1702
[2451] Segment cluster T08446_PEA.sub.--1_node.sub.--45 (SEQ ID
NO:732) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 788
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00836 TABLE 788 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2003 2091
[2452] Segment cluster T08446_PEA.sub.--1_node.sub.--46 (SEQ ID
NO:733) according to the present invention is supported by 18
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 789
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00837 TABLE 789 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2092 2148
[2453] Segment cluster T08446_PEA.sub.--1_node.sub.--48 (SEQ ID
NO:734) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 790
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00838 TABLE 790 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2149 2223
[2454] Segment cluster T08446_PEA.sub.--1_node.sub.--54 (SEQ ID
NO:735) according to the present invention can be found in the
following transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97).
Table 791 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00839 TABLE 791 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 2695 2706
[2455] Segment cluster T08446_PEA.sub.--1_node.sub.--58 (SEQ ID
NO:736) according to the present invention is supported by 13
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 792
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00840 TABLE 792 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3276 3359
[2456] Segment cluster T08446_PEA.sub.--1_node.sub.--60 (SEQ ID
NO:737) according to the present invention is supported by 27
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 793
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00841 TABLE 793 Segment location on transcripts Segment
Segment starting ending Transcript name position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3671 3720
[2457] Segment cluster T08446_PEA.sub.--1_node.sub.--61 (SEQ ID
NO:738) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 794
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00842 TABLE 794 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 3721 3782
[2458] Segment cluster T08446_YEA.sub.--1_node.sub.--64 (SEQ ID
NO:739) according to the present invention can be found in the
following transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97).
Table 795 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00843 TABLE 795 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 4415 4420
[2459] Segment cluster T08446_PEA.sub.--1_node.sub.--65 (SEQ ID
NO:740) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 796
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00844 TABLE 796 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 4421 4472
[2460] Segment cluster T08446_PEA.sub.--1_node.sub.--66 (SEQ ID
NO:741) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T08446_PEA.sub.--1_T2 (SEQ ID NO:97). Table 797
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00845 TABLE 797 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T08446_PEA_1_T2 (SEQ ID NO: 97) 4473 4539
[2461] Variant protein alignment to the previously known
protein:
TABLE-US-00846 Sequence name: SNXQ_HUMAN (SEQ ID NO: 1442) Sequence
documentation: Alignment of: T08446_PEA_1_P18 (SEQ ID NO: 1370)
.times. SNXQ_HUMAN (SEQ ID NO: 1442) . . . Alignment segment 1/1:
Quality: 1835.00 Escore: 0 Matching length: 185 Total length: 185
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00579## ##STR00580## ##STR00581##
##STR00582## Sequence name: Q9NT23 (SEQ ID NO: 1443) Sequence
documentation: Alignment of: T08446_PEA_1_P18 (SEQ ID NO: 1370)
.times. Q9NT23 (SEQ ID NO: 1443) Alignment segment 1/1: Quality:
8548.00 Escore: 0 Matching length: 862 Total length: 862 Matching
Percent Similarity: 99.88 Matching Percent Identity: 99.88 Total
Percent Similarity: 99.88 Total Percent Identity: 99.88 Gaps: 0
Alignment: ##STR00583## ##STR00584## ##STR00585## ##STR00586##
##STR00587## ##STR00588## ##STR00589## ##STR00590## ##STR00591##
##STR00592## ##STR00593## ##STR00594## ##STR00595## ##STR00596##
##STR00597## ##STR00598## ##STR00599## ##STR00600## Sequence name:
Q96CP3 (SEQ ID NO: 1444) Sequence documentation: Alignment of:
T08446_PEA_1_P18 (SEQ ID NO: 1370) .times. Q96CP3 (SEQ ID NO: 1444)
Alignment segment 1/1: Quality: 3019.00 Escore: 0 Matching length:
295 Total length: 295 Matching Percent Similarity: 100.00 Matching
Percent Identity: 100.00 Total Percent Similarity: 100.00 Total
Percent Identity: 100.00 Gaps: 0 Alignment: ##STR00601##
##STR00602## ##STR00603## ##STR00604## ##STR00605## ##STR00606##
Sequence name: BAC86902 (SEQ ID NO: 1445) Sequence documentation:
Alignment of: T08446_PEA_1_P18 (SEQ ID NO: 1370) .times. BAC86902
(SEQ ID NO: 1445) Alignment segment 1/1: Quality: 9651.00 Escore: 0
Matching length: 991 Total length: 1019 Matching Percent
Similarity: 99.90 Matching Percent Identity: 99.90 Total Percent
Similarity: 97.15 Total Percent Identity: 97.15 Gaps: 1 Alignment:
##STR00607## ##STR00608## ##STR00609## ##STR00610## ##STR00611##
##STR00612## ##STR00613## ##STR00614## ##STR00615## ##STR00616##
##STR00617## ##STR00618## ##STR00619## ##STR00620## ##STR00621##
##STR00622## ##STR00623## ##STR00624## ##STR00625## ##STR00626##
##STR00627##
Description for Cluster HUMCA1XIA
[2462] Cluster HUMCA1XIA features 4 transcript(s) and 46 segment(s)
of interest, the names for which are given in Tables 798 and 799,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
800
TABLE-US-00847 TABLE 798 Transcripts of interest Transcript Name
Sequence ID No. HUMCA1XIA_T16 99 HUMCA1XIA_T17 100 HUMCA1XIA_T19
101 HUMCA1XIA_T20 102
TABLE-US-00848 TABLE 799 Segments of interest Segment Name Sequence
ID No. HUMCA1XIA_node_0 742 HUMCA1XIA_node_2 743 HUMCA1XIA_node_4
744 HUMCA1XIA_node_6 745 HUMCA1XIA_node_8 746 HUMCA1XIA_node_9 747
HUMCA1XIA_node_18 748 HUMCA1XIA_node_54 749 HUMCA1XIA_node_55 750
HUMCA1XIA_node_92 751 HUMCA1XIA_node_11 752 HUMCA1XIA_node_15 753
HUMCA1XIA_node_19 754 HUMCA1XIA_node_21 755 HUMCA1XIA_node_23 756
HUMCA1XIA_node_25 757 HUMCA1XIA_node_27 758 HUMCA1XIA_node_29 759
HUMCA1XIA_node_31 760 HUMCA1XIA_node_33 761 HUMCA1XIA_node_35 762
HUMCA1XIA_node_37 763 HUMCA1XIA_node_39 764 HUMCA1XIA_node_41 765
HUMCA1XIA_node_43 766 HUMCA1XIA_node_45 767 HUMCA1XIA_node_47 769
HUMCA1XIA_node_49 769 HUMCA1XIA_node_51 770 HUMCA1XIA_node_57 771
HUMCA1XIA_node_59 772 HUMCA1XIA_node_62 773 HUMCA1XIA_node_64 774
HUMCA1XIA_node_66 775 HUMCA1XIA_node_68 776 HUMCA1XIA_node_70 777
HUMCA1XIA_node_72 778 HUMCA1XIA_node_74 779 HUMCA1XIA_node_76 780
HUMCA1XIA_node_78 782 HUMCA1XIA_node_81 783 HUMCA1XIA_node_83 784
HUMCA1XIA_node_85 785 HUMCA1XIA_node_87 786 HUMCA1XIA_node_89 787
HUMCA1XIA_node_91 788
TABLE-US-00849 TABLE 800 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) HUMCA1XIA_P14 1372 HUMCA1XIA_T16
(SEQ ID NO: 99) HUMCA1XIA_P15 1373 HUMCA1XIA_T17 (SEQ ID NO: 100)
HUMCA1XIA_P16 1374 HUMCA1XIA_T19 (SEQ ID NO: 101) HUMCA1XIA_P17
1375 HUMCA1XIA_T20 (SEQ ID NO: 102)
[2463] These sequences are variants of the known protein Collagen
alpha 1 (SwissProt accession identifier CA1B_HUMAN), SEQ ID NO:
1446, referred to herein as the previously known protein.
[2464] Protein Collagen alpha 1 (SEQ ID NO:1446) is known or
believed to have the following function(s): May play an important
role in fibrillogenesis by controlling lateral growth of collagen
II fibrils. The sequence for protein Collagen alpha 1 is given at
the end of the application, as "Collagen alpha 1 amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 801.
TABLE-US-00850 TABLE 801 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 625 G -> V (in STL2).
/FTId = VAR_013583. 676 G -> R (in STL2; overlapping phenotype
with Marshall syndrome). /FTId = VAR_013584. 921-926 Missing (in
STL2; overlapping phenotype with Marshall syndrome). /FTId =
VAR_013585. 1313-1315 Missing (in STL2; overlapping phenotype with
Marshall syndrome). /FTId = VAR_013586. 1516 G -> V (in STL2;
overlapping phenotype with Marshall syndrome). /FTId = VAR_013587.
941-944 KDGL -> RMGC 986 Y -> H 1074 R -> P 1142 G -> D
1218 M -> W 1758 T -> A 1786 S -> N
[2465] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: cartilage
condensation; vision; hearing; cell-cell adhesion; extracellular
matrix organization and biogenesis, which are annotation(s) related
to Biological Process; extracellular matrix structural protein;
extracellular matrix protein, adhesive, which are annotation(s)
related to Molecular Function; and extracellular matrix; collagen;
collagen type XI, which are annotation(s) related to Cellular
Component.
[2466] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2467] Cluster HUMCA1XIA can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the right hand column of the table and the numbers on
the y-axis of FIG. 32 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[2468] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 32 and Table 802. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: bone malignant tumors, epithelial
malignant tumors, a mixture of malignant tumors from different
tissues and lung malignant tumors.
TABLE-US-00851 TABLE 802 Normal tissue distribution Name of Tissue
Number adrenal 0 bone 207 brain 13 colon 0 epithelial 11 general 11
head and neck 0 kidney 0 lung 0 breast 8 pancreas 0 stomach 73
uterus 9
TABLE-US-00852 TABLE 803 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 4.2e-01
1.9e-01 9.6e-02 3.4 8.2e-02 3.6 bone 2.4e-01 6.3e-01 7.7e-10 4.3
5.3e-03 1.6 brain 5.0e-01 6.9e-01 1.8e-01 2.1 4.2e-01 1.3 colon
1.3e-02 2.9e-02 2.4e-01 3.0 3.5e-01 2.4 epithelial 3.9e-04 3.2e-03
1.3e-03 2.3 1.8e-02 1.7 general 5.6e-05 1.6e-03 9.5e-17 4.5 1.1e-09
2.8 head and neck 1.2e-01 2.1e-01 1 1.3 1 1.1 kidney 6.5e-01
7.2e-01 3.4e-01 2.4 4.9e-01 1.9 lung 5.3e-02 9.1e-02 5.5e-05 7.3
5.0e-03 4.0 breast 4.3e-01 5.6e-01 6.9e-01 1.4 8.2e-01 1.1 pancreas
3.3e-01 1.8e-01 4.2e-01 2.4 1.5e-01 3.7 stomach 5.0e-01 6.1e-01
6.9e-01 1.0 6.7e-01 0.8 Uterus 7.1e-01 7.0e-01 6.6e-01 1.1 6.4e-01
1.1
[2469] As noted above, cluster HUMCA1XIA features 4 transcript(s),
which were listed in Table 798 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Collagen alpha 1
(SEQ ID NO:1446). A description of each variant protein according
to the present invention is now provided.
[2470] Variant protein HUMCA1XIA_P14 (SEQ ID NO:1372) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s)
HUMCA1XIA_T16 (SEQ ID NO:99). An alignment is given to the known
protein (Collagen alpha 1 (SEQ ID NO:1446)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2471] Comparison report between HUMCA1XIA_P14 (SEQ ID NO:1372) and
CA1B_HUMAN_V5 (SEQ ID NO: 1447):
[2472] 1. An isolated chimeric polypeptide encoding for HUMCA 1
XIA_P 14 (SEQ ID NO:1372), comprising a first amino acid sequence
being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE
DTYLENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ
GPIGPPGEKGPQGKPGLAGLPGADGPPGHPGKEGQSGEKGALGPPGPGGPIGYPGPRGVKGADGVRGLKG
SKGEKGEDGFPGFKGDMGLKGDREVGQIGPRGEDGPEGPKGRAGTGDPGPSGQAGEKGKLGVPGLPG
YPGRQGPKGSTGFPGFPGANGEKGARGVAGKPGPRGQRGPTGPRGSRGARGPTGKPGPKGTSGGDGPPGP
PGERGPQGPQGPVGFPGKGPPGPPGKDGLPGHPGQRGETGFQGKTGPPGPGGVVGPQGPTGETGPIGERG
HPGPPGPPGEQGLPGAAGKEGAKGDPGPQGISGKDGPAGLRGFPGERGLPGAQGAPGLKGGEGPQGPPGP
V corresponding to amino acids 1-1056 of CA1B_HUMAN_V5 (SEQ ID
NO:1447), which also corresponds to amino acids 1-1056 of
HUMCA1XIA_P14 (SEQ ID NO:1372), and a second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO: 256) corresponding to amino
acids 1057-1081 of HUMCA1XIA_P14 (SEQ ID NO:1372), wherein said
first amino amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2473] 2. An isolated polypeptide encoding for a tail of
HUMCA1XIA_P14 (SEQ ID NO:1372), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
VSMMIINSQTIMVVNYSSSFITLML (SEQ ID NO: 256) in HUMCA1XIA_P14 (SEQ ID
NO:1372).
[2474] It should be noted that the known protein sequence
(CA1B_HUMAN (SEQ ID NO:1446)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for CA1B_HUMAN_V5 (SEQ ID NO:1447). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-00853 TABLE 804 Changes to CA1B_HUMAN_V5 (SEQ ID NO: 1447)
SNP position(s) on amino acid sequence Type of change 987
conflict
[2475] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2476] Variant protein HUMCA1XIA_P14 (SEQ ID NO:1372) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 805, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:1372)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00854 TABLE 805 Amino acid mutations SNP position(s) on
Alternative amino acid sequence amino acid(s) Previously known SNP?
8 W -> G Yes 46 D -> E Yes 559 G -> S Yes 832 G -> *
Yes 986 H -> Y Yes 1061 I -> M Yes 1070 V -> A Yes
[2477] Variant protein HUMCA1XIA_P14 (SEQ ID NO:1372) is encoded by
the following transcript(s): HUMCA1XIA_T16 (SEQ ID NO:99), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HUMCA1XIA_T16 (SEQ ID NO:99) is
shown in bold; this coding portion starts at position 319 and ends
at position 3561. The transcript also has the following SNPs as
listed in Table 806 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P14 (SEQ ID NO:1372)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00855 TABLE 806 Nucleic acid SNPs SNP position on
Alternative nucleotide sequence nucleic acid Previously known SNP?
157 A -> G No 241 T -> A Yes 340 T -> G Yes 456 T -> G
Yes 1993 G -> A Yes 2812 G -> T Yes 3274 C -> T Yes 3282 C
-> T Yes 3501 A -> G Yes 3527 T -> C Yes
[2478] Variant protein HUMCA1XIA_P15 (SEQ ID NO:1373) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s)
HUMCA1XIA_T17 (SEQ ID NO:100). An alignment is given to the known
protein (Collagen alpha 1 (SEQ ID NO:1446)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2479] Comparison report between HUMCA1XIA_P15 (SEQ ID NO:1373) and
CA1B_HUMAN (SEQ ID NO:1446):
[2480] 1. An isolated chimeric polypeptide encoding for
HUMCA1XIA_P15 (SEQ ID NO:1373), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALKDFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYRLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEEIFTEEYLTGEDYDSQRKNSE
DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKCQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGRPGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEAGPRGLLGPRGTPGAPGQPGMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQ
GPIGPPGEK corresponding to amino acids 1-714 of CA1B_HUMAN (SEQ ID
NO:1446), which also corresponds to amino acids 1-714 of
HUMCA1XIA_P15 (SEQ ID NO:1373), and a second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence MCCNLSFGILIPLQK
(SEQ ID NO: 257) corresponding to amino acids 715-729 of
HUMCA1XIA_P15 (SEQ ID NO:1373), wherein said first acid sequence
and second amino acid sequence are contiguous and in a sequential
order.
[2481] 2. An isolated polypeptide encoding for a tail of
HUMCA1XIA_P15 (SEQ ID NO:1373), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence MCCNLSFGILIPLQK (SEQ ID
NO: 257) in HUMCA1XIA_P15 (SEQ ID NO:1373).
[2482] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2483] Variant protein HUMCA1XIA_P15 (SEQ ID NO:1373) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 807, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:1373)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00856 TABLE 807 Amino acid mutations SNP position(s) on
Alternative amino acid sequence amino acid(s) Previously known SNP?
8 W -> G Yes 46 D -> E Yes 559 G -> S Yes
[2484] The glycosylation sites of variant protein HUMCA1XIA_P15
(SEQ ID NO:1373), as compared to the known protein Collagen alpha 1
(SEQ ID NO:1446), are described in Table 808 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00857 TABLE 808 Glycosylation site(s) Position(s) on known
amino acid sequence Present in variant protein? 1640 no
[2485] Variant protein HUMCA1XIA_P15 (SEQ ID NO:1373) is encoded by
the following transcript(s): HUMCA1XIA_T17 (SEQ ID NO:100), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HUMCA1XIA_T17 (SEQ ID NO:100) is
shown in bold; this coding portion starts at position 319 and ends
at position 2505. The transcript also has the following SNPs as
listed in Table 809 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P15 (SEQ ID NO:1373)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00858 TABLE 809 Nucleic acid SNPs SNP position on
Alternative nucleotide sequence nucleic acid Previously known SNP?
157 A -> G No 241 T -> A Yes 340 T -> G Yes 456 T -> G
Yes 1993 G -> A Yes 2473 C -> T Yes
[2486] Variant protein HUMCA1XIA_P16 (SEQ ID NO:1374) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s)
HUMCA1XIA_T19 (SEQ ID NO:101). An alignment is given to the known
protein (Collagen alpha 1 (SEQ ID NO:1446)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2487] Comparison report between HUMCA1XIA_P16 (SEQ ID NO:1374) and
CA1B_HUMAN (SEQ ID NO:1446):
[2488] 1. An isolated chimeric polypeptide encoding for
HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALDFHNSPEGISKTTGFCTNRKNSKG
SKTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDEYAPEDIIEYDYEYGEAEYKEAESVT
EGPTVTEETIAQTEANIVDDFQEYNYGTMESYQTEAPRHVSGTNEPNPVEIFTEEYLTGEDYDSQRKNSE
DTLYENKEIDGRDSDLLVDGDLGEYDFYEYKEYEDKPTSPPNEEFGPGVPAETDITETSINGHGAYGEKGQ
KGEPAVVEPGMLVEGPPGPAGPAGIMGPPGLQGPTGPPGDPGDRGPPGRPGLPGADGLPGPPGTMLMLPF
RYGGDGSKGPTISAQEAQAQAILQQARIALRGPPGPMGLTGRPGPVGGPGSSGAKGESGDPGPQGPRGVQ
GPPGPTGKPGKRGPRGADGGRGMPGEPGAKGDRGFDGLPGLPGDKGHRGERGPQGPPGPPGDDGMRGE
DGEIGPRGLPGEA corresponding to amino acids 1-648 of CA1B_HUMAN (SEQ
ID NO:1446), which also corresponds to amino acids 1-648 of
HUMCA1XIA_P16 (SEQ ID NO:1374), a second amino acid sequence being
at least 90% homologous to
GMAGVDGPPGPKGNMGPQGEPGPPGQQGNPGPQGLPGPQGPIGPPGEK corresponding to
amino acids 667-714 of CA1B_HUMAN (SEQ ID NO:1446), which also
corresponds to amino acids 649-696 of HUMCA1XIA_P16 (SEQ ID
NO:1374), and a third amino acid sequence being at least 70%
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence
VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO: 258)
corresponding to amino acids 697-738 of HUMCA1XIA_P16 (SEQ ID
NO:1374), wherein said first amino acid sequence, second amino acid
sequence and third amino acid sequence are contiguous and in a
sequential order.
[2489] 2. An isolated chimeric polypeptide encoding for an edge
portion of HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise AG, having a structure as follows: a sequence
starting from any of amino acid numbers 648-x to 648; and ending at
any of amino acid numbers 649+((n-2)-x), in which x varies from 0
to n-2.
[2490] 3. An isolated polypeptide encoding for a tail of
HUMCA1XIA_P16 (SEQ ID NO:1374), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
VSFSFSLFYKKVIKFACDKRFVGRHDERKVVKLSLPLYLIYE (SEQ ID NO: 258) in
HUMCA1XIA_P16 (SEQ ID NO:1374).
[2491] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2492] Variant protein HUMCA1XIA_P16 (SEQ ID NO:1374) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 810, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:1374)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00859 TABLE 810 Amino acid mutations SNP position(s) on
Alternative amino acid sequence amino acid(s) Previously known SNP?
8 W -> G Yes 46 D -> E Yes 559 G -> S Yes
[2493] The glycosylation sites of variant protein HUMCA1XIA_P16
(SEQ ID NO:1374), as compared to the known protein Collagen alpha 1
(SEQ ID NO:1446), are described in Table 811 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00860 TABLE 811 Glycosylation site(s) Position(s) on known
amino acid sequence Present in variant protein? 1640 no
[2494] Variant protein HUMCA1XIA_P16 (SEQ ID NO:1374) is encoded by
the following transcript(s): HUMCA1XIA_T19 (SEQ ID NO:101), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HUMCA1XIA_T19 (SEQ ID NO:101) is
shown in bold; this coding portion starts at position 319 and ends
at position 2532. The transcript also has the following SNPs as
listed in Table 812 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P16 (SEQ ID NO:1374)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00861 TABLE 812 Nucleic acid SNPs SNP position on
Alternative nucleotide sequence nucleic acid Previously known SNP?
157 A -> G No 241 T -> A Yes 340 T -> G Yes 456 T -> G
Yes 1993 G -> A Yes 2606 C -> A Yes 2677 T -> G Yes 2849 C
-> T Yes
[2495] Variant protein HUMCA1XIA_P17 (SEQ ID NO:1375) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s)
HUMCA1XIA_T20 (SEQ ID NO:102). An alignment is given to the known
protein (Collagen alpha 1 (SEQ ID NO:1446)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2496] Comparison report between HUMCA1XIA_P17 (SEQ ID NO:1375) and
CA1B_HUMAN (SEQ ID NO:1446):
[2497] 1. An isolated chimeric polypeptide encoding for
HUMCA1XIA_P17 (SEQ ID NO:1375), comprising a first amino acid
sequence being at least 90% homologous to
MEPWSSRWKTKRWLWDFTVTTLALTFLFQAREVRGAAPVDVLKALKFHNSPEGISKTTGFCTNRKNSKG
SDTAYRVSKQAQLSAPTKQLFPGGTFPEDFSILFTVKPKKGIQSFLLSIYNEHGIQQIGVEVGRSPVFLFEDH
TGKPAPEDYPLFRTVNIADGKWHRVAISVEKKTVTMIVDCKKKTTKPLDRSERAIVDTNGITVFGTRILDE
EVFEGDIQQFLITGDPKAAYDYCEHYSPDCDSSAPKAAQAQEPQIDE corresponding to
amino acids 1-260 of CA1B_HUMAN (SEQ ID NO:1446), which also
corresponds to amino acids 1-260 of HUMCA1XIA_P17 (SEQ ID NO:1375),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence VRSTRPEKVFVFQ (SEQ ID NO: 259) corresponding to amino
acids 261-273 of HUMCA1XIA_P17 (SEQ ID NO:1375), wherein said first
amino acid sequence and second amino acid sequence are contiguous
and in a sequential order.
[2498] 2. An isolated polypeptide encoding for a tail of
HUMCA1XIA_P17 (SEQ ID NO:1375), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VRSTRPEKVFVFQ (SEQ ID
NO: 259) in HUMCA1XIA_P17 (SEQ ID NO:1375).
[2499] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2500] Variant protein HUMCA1XIA_P17 (SEQ ID NO:1375) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 813, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:1375)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00862 TABLE 813 Amino acid mutations SNP position(s) on
Alternative amino acid sequence amino acid(s) Previously known SNP?
8 W -> G Yes 46 D -> E Yes
[2501] The glycosylation sites of variant protein HUMCA1XIA_P17
(SEQ ID NO:1375), as compared to the known protein Collagen alpha 1
(SEQ ID NO:1446), are described in Table 814 (given according to
their position(s) on the amino acid sequence in the first column;
the second column indicates whether the glycosylation site is
present in the variant protein; and the last column indicates
whether the position is different on the variant protein).
TABLE-US-00863 TABLE 814 Glycosylation site(s) Position(s) on known
amino acid sequence Present in variant protein? 1640 no
[2502] Variant protein HUMCA1XIA_P17 (SEQ ID NO:1375) is encoded by
the following transcript(s): HUMCA1XIA_T20 (SEQ ID NO:102), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HUMCA1XIA_T20 (SEQ ID NO:102) is
shown in bold; this coding portion starts at position 319 and ends
at position 1137. The transcript also has the following SNPs as
listed in Table 815 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HUMCA1XIA_P17 (SEQ ID NO:1375)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-00864 TABLE 815 Nucleic acid SNPs SNP position on
Alternative nucleotide sequence nucleic acid Previously known SNP?
157 A -> G No 241 T -> A Yes 340 T -> G Yes 456 T -> G
Yes 1150 A -> C Yes
[2503] As noted above, cluster HUMCA1XIA features 46 segment(s),
which were listed in Table 799 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[2504] Segment cluster HUMCA1XIA_node.sub.--0 (SEQ ID NO:742)
according to the present invention is supported by 13 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMCA1XIA_T16 (SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100),
HUMCA1XIA_T19 (SEQ ID NO:101) and HUMCA1XIA_T20 (SEQ ID NO:102).
Table 816 below starting and ending position of this segment on
each transcript.
TABLE-US-00865 TABLE 816 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1 424 HUMCA1XIA_T17 (SEQ ID NO: 100)
1 424 HUMCA1XIA_T19 (SEQ ID NO: 101) 1 424 HUMCA1XIA_T20 (SEQ ID
NO: 102) 1 424
[2505] Segment cluster HUMCA1XIA_node.sub.--2 (SEQ ID NO:743)
according to the present invention is supported by 9 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100), HUMCA1XIA_T19 (SEQ
ID NO:101) and HUMCA1XIA_T20 (SEQ ID NO:102). Table 817 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00866 TABLE 817 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 425 592 HUMCA1XIA_T17 (SEQ ID NO:
100) 425 592 HUMCA1XIA_T19 (SEQ ID NO: 101) 425 592 HUMCA1XIA_T20
(SEQ ID NO: 102) 425 592
[2506] Segment cluster HUMCA1XIA_node.sub.--4 (SEQ ID NO:744)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100), HUMCA1XIA_T19 (SEQ
ID NO:101) and HUMCA1XIA_T20 (SEQ ID NO:102). Table 818 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00867 TABLE 818 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 593 806 HUMCA1XIA_T17 (SEQ ID NO:
100) 593 806 HUMCA1XIA_T19 (SEQ ID NO: 101) 593 806 HUMCA1XIA_T20
(SEQ ID NO: 102) 593 806
[2507] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 819.
TABLE-US-00868 TABLE 819 Oligonucleotides related to this segment
Chip Oligonucleotide name Overexpressed in cancers reference
HUMCA1XIA_0_18_0 (SEQ ID lung malignant tumors LUN NO: 236)
[2508] Segment cluster HUMCA1XIA_node.sub.--6 (SEQ ID NO:745)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100), HUMCA1XIA_T19 (SEQ
ID NO:101) and HUMCA1XIA_T20 (SEQ ID NO:102). Table 820 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00869 TABLE 820 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 807 969 HUMCA1XIA_T17 (SEQ ID NO:
100) 807 969 HUMCA1XIA_T19 (SEQ ID NO: 101) 807 969 HUMCA1XIA_T20
(SEQ ID NO: 102) 807 969
[2509] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 821.
TABLE-US-00870 TABLE 821 Oligonucleotides related to this segment
Chip Oligonucleotide name Overexpressed in cancers reference
HUMCA1XIA_0_18_0 (SEQ ID lung malignant tumors LUN NO: 236)
[2510] Segment cluster HUMCA1XIA_node.sub.--8 (SEQ ID NO:746)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100), HUMCA1XIA_T19 (SEQ
ID NO:101) and HUMCA1XIA_T20 (SEQ ID NO:102). Table 822 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00871 TABLE 822 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 970 1098 HUMCA1XIA_T17 (SEQ ID NO:
100) 970 1098 HUMCA1XIA_T19 (SEQ ID NO: 101) 970 1098 HUMCA1XIA_T20
(SEQ ID NO: 102) 970 1098
[2511] Segment cluster HUMCA1XIA_node.sub.--9 (SEQ ID NO:747)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T20
(SEQ ID NO:102). Table 823 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00872 TABLE 823 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T20 (SEQ ID NO: 102) 1099 1271
[2512] Segment cluster HUMCA1XIA_node.sub.--18 (SEQ ID NO:748)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 824 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00873 TABLE 824 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1309 1522 HUMCA1XIA_T17 (SEQ ID NO:
100) 1309 1522 HUMCA1XIA_T19 (SEQ ID NO: 101) 1309 1522
[2513] Segment cluster HUMCA1XIA_node.sub.--54 (SEQ ID NO:749)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T19
(SEQ ID NO:101). Table 825 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00874 TABLE 825 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T19 (SEQ ID NO: 101) 2407 2836
[2514] Segment cluster HUMCA1XIA_node.sub.--55 (SEQ ID NO:750)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T17
(SEQ ID NO:100) and HUMCA1XIA_T19 (SEQ ID NO:101). Table 826 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00875 TABLE 826 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T17 (SEQ ID NO: 100) 2461 2648 HUMCA1XIA_T19 (SEQ ID NO:
101) 2837 3475
[2515] Segment cluster HUMCA1XIA_node.sub.--92 (SEQ ID NO:751)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 827 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00876 TABLE 827 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3487 3615
[2516] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2517] Segment cluster HUMCA1XIA_node.sub.--11 (SEQ ID NO:752)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 828 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00877 TABLE 828 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1099 1215 HUMCA1XIA_T17 (SEQ ID NO:
100) 1099 1215 HUMCA1XIA_T19 (SEQ ID NO: 101) 1099 1215
[2518] Segment cluster HUMCA1XIA_node.sub.--15 (SEQ ID NO:753)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 829 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00878 TABLE 829 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1216 1308 HUMCA1XIA_T17 (SEQ ID NO:
100) 1216 1308 HUMCA1XIA_T19 (SEQ ID NO: 101) 1216 1308
[2519] Segment cluster HUMCA1XIA_node.sub.--19 (SEQ ID NO:754)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 830 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00879 TABLE 830 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1523 1563 HUMCA1XIA_T17 (SEQ ID NO:
100) 1523 1563 HUMCA1XIA_T19 (SEQ ID NO: 101) 1523 1563
[2520] Segment cluster HUMCA1XIA_node.sub.--21 (SEQ ID NO:755)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 831 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00880 TABLE 831 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1564 1626 HUMCA1XIA_T17 (SEQ ID NO:
100) 1564 1626 HUMCA1XIA_T19 (SEQ ID NO: 101) 1564 1626
[2521] Segment cluster HUMCA1XIA_node.sub.--23 (SEQ ID NO:756)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 832 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00881 TABLE 832 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1627 1668 HUMCA1XIA_T17 (SEQ ID NO:
100) 1627 1668 HUMCA1XIA_T19 (SEQ ID NO: 101) 1627 1668
[2522] Segment cluster HUMCA1XIA_node.sub.--25 (SEQ ID NO:757)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 833 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00882 TABLE 833 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1669 1731 HUMCA1XIA_T17 (SEQ ID NO:
100) 1669 1731 HUMCA1XIA_T19 (SEQ ID NO: 101) 1669 1731
[2523] Segment cluster HUMCA1XIA_node.sub.--27 (SEQ ID NO:758)
according to the present invention is supported by 2 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 834 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00883 TABLE 834 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1732 1806 HUMCA1XIA_T17 (SEQ ID NO:
100) 1732 1806 HUMCA1XIA_T19 (SEQ ID NO: 101) 1732 1806
[2524] Segment cluster HUMCA1XIA_node.sub.--29 (SEQ ID NO:759)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 835 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00884 TABLE 835 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1807 1890 HUMCA1XIA_T17 (SEQ ID NO:
100) 1807 1890 HUMCA1XIA_T19 (SEQ ID NO: 101) 1807 1890
[2525] Segment cluster HUMCA1XIA_node.sub.--31 (SEQ ID NO:760)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 836 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00885 TABLE 836 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1891 1947 HUMCA1XIA_T17 (SEQ ID NO:
100) 1891 1947 HUMCA1XIA_T19 (SEQ ID NO: 101) 1891 1947
[2526] Segment cluster HUMCA1XIA_node.sub.--33 (SEQ ID NO:761)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 837 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00886 TABLE 837 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 1948 2001 HUMCA1XIA_T17 (SEQ ID NO:
100) 1948 2001 HUMCA1XIA_T19 (SEQ ID NO: 101) 1948 2001
[2527] Segment cluster HUMCA1XIA_node.sub.--35 (SEQ ID NO:762)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 838 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00887 TABLE 838 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2002 2055 HUMCA1XIA_T17 (SEQ ID NO:
100) 2002 2055 HUMCA1XIA_T19 (SEQ ID NO: 101) 2002 2055
[2528] Segment cluster HUMCA1XIA_node.sub.--37 (SEQ ID NO:763)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 839 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00888 TABLE 839 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2056 2109 HUMCA1XIA_T17 (SEQ ID NO:
100) 2056 2109 HUMCA1XIA_T19 (SEQ ID NO: 101) 2056 2109
[2529] Segment cluster HUMCA1XIA_node.sub.--39 (SEQ 11) NO:764)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 840 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00889 TABLE 840 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2110 2163 HUMCA1XIA_T17 (SEQ ID NO:
100) 2110 2163 HUMCA1XIA_T19 (SEQ ID NO: 101) 2110 2163
[2530] Segment cluster HUMCA1XIA_node.sub.--41 (SEQ ID NO:765)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 841 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00890 TABLE 841 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2164 2217 HUMCA1XIA_T17 (SEQ ID NO:
100) 2164 2217 HUMCA1XIA_T19 (SEQ ID NO: 101) 2164 2217
[2531] Segment cluster HUMCA1XIA_node.sub.--43 (SEQ ID NO:766)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 842 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00891 TABLE 842 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2218 2262 HUMCA1XIA_T17 (SEQ ID NO:
100) 2218 2262 HUMCA1XIA_T19 (SEQ ID NO: 101) 2218 2262
[2532] Segment cluster HUMCA1XIA_node.sub.--45 (SEQ ID NO:767)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99) and HUMCA1XIA_T17 (SEQ ID NO:100). Table 843 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-00892 TABLE 843 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2263 2316 HUMCA1XIA_T17 (SEQ ID NO:
100) 2263 2316
[2533] Segment cluster HUMCA1XIA_node.sub.--47 (SEQ ID NO:768)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 844 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00893 TABLE 844 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2317 2361 HUMCA1XIA_T17 (SEQ ID NO:
100) 2317 2361 HUMCA1XIA_T19 (SEQ ID NO: 101) 2263 2307
[2534] Segment cluster HUMCA1XIA_node.sub.--49 (SEQ ID NO:769)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 845 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00894 TABLE 845 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2362 2415 HUMCA1XIA_T17 (SEQ ID NO:
100) 2362 2415 HUMCA1XIA_T19 (SEQ ID NO: 101) 2308 2361
[2535] Segment cluster HUMCA1XIA_node.sub.--51 (SEQ ID NO:770)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99), HUMCA1XIA_T17 (SEQ ID NO:100) and HUMCA1XIA_T19
(SEQ ID NO:101). Table 846 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00895 TABLE 846 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2416 2460 HUMCA1XIA_T17 (SEQ ID NO:
100) 2416 2460 HUMCA1XIA_T19 (SEQ ID NO: 101) 2362 2406
[2536] Segment cluster HUMCA1XIA_node.sub.--57 (SEQ ID NO:771)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 847 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00896 TABLE 847 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2461 2514
[2537] Segment cluster HUMCA1XIA_node.sub.--59 (SEQ ID NO:772)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 848 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00897 TABLE 848 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2515 2559
[2538] Segment cluster HUMCA1XIA_node.sub.--62 (SEQ ID NO:773)
according to the present invention is supported by 3 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 849 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00898 TABLE 849 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2560 2613
[2539] Segment cluster HUMCA1XIA_node.sub.--64 (SEQ ID NO:774)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 850 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00899 TABLE 850 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2614 2658
[2540] Segment cluster HUMCA1XIA_node.sub.--66 (SEQ ID NO:775)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 851 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00900 TABLE 851 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2659 2712
[2541] Segment cluster HUMCA1XIA_node.sub.--68 (SEQ ID NO:776)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 852 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00901 TABLE 852 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2713 2820
[2542] Segment cluster HUMCA1XIA_node.sub.--70 (SEQ ID NO:777)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 853 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00902 TABLE 853 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2821 2874
[2543] Segment cluster HUMCA1XIA_node.sub.--72 (SEQ ID NO:778)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 854 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00903 TABLE 854 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2875 2928
[2544] Segment cluster HUMCA1XIA_node.sub.--74 (SEQ ID NO:779)
according to the present invention is supported by 5 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 855 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00904 TABLE 855 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2929 2973
[2545] Segment cluster HUMCA1XIA_node.sub.--76 (SEQ ID NO:780)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 856 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00905 TABLE 856 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 2974 3027
[2546] Segment cluster HUMCA1XIA_node.sub.--78 (SEQ ID NO:782)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 857 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00906 TABLE 857 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3028 3072
[2547] Segment cluster HUMCA1XIA_node.sub.--81 (SEQ ID NO:783)
according to the present invention is supported by 8 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 858 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00907 TABLE 858 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3073 3126
[2548] Segment cluster HUMCA1XIA_node.sub.--83 (SEQ ID NO:784)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 859 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00908 TABLE 859 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3127 3180
[2549] Segment cluster HUMCA1XIA_node.sub.--85 (SEQ ID NO:785)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 860 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00909 TABLE 860 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3181 3234
[2550] Segment cluster HUMCA1XIA_node.sub.--87 (SEQ ID NO:786)
according to the present invention is supported by 10 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMCA1XIA_T16 (SEQ ID NO:99). Table 861 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00910 TABLE 861 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3235 3342
[2551] Segment cluster HUMCA1XIA_node.sub.--89 (SEQ ID NO:787)
according to the present invention is supported by 9 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HUMCA1XIA_T16
(SEQ ID NO:99). Table 862 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00911 TABLE 862 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3343 3432
[2552] Segment cluster HUMCA1XIA_node.sub.--91 (SEQ ID NO:788)
according to the present invention is supported by 11 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMCA1XIA_T16 (SEQ ID NO:99). Table 863 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-00912 TABLE 863 Segment location on transcripts Segment
starting Segment Transcript name position ending position
HUMCA1XIA_T16 (SEQ ID NO: 99) 3433 3486
Variant protein alignment to the previously known protein:
TABLE-US-00913 Sequence name: CA1B_HUMAN_V5 (SEQ ID NO: 1447)
Sequence documentation: Alignment of: HUMCA1XIA_P14 (SEQ ID NO:
1372) .times. CA1B_HUMAN_V5 (SEQ ID NO: 1447) . . . Alignment
segment 1/1: Quality: 10456.00 Escore: 0 Matching length: 1058
Total length: 1058 Matching Percent Similarity: 99.91 Matching
Percent Identity: 99.91 Total Percent Similarity: 99.91 Total
Percent Identity: 99.91 Gaps: 0 Alignment: ##STR00628##
##STR00629## ##STR00630## ##STR00631## ##STR00632## ##STR00633##
##STR00634## ##STR00635## ##STR00636## ##STR00637## ##STR00638##
##STR00639## ##STR00640## ##STR00641## ##STR00642## ##STR00643##
##STR00644## ##STR00645## ##STR00646## ##STR00647## ##STR00648##
##STR00649## Sequence name: CA1B_HUMAN (SEQ ID NO: 1446) Sequence
documentation: Alignment of: HUMCA1XIA_P15 (SEQ ID NO: 1373)
.times. CA1B_HUMAN (SEQ ID NO: 1446) Alignment segment 1/1:
Quality: 7073.00 Escore: 0 Matching length: 714 Total length: 714
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00650## ##STR00651## ##STR00652##
##STR00653## ##STR00654## ##STR00655## ##STR00656## ##STR00657##
##STR00658## ##STR00659## ##STR00660## ##STR00661## ##STR00662##
##STR00663## ##STR00664## Sequence name: CA1B_HUMAN (SEQ ID NO:
1446) Sequence documentation: Alignment of: HUMCA1XIA_P16 (SEQ ID
NO: 1374) .times. CA1B_HUMAN (SEQ ID NO: 1446) Alignment segment
1/1: Quality: 6795.00 Escore: 0 Matching length: 696 Total length:
714 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 97.48 Total Percent Identity:
97.48 Gaps: 1 Alignment: ##STR00665## ##STR00666## ##STR00667##
##STR00668## ##STR00669## ##STR00670## ##STR00671## ##STR00672##
##STR00673## ##STR00674## ##STR00675## ##STR00676## ##STR00677##
##STR00678## ##STR00679## Sequence name: CA1B_HUMAN (SEQ ID NO:
1446) Sequence documentation: Alignment of: HUMCA1XIA_P17 (SEQ ID
NO: 1375) .times. CA1B_HUMAN (SEQ ID NO: 1446) Alignment segment
1/1: Quality: 2561.00 Escore: 0 Matching length: 260 Total length:
260 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00680## ##STR00681## ##STR00682##
##STR00683## ##STR00684## ##STR00685##
Expression of Homo sapiens Collagen, Type XI, Alpha 1 (COL11A1)
HUMCA1X1A Transcripts which are Detectable by Amplicon as Depicted
in Sequence Name HUMCA1X1A Seg55 (SEQ ID NO:1663) in Normal and
Cancerous Lung Tissues
[2553] Expression of Homo sapiens collagen, type XI, alpha 1
(COL11A1) transcripts detectable by or according to seg55,
HUMCA1X1A seg55 amplicon (SEQ ID NO:1663) and primers HUMCA1X1A
seg55F (SEQ ID NO:1661) and HUMCA1X1A seg55R (SEQ ID NO:1662) was
measured by real time PCR. In parallel the expression of four
housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[2554] FIG. 67 is a histogram showing over expression of the
above-indicated Homo sapiens collagen, type XI, alpha 1 (COL11A1)
transcripts in cancerous lung samples relative to the normal
samples. Values represent the average of duplicate experiments.
Error bars indicate the minimal and maximal values obtained.
[2555] As is evident from FIG. 67, the expression of Homo sapiens
collagen, type XI, alpha 1 (COL11A1) transcripts detectable by the
above amplicon(s) in cancer samples was significantly higher than
in the non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99 Table
2). Notably an over-expression of at least 5 fold found in 11 out
of 15 adenocarcinoma samples, 11 out of 16 squamous cell carcinoma
samples, and in 2 out of 4 large cell carcinoma samples.
[2556] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: HUMCA1X1A
seg55F forward primer (SEQ ID NO:1661); and HUMCA1X1A seg55R
reverse primer (SEQ ID NO:16623).
[2557] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: HUMCA1X1A seg55 (SEQ ID NO:1663).
TABLE-US-00914 Forward primer-HUMCA1X1A seg55F (SEQ ID NO: 1661):
TTCTCATAGTATTCCATTGATTGGGTA Reverse primer-HUMCA1X1A seg55R (SEQ ID
NO: 1662): CACCGGTATGGAGAATAGCGA Amplicon (SEQ ID NO: 1663):
TTCTCATAGTATTCCATTGATTGGGTATACCAGGTTCTGTTTACTTTTAC
TTGGCAGTTGATAGAATAGGTGTAGTTTATACTTTTTCGCTATTCTCCAT ACCGGTG
Description for Cluster T11628
[2558] Cluster T11628 features 6 transcript(s) and 25 segment(s) of
interest, the names for which are given in Tables 864 and 865,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
866.
TABLE-US-00915 TABLE 864 Transcripts of interest Transcript Name
Sequence ID No. T11628_PEA_1_T3 103 T11628_PEA_1_T4 104
T11628_PEA_1_T5 105 T11628_PEA_1_T7 106 T11628_PEA_1_T9 107
T11628_PEA_1_T11 108
TABLE-US-00916 TABLE 865 Segments of interest Segment Name Sequence
ID No. T11628_PEA_1_node_7 789 T11628_PEA_1_node_11 790
T11628_PEA_1_node_16 791 T11628_PEA_1_node_22 792
T11628_PEA_1_node_25 793 T11628_PEA_1_node_31 794
T11628_PEA_1_node_37 795 T11628_PEA_1_node_0 796
T11628_PEA_1_node_4 797 T11628_PEA_1_node_9 798
T11628_PEA_1_node_13 799 T11628_PEA_1_node_14 800
T11628_PEA_1_node_17 801 T11628_PEA_1_node_18 802
T11628_PEA_1_node_19 803 T11628_PEA_1_node_24 804
T11628_PEA_1_node_27 805 T11628_PEA_1_node_28 806
T11628_PEA_1_node_29 807 T11628_PEA_1_node_30 808
T11628_PEA_1_node_32 809 T11628_PEA_1_node_33 810
T11628_PEA_1_node_34 811 T11628_PEA_1_node_35 812
T11628_PEA_1_node_36 813
TABLE-US-00917 TABLE 866 Proteins of interest Protein Name Sequence
ID No. Corresponding Transcript(s) T11628_PEA_1_P2 1376
T11628_PEA_1_T9 (SEQ ID NO: 103); T11628_PEA_1_T5 (SEQ ID NO: 105);
T11628_PEA_1_T7 (SEQ ID NO: 106) T11628_PEA_1_P5 1377
T11628_PEA_1_T9 (SEQ ID NO: 107) T11628_PEA_1_P7 1378
T11628_PEA_1_T11 (SEQ ID NO: 108) T11628_PEA_1_P10 1379
T11628_PEA_1_T4 (SEQ ID NO: 104)
[2559] These sequences are variants of the known protein Myoglobin
(SwissProt accession identifier MYG_HUMAN), SEQ ID NO: 1448,
referred to herein as the previously known protein.
[2560] Protein Myoglobin (SEQ ID NO:1448) is known or believed to
have the following function(s): Serves as a reserve supply of
oxygen and facilitates the movement of oxygen within muscles. The
sequence for protein Myoglobin is given at the end of the
application, as "Myoglobin amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 867.
TABLE-US-00918 TABLE 867 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 54 E -> K. /FTId =
VAR_003180. 133 K -> N. /FTId = VAR_003181. 139 R -> Q. /FTId
= VAR_003182. 139 R -> W. /FTId = VAR_003183. 128 Q -> E
[2561] As noted above, cluster T11628 features 6 transcript(s),
which were listed in Table 864 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Myoglobin (SEQ ID
NO:1448). A description of each variant protein according to the
present invention is now provided.
[2562] Variant protein T11628_PEA.sub.--1_P2 (SEQ ID NO:1376)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T11628_PEA.sub.--1_T3 (SEQ ID NO:103). An alignment is given to the
known protein (Myoglobin (SEQ ID NO:1448)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2563] Comparison report between T11628_PEA.sub.--1_P2 (SEQ ID
NO:1376) and Q8WVH6 (SEQ ID NO:1450):
[2564] 1. An isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE
(SEQ ID NO: 1735) corresponding to amino acids 1-55 of
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), and a second amino acid
sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFG-
A DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of
Q8WVH6 (SEQ ID NO:1450), which also corresponds to amino acids
56-154 of T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2565] 2. An isolated polypeptide encoding for a head of
T11628_PEA.sub.--1_P2 (SEQ ID NO:1376), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFKFKHLKSEDE (SEQ ID NO:
1735) of T11628_PEA.sub.--1_P2 (SEQ ID NO:1376).
[2566] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2567] Variant protein T11628_PEA.sub.--1_P2 (SEQ ID NO:1376) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 868, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T11628_PEA.sub.--1_P2
(SEQ ID NO:1376) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00919 TABLE 868 Amino acid mutations SNP position(s) on
amino Alternative amino acid sequence acid(s) Previously known SNP?
26 G -> No 44 F -> No 92 Q -> R No 135 A -> No 141 K
-> No 153 Q -> No
[2568] Variant protein T11628_PEA.sub.--1_P2 (SEQ ID NO:1376) is
encoded by the following transcript(s): T11628 _PEA.sub.--1_T3 (SEQ
ID NO:103), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
T11628_PEA.sub.--1_T3 (SEQ ID NO:103) is shown in bold; this coding
portion starts at position 220 and ends at position 681. The
transcript also has the following SNPs as listed in Table 869
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T11628_PEA.sub.--1_P2 (SEQ ID NO:1376) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00920 TABLE 869 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
83 G -> A Yes 93 G -> A Yes 95 G -> A Yes 146 G -> A
Yes 295 G -> No 349 T -> No 393 G -> A Yes 423 C -> T
Yes 494 A -> G No 498 G -> A No 623 C -> No 642 G -> No
678 G -> No 686 C -> No 686 C -> A No 717 C -> No 787 T
-> G No 820 G -> T No 826 G -> T No 850 C -> No 934 T
-> G No 975 A -> G Yes 1117 G -> No 1218 A -> G No
[2569] Variant protein T11628_PEA.sub.--1_P5 (SEQ ID NO:1377)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T11628_PEA.sub.--1_T9 (SEQ ID NO:107). An alignment is given to the
known protein (Myoglobin (SEQ ID NO:1448)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2570] Comparison report between T11628_PEA.sub.--1_P5 (SEQ ID
NO:1377) and MYG_HUMAN_V1 (SEQ ID NO:1449):
[2571] 1. An isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P5 (SEQ ID NO:1377), comprising a first amino
acid sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGA
DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 56-154 of
MYG_HUMAN_V1 (SEQ ID NO:1449), which also corresponds to amino
acids 1-99 of T11628_PEA.sub.--1_P5 (SEQ ID NO:1377).
[2572] It should be noted that the known protein sequence
(MYG_HUMAN (SEQ ID NO:1448)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for MYG_HUMAN_V1 (SEQ ID NO:1449). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-00921 TABLE 870 Changes to MYG_HUMAN_V1 (SEQ ID NO: 1449)
SNP position(s) on amino acid sequence Type of change 1
init_met
[2573] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2574] Variant protein T11628_PEA.sub.--1_P5 (SEQ ID NO:1377) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 871, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T11628_PEA.sub.--1_P5
(SEQ ID NO:1377) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00922 TABLE 871 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
37 Q -> R No 80 A -> No 86 K -> No 98 Q -> No
[2575] Variant protein T11628_PEA.sub.--1_P5 (SEQ ID NO:1377) is
encoded by the following transcript(s): T11628_PEA.sub.--1_T9 (SEQ
ID NO:107), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) is shown in bold; this coding
portion starts at position 211 and ends at position 507. The
transcript also has the following SNPs as listed in Table 872
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T11628_PEA.sub.--1_P5 (SEQ ID NO:1377) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00923 TABLE 872 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
2 C -> T Yes 175 T -> No 219 G -> A Yes 249 C -> T Yes
320 A -> G No 324 G -> A No 449 C -> No 468 G -> No 504
G -> No 512 C -> No 512 C -> A No 543 C -> No 613 T
-> G No 646 G -> T No 652 G -> T No 676 C -> No 760 T
-> G No 801 A -> G Yes 943 G -> No 1044 A -> G No
[2576] Variant protein T11628_PEA.sub.--1_P7 (SEQ ID NO:1378)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T11628_PEA.sub.--1_T11 (SEQ ID NO:108). An alignment is given to
the known protein (Myoglobin (SEQ ID NO:1448)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2577] Comparison report between T11628_PEA.sub.--1_P7 (SEQ ID
NO:1378) and MYG_HUMAN_V1 (SEQ ID NO:1449):
[2578] 1. An isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P7 (SEQ ID NO:1378), comprising a first amino
acid sequence being at least 90% homologous to
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASEDLKKHGATV
LTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFGADAQGAMNK
corresponding to amino acids 1-134 of MYG_HUMAN_V1 (SEQ ID
NO:1449), which also corresponds to amino acids 1-134 of
T11628_PEA.sub.--1_P7 (SEQ ID NO:1378), and a second amino acid
sequence being at least 70% optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence G
corresponding to amino acids 135-135 of T11628_PEA.sub.--1_P7 (SEQ
ID NO:1378), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[2579] It should be noted that the known protein sequence
(MYG_HUMAN (SEQ ID NO:1448)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for MYG_HUMAN_V1 (SEQ ID NO:1449). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-00924 TABLE 873 Changes to MYG_HUMAN_V1 (SEQ ID NO: 1449)
SNP position(s) on amino acid sequence Type of change 1
init_met
[2580] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2581] Variant protein T11628_PEA.sub.--1_P7 (SEQ ID NO:1378) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 874, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T11628_PEA.sub.--1_P7
(SEQ ID NO:1378) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00925 TABLE 874 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
26 G -> No 44 F -> No 92 Q -> R No
[2582] Variant protein T11628_PEA.sub.--1_P7 (SEQ ID NO:1378) is
encoded by the following transcript(s): T11628_PEA.sub.--1_T11 (SEQ
ID NO:108), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
T11628_PEA.sub.--1_T11 (SEQ ID NO:108) is shown in bold; this
coding portion starts at position 319 and ends at position 723. The
transcript also has the following SNPs as listed in Table 875
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T11628_PEA.sub.--1_P7 (SEQ ID NO:1378) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00926 TABLE 875 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
394 G -> No 448 T -> No 492 G -> A Yes 522 C -> T Yes
593 A -> G No 597 G -> A No 728 C -> No 728 C -> A No
759 C -> No 829 T -> G No 862 G -> T No 868 G -> T No
892 C -> No 976 T -> G No 1017 A -> G Yes 1159 G -> No
1260 A -> G No
[2583] Variant protein T11628_PEA.sub.--1_P10 (SEQ ID NO:1379)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
T11628_PEA_l_T4 (SEQ ID NO:104). An alignment is given to the known
protein (Myoglobin (SEQ ID NO:1448)) at the end of the application.
One or more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[2584] Comparison report between T11628_PEA.sub.--1_P10 (SEQ ID
NO:1379) and Q8WVH6 (SEQ ID NO: 1450):
[2585] 1.An isolated chimeric polypeptide encoding for
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE
(SEQ ID NO: 1735) corresponding to amino acids 1-55 of
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), and a second amino acid
sequence being at least 90% homologous to
MKASEDLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKHPGDFG-
A DAQGAMNKALELFRKDMASNYKELGFQG corresponding to amino acids 1-99 of
Q8WVH6 (SEQ ID NO:1450), which also corresponds to amino acids
56-154 of T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[2586] 2. An isolated polypeptide encoding for a head of
T11628_PEA.sub.--1_P10 (SEQ ID NO:1379), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDE (SEQ ID NO:
1735) of T11628_PEA.sub.--1_P10 (SEQ ID NO:1379).
[2587] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2588] Variant protein T11628_PEA.sub.--1_P10 (SEQ ID NO:1379) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 876, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein T11628_PEA.sub.--1_P10
(SEQ ID NO:1379) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00927 TABLE 876 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
26 G -> No 44 F -> No 92 Q -> R No 135 A -> No 141 K
-> No 153 Q -> No
[2589] Variant protein T11628_PEA.sub.--1_P10 (SEQ ID NO:1379) is
encoded by the following transcript(s): T11628_PEA.sub.--1_T4 (SEQ
ID NO:104), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
T11628_PEA.sub.--1_T4 (SEQ ID NO:104) is shown in bold; this coding
portion starts at position 205 and ends at position 666. The
transcript also has the following SNPs as listed in Table 877
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein T11628_PEA.sub.--1_P10 (SEQ ID NO:1379) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00928 TABLE 877 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
280 G -> No 334 T -> No 378 G -> A Yes 408 C -> T Yes
479 A -> G No 483 G -> A No 608 C -> No 627 G -> No 663
G -> No 671 C -> No 671 C -> A No 702 C -> No 772 T
-> G No 805 G -> T No 811 G -> T No 835 C -> No 919 T
-> G No 960 A -> G Yes 1102 G -> No 1203 A -> G No
[2590] As noted above, cluster T116123 features 25 segment(s),
winch were listed in Table 865 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[2591] Segment cluster T11628_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:789) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103). Table 878
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00929 TABLE 878 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 1 211
[2592] Segment cluster T11628_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:790) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T5 (SEQ ID NO:105). Table 879
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00930 TABLE 879 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T5 (SEQ ID NO: 105) 48 178
[2593] Segment cluster T11628_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:791) according to the present invention is supported by 38
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T11 (SEQ ID NO:108). Table 880
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00931 TABLE 880 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T11 (SEQ ID NO: 108) 1 214
[2594] Segment cluster T11628_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:792) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T9 (SEQ ID NO:107). Table 881
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00932 TABLE 881 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T9 (SEQ ID NO: 107) 1 140
[2595] Segment cluster T11628_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:793) according to the present invention is supported by 129
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 882 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00933 TABLE 882 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 395 537 T11628_PEA_1_T4 (SEQ ID
NO: 104) 380 522 T11628_PEA_1_T5 (SEQ ID NO: 105) 362 504
T11628_PEA_1_T7 (SEQ ID NO: 106) 347 489 T11628_PEA_1_T9 (SEQ ID
NO: 107) 221 363 T11628_PEA_1_T11 (SEQ ID NO: 108) 494 636
[2596] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 883.
TABLE-US-00934 TABLE 883 Oligonucleotides related to this segment
Overexpressed in Chip Oligonucleotide name cancers reference
T11628_0_9_0 (SEQ ID NO: 237) lung malignant tumors LUN
[2597] Segment cluster T11628_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:794) according to the present invention is supported by 137
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 884 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00935 TABLE 884 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 702 831 T11628_PEA_1_T4 (SEQ ID
NO: 104) 687 816 T11628_PEA_1_T5 (SEQ ID NO: 105) 669 798
T11628_PEA_1_T7 (SEQ ID NO: 106) 654 783 T11628_PEA_1_T9 (SEQ ID
NO: 107) 528 657 T11628_PEA_1_T11 (SEQ ID NO: 108) 744 873
[2598] Segment cluster T11628_PEA.sub.--1.sub.--37 (SEQ ID NO:795)
according to the present invention is supported by 99 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
T11628_PEA.sub.--1_T3 (SEQ ID NO:103), T11628_PEA.sub.--1_T4 (SEQ
ID NO:104), T11628_PEA.sub.--1_T5 (SEQ ID NO:105),
T11628_PEA.sub.--1_T7 (SEQ ID NO:106), T11628_PEA.sub.--1_T9 (SEQ
ID NO:107) and T11628_PEA.sub.--1_T11 (SEQ ID NO:108). Table 885
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00936 TABLE 885 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 1086 1225 T11628_PEA_1_T4 (SEQ ID
NO: 104) 1071 1210 T11628_PEA_1_T5 (SEQ ID NO: 105) 1053 1192
T11628_PEA_1_T7 (SEQ ID NO: 106) 1038 1177 T11628_PEA_1_T9 (SEQ ID
NO: 107) 912 1051 T11628_PEA_1_T11 (SEQ ID NO: 108) 1128 1267
[2599] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2600] Segment cluster T11628_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:796) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T4 (SEQ ID NO:104). Table 886
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00937 TABLE 886 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T4 (SEQ ID NO: 104) 1 93
[2601] Segment cluster T11628_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:797) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T4 (SEQ ID NO:104). Table 887
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00938 TABLE 887 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T4 (SEQ ID NO: 104) 94 196
[2602] Segment cluster T11628_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:798) according to the present invention is supported by 16
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T5 (SEQ ID NO:105) and
T11628_PEA.sub.--1_T7 (SEQ ID NO:106). Table 888 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00939 TABLE 888 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T5 (SEQ ID NO: 105) 1 47 T11628_PEA_1_T7 (SEQ ID NO:
106) 1 47
[2603] Segment cluster T11628_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:799) according to the present invention can be found in the
following transcript(s): T11628_PEA.sub.--1_T7 (SEQ ID NO:106).
Table 889 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-00940 TABLE 889 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T7 (SEQ ID NO: 106) 48 65
[2604] Segment cluster T11628_PEA.sub.--1_node.sub.--14 (SEQ ID
NO:800) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T7 (SEQ ID NO:106). Table 890
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00941 TABLE 890 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T7 (SEQ ID NO: 106) 66 163
[2605] Segment cluster T11628_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:801) according to the present invention is supported by 55
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T11 (SEQ ID NO:108). Table 891
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00942 TABLE 891 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T11 (SEQ ID NO: 108) 215 310
[2606] Segment cluster T11628_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:802) according to the present invention is supported by 98
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106) and
T11628_PEA.sub.--1_T11 (SEQ ID NO:108). Table 892 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00943 TABLE 892 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 212 289 T11628_PEA_1_T4 (SEQ ID
NO: 104) 197 274 T11628_PEA_1_T5 (SEQ ID NO: 105) 179 256
T11628_PEA_1_T7 (SEQ ID NO: 106) 164 241 T11628_PEA_1_T11 (SEQ ID
NO: 108) 311 388
[2607] Segment cluster T11628_PEA.sub.--1_node.sub.--19 (SEQ 11)
NU:803) according to the present invention can be found in the
following transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106) and
T11628_PEA.sub.--1_T11 (SEQ ID NO:108). Table 893 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00944 TABLE 893 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 290 314 T11628_PEA_1_T4 (SEQ ID
NO: 104) 275 299 T11628_PEA_1_T5 (SEQ ID NO: 105) 257 281
T11628_PEA_1_T7 (SEQ ID NO: 106) 242 266 T11628_PEA_1_T11 (SEQ ID
NO: 108) 389 413
[2608] Segment cluster T11628_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:804) according to the present invention is supported by 112
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 894 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00945 TABLE 894 Segment location on transcripts Segment
starting Segment Transcript name position ending position
T11628_PEA_1_T3 (SEQ ID NO: 103) 315 394 T11628_PEA_1_T4 (SEQ ID
NO: 104) 300 379 T11628_PEA_1_T5 (SEQ ID NO: 105) 282 361
T11628_PEA_1_T7 (SEQ ID NO: 106) 267 346 T11628_PEA_1_T9 (SEQ ID
NO: 107) 141 220 T11628_PEA_1_T11 (SEQ ID NO: 108) 414 493
[2609] Segment cluster T11628_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:805) according to the present invention is supported by 119
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 895 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00946 TABLE 895 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 538 621 T11628_PEA_1_T4 (SEQ ID
NO: 104) 523 606 T11628_PEA_1_T5 (SEQ ID NO: 105) 505 588
T11628_PEA_1_T7 (SEQ ID NO: 106) 490 573 T11628_PEA_1_T9 (SEQ ID
NO: 107) 364 447 T11628_PEA_1_T11 (SEQ ID NO: 108) 637 720
[2610] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 896
TABLE-US-00947 TABLE 896 Oligonucleotides related to this segment
Overexpressed Chip Oligonucleotide name in cancers reference
T11628_0_9_0 (SEQ ID NO: 237) lung malignant tumors LUN
[2611] Segment cluster T11628_PEA.sub.--1_node.sub.--28 (SEQ ID
NO:806) according to me present invention is supported by 115
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106) and
T11628_PEA.sub.--1_T9 (SEQ ID NO:107). Table 897 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00948 TABLE 897 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 622 650 T11628_PEA_1_T4 (SEQ ID
NO: 104) 607 635 T11628_PEA_1_T5 (SEQ ID NO: 105) 589 617
T11628_PEA_1_T7 (SEQ ID NO: 106) 574 602 T11628_PEA_1_T9 (SEQ ID
NO: 107) 448 476
[2612] Segment cluster T11628_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:807) according to the present invention is supported by 113
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106) and
T11628_PEA.sub.--1_T9 (SEQ ID NO:107). Table 898 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00949 TABLE 898 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 651 678 T11628_PEA_1_T4 (SEQ ID
NO: 104) 636 663 T11628_PEA_1_T5 (SEQ ID NO: 105) 618 645
T11628_PEA_1_T7 (SEQ ID NO: 106) 603 630 T11628_PEA_1_T9 (SEQ ID
NO: 107) 477 504
[2613] Segment cluster T11628_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:808) according to the present invention can be found in the
following transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 899 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00950 TABLE 899 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 679 701 T11628_PEA_1_T4 (SEQ ID
NO: 104) 664 686 T11628_PEA_1_T5 (SEQ ID NO: 105) 646 668
T11628_PEA_1_T7 (SEQ ID NO: 106) 631 653 T11628_PEA_1_T9 (SEQ ID
NO: 107) 505 527 T11628_PEA_1_T11 (SEQ ID NO: 108) 721 743
[2614] Segment cluster T11628_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:809) according to the present invention can be found in the
following transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 900 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00951 TABLE 900 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 832 844 T11628_PEA_1_T4 (SEQ ID
NO: 104) 817 829 T11628_PEA_1_T5 (SEQ ID NO: 105) 799 811
T11628_PEA_1_T7 (SEQ ID NO: 106) 784 796 T11628_PEA_1_T9 (SEQ ID
NO: 107) 658 670 T11628_PEA_1_T11 (SEQ ID NO: 108) 874 886
[2615] Segment cluster T11628_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:810) according to the present invention can be found in the
following transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 901 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00952 TABLE 901 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 845 866 T11628_PEA_1_T4 (SEQ ID
NO: 104) 830 851 T11628_PEA_1_T5 (SEQ ID NO: 105) 812 833
T11628_PEA_1_T7 (SEQ ID NO: 106) 797 818 T11628_PEA_1_T9 (SEQ ID
NO: 107) 671 692 T11628_PEA_1_T11 (SEQ ID NO: 108) 887 908
[2616] Segment cluster T11628_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:811) according to the present invention is supported by 122
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 902 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00953 TABLE 902 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 867 911 T11628_PEA_1_T4 (SEQ ID
NO: 104) 852 896 T11628_PEA_1_T5 (SEQ ID NO: 105) 834 878
T11628_PEA_1_T7 (SEQ ID NO: 106) 819 863 T11628_PEA_1_T9 (SEQ ID
NO: 107) 693 737 T11628_PEA_1_T11 (SEQ ID NO: 108) 909 953
[2617] Segment cluster T11628_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:812) according to the present invention is supported by 126
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 903 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00954 TABLE 903 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 912 967 T11628_PEA_1_T4 (SEQ ID
NO: 104) 897 952 T11628_PEA_1_T5 (SEQ ID NO: 105) 879 934
T11628_PEA_1_T7 (SEQ ID NO: 106) 864 919 T11628_PEA_1_T9 (SEQ ID
NO: 107) 738 793 T11628_PEA_1_T11 (SEQ ID NO: 108) 954 1009
[2618] Segment cluster T11628_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:813) according to the present invention is supported by 122
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): T11628_PEA.sub.--1_T3 (SEQ ID NO:103),
T11628_PEA.sub.--1_T4 (SEQ ID NO:104), T11628_PEA.sub.--1_T5 (SEQ
ID NO:105), T11628_PEA.sub.--1_T7 (SEQ ID NO:106),
T11628_PEA.sub.--1_T9 (SEQ ID NO:107) and T11628_PEA.sub.--1_T11
(SEQ ID NO:108). Table 904 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00955 TABLE 904 Segment location on transcripts Segment
Segment ending Transcript name starting position position
T11628_PEA_1_T3 (SEQ ID NO: 103) 968 1085 T11628_PEA_1_T4 (SEQ ID
NO: 104) 953 1070 T11628_PEA_1_T5 (SEQ ID NO: 105) 935 1052
T11628_PEA_1_T7 (SEQ ID NO: 106) 920 1037 T11628_PEA_1_T9 (SEQ ID
NO: 107) 794 911 T11628_PEA_1_T11 (SEQ ID NO: 108) 1010 1127
Variant protein alignment to the previously known protein:
TABLE-US-00956 Sequence name: Q8WVH6 (SEQ ID NO: 1450) Sequence
documentation: Alignment of: T11628_PEA_1_P2 (SEQ ID NO: 1376)
.times. Q8WVH6 (SEQ ID NO: 1450) Alignment segment 1/1: Quality:
962.00 Escore: 0 Matching length: 99 Total length: 99 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00686## ##STR00687## Sequence name: MYG_HUMAN_V1
(SEQ ID NO: 1449) Sequence documentation: Alignment of:
T11628_PEA_1_P5 (SEQ ID NO: 1377) .times. MYG_HUMAN_V1 (SEQ ID NO:
1449) . . . Alignment segment 1/1: Quality: 962.00 Escore: 0
Matching length: 99 Total length: 99 Matching Percent Similarity:
100.00 Matching Percent Identity: 100.00 Total Percent Similarity:
100.00 Total Percent Identity: 100.00 Gaps: 0 Alignment:
##STR00688## ##STR00689## Sequence name: MYG_HUMAN_V1 (SEQ ID NO:
1449) Sequence documentation: Alignment of: T11628_PEA_1_P7 (SEQ ID
NO: 1378) .times. MYG_HUMAN_V1 (SEQ ID NO: 1449) . . . Alignment
segment 1/1: Quality: 1315.00 Escore: 0 Matching length: 134 Total
length: 134 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 100.00 Total Percent
Identity: 100.00 Gaps: 0 Alignment: ##STR00690## ##STR00691##
##STR00692## Sequence name: Q8WVHG (SEQ ID NO: 1450) Sequence
documentation: Alignment of: T11628_PEA_1_P10 (SEQ ID NO: 1379)
.times. Q8WVHG (SEQ ID NO: 1450) Alignment segment 1/1: Quality:
962.00 Escore: 0 Matching length: 99 Total length: 99 Matching
Percent Similarity: 100.00 Matching Percent Identity: 100.00 Total
Percent Similarity: 100.00 Total Percent Identity: 100.00 Gaps: 0
Alignment: ##STR00693## ##STR00694##
[2619] Description for Cluster Humcea
[2620] Cluster HUMCEA features 5 transcript(s) and 42 segment(s) of
interest, the names for which are given in Tables 905 and 906,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
907.
TABLE-US-00957 TABLE 905 Transcripts of interest Transcript Name
Sequence ID No. HUMCEA_PEA_1_T8 109 HUMCEA_PEA_1_T9 110
HUMCEA_PEA_1_T20 111 HUMCEA_PEA_1_T25 112 HUMCEA_PEA_1_T26 113
TABLE-US-00958 TABLE 906 Segments of interest Segment Name Sequence
ID No. HUMCEA_PEA_1_node_0 814 HUMCEA_PEA_1_node_2 815
HUMCEA_PEA_1_node_11 816 HUMCEA_PEA_1_node_12 817
HUMCEA_PEA_1_node_31 818 HUMCEA_PEA_1_node_36 819
HUMCEA_PEA_1_node_44 820 HUMCEA_PEA_1_node_46 821
HUMCEA_PEA_1_node_63 822 HUMCEA_PEA_1_node_65 823
HUMCEA_PEA_1_node_67 824 HUMCEA_PEA_1_node_3 825
HUMCEA_PEA_1_node_7 826 HUMCEA_PEA_1_node_8 827 HUMCEA_PEA_1_node_9
828 HUMCEA_PEA_1_node_10 829 HUMCEA_PEA_1_node_15 830
HUMCEA_PEA_1_node_16 831 HUMCEA_PEA_1_node_17 832
HUMCEA_PEA_1_node_18 833 HUMCEA_PEA_1_node_19 834
HUMCEA_PEA_1_node_20 835 HUMCEA_PEA_1_node_21 836
HUMCEA_PEA_1_node_22 837 HUMCEA_PEA_1_node_23 838
HUMCEA_PEA_1_node_24 839 HUMCEA_PEA_1_node_27 840
HUMCEA_PEA_1_node_29 841 HUMCEA_PEA_1_node_30 842
HUMCEA_PEA_1_node_33 843 HUMCEA_PEA_1_node_34 844
HUMCEA_PEA_1_node_35 845 HUMCEA_PEA_1_node_45 846
HUMCEA_PEA_1_node_50 847 HUMCEA_PEA_1_node_51 848
HUMCEA_PEA_1_node_56 849 HUMCEA_PEA_1_node_57 850
HUMCEA_PEA_1_node_58 851 HUMCEA_PEA_1_node_60 852
HUMCEA_PEA_1_node_61 853 HUMCEA_PEA_1_node_62 854
HUMCEA_PEA_1_node_64 855
TABLE-US-00959 TABLE 907 Proteins of interest Sequence Protein Name
ID No. Corresponding Transcript(s) HUMCEA_PEA_1_P4 1380
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) HUMCEA_PEA_1_P5 1381
HUMCEA_PEA_1_T9 (SEQ ID NO: 110) HUMCEA_PEA_1_P14 1382
HUMCEA_PEA_1_T20 (SEQ ID NO: 111) HUMCEA_PEA_1_P19 1383
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) HUMCEA_PEA_1_P20 1384
HUMCEA_PEA_1_T26 (SEQ ID NO: 113)
[2621] These sequences are variants of the known protein
Carcinoembryonic antigen-related cell adhesion molecule 5 precursor
(SwissProt accession identifier CEA5_HUMAN; known also according to
the synonyms Carcinoembryonic antigen; CEA; Meconium antigen 100;
CD66e antigen), SEQ ID NO: 1451, referred to herein as the
previously known protein.
[2622] The sequence for protein Carcinoembryonic antigen-related
cell adhesion molecule 5 precursor (SEQ ID NO:1451) is given at the
end of the application, as "Carcinoembryonic antigen-related cell
adhesion molecule 5 precursor amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 908
TABLE-US-00960 TABLE 908 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 320 Missing
[2623] Protein Carcinoembryonic antigen-related cell adhesion
molecule 5 precursor (SEQ ID NO:1451) localization is believed to
be attached to the membrane by a GPI-anchor.
[2624] The previously known protein also has the following
indication(s) and/or potential therapeutic use(s): Cancer. It has
been investigated for clinical/therapeutic use in humans, for
example as a target for an antibody or small molecule, and/or as a
direct therapeutic; available information related to these
investigations is as follows. Potential pharmaceutically related or
therapeutically related activity or activities of the previously
known protein are as follows: Immunostimulant. A therapeutic role
for a protein represented by the cluster has been predicted. The
cluster was assigned this field because there was information in
the drug database or the public databases (e.g., described herein
above) that this protein, or part thereof, is used or can be used
for a potential therapeutic indication: Imaging agent; Anticancer;
Immunostimulant; Immunoconjugate; Monoclonal antibody, murine;
Antisense therapy; antibody.
[2625] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: integral plasma
membrane protein; membrane, which are annotation(s) related to
Cellular Component.
[2626] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2627] Cluster HUMCEA can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 33 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[2628] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 33 and Table 909. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues and pancreas carcinoma.
TABLE-US-00961 TABLE 909 Normal tissue distribution Name of Tissue
Number colon 1175 epithelial 92 general 29 head and neck 81 kidney
0 lung 0 lymph nodes 0 breast 0 pancreas 0 prostate 0 stomach
256
TABLE-US-00962 TABLE 910 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 colon 2.0e-01
2.7e-01 9.8e-01 0.5 1 0.5 epithelial 2.1e-03 2.7e-02 6.4e-04 1.4
2.1e-01 1.0 general 3.9e-08 8.2e-06 9.2e-18 3.2 1.3e-10 2.2 head
and neck 3.4e-01 5.0e-01 2.1e-01 1.8 5.6e-01 0.9 kidney 4.3e-01
5.3e-01 5.8e-01 2.1 7.0e-01 1.6 lung 1.3e-01 2.6e-01 1 1.1 1 1.1
lymph nodes 3.1e-01 5.7e-01 8.1e-02 6.0 3.3e-01 2.5 breast 3.8e-01
1.5e-01 1 1.0 6.8e-01 1.5 pancreas 2.2e-02 2.3e-02 1.4e-08 7.8
7.4e-07 6.4 prostate 5.3e-01 6.0e-01 3.0e-01 2.5 4.2e-01 2.0
stomach 1.5e-01 4.7e-01 8.9e-01 0.6 7.2e-01 0.4
[2629] For this cluster, at least one oligonucleotide was found to
demonstrate overexpression of the cluster, although not of at least
one transcript/segment as listed below. Microarray (chip) data is
also available for this cluster as follows. Various
oligonucleotides were tested for being differentially expressed in
various disease conditions, particularly cancer, as previously
described. The following oligonucleotides were found to hit this
cluster but not other segments/transcripts below (in relation to
lung cancer), shown in Table 911.
TABLE-US-00963 TABLE 911 Oligonucleotides related to this cluster
Overexpressed Chip Oligonucleotide name in cancers reference
HUMCEA_0_0_15168 lung malignant tumors LUN (SEQ ID NO: 243)
[2630] As noted above, cluster HUMCEA features 5 transcript(s),
which were listed in Table 905 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Carcinoembryonic
antigen-related cell adhesion molecule 5 precursor (SEQ ID
NO:1451). A description of each variant protein according to the
present invention is now provided.
[2631] Variant protein HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109). An alignment is given to the
known protein (Carcinoembryonic antigen-related cell adhesion
molecule 5 precursor (SEQ ID NO:1451)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2632] Comparison report between HUMCEA_PEA.sub.--1_P4 (SEQ ID
NO:1380) and CEA5_HUMAN (SEQ ID NO:1451):
[2633] 1. An isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILNVL corresponding to amino acids 1-234 of
CEA5_HUMAN (SEQ ID NO:1451), which also corresponds to amino acids
1-234 of HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), and a second amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG
SGSTPYDGRNR (SEQ ID NO: 1749) corresponding to amino acids 235-315
of HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2634] 2. An isolated polypeptide encoding for a tail of
HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
CEYICSSLAQAASPNPQGQRQDFSVPLRFKYTDPQPWTSRLSVTFCPRKTWADQVLTKNRRGGAASVLGG
SGSTPYDGRNR (SEQ ID NO: 1749) in HUMCEA_PEA.sub.--1_P4 (SEQ ID
NO:1380).
[2635] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2636] Variant protein HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 912, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein HUMCEA_PEA.sub.--1_P4
(SEQ ID NO:1380) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00964 TABLE 912 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
63 F -> L No 80 I -> V Yes 83 V -> A Yes 137 Q -> P Yes
173 D -> N No
[2637] The glycosylation sites of variant protein
HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380), as compared to the known
protein Carcinoembryonic antigen-related cell adhesion molecule 5
precursor (SEQ ID NO:1451), are described in Table 913 (given
according to their position(s) on the amino acid sequence in the
first column; the second column indicates whether the glycosylation
site is present in the variant protein; and the last column
indicates whether the position is different on the variant
protein).
TABLE-US-00965 TABLE 913 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 197 yes 197 466 no 360 no 288 no 665 no 560 no 650 no 480
no 104 yes 104 580 no 204 yes 204 115 yes 115 208 yes 208 152 yes
152 309 no 432 no 351 no 246 no 182 yes 182 612 no 256 no 508 no
330 no 274 no 292 no 553 no 529 no 375 no
[2638] Variant protein HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380) is
encoded by the following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ
ID NO:109), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109) is shown in bold; this coding
portion starts at position 115 and ends at position 1059. The
transcript also has the following SNPs as listed in Table 914
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMCEA_PEA.sub.--1_P4 (SEQ ID NO:1380) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00966 TABLE 914 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
49 T -> No 273 A -> C Yes 303 T -> G No 324 T -> C Yes
352 A -> G Yes 362 T -> C Yes 524 A -> C Yes 631 G -> A
No 1315 A -> G No 1380 T -> C No 1533 C -> A Yes 1706 G
-> A Yes 2308 T -> C No 2362 C -> T No 2455 A -> No
2504 C -> A Yes 2558 G -> No 2623 G -> No 2639 T -> A
No 2640 T -> A No 2832 G -> A Yes 2885 C -> T No 3396 A
-> G Yes 3562 C -> T Yes 3753 C -> T Yes
[2639] Variant protein HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110). An alignment is given to the
known protein (Carcinoembryonic antigen-related cell adhesion
molecule 5 precursor (SEQ ID NO:1451)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2640] Comparison report between HUMCEA_PEA.sub.--1_P5 (SEQ ID
NO:1381) and CEA5_HUMAN (SEQ ID NO:1451):
[2641] 1. An isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILNVLYGPDAPTISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFI
PNITVNNSGSYTCQAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWW
VNNQSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILNVLYGPDDPTISPSYTYYRP
GVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQANNSASGHSRTTVKTITVSAELP
KPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARAYVC
GIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAK-
I TPNNNGTYACFVSNLATGRNNSIVKSITVS corresponding to amino acids 1-675
of CEA5_HUMAN (SEQ ID NO:1451), which also corresponds to amino
acids 1-675 of HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO:
1750) corresponding to amino acids 676-719 of HUMCEA_PEA.sub.--1_P5
(SEQ ID NO:1381), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[2642] 2. An isolated polypeptide encoding for a tail of
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
GKWLPGASASYSGVESIWFSPKSQEDIFFPSLCSMGTRKSQILS (SEQ ID NO: 1750) in
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381).
[2643] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2644] Variant protein HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 915, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein HUMCEA_PEA.sub.--1_P5
(SEQ ID NO:1381) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00967 TABLE 915 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
63 F -> L No 80 I -> V Yes 83 V -> A Yes 137 Q -> P Yes
173 D -> N No 289 I -> T No 340 A -> D Yes 398 E -> K
Yes 647 P -> No 664 R -> S Yes
[2645] The glycosylation sites of variant protein
HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381), as compared to the known
protein Carcinoembryonic antigen-related cell adhesion molecule 5
precursor (SEQ ID NO:1451), are described in Table 916 (given
according to their position(s) on the amino acid sequence in the
first column; the second column indicates whether the glycosylation
site is present in the variant protein; and the last column
indicates whether the position is different on the variant
protein).
TABLE-US-00968 TABLE 916 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 197 yes 197 466 yes 466 360 yes 360 288 yes 288 665 yes
665 560 yes 560 650 yes 650 480 yes 480 104 yes 104 580 yes 580 204
yes 204 115 yes 115 208 yes 208 152 yes 152 309 yes 309 432 yes 432
351 yes 351 246 yes 246 182 yes 182 612 yes 612 256 yes 256 508 yes
508 330 yes 330 274 yes 274 292 yes 292 553 yes 553 529 yes 529 375
yes 375
[2646] Variant protein HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381) is
encoded by the following transcript(s): HUMCEA_PEA.sub.--1_T9 (SEQ
ID NO:110), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) is shown in bold; this coding
portion starts at position 115 and ends at position 2271. The
transcript also has the following SNPs as listed in Table 917
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMCEA_PEA.sub.--1_P5 (SEQ ID NO:1381) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00969 TABLE 917 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
49 T -> No 273 A -> C Yes 303 T -> G No 324 T -> C Yes
352 A -> G Yes 362 T -> C Yes 524 A -> C Yes 631 G -> A
No 915 A -> G No 980 T -> C No 1133 C -> A Yes 1306 G
-> A Yes 1908 T -> C No 1962 C -> T No 2055 A -> No
2104 C -> A Yes 3259 T -> C Yes
[2647] Variant protein HUMCEA_PEA.sub.--1_P14 (SEQ ID NO:1382)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMCEA_PEA.sub.--1_T20 (SEQ ID NO:111). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[2648] Variant protein HUMCEA_PEA.sub.--1_P14 (SEQ ID NO:1382) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 918, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein HUMCEA_PEA.sub.--1_P14
(SEQ ID NO:1382) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00970 TABLE 918 Amino acid mutations SNP position(s) on
amino acid Alternative Previously sequence amino acid(s) known SNP?
63 F -> L No 80 I -> V Yes 83 V -> A Yes 137 Q -> P Yes
173 D -> N No 289 I -> T No 340 A -> D Yes 398 E -> K
Yes
[2649] Variant protein HUMCEA_PEA.sub.--1_P14 (SEQ ID NO:1382) is
encoded by the following transcript(s): HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
HUMCEA_PEA.sub.--1_T20 (SEQ ID NO:111) is shown in bold; this
coding portion starts at position 115 and ends at position 1821.
The transcript also has the following SNPs as listed in Table 919
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMCEA_PEA.sub.--1_P14 (SEQ ID NO:1382) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00971 TABLE 919 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
49 T -> No 273 A -> C Yes 303 T -> G No 324 T -> C Yes
352 A -> G Yes 362 T -> C Yes 524 A -> C Yes 631 G -> A
No 915 A -> G No 980 T -> C No 1133 C -> A Yes 1306 G
-> A Yes
[2650] Variant protein HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112). An alignment is given to
the known protein (Carcinoembryonic antigen-related cell adhesion
molecule 5 precursor (SEQ ID NO:1451)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2651] Comparison report between HUMCEA_PEA.sub.--1_P19 (SEQ ID
NO:1383) and CEA5_HUMAN (SEQ ID NO:1451):
[2652] 1. An isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFYTLHVIKSDLVNEEATGQFRVYPEL
PKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWVNNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYK
CETQNPVSARRSDSVILN corresponding to amino acids 1-232 of CEA5_HUMAN
(SEQ ID NO:1451), which also corresponds to amino acids 1-232 of
HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), and a second amino acid
sequence being at least 90% homologous to
VLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNLA
TGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI corresponding to amino
acids 589-702 of CEA5_HUMAN (SEQ ID NO:1451), which also
corresponds to amino acids 233-346 of HUMCEA_PEA.sub.--1_P19 (SEQ
ID NO:1383), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[2653] 2. An isolated chimeric polypeptide encoding for an edge
portion of HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise NV, having a structure as follows: a
sequence starting from any of amino acid numbers 232-x to 232; and
ending at any of amino acid numbers 233+((n-2)-x), in which x
varies from 0 to n-2.
[2654] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because of manual inspection of known
protein localization and/or gene structure.
[2655] Variant protein HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 920, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein HUMCEA_PEA.sub.--1_P19
(SEQ ID NO:1383) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00972 TABLE 920 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
63 F -> L No 80 I -> V Yes 83 V -> A Yes 137 Q -> P Yes
173 D -> N No 291 P -> No 308 R -> S Yes 326 G ->
No
[2656] The glycosylation sites of variant protein
HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383), as compared to the known
protein Carcinoembryonic antigen-related cell adhesion molecule 5
precursor (SEQ ID NO:1451), are described in Table 921 (given
according to their position(s) on the amino acid sequence in the
first column; the second column indicates whether the glycosylation
site is present in the variant protein; and the last column
indicates whether the position is different on the variant
protein).
TABLE-US-00973 TABLE 921 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 197 yes 197 466 no 360 no 288 no 665 yes 309 560 no 650
yes 294 480 no 104 yes 104 580 no 204 yes 204 115 yes 115 208 yes
208 152 yes 152 309 no 432 no 351 no 246 no 182 yes 182 612 yes 256
256 no 508 no 330 no 274 no 292 no 553 no 529 no 375 no
[2657] Variant protein HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383) is
encoded by the following transcript(s): HUMCEA_PEA.sub.--1_T25 (SEQ
ID NO:112), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) is shown in bold; this
coding portion starts at position 115 and ends at position 1152.
The transcript also has the following SNPs as listed in Table 922
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMCEA_PEA.sub.--1_P19 (SEQ ID NO:1383) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00974 TABLE 922 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
49 T -> No 273 A -> C Yes 303 T -> G No 324 T -> C Yes
352 A -> G Yes 362 T -> C Yes 524 A -> C Yes 631 G -> A
No 840 T -> C No 894 C -> T No 987 A -> No 1036 C -> A
Yes 1090 G -> No 1155 G -> No 1171 T -> A No 1172 T ->
A No 1364 G -> A Yes 1417 C -> T No 1928 A -> G Yes 2094 C
-> T Yes 2285 C -> T Yes
[2658] Variant protein HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113). An alignment is given to
the known protein (Carcinoembryonic antigen-related cell adhesion
molecule 5 precursor (SEQ ID NO:1451)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2659] Comparison report between HUMCEA_PEA.sub.--1_P20 (SEQ ID
NO:1384) and CEA5_HUMAN (SEQ ID NO:1451):
[2660] 1. An isolated chimeric polypeptide encoding for
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), comprising a first amino
acid sequence being at least 90% homologous to
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQHLFGYSWYKGE
RVDGNRQIIGYVIGTQQATPGPAYSGREHYPNASLLIQNHQNDTGFYTLHVIKSDLVNEEATGQFRVYP
corresponding to amino acids 1-142 of CEA5_HUMAN (SEQ ID NO:1451),
which also corresponds to amino acids 1-142 of
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), and a second amino acid
sequence being at least 90% homologous to
ELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQSLPVSPRLQLSNGNRTLTLFNVTRNDARA
YVCGIQNSVSANRSDPVTLDVLYGPDTPIISPPDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLF
IAKITPNNNGTYACFVSNLATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
corresponding to amino acids 499-702 of CEA5_HUMAN (SEQ ID
NO:1451), which also corresponds to amino acids 143-346 of
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[2661] 2. An isolated chimeric polypeptide encoding for an edge
portion of HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise PE, having a structure as follows: a
sequence starting from any of amino acid numbers 142-x to 142; and
ending at any of amino acid numbers 143+((n-2)-x), in which x
varies from 0 to n-2.
[2662] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because of manual inspection of known
protein localization and/or gene structure.
[2663] Variant protein HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 923, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein HUMCEA_PEA.sub.--1_P20
(SEQ ID NO:1384) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-00975 TABLE 923 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
63 F -> L No 80 I -> V Yes 83 V -> A Yes 137 Q -> P Yes
291 P -> No 308 R -> S Yes 326 G -> No
[2664] The glycosylation sites of variant protein
HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384), as compared to the known
protein Carcinoembryonic antigen-related cell adhesion molecule 5
precursor (SEQ ID NO:1451), are described in Table 924 (given
according to their position(s) on the amino acid sequence in the
first column; the second column indicates whether the glycosylation
site is present in the variant protein; and the last column
indicates whether the position is different on the variant
protein).
TABLE-US-00976 TABLE 924 Glycosylation site(s) Position(s) on known
Present in Position in amino acid sequence variant protein? variant
protein? 197 no 466 no 360 no 288 no 665 yes 309 560 yes 204 650
yes 294 480 no 104 yes 104 580 yes 224 204 no 115 yes 115 208 no
152 no 309 no 432 no 351 no 246 no 182 no 612 yes 256 256 no 508
yes 152 330 no 274 no 292 no 553 yes 197 529 yes 173 375 no
[2665] Variant protein HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384) is
encoded by the following transcript(s): HUMCEA_PEA.sub.--1_T26 (SEQ
ID NO:113), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113) is shown in bold; this
coding portion starts at position 115 and ends at position 1152.
The transcript also has the following SNPs as listed in Table 925
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMCEA_PEA.sub.--1_P20 (SEQ ID NO:1384) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-00977 TABLE 925 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
49 T -> No 273 A -> C Yes 303 T -> G No 324 T -> C Yes
352 A -> G Yes 362 T -> C Yes 524 A -> C Yes 840 T -> C
No 894 C -> T No 987 A -> No 1036 C -> A Yes 1090 G ->
No 1155 G -> No 1171 T -> A No 1172 T -> A No 1364 G ->
A Yes 1417 C -> T No 1928 A -> G Yes 2094 C -> T Yes 2285
C -> T Yes
[2666] As noted above, cluster HUMCEA features 42 segment(s), which
were listed in Table 906 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2667] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:814) according to the present invention is supported by 56
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111), HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and
HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113). Table 926 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00978 TABLE 926 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1 178 HUMCEA_PEA_1_T9 (SEQ ID NO:
110) 1 178 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1 178 HUMCEA_PEA_1_T25
(SEQ ID NO: 112) 1 178 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1 178
[2668] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:815) according to the present invention is supported by 83
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111), HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and
HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113). Table 927 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00979 TABLE 927 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 179 456 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 179 456 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 179 456
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 179 456 HUMCEA_PEA_1_T26 (SEQ ID
NO: 113) 179 456
[2669] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:816) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109). Table 928
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00980 TABLE 928 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 818 1217
[2670] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 929.
TABLE-US-00981 TABLE 929 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
HUMCEA_0_0_96 lung malignant tumors LUN (SEQ ID NO: 240)
[2671] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:817) according to the present invention is supported by 83
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 930 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00982 TABLE 930 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1218 1472 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 818 1072 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 818 1072
[2672] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:818) according to the present invention is supported by 87
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 931 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00983 TABLE 931 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1817 2006 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1417 1606 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1417 1606
[2673] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:819) according to the present invention is supported by 94
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 932 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00984 TABLE 932 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2159 2285 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1759 1885 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 691 817
[2674] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--44 (SEQ ID
NO:820) according to the present invention is supported by 112
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T25 (SEQ
ID NO:112) and HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113). Table 933
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00985 TABLE 933 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2286 2540 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1886 2140 HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 818 1072
HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 818 1072
[2675] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--46 (SEQ ID
NO:821) according to the present invention is supported by 15
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110). Table 934
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00986 TABLE 934 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T9 (SEQ ID NO: 110) 2174 3347
[2676] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--63 (SEQ ID
NO:822) according to the present invention is supported by 68
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 935 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00987 TABLE 935 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2957 3135 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1489 1667 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1489 1667
[2677] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--65 (SEQ ID
NO:823) according to the present invention is supported by 54
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 936 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00988 TABLE 936 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 3166 3897 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1698 2429 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1698 2429
[2678] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--67 (SEQ ID
NO:824) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T20 (SEQ ID NO:111). Table 937
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00989 TABLE 937 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1607 1886
[2679] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2680] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:825) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111), HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and
HUMCEA_PEA.sub.--1_T26 (SEQ ID NO:113). Table 938 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-00990 TABLE 938 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 457 538 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 457 538 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 457 538
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 457 538 HUMCEA_PEA_1_T26 (SEQ ID
NO: 113) 457 538
[2681] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:826) according to the present invention is supported by 73
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111) and HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112). Table 939
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00991 TABLE 939 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 539 642 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 539 642 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 539 642
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 539 642
[2682] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:827) according to me present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111) and HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112). Table 940
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00992 TABLE 940 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 643 690 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 643 690 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 643 690
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 643 690
[2683] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:828) according to the present invention is supported by 71
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111) and HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112). Table 941
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00993 TABLE 941 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 691 738 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 691 738 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 691 738
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 691 738
[2684] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:829) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110), HUMCEA_PEA.sub.--1_T20 (SEQ
ID NO:111) and HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112). Table 942
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-00994 TABLE 942 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 739 817 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 739 817 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 739 817
HUMCEA_PEA_1_T25 (SEQ ID NO: 112) 739 817
[2685] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:830) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 943 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00995 TABLE 943 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1473 1475 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1073 1075 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1073 1075
[2686] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:831) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 944 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00996 TABLE 944 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1476 1481 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1076 1081 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1076 1081
[2687] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:832) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 945 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00997 TABLE 945 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1482 1488 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1082 1088 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1082 1088
[2688] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:833) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 946 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00998 TABLE 946 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1489 1506 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1089 1106 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1089 1106
[2689] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:834) according to the present invention is supported by 69
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 947 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-00999 TABLE 947 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1507 1576 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1107 1176 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1107 1176
[2690] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:835) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 948 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01000 TABLE 948 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1577 1600 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1177 1200 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1177 1200
[2691] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:836) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 949 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01001 TABLE 949 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1601 1624 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1201 1224 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1201 1224
[2692] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:837) according to the present invention is supported by 77
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 950 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01002 TABLE 950 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1625 1702 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1225 1302 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1225 1302
[2693] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:838) according to the present invention is supported by 72
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 951 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01003 TABLE 951 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1703 1732 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1303 1332 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1303 1332
[2694] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:839) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 952 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01004 TABLE 952 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1733 1751 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1333 1351 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1333 1351
[2695] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:840) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20 (SEQ ID
NO:111). Table 953 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01005 TABLE 953 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1752 1770 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1352 1370 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1352 1370
[2696] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:841) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 954 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01006 TABLE 954 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1771 1788 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1371 1388 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1371 1388
[2697] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:842) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T20
(SEQ ID NO:111). Table 955 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01007 TABLE 955 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 1789 1816 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1389 1416 HUMCEA_PEA_1_T20 (SEQ ID NO: 111) 1389 1416
[2698] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:843) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 956 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01008 TABLE 956 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2007 2028 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1607 1628 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 539 560
[2699] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:844) according to the present invention is supported by 80
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 957 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01009 TABLE 957 Segment location on transcripts Segment
Segment starting end ing Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2029 2110 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1629 1710 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 561 642
[2700] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:845) according to the present invention is supported by 75
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 958 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01010 TABLE 958 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2111 2158 HUMCEA_PEA_1_T9 (SEQ ID
NO: 110) 1711 1758 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 643 690
[2701] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--45 (SEQ ID
NO:846) according to the present invention is supported by 9
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T9 (SEQ ID NO:110). Table 959
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01011 TABLE 959 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T9 (SEQ ID NO: 110) 2141 2173
[2702] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--50 (SEQ ID
NO:847) according to the present invention is supported by 64
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 960 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01012 TABLE 960 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2541 2567 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1073 1099 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1073 1099
[2703] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--51 (SEQ ID
NO:848) according to the present invention is supported by 88
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 961 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01013 TABLE 961 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2568 2659 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1100 1191 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1100 1191
[2704] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--56 (SEQ ID
NO:849) according to the present invention supported by 75
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 962 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01014 TABLE 962 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2660 2685 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1192 1217 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1192 1217
[2705] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--57 (SEQ ID
NO:850) according to the present invention is supported by 82
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 963 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01015 TABLE 963 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2686 2786 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1218 1318 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1218 1318
[2706] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--58 (SEQ ID
NO:851) according to the present invention is supported by 63
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 964 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01016 TABLE 964 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2787 2820 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1319 1352 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1319 1352
[2707] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--60 (SEQ ID
NO:852) according to the present invention is supported by 55
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1 T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 965 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01017 TABLE 965 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2821 2864 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1353 1396 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1353 1396
[2708] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--61 (SEQ ID
NO:853) according to the present invention can be found in the
following transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 966 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01018 TABLE 966 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2865 2868 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1397 1400 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1397 1400
[2709] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--62 (SEQ ID
NO:854) according to the present invention is supported by 60
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 967 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01019 TABLE 967 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 2869 2956 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1401 1488 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1401 1488
[2710] Segment cluster HUMCEA_PEA.sub.--1_node.sub.--64 (SEQ ID
NO:855) according to the present invention is supported by 45
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMCEA_PEA.sub.--1_T8 (SEQ ID NO:109),
HUMCEA_PEA.sub.--1_T25 (SEQ ID NO:112) and HUMCEA_PEA.sub.--1_T26
(SEQ ID NO:113). Table 968 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01020 TABLE 968 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMCEA_PEA_1_T8 (SEQ ID NO: 109) 3136 3165 HUMCEA_PEA_1_T25 (SEQ ID
NO: 112) 1668 1697 HUMCEA_PEA_1_T26 (SEQ ID NO: 113) 1668 1697
Variant Protein Alignment to the Previously Known Protein:
TABLE-US-01021 [2711] Sequence name: CEA5_HUMAN (SEQ ID NO: 1451)
Sequence documentation: Alignment of: HUMCEA_PEA_1_P4 (SEQ ID NO:
1380) .times. CEA5_HUMAN (SEQ ID NO: 1451) Alignment segment 1/1:
Quality: 2320.00 Escore: 0 Matching length: 234 Total length: 234
Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00695## ##STR00696## ##STR00697##
##STR00698## ##STR00699## Sequence name: CEA5_HUMAN (SEQ ID NO:
1451) Sequence documentation: Alignment of: HUMCEA_PEA_1_P5 (SEQ ID
NO: 1381) .times. CEA5_HUMAN (SEQ ID NO: 1451) Alignment segment
1/1: Quality: 6692.00 Escore: 0 Matching length: 675 Total length:
675 Matching Percent Similarity: 100.00 Matching Percent Identity:
100.00 Total Percent Similarity: 100.00 Total Percent Identity:
100.00 Gaps: 0 Alignment: ##STR00700## ##STR00701## ##STR00702##
##STR00703## ##STR00704## ##STR00705## ##STR00706## ##STR00707##
##STR00708## ##STR00709## ##STR00710## ##STR00711## ##STR00712##
##STR00713## ##STR00714## Sequence name: CEA5_HUMAN (SEQ ID NO:
1451) Sequence documentation: Alignment of: HUMCEA_PEA_1_P19 (SEQ
ID NO: 1383) .times. CEA5_HUMAN (SEQ ID NO: 1451) . . . Alignment
segment 1/1: Quality: 3298.00 Escore: 0 Matching length: 346 Total
length: 702 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 49.29 Total Percent
Identity: 49.29 Gaps: 1 Alignment: ##STR00715## ##STR00716##
##STR00717## ##STR00718## ##STR00719## ##STR00720## ##STR00721##
##STR00722## ##STR00723## Sequence name: CEA5_HUMAN (SEQ ID NO:
1451) Sequence documentation: Alignment of: HUMCEA_PEA_1_P20 (SEQ
ID NO: 1384) .times. CEA5_HUMAN (SEQ ID NO: 1451) . . . Alignment
segment 1/1: Quality: 3294.00 Escore: 0 Matching length: 346 Total
length: 702 Matching Percent Similarity: 100.00 Matching Percent
Identity: 100.00 Total Percent Similarity: 49.29 Total Percent
Identity: 49.29 Gaps: 1 Alignment: ##STR00724## ##STR00725##
##STR00726## ##STR00727## ##STR00728## ##STR00729## ##STR00730##
##STR00731## ##STR00732##
Description for Cluster R35137
[2712] Cluster R35137 features 6 transcript(s) and 20 segment(s) of
interest, the names for which are given in Tables 969 and 970,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
971.
TABLE-US-01022 TABLE 969 Transcripts of interest Transcript Name
Sequence ID No. R35137_PEA_1_PEA_1_PEA_1_T3 114
R35137_PEA_1_PEA_1_PEA_1_T5 115 R35137_PEA_1_PEA_1_PEA_1_T10 116
R35137_PEA_1_PEA_1_PEA_1_T11 117 R35137_PEA_1_PEA_1_PEA_1_T12 118
R35137_PEA_1_PEA_1_PEA_1_T14 119
TABLE-US-01023 TABLE 970 Segments of interest Segment Name Sequence
ID No. R35137_PEA_1_PEA_1_PEA_1_node_2 856
R35137_PEA_1_PEA_1_PEA_1_node_3 857 R35137_PEA_1_PEA_1_PEA_1_node_9
858 R35137_PEA_1_PEA_1_PEA_1_node_11 859
R35137_PEA_1_PEA_1_PEA_1_node_16 860
R35137_PEA_1_PEA_1_PEA_1_node_18 861
R35137_PEA_1_PEA_1_PEA_1_node_20 862
R35137_PEA_1_PEA_1_PEA_1_node_27 863
R35137_PEA_1_PEA_1_PEA_1_node_5 864 R35137_PEA_1_PEA_1_PEA_1_node_7
865 R35137_PEA_1_PEA_1_PEA_1_node_12 866
R35137_PEA_1_PEA_1_PEA_1_node_14 867
R35137_PEA_1_PEA_1_PEA_1_node_15 868
R35137_PEA_1_PEA_1_PEA_1_node_17 869
R35137_PEA_1_PEA_1_PEA_1_node_21 870
R35137_PEA_1_PEA_1_PEA_1_node_22 871
R35137_PEA_1_PEA_1_PEA_1_node_23 872
R35137_PEA_1_PEA_1_PEA_1_node_24 873
R35137_PEA_1_PEA_1_PEA_1_node_25 874
R35137_PEA_1_PEA_1_PEA_1_node_26 875
TABLE-US-01024 TABLE 971 Proteins of interest Sequence ID Protein
Name No. Corresponding Transcript(s) R35137_PEA_1_PEA_1_PEA_1_P9
1385 R35137_PEA_1_PEA_1_PEA_1_T10 (SEQ ID NO: 116);
R35137_PEA_1_PEA_1_PEA_1_T12 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_P8 1386 R35137_PEA_1_PEA_1_PEA_1_T11 (SEQ
ID NO: 117) R35137_PEA_1_PEA_1_PEA_1_P11 1387
R35137_PEA_1_PEA_1_PEA_1_T14 (SEQ ID NO: 119)
R35137_PEA_1_PEA_1_PEA_1_P2 1388 R35137_PEA_1_PEA_1_PEA_1_T3 (SEQ
ID NO: 114) R35137_PEA_1_PEA_1_PEA_1_P4 1389
R35137_PEA_1_PEA_1_PEA_1_T5 (SEQ ID NO: 115)
[2713] These sequences are variants of the known protein Alanine
aminotransferase (SwissProt accession identifier ALAT_HUMAN; known
also according to the synonyms EC 2.6.1.2; Glutamic-pyruvic
transaminase; GPT; Glutamic-alanine transaminase), SEQ ID NO: 1452,
referred to herein as the previously known protein.
[2714] Protein Alanine aminotransferase (SEQ ID NO:1452) is known
or believed to have the following function(s): Participates in
cellular nitrogen metabolism and also in liver gluconeogenesis
starting with precursors transported from skeletal muscles. The
sequence for protein Alanine aminotransferase is given at the end
of the application, as "Alanine aminotransferase amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 972.
TABLE-US-01025 TABLE 972 Amino acid mutations for Known Protein SNP
position(s) on amino acid sequence Comment 13 H -> N (in allele
GPT*2; dbSNP: 1063739). /FTId = VAR_000561. 3-6 STGD -> RRGN 38
G -> S 221 A -> H
[2715] Protein Alanine Aminotransferase (SEQ ID NO:1452)
Localization is Believed to be Cytoplasmic.
[2716] Cluster R35137 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 34 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[2717] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 34 and Table 973. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: hepatocellular carcinoma.
TABLE-US-01026 TABLE 973 Normal tissue distribution Name of Tissue
Number brain 12 epithelial 16 general 8 kidney 20 liver 0 lung 0
pancreas 2 prostate 0
TABLE-US-01027 TABLE 974 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 brain 3.2e-01
4.8e-01 1.8e-01 2.5 4.2e-01 1.5 epithelial 7.6e-01 7.7e-01 8.9e-01
0.5 9.8e-01 0.4 general 6.7e-01 8.2e-01 4.2e-01 1.0 8.5e-01 0.7
kidney 8.6e-01 9.0e-01 5.8e-01 0.9 7.0e-01 0.8 liver 1.8e-01
4.5e-01 3.0e-03 7.6 1.6e-01 2.3 lung 1 6.3e-01 1 1.0 6.2e-01 1.6
pancreas 2.3e-01 4.0e-01 1.8e-01 3.1 2.8e-01 2.3 prostate 1 7.8e-01
1 1.0 7.5e-01 1.3
[2718] As noted above, cluster 835137 features 6 transcript(s),
which were listed in Table 969 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Alanine
aminotransferase (SEQ ID NO:1452). A description of each variant
protein according to the present invention is now provided.
[2719] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R35137PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID NO:116). An
alignment is given to the known protein (Alanine aminotransferase
(SEQ ID NO:1452)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[2720] Comparison report between
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385) and
ALAT_HUMAN_V1 (SEQ ID NO: 1453):
[2721] 1. An isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEV
corresponding to amino acids 1-274 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-274 of R35137
_PEA .sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
AYEAGGGSRAMARPSSPDGPPPPPHLTWPCAGAGSAAAMWRW (SEQ ID NO: 1737)
corresponding to amino acids 275-385 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2722] 2. An isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
AYEAGGGSRAMARPSSPDGPPPPPHLTWPCAGAGSAAAMWRW (SEQ ID NO: 1737) in
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385).
[2723] It should be noted that the known protein sequence (ALAI
HUMAN (SEQ ID NO:1452)) has one or more changes than the sequence
given at the end of the application and named as being the amino
acid sequence for ALAT_HUMAN_V1 (SEQ ID NO:1453). These changes
were previously known to occur and are listed in the table
below.
TABLE-US-01028 TABLE 975 Changes to ALAT_HUMAN_V1 (SEQ ID NO: 1453)
SNP position(s) on amino acid sequence Type of change 1 init_met
222 conflict
[2724] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2725] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385) is
encoded by the following transcript(s):
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID NO:116), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID NO:116) is
shown in bold; this coding portion starts at position 271 and ends
at position 1425. The transcript also has the following SNPs as
listed in Table 976 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P9 (SEQ ID NO:1385)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01029 TABLE 976 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
230 C -> T No 231 C -> T No 310 C -> A Yes 432 G -> No
969 C -> No 1225 G -> No 1745 T -> G No 1957 C -> No
2018 G -> A No 2019 C -> A No 2101 A -> G No 2102 A ->
G No 2159 C -> T Yes 2710 G -> C No 2789 C -> A Yes 3622 G
-> A Yes
[2726] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID NO:117). An
alignment is given to the known protein (Alanine aminotransferase
(SEQ ID NO:1452)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[2727] Comparison report between
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386) and
ALAT_HUMAN_V1 (SEQ ID NO:1453):
[2728] 1. An isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEVYQDNVYAAG
SQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGEC corresponding to amino acids
1-320 of ALAT_HUMAN_V1 (SEQ ID NO:1453), which also corresponds to
amino acids 1-320 of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8
(SEQ ID NO:1386), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence VRTRRVGARGPWPGPPRPMGHPLLRT
(SEQ ID NO: 1738) corresponding to amino acids 321-346 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2729] 2. An isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence VRTRRVGARGPWPGPPRPMGHPLLRT (SEQ ID NO: 1738) in
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386).
[2730] It should be noted that the known protein sequence
(ALAT_HUMAN (SEQ ID NO:1452)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ALAT_HUMAN_V1 (SEQ ID NO:1453). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-01030 TABLE 977 Changes to ALAT_HUMAN_V1 (SEQ ID NO: 1453)
SNP position(s) on amino acid sequence Type of change 1 init_met
222 conflict
[2731] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2732] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 978, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01031 TABLE 978 Amino acid mutations SNP position(s) on
amino Alternative Previously acid sequence amino acid(s) known SNP?
14 H -> N Yes 54 Q -> No 233 R -> No 296 M -> No
[2733] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386) is
encoded by the following transcript(s):
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID NO:117), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID NO:117) is
shown in bold; this coding portion starts at position 271 and ends
at position 1308. The transcript also has the following SNPs as
listed in Table 979 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P8 (SEQ ID NO:1386)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01032 TABLE 979 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
230 C -> T No 231 C -> T No 310 C -> A Yes 432 G -> No
969 C -> No 1158 G -> No 1752 T -> G No 2030 C -> No
2091 G -> A No 2092 C -> A No 2174 A -> G No 2175 A ->
G No 2232 C -> T Yes 2783 G -> C No 2862 C -> A Yes 3695 G
-> A Yes
[2734] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:119). An
alignment is given to the known protein (Alanine aminotransferase
(SEQ ID NO:1452)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[2735] Comparison report between
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387) and
ALAT_HUMAN_V1 (SEQ ID NO:1453):
[2736] 1. An isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQAR corresponding to amino acids 1-229 of
ALAT_HUMAN_V1 (SEQ ID NO:1453), which also corresponds to amino
acids 1-229 of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ
ID NO:1387), and a second amino acid sequence being at least 90%
homologous to SGFGQREGTYHFRMTILPPLEKLRLLLEKLSRFHAKFTLEYS
corresponding to amino acids 455-496 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 230-271 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2737] 2. An isolated chimeric polypeptide encoding for an edge
portion of R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID
NO:1387), comprising a polypeptide having a length "n", wherein n
is at least about 10 amino acids in length, optionally at least
about 20 amino acids in length, preferably at least about 30 amino
acids in length, more preferably at least about 40 amino acids in
length and most preferably at least about 50 amino acids in length,
wherein at least two amino acids comprise RS, having a structure as
follows: a sequence starting from any of amino acid numbers 229-x
to 229; and ending at any of amino acid numbers 230+((n-2)-x), in
which x varies from 0 to n-2.
[2738] It should be noted that the known protein sequence
(ALAT_HUMAN (SEQ ID NO:1452)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ALAT_HUMAN_V1 (SEQ ID NO:1453). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-01033 TABLE 980 Changes to ALAT_HUMAN_V1 (SEQ ID NO: 1453)
SNP position(s) on amino acid sequence Type of change 1 init_met
222 conflict
[2739] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2740] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 981, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01034 TABLE 981 Amino acid mutations SNP position(s) on
amino Alternative Previously acidsequence amino acid(s) known SNP?
14 H -> N Yes 54 Q -> No
[2741] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387) is
encoded by the following transcript(s):
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:119), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:119) is
shown in bold; this coding portion starts at position 271 and ends
at position 1083. The transcript also has the following SNPs as
listed in Table 982 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P11 (SEQ ID NO:1387)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01035 TABLE 982 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
230 C -> T No 231 C -> T No 310 C -> A Yes 432 G -> No
1115 C -> No 1176 G -> A No 1177 C -> A No
[2742] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R35137 _PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ ID NO:114). An
alignment is given to the known protein (Alanine aminotransferase
(SEQ ID NO:1452)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[2743] Comparison report between
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388) and
ALAT_HUMAN_V1 (SEQ ID NO:1453):
[2744] 1. An isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEV
corresponding to amino acids 1-274 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-274 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
VPRRLCGGGEHGRCSAAADAEADECAAVPAGARTGPAGPGGQPARAHRPLLCAVPG (SEQ ID
NO: 1739) corresponding to amino acids 275-399 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2745] 2. An isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
RGAGEREAGQQSAPVTPCALPGVPGQRVRRGFAVPLIQEGAHGDGAALRRAAGACLLPLHLQGLHGRVR
VPRRLCGGGEHGRCSAAADAEADECAAVPAGARTGPAGPGGQPARAHRPLLCAVPG (SEQ ID
NO: 1739) in R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID
NO:1388).
[2746] It should be noted that the known protein sequence
(ALA_HUMAN (SEQ ID NO:1452)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ALAT_HUMAN_V1 (SEQ ID NO:1453). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-01036 TABLE 983 Changes to ALAT_HUMAN_V1 (SEQ ID NO: 1453)
SNP position(s) on amino acid sequence Type of change 1 init_met
222 conflict
[2747] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2748] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 984, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01037 TABLE 984 Amino acid mutations SNP position(s) on
amino Alternative Previously acid sequence amino acid(s) known SNP?
14 H -> N Yes 54 Q -> No 233 R -> No 319 G -> No
[2749] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388) is
encoded by the following transcript(s):
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ ID NO:114), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ ID NO:114) is
shown in bold; this coding portion starts at position 271 and ends
at position 1467. The transcript also has the following SNPs as
listed in Table 985 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P2 (SEQ ID NO:1388)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01038 TABLE 985 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
230 C -> T No 231 C -> T No 310 C -> A Yes 432 G -> No
969 C -> No 1225 G -> No 1645 T -> G No 1857 C -> No
1918 G -> A No 1919 C -> A No 2001 A -> G No 2002 A ->
G No 2059 C -> T Yes 2610 G -> C No 2689 C -> A Yes 3522 G
-> A Yes
[2750] Variant protein R35137
_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389) according
to the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s)
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID NO:115). An
alignment is given to the known protein (Alanine aminotransferase
(SEQ ID NO:1452)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[2751] Comparison report between
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389) and
ALAT_HUMAN_V1 (SEQ ID NO:1453):
[2752] 1. An isolated chimeric polypeptide encoding for
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
comprising a first amino acid sequence being at least 90%
homologous to
MASSTGDRSQAVRHGLRAKVLTLDGMNPRVRRVEYAVRGPIVQRALELEQELRQGVKKPFTEVIRANIGD
AQAMGQRPITFLRQVLALCVNPDLLSSPNFPDDAKKRAERILQACGGHSLGAYSVSSGIQLIREDVARYIER
RDGGIPADPNNVFLSTGASDAIVTVLKLLVAGEGHTRTGVLIPIPQYPLYSATLAELGAVQVDYYLDEERA
WALDVAELHRALGQARDHCRPRALCVINPGNPTGQVQTRECIEAVIRFAFEERLFLLADEVYQDNVYAAG
SQFHSFKKVLMEMGPPYAGQQELASFHSTSKGYMGECGFRGGYVEVVNMDAAVQQQMLKLMSVRLCPP
VPGQALLDLVVSPPAPTDPSFAQFQAEKQAVLAELAAKAKLTEQVFNEAPGISCNPVQGAMYSFPRVQLP
PRAVERAQELGLAPDMFFCLRLLEETGICVVPGSGFGQREGTYHFRMTILPPLEKLRLLLEKLSRFHAKFTL
E corresponding to amino acids 1-494 of ALAT_HUMAN_V1 (SEQ ID
NO:1453), which also corresponds to amino acids 1-494 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389), and
a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence
SPGRLWSPLYLLLMPGGVGWGGCWAPASLQVPNKAVWQSDSKKEALAAAWPAPTCLPFLQA (SEQ
ID NO: 1740) corresponding to amino acids 495-555 of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[2753] 2. An isolated polypeptide encoding for a tail of
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389),
comprising a polypeptide being at least 70%, optionally at least
about 80%, preferably at least about 85%, more preferably at least
about 90% and most preferably at least about 95% homologous to the
sequence
SPGRLWSPLYLLLMPGGVGWGGCWAPASLQVPNKAVWQSDSKKEALAAAWPAPTCLPFLQA (SEQ
ID NO: 1740) in R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ
ID NO:1389).
[2754] It should be noted that the known protein sequence
(ALAT_HUMAN (SEQ ID NO:1452)) has one or more changes than the
sequence given at the end of the application and named as being the
amino acid sequence for ALAT_HUMAN_V1 (SEQ ID NO:1453). These
changes were previously known to occur and are listed in the table
below.
TABLE-US-01039 TABLE 986 Changes to ALAT_HUMAN_V1 (SEQ ID NO: 1453)
SNP position(s) on amino acid sequence Type of change 1 init_met
222 conflict
[2755] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: intracellularly. The protein localization
is believed to be intracellularly because neither of the
trans-membrane region prediction programs predicted a
trans-membrane region for this protein. In addition both
signal-peptide prediction programs predict that this protein is a
non-secreted protein.
[2756] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 987, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01040 TABLE 987 Amino acid mutations SNP position(s) on
amino Alternative Previously acid sequence amino acid(s) known SNP?
14 H -> N Yes 54 Q -> No 233 R -> No 296 M -> No 436 D
-> E No 508 M -> I No 509 P -> T No 536 K -> R No
[2757] Variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389) is
encoded by the following transcript(s):
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID NO:115), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID NO:115) is
shown in bold; this coding portion starts at position 271 and ends
at position 1935. The transcript also has the following SNPs as
listed in Table 988 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_P4 (SEQ ID NO:1389)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01041 TABLE 988 Nucleic acid SNPs SNP position on
nucleotide Alternative Previously sequence nucleic acid known SNP?
230 C -> T No 231 C -> T No 310 C -> A Yes 432 G -> No
969 C -> No 1158 G -> No 1578 T -> G No 1794 G -> A No
1795 C -> A No 1877 A -> G No 1878 A -> G No 1935 C ->
T Yes 2486 G -> C No 2565 C -> A Yes 3398 G -> A Yes
[2758] As noted above, cluster R35137 features 20 segment(s), which
were listed in Table 970 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2759] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:856) according to the present invention is supported by 19
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 989 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01042 TABLE 989 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R35137_PEA_1_PEA_1_PEA_1_T3 1 266 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1 266 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1 266 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1 266 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1 266 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 1 266 (SEQ ID NO: 119)
[2760] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:857) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 990 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01043 TABLE 990 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 267 432 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 267 432 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 267 432 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 267 432 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 267 432 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 267 432 (SEQ ID NO: 119)
[2761] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--9 (SEQ ID
NO:858) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 991 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01044 TABLE 991 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 632 765 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 632 765 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 632 765 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 632 765 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 632 765 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 632 765 (SEQ ID NO: 119)
[2762] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:859) according to the present invention is supported by 30
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 992 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01045 TABLE 992 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 766 955 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 766 955 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 766 955 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 766 955 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 766 955 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 766 955 (SEQ ID NO: 119)
[2763] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:860) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 993 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01046 TABLE 993 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1157 1293 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1090 1226 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1157 1293 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1090 1226 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1157 1293 (SEQ ID NO: 118)
[2764] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:861) according to the present invention is supported by 24
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 994 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01047 TABLE 994 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1294 1468 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1227 1401 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1394 1568 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1327 1501 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1394 1568 (SEQ ID NO: 118)
[2765] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment (in
relation to lung cancer), shown in Table 995.
TABLE-US-01048 TABLE 995 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference
R35137_0_5_0 lung malignant tumors LUN (SEQ ID NO: 245)
[2766] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:862) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 996 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01049 TABLE 996 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1469 1624 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1402 1557 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1569 1724 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1502 1657 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1569 1724 (SEQ ID NO: 118)
[2767] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:863) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 997 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01050 TABLE 997 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1876 3898 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1752 3774 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1976 3998 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 2049 4071 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 2116 4138 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 1134 1250 (SEQ ID NO: 119)
[2768] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2769] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:864) according to the present invention is supported by 20
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 998 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01051 TABLE 998 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 433 522 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 433 522 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 433 522 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 433 522 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 433 522 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 433 522 (SEQ ID NO: 119)
[2770] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:865) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 999 below describes the starting and ending position
of this segment on each transcript.
TABLE-US-01052 TABLE 999 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 523 631 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 523 631 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 523 631 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 523 631 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 523 631 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 523 631 (SEQ ID NO: 119)
[2771] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:866) according to the present invention is supported by 22
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 1000 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01053 TABLE 1000 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R35137_PEA_1_PEA_1_PEA_1_T3 956 1009 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 956 1009 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 956 1009 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 956 1009 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 956 1009 (SEQ ID NO: 118)
[2772] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--14 (SEQ ID
NO:867) according to the present invention is supported by 23
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 1001 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01054 TABLE 1001 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R35137_PEA_1_PEA_1_PEA_1_T3 1010 1089 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1010 1089 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1010 1089 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1010 1089 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1010 1089 (SEQ ID NO: 118)
[2773] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:868) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 1002 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01055 TABLE 1002 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1090 1156 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T10 1090 1156 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T12 1090 1156 (SEQ ID NO: 118)
[2774] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--17 (SEQ ID
NO:869) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ
ID NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 1003 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01056 TABLE 1003 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R35137_PEA_1_PEA_1_PEA_1_T10 1294 1393 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1227 1326 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1294 1393 (SEQ ID NO: 118)
[2775] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--21 (SEQ ID
NO:870) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ
ID NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ
ID NO:118). Table 1004 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01057 TABLE 1004 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T11 1658 1731 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1725 1798 (SEQ ID NO: 118)
[2776] Segment cluster R35137_PEA.sub.--1_PEA.sub.--1_node.sub.--22
(SEQ ID NO:871) according to the present invention is supported by
31 libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118). Table 1005 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01058 TABLE 1005 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1625 1697 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1558 1630 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1725 1797 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1732 1804 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1799 1871 (SEQ ID NO: 118)
[2777] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:872) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA .sub.--1_T14 (SEQ ID
NO:119). Table 1006 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01059 TABLE 1006 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1698 1737 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1631 1670 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1798 1837 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1805 1844 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1872 1911 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 956 995 (SEQ ID NO: 119)
[2778] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:873) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ
ID NO:117) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ
ID NO:118). Table 1007 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01060 TABLE 1007 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T11 1845 1910 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1912 1977 (SEQ ID NO: 118)
[2779] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:874) according to the present invention is supported by 30
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T5 (SEQ ID
NO:115), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 1008 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01061 TABLE 1008 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1738 1818 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T5 1671 1751 (SEQ ID NO: 115)
R35137_PEA_1_PEA_1_PEA_1_T10 1838 1918 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1911 1991 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 1978 2058 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 996 1076 (SEQ ID NO: 119)
[2780] Segment cluster
R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:875) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T3 (SEQ
ID NO:114), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T10 (SEQ ID
NO:116), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T11 (SEQ ID
NO:117), R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T12 (SEQ ID
NO:118) and R35137_PEA.sub.--1_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:119). Table 1009 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01062 TABLE 1009 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R35137_PEA_1_PEA_1_PEA_1_T3 1819 1875 (SEQ ID NO: 114)
R35137_PEA_1_PEA_1_PEA_1_T10 1919 1975 (SEQ ID NO: 116)
R35137_PEA_1_PEA_1_PEA_1_T11 1992 2048 (SEQ ID NO: 117)
R35137_PEA_1_PEA_1_PEA_1_T12 2059 2115 (SEQ ID NO: 118)
R35137_PEA_1_PEA_1_PEA_1_T14 1077 1133 (SEQ ID NO: 119)
Variant Protein Alignment to the Previously Known Protein:
TABLE-US-01063 ##STR00733## [2781] ##STR00734## ##STR00735##
##STR00736## ##STR00737## ##STR00738## ##STR00739## ##STR00740##
##STR00741## ##STR00742##
Description for Cluster Z25299
[2782] Cluster Z25299 features 5 transcript(s) and 11 segment(s) of
interest, the names for which are given in Tables 1010 and 1011,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1012.
TABLE-US-01064 TABLE 1010 Transcripts of interest Transcript Name
Sequence ID No. Z25299_PEA_2_T1 120 Z25299_PEA_2_T2 121
Z25299_PEA_2_T3 122 Z25299_PEA_2_T6 123 Z25299_PEA_2_T9 124
TABLE-US-01065 TABLE 1011 Segments of interest Segment Name
Sequence ID No. Z25299_PEA_2_node_20 876 Z25299_PEA_2_node_21 877
Z25299_PEA_2_node_23 878 Z25299_PEA_2_node_24 879
Z25299_PEA_2_node_8 880 Z25299_PEA_2_node_12 881
Z25299_PEA_2_node_13 882 Z25299_PEA_2_node_14 883
Z25299_PEA_2_node_17 884 Z25299_PEA_2_node_18 885
Z25299_PEA_2_node_19 886
TABLE-US-01066 TABLE 1012 Proteins of interest Protein Name
Sequence ID No. Z25299_PEA_2_P2 1390 Z25299_PEA_2_P3 1391
Z25299_PEA_2_P7 1392 Z25299_PEA_2_P10 1393
[2783] These sequences are variants of the known protein
Antileukoproteinase 1 precursor (SwissProt accession identifier
ALK1_HUMAN; known also according to the synonyms ALP; HUSI-1;
Seminal proteinase inhibitor; Secretory leukocyte protease
inhibitor; BLPI; Mucus proteinase inhibitor; MPI; WAP
four-disulfide core domain protein 4; Protease inhibitor WAP4), SEQ
ID NO: 1454, referred to herein as the previously known
protein.
[2784] Protein Antileukoproteinase 1 precursor (SEQ ID NO:1454) is
known or believed to have the following function(s): Acid-stable
proteinase inhibitor with strong affinities for trypsin,
chymotrypsin, elastase, and cathepsin G. May prevent
elastase-mediated damage to oral and possibly other mucosal
tissues. The sequence for protein Antileukoproteinase 1 precursor
is given at the end of the application, as "Antileukoproteinase 1
precursor amino acid sequence". Protein Antileukoproteinase 1
precursor localization is believed to be Secreted.
[2785] It has been investigated for clinical/therapeutic use in
humans, for example as a target for an antibody or small molecule,
and/or as a direct therapeutic; available information related to
these investigations is as follows. Potential pharmaceutically
related or therapeutically related activity or activities of the
previously known protein are as follows: Elastase inhibitor;
Tryptase inhibitor. A therapeutic role for a protein represented by
the cluster has been predicted. The cluster was assigned this field
because there was information in the drug database or the public
databases (e.g., described herein above) that this protein, or part
thereof, is used or can be used for a potential therapeutic
indication: Anti-inflammatory; Antiasthma.
[2786] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: proteinase
inhibitor; serine protease inhibitor, which are annotation(s)
related to Molecular Function.
[2787] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2788] Cluster Z25299 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 35 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[2789] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 35 and Table 1013. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: brain malignant tumors, a mixture of
malignant tumors from different tissues and ovarian carcinoma.
TABLE-US-01067 TABLE 1013 Normal tissue distribution Name of Tissue
Number bladder 82 bone 6 brain 0 colon 37 epithelial 145 general 73
head and neck 638 kidney 26 liver 68 lung 465 breast 52 ovary 0
pancreas 20 prostate 36 skin 215 stomach 219 uterus 113
TABLE-US-01068 TABLE 1014 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 8.2e-01
8.5e-01 9.2e-01 0.6 9.7e-01 0.5 bone 5.5e-01 7.3e-01 4.0e-01 2.1
4.9e-01 1.5 brain 8.8e-02 1.5e-01 2.3e-03 7.7 1.2e-02 4.8 colon
3.3e-01 2.8e-01 4.2e-01 1.6 4.2e-01 1.5 epithelial 2.5e-01 7.6e-01
3.8e-01 1.0 1 0.6 general 6.4e-03 2.5e-01 1.7e-06 1.6 5.2e-01 0.9
head and neck 3.6e-01 5.9e-01 7.6e-01 0.6 1 0.3 kidney 7.4e-01
8.4e-01 2.1e-01 2.1 4.2e-01 1.4 liver 4.1e-01 9.1e-01 4.2e-02 3.2
6.4e-01 0.8 lung 7.6e-01 8.3e-01 9.8e-01 0.5 1 0.3 breast 5.0e-01
5.5e-01 9.8e-02 1.6 3.4e-01 1.1 ovary 3.7e-02 3.0e-02 6.9e-03 6.1
4.9e-03 5.6 pancreas 3.8e-01 3.6e-01 3.6e-01 1.7 3.9e-01 1.5
prostate 9.1e-01 9.2e-01 8.9e-01 0.5 9.4e-01 0.5 skin 6.0e-01
8.1e-01 9.3e-01 0.4 1 0.1 stomach 3.0e-01 8.1e-01 9.1e-01 0.6 1 0.3
uterus 1.6e-01 1.3e-01 3.2e-02 1.6 3.0e-01 1.1
[2790] As noted above, cluster Z25299 features 5 transcript(s),
which were listed in Table 1010 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Antileukoproteinase
1 precursor (SEQ ID NO:1454). A description of each variant protein
according to the present invention is now provided.
[2791] Variant protein Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z25299_PEA.sub.--2_T1 (SEQ ID NO:120). An alignment is given to the
known protein (Antileukoproteinase 1 precursor (SEQ ID NO:1454)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2792] Comparison report between Z25299_PEA.sub.--2_P2 (SEQ ID
NO:1390) and ALK1_HUMAN (SEQ ID NO:1454):
[2793] 1. An isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK
corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:1454),
which also corresponds to amino acids 1-131 of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GKQGMRAH
(SEQ ID NO: 279) corresponding to amino acids 132-139 of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[2794] 2. An isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GKQGMRAH
(SEQ ID NO: 279) in Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390).
[2795] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2796] Variant protein Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1015, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z25299_PEA.sub.--2_P2
(SEQ ID NO:1390) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01069 TABLE 1015 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
136 M -> T Yes 20 P -> No 43 C -> R No 48 K -> N No 83
R -> K No 84 R -> W No
[2797] Variant protein Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390) is
encoded by the following transcript(s): Z25299_PEA.sub.--2_T1 (SEQ
ID NO:120), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
Z25299_PEA.sub.--2_T1 (SEQ ID NO:120) is shown in bold; this coding
portion starts at position 124 and ends at position 540. The
transcript also has the following SNPs as listed in Table 1016
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein Z25299_PEA.sub.--2_P2 (SEQ ID NO:1390) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01070 TABLE 1016 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
122 C -> T No 123 C -> T No 530 T -> C Yes 989 C -> T
Yes 1127 C -> T Yes 1162 A -> C Yes 1180 A -> C Yes 1183 A
-> C Yes 1216 A -> C Yes 1262 G -> A Yes 183 T -> No
250 T -> C No 267 A -> C No 267 A -> G No 339 C -> T
Yes 371 G -> A No 373 A -> T No 435 C -> T No
[2798] Variant protein Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121). An alignment is given to the
known protein (Antileukoproteinase 1 precursor (SEQ ID NO:1454)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2799] Comparison report between Z25299_PEA.sub.--2_P3 (SEQ ID
NO:1391) and ALK1_HUMAN (SEQ ID NO:1454):
[2800] 1. An isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVK
corresponding to amino acids 1-131 of ALK1_HUMAN (SEQ ID NO:1454),
which also corresponds to amino acids 1-131 of
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO: 269) corresponding to amino
acids 132-156 of Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), wherein
said first and second amino acid sequences are contiguous and in a
sequential order.
[2801] 2. An isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
GEKRHHKQLRDQEVDPLEMRRHSAG (SEQ ID NO: 269) in Z25299_PEA.sub.--2_P3
(SEQ ID NO:1391).
[2802] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2803] Variant protein Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1017, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z25299_PEA.sub.--2_P3
(SEQ ID NO:1391) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01071 TABLE 1017 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
20 P -> No 43 C -> R No 48 K -> N No 83 R -> K No 84 R
-> W No
[2804] Variant protein Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391) is
encoded by the following transcript(s): Z25299_PEA.sub.--2_T2 (SEQ
ID NO:121), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121) is shown in bold; this coding
portion starts at position 124 and ends at position 591. The
transcript also has the following SNPs as listed in Table 1018
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein Z25299_PEA.sub.--2_P3 (SEQ ID NO:1391) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01072 TABLE 1018 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
122 C -> T No 123 C -> T No 183 T -> No 250 T -> C No
267 A -> C No 267 A -> G No 339 C -> T Yes 371 G -> A
No 373 A -> T No 435 C -> T No
[2805] Variant protein Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z25299_PEA.sub.--2_T6 (SEQ ID NO:123). An alignment is given to the
known protein (Antileukoproteinase 1 precursor (SEQ ID NO:1454)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2806] Comparison report between Z25299_PEA.sub.--2_P7 (SEQ ID
NO:1392) and ALK1_HUMAN (SEQ ID NO:1454):
[2807] 1. An isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNP corresponding to amino acids 1-81 of ALK1_HUMAN (SEQ ID
NO:1454), which also corresponds to amino acids 1-81 of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence RGSLGSAQ
(SEQ ID NO: 622) corresponding to amino acids 82-89 of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[2808] 2. An isolated polypeptide encoding for a tail of
Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence RGSLGSAQ
(SEQ ID NO: 622) in Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392).
[2809] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2810] Variant protein Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1019, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z25299_PEA.sub.--2_P7
(SEQ ID NO:1392) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01073 TABLE 1019 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
20 P -> No 43 C -> R No 48 K -> N No 82 R -> S No
[2811] Variant protein Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392) is
encoded by the following transcript(s): Z25299_PEA.sub.--2_T6 (SEQ
ID NO:123), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) is shown in bold; this coding
portion starts at position 124 and ends at position 390. The
transcript also has the following SNPs as listed in Table 1020
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein Z25299_PEA.sub.--2_P7 (SEQ ID NO:1392) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01074 TABLE 1020 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
122 C -> T No 123 C -> T No 576 A -> C Yes 594 A -> C
Yes 597 A -> C Yes 630 A -> C Yes 676 G -> A Yes 183 T
-> No 250 T -> C No 267 A -> C No 267 A -> G No 339 C
-> T Yes 369 A -> T No 431 C -> T No 541 C -> T Yes
[2812] Variant protein Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124). An alignment is given to the
known protein (Antileukoproteinase 1 precursor (SEQ ID NO:1454)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2813] Comparison report between Z25299_PEA.sub.--2_P10 (SEQ ID
NO:1393) and ALK1_HUMAN (SEQ ID NO:1454):
[2814] 1. An isolated chimeric polypeptide encoding for
Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393), comprising a first amino
acid sequence being at least 90% homologous to
MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGI
KCLDPVDTPNPT corresponding to amino acids 1-82 of ALK1_HUMAN (SEQ
ID NO:1454), which also corresponds to amino acids 1-82 of
Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393).
[2815] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2816] Variant protein Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1021, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein Z25299_PEA.sub.--2_P10
(SEQ ID NO:1393) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01075 TABLE 1021 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
20 P -> No 43 C -> R No 48 K -> N No
[2817] Variant protein Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393) is
encoded by the following transcript(s): Z25299_PEA.sub.--2_T9 (SEQ
ID NO:124), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124) is shown in bold; this coding
portion starts at position 124 and ends at position 369. The
transcript also has the following SNPs as listed in Table 1022
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein Z25299_PEA.sub.--2_P10 (SEQ ID NO:1393) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01076 TABLE 1022 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
122 C -> T No 123 C -> T No 451 A -> C Yes 484 A -> C
Yes 530 G -> A Yes 183 T -> No 250 T -> C No 267 A -> C
No 267 A -> G No 339 C -> T Yes 395 C -> T Yes 430 A ->
C Yes 448 A -> C Yes
[2818] As noted above, cluster Z25299 features 11 segment(s), which
were listed m Table 2 above and for which the sequence(s) are given
at the end of the application. These segment(s) are portions of
nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[2819] Segment cluster Z25299_PEA.sub.--2_node.sub.--20 (SEQ ID
NO:876) according to the present invention is supported by 6
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120). Table 1023
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01077 TABLE 1023 Segment location on transcripts Segment
starting Segment Transcript name position ending position
Z25299_PEA_2_T1 518 1099 (SEQ ID NO: 120)
[2820] Segment cluster Z25299_PEA.sub.--2_node.sub.--21 (SEQ ID
NO:877) according to the present invention is supported by 162
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) and Z25299_PEA.sub.--2_T9
(SEQ ID NO:124). Table 1024 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01078 TABLE 1024 Segment location on transcripts Segment
Segment Transcript name starting position ending position
Z25299_PEA_2_T1 (SEQ ID 1100 1292 NO: 120) Z25299_PEA_2_T6 (SEQ ID
514 706 NO: 123) Z25299_PEA_2_T9 (SEQ ID 368 560 NO: 124)
[2821] Segment cluster Z25299_PEA.sub.--2_node.sub.--23 (SEQ ID
NO:878) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T2 (SEQ ID NO:121). Table 1025
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01079 TABLE 1025 Segment location on transcripts Segment
Transcript name starting position Segment ending position
Z25299_PEA_2_T2 518 707 (SEQ ID NO: 121)
[2822] Segment cluster Z25299_PEA.sub.--2_node.sub.--24 (SEQ ID
NO:879) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T2 (SEQ ID NO:121) and
Z25299_PEA.sub.--2_T3 (SEQ ID NO:122). Table 1026 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01080 TABLE 1026 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z25299_PEA_2_T2 (SEQ ID NO: 121) 708 886 Z25299_PEA_2_T3 (SEQ ID
NO: 122) 518 696
[2823] Segment cluster Z25299_PEA.sub.--2_node.sub.--8 (SEQ ID
NO:880) according to the present invention is supported by 218
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122), Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) and
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124). Table 1027 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01081 TABLE 1027 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 1 208 Z25299_PEA_2_T2 (SEQ ID NO:
121) 1 208 Z25299_PEA_2_T3 (SEQ ID NO: 122) 1 208 Z25299_PEA_2_T6
(SEQ ID NO: 123) 1 208 Z25299_PEA_2_T9 (SEQ ID NO: 124) 1 208
[2824] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2825] Segment cluster Z25299_PEA.sub.--2_node.sub.--12 (SEQ ID
NO:881) according to the present invention is supported by 228
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122), Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) and
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124). Table 1028 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01082 TABLE 1028 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 209 245 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 209 245 Z25299_PEA_2_T3 (SEQ ID NO: 122) 209 245
Z25299_PEA_2_T6 (SEQ ID NO: 123) 209 245 Z25299_PEA_2_T9 (SEQ ID
NO: 124) 209 245
[2826] Segment cluster Z25299_PEA.sub.--2_node.sub.--13 (SEQ ID
NO:882) according to the present invention is supported by 246
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122), Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) and
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124). Table 1029 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01083 TABLE 1029 Segment location on transcripts Segment
Segment starting ending Transcript name position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 246 357 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 246 357 Z25299_PEA_2_T3 (SEQ ID NO: 122) 246 357
Z25299_PEA_2_T6 (SEQ ID NO: 123) 246 357 Z25299_PEA_2_T9 (SEQ ID
NO: 124) 246 357
[2827] Segment cluster Z25299_PEA.sub.--2_node.sub.--14 (SEQ ID
NO:883) according to the present invention can be found in the
following transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122), Z25299_PEA.sub.--2_T6 (SEQ ID NO:123) and
Z25299_PEA.sub.--2_T9 (SEQ ID NO:124). Table 1030 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01084 TABLE 1030 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 358 367 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 358 367 Z25299_PEA_2_T3 (SEQ ID NO: 122) 358 367
Z25299_PEA_2_T6 (SEQ ID NO: 123) 358 367 Z25299_PEA_2_T9 (SEQ ID
NO: 124) 358 367
[2828] Segment cluster Z25299_PEA2_node.sub.--17 (SEQ ID NO:884)
according to the present invention can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121) and Z25299_PEA.sub.--2_T3
(SEQ ID NO:122). Table 1031 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01085 TABLE 1031 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 368 371 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 368 371 Z25299_PEA_2_T3 (SEQ ID NO: 122) 368 371
[2829] Segment cluster Z25299_PEA.sub.--2_node.sub.--18 (SEQ ID
NO:885) according to the present invention is supported by 221
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122) and Z25299_PEA.sub.--2_T6 (SEQ ID NO:123). Table 1032
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01086 TABLE 1032 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 372 427 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 372 427 Z25299_PEA_2_T3 (SEQ ID NO: 122) 372 427
Z25299_PEA_2_T6 (SEQ ID NO: 123) 368 423
[2830] Segment cluster Z25299_PEA.sub.--2_node.sub.--19 (SEQ ID
NO:886) according to the present invention is supported by 197
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): Z25299_PEA.sub.--2_T1 (SEQ ID NO:120),
Z25299_PEA.sub.--2_T2 (SEQ ID NO:121), Z25299_PEA.sub.--2_T3 (SEQ
ID NO:122) and Z25299_PEA.sub.--2_T6 (SEQ ID NO:123). Table 1033
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01087 TABLE 1033 Segment location on transcripts Segment
Segment ending Transcript name starting position position
Z25299_PEA_2_T1 (SEQ ID NO: 120) 428 517 Z25299_PEA_2_T2 (SEQ ID
NO: 121) 428 517 Z25299_PEA_2_T3 (SEQ ID NO: 122) 428 517
Z25299_PEA_2_T6 (SEQ ID NO: 123) 424 513
Variant Protein Alignment to the Previously Known Protein:
TABLE-US-01088 ##STR00743## [2831] ##STR00744## ##STR00745##
##STR00746##
Expression of Secretory Leukocyte Protease Inhibitor Acid-Stable
Proteinase Inhibitor Z25299 Transcripts, Which are Detectable by
Amplicon as Depicted in Sequence Name Z25299 Junc13-14-21 (SEQ ID
NO: 1666) in Normal and Cancerous Lung Tissues
[2832] Expression of Secretory leukocyte protease inhibitor
Acid-stable proteinase inhibitor transcripts detectable by or
according to junc13-14-21, Z25299 junc13-14-21 amplicon (SEQ ID NO:
1666) and Z25299 junc13-14-21F (SEQ ID NO: 1664) and Z25299
junc13-14-21R (SEQ ID NO: 1665) primers was measured by real time
PCR. In parallel the expression of four housekeeping genes--PBGD
(GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO:1714); amplicon--HPRT1-amplicon, SEQ
ID NO:1297), Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2 "Tissue sample in testing
panel", above), to obtain a value of fold differential expression
for each sample relative to median of the normal PM samples.
[2833] FIG. 36 is a histogram showing down regulation of the
above-indicated Secretory leukocyte protease inhibitor Acid-stable
proteinase inhibitor transcripts in cancerous lung samples relative
to the normal samples.
[2834] As is evident from FIG. 36, the expression of Secretory
leukocyte protease inhibitor Acid-stable proteinase inhibitor
transcripts detectable by the above amplicon(s) in cancer samples
was significantly lower than in the non-cancerous samples (Sample
Nos. 47-50, 90-93, 96-99 Table 2, "Tissue sample in testing
panel").
[2835] Statistical analysis was applied to verify the significance
of these results, as described below.
[2836] The P value for the difference in the expression levels of
Secretory leukocyte protease inhibitor Acid-stable proteinase
inhibitor transcripts detectable by the above amplicon(s) in lung
cancer samples versus the normal tissue samples was determined by T
test as 1.98E-04. This value demonstrates statistical significance
of the results.
[2837] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: Z25299
junc13-14-21F forward primer (SEQ ID NO: 1664); and Z25299
junc13-14-21R reverse primer (SEQ ID NO: 1665).
[2838] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z25299 junc13-14-21 (SEQ ID NO: 1666).
TABLE-US-01089 Forward primer (SEQ ID NO: 1664):
ACCCCAAACCCAACTTGATTC Reverse primer (SEQ ID NO: 1665):
TCAGTGGTGGAGCCAAGTCTC Amplicon (SEQ ID NO: 1666):
ACCCCAAACCCAACTTGATTCCTGCCATATGGAGGAGGCTCTGGAGTCC
TGCTCTGTGTGGTCCAGGTCCTTTCCACCCTGAGACTTGGCTCCACCAC TGA
Z25299 Transcripts, Which are Detectable by Amplicon as Depicted in
Sequence Name Z25299 Seg20 (SEQ ID NO: 1669) in Normal and
Cancerous Lung Tissues
[2839] Expression of Secretory leukocyte protease inhibitor
Acid-stable proteinase inhibitor transcripts detectable by or
according to seg20, Z25299 seg20 amplicon (SEQ ID NO: 1669) and
Z25299 seg2OF (SEQ ID NO: 1667) and Z25299 seg20R (SEQ ID NO: 1668)
primers was measured by real time PCR. In parallel the expression
of four housekeeping genes--PBGD (GenBank Accession No. BC019323
(SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above). Then the reciprocal of this ratio was
calculated, to obtain a value of fold down-regulation for each
sample relative to median of the normal PM samples.
[2840] FIG. 37 is a histogram showing down regulation of the
above-indicated Secretory leukocyte protease inhibitor Acid-stable
proteinase inhibitor transcripts in cancerous lung samples relative
to the normal samples. The number and percentage of samples that
exhibit at least 5 fold down regulation, out of the total number of
samples tested is indicated in the bottom.
[2841] As is evident from FIG. 37, the expression of Secretory
leukocyte protease inhibitor Acid-stable proteinase inhibitor
transcripts detectable by the above amplicon(s) in cancer samples
was significantly lower than in the non-cancerous samples (Sample
Nos. 47-50, 90-93, 96-99 Table 2, "Tissue sample in testing
panel"). Notably an down regulation of at least 5 fold was found in
6 out of 15 adenocarcinoma samples, 9 out of 16 squamous cell
carcinoma samples, 3 out of 4 large cell carcinoma samples and in 8
out of 8 small cell carcinoma samples.
[2842] Statistical analysis was applied to verify the significance
of these results, as described below.
[2843] The P value for the difference in the expression levels of
Secretory leukocyte protease inhibitor Acid-stable proteinase
inhibitor transcripts detectable by the above amplicon(s) in lung
cancer samples versus the normal tissue samples was determined by T
test as 9.43E-02 in adenocarcinoma, 5.62E-02 in squamous cell
carcinoma, 3.38E-01 in large cell carcinoma and 3.78E-02 in small
cell carcinoma.
[2844] Threshold of 5 fold down regulation was found to
differentiate between cancer and normal samples with P value of
3.73E-02 in adenocarcinoma, 1.10E-02 in squamous cell carcinoma,
2.64E-02 in large cell carcinoma and 7.14E-05 in small cell
carcinoma checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[2845] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: Z25299 seg2OF
forward primer (SEQ ID NO: 1667); and Z25299 seg20R reverse primer
(SEQ ID NO: 1668).
[2846] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z25299 seg20 (SEQ ID NO: 1669).
TABLE-US-01090 Forward primer (SEQ ID NO: 1667):
CTCCTGAACCCTACTCCAAGCA Reverse primer (SEQ ID NO: 1668):
CAGGCGATCCTATGGAAATCC Amplicon (SEQ ID NO: 1669):
CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTC
AAGAGAACTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCCT G
Expression of Homo sapiens Secretory Leukocyte Protease Inhibitor
(Antileukoproteinase) (SLPI) Z25299 Transcripts Which are
Detectable by Amplicon as Depicted in Sequence Name Z25299
seg23(SEQ ID NO: 1672) in Normal and Cancerous Lung Tissues
[2847] Expression of Homo sapiens secretory leukocyte protease
inhibitor (antileukoproteinase) (SLPI) transcripts detectable by or
according to seg23, Z25299 seg23 amplicon (SEQ ID NO: 1672) and
primers Z25299 seg23F (SEQ ID NO: 1670) and Z25299 seg23R (SEQ ID
NO: 1671) was measured by real time PCR. In parallel the expression
of four housekeeping genes--PBGD (GenBank Accession No. BC019323
(SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above). Then the reciprocal of this ratio was calculated, to obtain
a value of fold down-regulation for each sample relative to median
of the normal PM samples.
[2848] FIG. 68 is a histogram showing down regulation of the
above-indicated Homo sapiens secretory leukocyte protease inhibitor
(antileukoproteinase) (SLPI) transcripts in cancerous lung samples
relative to the normal samples.
[2849] As is evident from FIG. 68, the expression of Homo sapiens
secretory leukocyte protease inhibitor (antileukoproteinase) (SLPI)
transcripts detectable by the above amplicon(s) in cancer samples
was significantly lower than in the non-cancerous samples (Sample
Nos. 46-50, 90-93, 96-99 Table 2). Notably down regulation of at
least 10 fold was found in 7 out of 15 adenocarcinoma samples, 9
out of 16 squamous cell carcinoma samples, 3 out of 4 large cell
carcinoma samples and in 8 out of 8 small cells carcinoma
samples.
[2850] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: Z25299 seg23F
forward primer (SEQ ID NO: 1670); and Z25299 seg23R reverse primer
(SEQ ID NO: 1671).
[2851] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Z25299 seg23 (SEQ ID NO: 1672).
TABLE-US-01091 Primers: Forward primer Z25299 seg23F (SEQ ID NO:
1670): CAAGCAATTGAGGGACCAGG Reverse primer Z25299 seg23R (SEQ ID
NO: 1671): CAAAAAACATTGTTAATGAGAGAGATGAC Amplicon Z25299 seg23F
(SEQ ID NO: 1672):
CAAGCAATTGAGGGACCAGGAAGTGGATCCTCTAGAGATGAGGAGGCATT
CTGCTGGATGACTTTTAAAAATGTTTTCTCCAGAGTCATCTCTCTCATTA
ACAATGTTTTTTG
[2852] Expression of Secretory leukocyte protease inhibitor
Acid-stable proteinase inhibitor Z25299 transcripts which are
detectable by amplicon as depicted in sequence name Z25299seg20
(SEQ ID NO: 1669) in different normal tissues
[2853] Expression of Secretory leukocyte protease inhibitor
transcripts detectable by or according to Z25299seg20 amplicon (SEQ
ID NO: 1669) and primers: Z25299seg23F (SEQ ID NO: 1667)
Z25299seg20R (SEQ ID NO: 1668) was measured by real time PCR. In
parallel the expression of four housekeeping genes--RPL19 (GenBank
Accession No. NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ
ID NO:1630), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ
ID NO:1716); TATA amplicon, SEQ ID NO:1633), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the ovary samples (Sample Nos. 18-20,
Table 3), to obtain a value of relative expression of each sample
relative to median of the ovary samples.
TABLE-US-01092 Primers: Forward primer (SEQ ID NO: 1667):
CTCCTGAACCCTACTCCAAGCA Reverse primer (SEQ ID NO: 1668):
CAGGCGATCCTATGGAAATCC Amplicon (SEQ ID NO: 1669):
CTCCTGAACCCTACTCCAAGCACAGCCTCTGTCTGACTCCCTTGTCCTTC
AAGAGAACTGTTCTCCAGGTCTCAGGGCCAGGATTTCCATAGGATCGCCT G
[2854] The results are demonstrated in FIG. 69, showing the
expression of Secretory leukocyte protease inhibitor Acid-stable
proteinase inhibitor Z25299 transcripts which are detectable by
amplicon as depicted in sequence name Z25299seg20 (SEQ ID NO: 1669)
in different normal tissues.
Expression of Secretory Leukocyte Protease Inhibitor Z25299
Transcripts Which are Detectable by Amplicon as Depicted in
Sequence Name Z25299seg23 (SEQ ID NO: 1672) in Different Normal
Tissues
[2855] Expression of Secretory leukocyte protease inhibitor
transcripts detectable by or according to Z25299seg23 amplicon (SEQ
ID NO: 1672) and primers: Z25299seg23F (SEQ ID NO: 1670)
Z25299seg23R (SEQ ID NO: 1671) was measured by real time PCR. In
parallel the expression of four housekeeping genes--RPL19 (GenBank
Accession No. NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ
ID NO:1630), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ
ID NO:1716); TATA amplicon, SEQ ID NO:1633), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the ovary samples (Sample Nos. 18-20,
Table 3), to obtain a value of relative expression of each sample
relative to median of the ovary samples.
TABLE-US-01093 Primers: Forward primer Z25299 seg23F (SEQ ID NO:
1670): CAAGCAATTGAGGGACCAGG Reverse primer Z25299 seg23R (SEQ ID
NO: 1671): CAAAAAACATTGTTAATGAGAGAGATGAC Amplicon Z25299 seg23F
(SEQ ID NO: 1672):
CAAGCAATTGAGGGACCAGGAAGTGGATCCTCTAGAGATGAGGAGGCATT
CTGCTGGATGACTTTTAAAAATGTTTTCTCCAGAGTCATCTCTCTCATTA ACAATGTTTTTG
[2856] The results are demonstrated in FIG. 70, showing the
expression of Secretory leukocyte protease inhibitor Acid-stable
proteinase inhibitor Z25299 transcripts which are detectable by
amplicon as depicted in sequence name Z25299seg23 (SEQ ID NO: 1672)
in different normal tissues.
Description for Cluster HSSTROL3
[2857] Cluster HSSTROL3 features 6 transcript(s) and 16 segment(s)
of interest, the names for which are given in Tables 1034 and 1035,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1036.
TABLE-US-01094 TABLE 1034 Transcripts of interest Transcript Name
Sequence ID No. HSSTROL3_T5 125 HSSTROL3_T8 126 HSSTROL3_T9 127
HSSTROL3_T10 128 HSSTROL3_T11 129 HSSTROL3_T12 130
TABLE-US-01095 TABLE 1035 Segments of interest Segment Name
Sequence ID No. HSSTROL3_node_6 887 HSSTROL3_node_10 888
HSSTROL3_node_13 889 HSSTROL3_node_15 890 HSSTROL3_node_19 891
HSSTROL3_node_21 892 HSSTROL3_node_24 893 HSSTROL3_node_25 894
HSSTROL3_node_26 895 HSSTROL3_node_28 896 HSSTROL3_node_29 897
HSSTROL3_node_11 898 HSSTROL3_node_17 899 HSSTROL3_node_18 900
HSSTROL3_node_20 901 HSSTROL3_node_27 902
TABLE-US-01096 TABLE 1036 Proteins of interest Sequence Protein
Name ID No. Corresponding Transcript(s) HSSTROL3_P4 1394
HSSTROL3_T5 (SEQ ID NO: 125) HSSTROL3_P5 1395 HSSTROL3_T8 (SEQ ID
NO: 126); HSSTROL3_T9 (SEQ ID NO: 127) HSSTROL3_P7 1396
HSSTROL3_T10 (SEQ ID NO: 128) HSSTROL3_P8 1397 HSSTROL3_T11 (SEQ ID
NO: 129) HSSTROL3_P9 1398 HSSTROL3_T12 (SEQ ID NO: 130)
[2858] These sequences are variants of the known protein
Stromelysin-3 precursor (SwissProt accession identifier MM11_HUMAN;
known also according to the synonyms EC 3.4.24.-; Matrix
metalloproteinase-11; MMP-11; ST3; SL-3), SEQ ID NO: 1455, referred
to herein as the previously known protein.
[2859] Protein Stromelysin-3 precursor (SEQ ID NO:1455) is known or
believed to have the following function(s): May play an important
role in the progression of epithelial malignancies. The sequence
for protein Stromelysin-3 precursor is given at the end of the
application, as "Stromelysin-3 precursor amino acid sequence".
[2860] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: proteolysis, and
peptidolysis; developmental processes; morphogenesis, which are
annotation(s) related to Biological Process; stromelysin 3; calcium
binding; zinc binding; hydrolase, which are annotations) related to
Molecular Function; and extracellular matrix, which are
annotation(s) related to Cellular Component.
[2861] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[2862] Cluster HSSTROL3 can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the left hand column of the table and the numbers on
the y-axis of FIG. 38 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[2863] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 38 and Table 1037. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: transitional cell carcinoma, epithelial
malignant tumors, a mixture of malignant tumors from different
tissues and pancreas carcinoma.
TABLE-US-01097 TABLE 1037 Normal tissue distribution Name of Tissue
Number adrenal 0 bladder 0 brain 1 colon 63 epithelial 33 general
13 head and neck 101 kidney 0 lung 11 breast 8 ovary 14 pancreas 0
prostate 2 skin 99 Thyroid 0 uterus 181
TABLE-US-01098 TABLE 1038 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 1
4.6e-01 1 1.0 5.3e-01 1.9 bladder 2.7e-01 3.4e-01 3.3e-03 4.9
2.1e-02 3.3 brain 3.5e-01 2.6e-01 1 1.7 3.3e-01 2.8 colon 7.7e-02
1.5e-01 3.1e-01 1.4 5.2e-01 1.0 epithelial 1.2e-04 1.2e-02 1.3e-06
2.7 4.6e-02 1.4 general 5.4e-09 3.1e-05 1.8e-16 5.0 3.1e-07 2.6
head and neck 4.6e-01 4.3e-01 1 0.6 9.4e-01 0.7 kidney 2.5e-01
3.5e-01 1.1e-01 4.0 2.4e-01 2.8 lung 1.8e-01 4.5e-01 1.9e-01 2.7
5.1e-01 1.4 breast 2.0e-01 3.4e-01 7.3e-02 3.3 2.5e-01 2.0 ovary
2.6e-01 3.2e-01 2.2e-02 2.0 7.0e-02 1.6 pancreas 9.5e-02 1.8e-01
1.8e-04 7.8 1.6e-03 5.5 prostate 8.2e-01 7.8e-01 4.5e-01 1.8
5.6e-01 1.5 skin 5.2e-01 5.8e-01 7.1e-01 0.8 1 0.3 Thyroid 2.9e-01
2.9e-01 1 1.1 1 1.1 uterus 4.2e-01 8.0e-01 7.5e-01 0.6 9.9e-01
0.4
[2864] As notes above, cluster HSSTROL3 features b transcript(s),
which were listed in Table 1034 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Stromelysin-3
precursor (SEQ ID NO:1455). A description of each variant protein
according to the present invention is now provided.
[2865] Variant protein HSSTROL3_P4 (SEQ ID NO:1394) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSSTROL3_T5
(SEQ ID NO:125). An alignment is given to the known protein
(Stromelysin-3 precursor (SEQ ID NO:1455)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2866] Comparison report between HSSTROL3_P4 (SEQ ID NO:1394) and
MM11_HUMAN (SEQ ID NO:1455)
[2867] 1. An isolated chimeric polypeptide encoding for HSSTROL3_P4
(SEQ ID NO:1394), comprising a first amino acid sequence being at
least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P4 (SEQ ID NO:1394), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P4 (SEQ ID NO:1394), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQGAQYWVYDGEKPVLG
PAPLTELGLVRFPVHAALVWGPEKNKIYFFRGRDYWRFHPSTRRVDSPVPRRATDWRGVPSEIDAAFQDA
DG corresponding to amino acids 165-445 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 165-445 of
HSSTROL3_P4 (SEQ ID NO:1394), and a third amino acid sequence being
at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:
251) corresponding to amino acids 446-496 of HSSTROL3_P4 (SEQ ID
NO:1394), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[2868] 2. An isolated polypeptide encoding for a tail of
HSSTROL3_P4 (SEQ ID NO:1394), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence
ALGVRQLVGGGHSSRFSHLVVAGLPHACHRKSGSSSQVLCPEPSALLSVAG (SEQ ID NO:
251) in HSSTROL3_P4 (SEQ ID NO:1394).
[2869] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2870] Variant protein HSSTROL3_P4 (SEQ ID NO:1394) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1039, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:1394)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01099 TABLE 1039 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
38 V -> A Yes 104 R -> P Yes 214 A -> No 323 Q -> H
Yes
[2871] Variant protein HSSTROL3_P4 (SEQ ID NO:1394) is encoded by
the following transcript(s): HSSTROL3_T5 (SEQ ID NO:125), for which
the sequence(s) is/are given at the end of the application. The
coding portion of transcript HSSTROL3_T5 (SEQ ID NO:125) is shown
in bold; this coding portion starts at position 24 and ends at
position 1511. The transcript also has the following SNPs as listed
in Table 1040 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein HSSTROL3_P4 (SEQ ID NO:1394) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01100 TABLE 1040 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 334 G -> C Yes 663 G -> No 699 -> T No
992 G -> C Yes 1528 A -> G Yes 1710 A -> G Yes 2251 A
-> G Yes 2392 C -> No 2444 C -> A Yes 2470 A -> T Yes
2687 -> G No 2696 -> G No 2710 C -> No 2729 -> A No
2755 T -> C No 2813 A -> No 2813 A -> C No 2963 A -> No
2963 A -> C No 2993 T -> C Yes 3140 -> T No
[2872] Variant protein HSSTROL3_P5 (SEQ ID NO:1395) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSSTROL3_T8
(SEQ ID NO:126) and HSSTROL3_T9 (SEQ ID NO:127). An alignment is
given to the known protein (Stromelysin-3 precursor (SEQ ID
NO:1455)) at the end of the application. One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[2873] Comparison report between HSSTROL3_P5 (SEQ ID NO:1395) and
MM11_HUMAN (SEQ ID NO:1455)
[2874] 1. An isolated chimeric polypeptide encoding for HSSTROL3_P5
(SEQ ID NO:1395), comprising a first amino acid sequence being at
least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P5 (SEQ ID NO:1395), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P5 (SEQ ID NO:1395), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQ corresponding
to amino acids 165-358 of MM11_HUMAN (SEQ ID NO:1455), which also
corresponds to amino acids 165-358 of HSSTROL3_P5 (SEQ ID NO:1395),
and a third amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence ELGFPSSTGRDESLEHCRCQGLHK (SEQ ID NO: 252)
corresponding to amino acids 359-382 of HSSTROL3_P5 (SEQ ID
NO:1395), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[2875] 2. An isolated polypeptide encoding for a tail of
HSSTROL3_P5 (SEQ ID NO:1395), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence ELGFPSSTGRDESLEHCRCQGLHK
(SEQ ID NO: 252) in HSSTROL3_P5 (SEQ ID NO:1395).
[2876] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2877] Variant protein HSSTROL3_P5 (SEQ ID NO:1395) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1041, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:1395)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01101 TABLE 1041 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
38 V -> A Yes 104 R -> P Yes 214 A -> No 323 Q -> H
Yes
[2878] Variant protein HSSTROL3_P5 (SEQ ID NO:1395) is encoded by
the following transcript(s): HSSTROL3_T8 (SEQ ID NO:126) and
HSSTROU_T9 (SEQ ID NO:127), for which the sequence(s) is/are given
at the end of the application.
[2879] The coding portion of transcript HSSTROL3_T8 (SEQ ID NO:126)
is shown in bold; this coding portion starts at position 24 and
ends at position 1169. The transcript also has the following SNPs
as listed in Table 1042 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:1395)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01102 TABLE 1042 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 334 G -> C Yes 663 G -> No 699 -> T No
992 G -> C Yes 1903 C -> No 1955 C -> A Yes 1981 A -> T
Yes 2198 -> G No 2207 -> G No 2221 C -> No 2240 -> A No
2266 T -> C No 2324 A -> No 2324 A -> C No 2474 A -> No
2474 A -> C No 2504 T -> C Yes 2651 -> T No
[2880] The coding portion of transcript HSSTROL3_T9 (SEQ ID NO:127)
is shown in bold; this coding portion starts at position 24 and
ends at position 1169. The transcript also has the following SNPs
as listed in Table 1043 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P5 (SEQ ID NO:1395)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01103 TABLE 1043 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 334 G -> C Yes 663 G -> No 699 -> T No
992 G -> C Yes 1666 A -> G Yes 1848 A -> G Yes 2389 A
-> G Yes 2530 C -> No 2582 C -> A Yes 2608 A -> T Yes
2825 -> G No 2834 -> G No 2848 C -> No 2867 -> A No
2893 T -> C No 2951 A -> No 2951 A -> C No 3101 A -> No
3101 A -> C No 3131 T -> C Yes 3278 -> T No
[2881] Variant protein HSSTROL3_P7 (SEQ ID NO:1396) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSSTROL3_T10
(SEQ ID NO:128). An alignment is given to the known protein
(Stromelysin-3 precursor (SEQ ID NO:1455)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2882] Comparison report between HSSTROL3_P7 (SEQ ID NO:1396) and
MM11_HUMAN (SEQ ID NO:1455) 1. An isolated chimeric polypeptide
encoding for HSSTROL3_P7 (SEQ ID NO:1396), comprising a first amino
acid sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P7 (SEQ ID NO:1396), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P7 (SEQ ID NO:1396), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG
corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 165-359 of
HSSTROL3_P7 (SEQ ID NO:1396), and a third amino acid sequence being
at least 70%, optionally at least 80%, preferably at least 85%,
more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID
NO: 253) corresponding to amino acids 360-370 of HSSTROL3_P7 (SEQ
ID NO:1396), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[2883] 2. An isolated polypeptide encoding for a tail of
HSSTROL3_P7 (SEQ ID NO:1396), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:
253) in HSSTROL3_P7 (SEQ ID NO:1396).
[2884] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2885] Variant protein HSSTROL3_P7 (SEQ ID NO:1396) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1044, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:1396)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01104 TABLE 1044 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
38 V -> A Yes 104 R -> P Yes 214 A -> No 323 Q -> H
Yes
[2886] Variant protein HSSTROL3_P7 (SEQ ID NO:1396) is encoded by
the following transcript(s): HSSTROL3_T10 (SEQ ID NO:128), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HSSTROL3_T10 (SEQ ID NO:128) is
shown in bold; this coding portion starts at position 24 and ends
at position 1133. The transcript also has the following SNPs as
listed in Table 1045 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P7 (SEQ ID NO:1396)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01105 TABLE 1045 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 334 G -> C Yes 663 G -> No 699 -> T No
992 G -> C Yes 1386 A -> G Yes 1568 A -> G Yes 2109 A
-> G Yes 2250 C -> No 2302 C -> A Yes 2328 A -> T Yes
2545 -> G No 2554 -> G No 2568 C -> No 2587 -> A No
2613 T -> C No 2671 A -> No 2671 A -> C No 2821 A -> No
2821 A -> C No 2851 T -> C Yes 2998 -> T No
[2887] Variant protein HSSTROL3_P8 (SEQ ID NO:1397) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSSTROL3_T11
(SEQ ID NO:129). An alignment is given to the known protein
(Stromelysin-3 precursor (SEQ ID NO:1455)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2888] Comparison report between HSSTROL3_P8 (SEQ ID NO:1397) and
MM11_HUMAN (SEQ ID NO:1455) 1. An isolated chimeric polypeptide
encoding for HSSTROL3_P8 (SEQ ID NO:1397), comprising a first amino
acid sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQKRFVLSGGRWEKTDLTYRILRFPWQLVQEQVRQTMAEALKVWSD
VTPLTFTEVHEGRADIMIDFARYW corresponding to amino acids 1-163 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-163 of HSSTROL3_P8 (SEQ ID NO:1397), a bridging amino acid H
corresponding to amino acid 164 of HSSTROL3_P8 (SEQ ID NO:1397), a
second amino acid sequence being at least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLE corresponding
to amino acids 165-286 of MM.sub.11_HUMAN (SEQ ID NO:1455), which
also corresponds to amino acids 165-286 of HSSTROL3_P8 (SEQ ID
NO:1397), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VRPCLPVPLLLCWPL (SEQ ID NO: 254)
corresponding to amino acids 287-301 of HSSTROL3_P8 (SEQ ID
NO:1397), wherein said first amino acid sequence, bridging amino
acid, second amino acid sequence and third amino acid sequence are
contiguous and in a sequential order.
[2889] 2. An isolated polypeptide encoding for a tail of
HSSTROL3_P8 (SEQ ID NO:1397), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence VRPCLPVPLLLCWPL (SEQ ID
NO: 254) in HSSTROL3_P8 (SEQ ID NO:1397).
[2890] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2891] Variant protein HSSTROL3_P8 (SEQ ID NO:1397) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1046, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:1397)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01106 TABLE 1046 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
38 V -> A Yes 104 R -> P Yes 214 A -> No
[2892] Variant protein HSSTROL3_P8 (SEQ ID NO:1397) is encoded by
the following transcript(s): HSSTROL3_T11 (SEQ ID NO:129), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HSSTROL3_T11 (SEQ ID NO:129) is
shown in bold; this coding portion starts at position 24 and ends
at position 926. The transcript also has the following SNPs as
listed in Table 1047 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P8 (SEQ ID NO:1397)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01107 TABLE 1047 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 334 G -> C Yes 663 G -> No 699 -> T No
935 G -> A Yes 948 G -> A Yes 1084 G -> C Yes 1557 C ->
No 1609 C -> A Yes 1635 A -> T Yes 1852 -> G No 1861 ->
G No 1875 C -> No 1894 -> A No 1920 T -> C No 1978 A ->
No 1978 A -> C No 2128 A -> No 2128 A -> C No 2158 T ->
C Yes 2305 -> T No
[2893] Variant protein HSSTROL3_P9 (SEQ ID NO:1398) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSSTROL3_T12
(SEQ ID NO:130). An alignment is given to the known protein
(Stromelysin-3 precursor (SEQ ID NO:1455)) at the end of the
application. One or more alignments to one or more previously
published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[2894] Comparison report between HSSTROL3_P9 (SEQ ID NO:1398) and
MM11_HUMAN (SEQ ID NO:1455) 1. An isolated chimeric polypeptide
encoding for HSSTROL3_P9 (SEQ ID NO:1398), comprising a first amino
acid sequence being at least 90% homologous to
MAPAAWLRSAAARALLPPMLLLLLQPPPLLARALPPDVHHLHAERRGPQPWHAALPSSPAPAPATQEAPR
PASSLRPPRCGVPDPSDGLSARNRQK corresponding to amino acids 1-96 of
MM11_HUMAN (SEQ ID NO:1455), which also corresponds to amino acids
1-96 of HSSTROL3_P9 (SEQ ID NO:1398), a second amino acid sequence
being at least 90% homologous to
RILRFPWQLVQEQVRQTMAEALKVWSDVTPLTFTEVHEGRADIMIDFARYW corresponding
to amino acids 113-163 of MM11_HUMAN (SEQ ID NO:1455), which also
corresponds to amino acids 97-147 of HSSTROL3_P9 (SEQ ID NO:1398),
a bridging amino acid H corresponding to amino acid 148 of
HSSTROL3_P9 (SEQ ID NO:1398), a third amino acid sequence being at
least 90% homologous to
GDDLPFDGPGGILAHAFFPKTHREGDVHFDYDETWTIGDDQGTDLLQVAAHEFGHVLGLQHTTAAKALM
SAFYTFRYPLSLSPDDCRGVQHLYGQPWPTVTSRTPALGPQAGIDTNEIAPLEPDAPPDACEASFDAVSTIR
GELFFFKAGFVWRLRGGQLQPGYPALASRHWQGLPSPVDAAFEDAQGHIWFFQG
corresponding to amino acids 165-359 of MM11_HUMAN (SEQ ID
NO:1455), which also corresponds to amino acids 149-343 of
HSSTROL3_P9 (SEQ ID NO:1398), and a fourth amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence TTGVSTPAPGV (SEQ ID
NO: 253) corresponding to amino acids 344-354 of HSSTROL3_P9 (SEQ
ID NO:1398), wherein said first amino acid sequence, second amino
acid sequence, bridging amino acid, third amino acid sequence and
fourth amino acid sequence are contiguous and in a sequential
order.
[2895] 2. An isolated chimeric polypeptide encoding for an edge
portion of HSSTROL3_P9 (SEQ ID NO:1398), comprising a polypeptide
having a length "n", wherein n is at least about 10 amino acids in
length, optionally at least about 20 amino acids in length,
preferably at least about 30 amino acids in length, more preferably
at least about 40 amino acids in length and most preferably at
least about 50 amino acids in length, wherein at least two amino
acids comprise KR, having a structure as follows: a sequence
starting from any of amino acid numbers 96-x to 96; and ending at
any of amino acid numbers 97+((n-2)-x), in which x varies from 0 to
n-2.
[2896] 3. An isolated polypeptide encoding for a tail of
HSSTROL3_P9 (SEQ ID NO:1398), comprising a polypeptide being at
least 70%, optionally at least about 80%, preferably at least about
85%, more preferably at least about 90% and most preferably at
least about 95% homologous to the sequence TTGVSTPAPGV (SEQ ID NO:
253) in HSSTROL3_P9 (SEQ ID NO:1398).
[2897] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[2898] Variant protein HSSTROL3_P9 (SEQ ID NO:1398) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1048, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:1398)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01108 TABLE 1048 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
38 V -> A Yes 198 A -> No 307 Q -> H Yes
[2899] Variant protein HSSTROL3_P9 (SEQ ID NO:1398) is encoded by
the following transcript(s): HSSTROL3_T12 (SEQ ID NO:130), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HSSTROL3_T12 (SEQ ID NO:130) is
shown in bold; this coding portion starts at position 24 and ends
at position 1085. The transcript also has the following SNPs as
listed in Table 1049 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSSTROL3_P9 (SEQ ID NO:1398)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01109 TABLE 1049 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
136 T -> C Yes 615 G -> No 651 -> T No 944 G -> C Yes
1275 C -> No 1327 C -> A Yes 1353 A -> T Yes 1570 -> G
No 1579 -> G No 1593 C -> No 1612 -> A No 1638 T -> C
No 1696 A -> No 1696 A -> C No 1846 A -> No 1846 A -> C
No 1876 T -> C Yes 2023 -> T No
[2900] As noted above, cluster HSSTROL3 features 16 segment(s),
which were listed in Table 1035 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[2901] Segment cluster HSSTROL3_node.sub.--6 (SEQ ID NO:887)
according to the present invention is supported by 14 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1050 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01110 TABLE 1050 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 1 131 HSSTROL3_T8 (SEQ ID NO: 126) 1
131 HSSTROL3_T9 (SEQ ID NO: 127) 1 131 HSSTROL3_T10 (SEQ ID NO:
128) 1 131 HSSTROL3_T11 (SEQ ID NO: 129) 1 131 HSSTROL3_T12 (SEQ ID
NO: 130) 1 131
[2902] Segment cluster HSSTROL3_node.sub.--10 (SEQ ID NO:888)
according to the present invention is supported by 21 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1051 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01111 TABLE 1051 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 132 313 HSSTROL3_T8 (SEQ ID NO: 126)
132 313 HSSTROL3_T9 (SEQ ID NO: 127) 132 313 HSSTROL3_T10 (SEQ ID
NO: 128) 132 313 HSSTROL3_T11 (SEQ ID NO: 129) 132 313 HSSTROL3_T12
(SEQ ID NO: 130) 132 313
[2903] Segment cluster HSSTROL3_node.sub.--13 (SEQ ID NO:889)
according to the present invention is supported by 36 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1052 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01112 TABLE 1052 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 362 505 HSSTROL3_T8 (SEQ ID NO: 126)
362 505 HSSTROL3_T9 (SEQ ID NO: 127) 362 505 HSSTROL3_T10 (SEQ ID
NO: 128) 362 505 HSSTROL3_T11 (SEQ ID NO: 129) 362 505 HSSTROL3_T12
(SEQ ID NO: 130) 314 457
[2904] Segment cluster HSSTROL3_node.sub.--15 (SEQ ID NO:890)
according to the present invention is supported by 47 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1053 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01113 TABLE 1053 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 506 639 HSSTROL3_T8 (SEQ ID NO: 126)
506 639 HSSTROL3_T9 (SEQ ID NO: 127) 506 639 HSSTROL3_T10 (SEQ ID
NO: 128) 506 639 HSSTROL3_T11 (SEQ ID NO: 129) 506 639 HSSTROL3_T12
(SEQ ID NO: 130) 458 591
[2905] Segment cluster HSSTRO3_node.sub.--19 (SED ID NO:891)
according to me present invention is supported by 63 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HSSTROL3_T5
(SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126), HSSTROL3_T9 (SEQ ID
NO:127), HSSTROL3_T10 (SEQ ID NO:128), HSSTROL3_T11 (SEQ ID NO:129)
and HSSTROL3_T12 (SEQ ID NO:130). Table 1054 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01114 TABLE 1054 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 699 881 HSSTROL3_T8 (SEQ ID NO: 126)
699 881 HSSTROL3_T9 (SEQ ID NO: 127) 699 881 HSSTROL3_T10 (SEQ ID
NO: 128) 699 881 HSSTROL3_T11 (SEQ ID NO: 129) 699 881 HSSTROL3_T12
(SEQ ID NO: 130) 651 833
[2906] Segment cluster HSSTROL3_node.sub.--21 (SEQ ID NO:892)
according to the present invention is supported by 61 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1055 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01115 TABLE 1055 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 882 1098 HSSTROL3_T8 (SEQ ID NO: 126)
882 1098 HSSTROL3_T9 (SEQ ID NO: 127) 882 1098 HSSTROL3_T10 (SEQ ID
NO: 128) 882 1098 HSSTROL3_T11 (SEQ ID NO: 129) 974 1190
HSSTROL3_T12 (SEQ ID NO: 130) 834 1050
[2907] Segment cluster HSSTROL3_node.sub.--24 (SEQ ID NO:893)
according to the present invention is supported by 7 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HSSTROL3_T8
(SEQ ID NO:126) and HSSTROL3_T9 (SEQ ID NO:127). Table 1056 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01116 TABLE 1056 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T8 (SEQ ID NO: 126) 1099 1236 HSSTROL3_T9 (SEQ ID NO: 127)
1099 1236
[2908] Segment cluster HSSTROL3_node.sub.--25 (SEQ ID NO:894)
according to the present invention is supported by 13 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T8 (SEQ ID NO:126). Table 1057 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01117 TABLE 1057 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T8 (SEQ ID NO: 126) 1237 1536
[2909] Segment cluster HSSTRO3_node.sub.--26 (SEQ ID NO:895)
according to the present invention is supported by 55 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127) and HSSTROL3_T11 (SEQ ID NO:129). Table
1058 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01118 TABLE 1058 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 1099 1240 HSSTROL3_T8 (SEQ ID NO: 126)
1537 1678 HSSTROL3_T9 (SEQ ID NO: 127) 1237 1378 HSSTROL3_T11 (SEQ
ID NO: 129) 1191 1332
[2910] Segment cluster HSSTROL3_node.sub.--28 (SEQ ID NO:896)
according to the present invention is supported by 10 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T9 (SEQ ID NO:127) and
HSSTROL3_T10 (SEQ ID NO:128). Table 1059 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01119 TABLE 1059 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSSTROL3_T5 (SEQ ID NO: 125) 1357 2283 HSSTROL3_T9 (SEQ ID NO: 127)
1495 2421 HSSTROL3_T10 (SEQ ID NO: 128) 1215 2141
[2911] Segment cluster HSSTROL3_node.sub.--29 (SEQ ID NO:897)
according to the present invention is supported by 109 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1060 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01120 TABLE 1060 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 2284 3194 HSSTROL3_T8 (SEQ ID NO: 126)
1795 2705 HSSTROL3_T9 (SEQ ID NO: 127) 2422 3332 HSSTROL3_T10 (SEQ
ID NO: 128) 2142 3052 HSSTROL3_T11 (SEQ ID NO: 129) 1449 2359
HSSTROL3_T12 (SEQ ID NO: 130) 1167 2077
[2912] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[2913] Segment cluster HSSTROL3_node.sub.--11 (SEQ ID NO:898)
according to the present invention is supported by 25 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128) and
HSSTROL3_T11 (SEQ ID NO:129). Table 1061 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01121 TABLE 1061 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 314 361 HSSTROL3_T8 (SEQ ID NO: 126)
314 361 HSSTROL3_T9 (SEQ ID NO: 127) 314 361 HSSTROL3_T10 (SEQ ID
NO: 128) 314 361 HSSTROL3_T11 (SEQ ID NO: 129) 314 361
[2914] Segment cluster HSSTROL3_node.sub.--17 (SEQ ID NO:899)
according to the present invention is supported by 45 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1062 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01122 TABLE 1062 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 640 680 HSSTROL3_T8 (SEQ ID NO: 126)
640 680 HSSTROL3_T9 (SEQ ID NO: 127) 640 680 HSSTROL3_T10 (SEQ ID
NO: 128) 640 680 HSSTROL3_T11 (SEQ ID NO: 129) 640 680 HSSTROL3_T12
(SEQ ID NO: 130) 592 632
[2915] Segment cluster HSSTROL3_node.sub.--18 (SEQ ID NO:900)
according to the present invention can be found in the following
transcript(s): HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID
NO:126), HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1063 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01123 TABLE 1063 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 681 698 HSSTROL3_T8 (SEQ ID NO: 126)
681 698 HSSTROL3_T9 (SEQ ID NO: 127) 681 698 HSSTROL3_T10 (SEQ ID
NO: 128) 681 698 HSSTROL3_T11 (SEQ ID NO: 129) 681 698 HSSTROL3_T12
(SEQ ID NO: 130) 633 650
[2916] Segment cluster HSSTROL3_node.sub.--20 (SEQ ID NO:901)
according to the present invention is supported by 1 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): HSSTROL3_T11
(SEQ ID NO:129). Table 1064 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01124 TABLE 1064 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T11 (SEQ ID NO: 129) 882 973
[2917] Segment cluster HSSTROL3_node.sub.--27 (SEQ ID NO:902)
according to the present invention is supported by 50 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSSTROL3_T5 (SEQ ID NO:125), HSSTROL3_T8 (SEQ ID NO:126),
HSSTROL3_T9 (SEQ ID NO:127), HSSTROL3_T10 (SEQ ID NO:128),
HSSTROL3_T11 (SEQ ID NO:129) and HSSTROL3_T12 (SEQ ID NO:130).
Table 1065 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01125 TABLE 1065 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSSTROL3_T5 (SEQ ID NO: 125) 1241 1356 HSSTROL3_T8 (SEQ ID NO: 126)
1679 1794 HSSTROL3_T9 (SEQ ID NO: 127) 1379 1494 HSSTROL3_T10 (SEQ
ID NO: 128) 1099 1214 HSSTROL3_T11 (SEQ ID NO: 129) 1333 1448
HSSTROL3_T12 (SEQ ID NO: 130) 1051 1166
Variant protein alignment to the previously known protein:
TABLE-US-01126 ##STR00747## ##STR00748## ##STR00749## ##STR00750##
##STR00751## ##STR00752## ##STR00753## ##STR00754## ##STR00755##
##STR00756##
[2918] The data given below shows that HSSTROL3 splice variants of
the present invention can be used as useful diagnostic agents for
lung cancer. In particular, differential overexpression in lung
cancer cells (as opposed to normal lung cells and normal tissue of
other types) was demonstrated through determination of mRNA
expression, while antibodies selective for HSSTROL3_P9 (SEQ ID
NO:1398) splice variant were found to be capable of detecting
HSSTROL3_P9 (SEQ ID NO:1398) splice variant in human serum (blood
samples), further confirming the existence of HSSTROL3_P9 (SEQ ID
NO:1398) splice variant protein. HSSTROL3_P9 (SEQ ID NO:1398)
splice variant protein was found consistently to be present in one
serum sample taken from a patient with a lung cancer and not in any
other healthy subjects, suggesting a differential expression in
serum samples derived from lung cancer patients as compared to
healthy individuals, thereby supporting the utility of HSSTROL3_P9
(SEQ ID NO:1398) splice variant as a diagnostic agent for lung
cancer.
Expression of Stromelysin-3 Precursor HSSTROL3 Transcripts which
are Detectable by Amplicon as Depicted in Sequence Same HSSTROL3
seg24 (SEQ ID NO: 1675) in Normal and Cancerous Lung Tissues
[2919] Expression of Stromelysin-3 precursor (EC 3.4.24.-) (Matrix
metalloproteinase-11) (MMP-11) (ST3) (SL-3) transcripts detectable
by or according to seg24, HSSTROL3 seg24 amplicon (SEQ ID NO: 1675)
and HSSTROL3 seg24F (SEQ ID NO: 1673) and HSSTROL3 seg24R (SEQ ID
NO: 1674) primers was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334),
HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2 "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[2920] FIG. 39 is a histogram showing over expression of the
above-indicated Stromelysin-3 precursor transcripts in cancerous
lung samples relative to the normal samples. Values represent the
average of duplicate experiments. Error bars indicate the minimal
and maximal values obtained.)
[2921] As is evident from FIG. 39, the expression of Stromelysin-3
precursor transcripts detectable by the above amplicon(s) in cancer
samples was significantly higher than in the non-cancerous samples
(Sample Nos. 47-50, 90-93, 96-99 Table 2, "Tissue samples in
testing panel"). Notably an over-expression of at least 5 fold was
found in 13 out of 15 adenocarcinoma samples, 8 out of 16 squamous
cell carcinoma samples, 3 out of 4 large cell carcinoma samples and
in 7 out of 8 small cell carcinoma samples.
[2922] Threshold of 5 fold overexpression was found to
differentiate between cancer and normal samples with P value of
4.04E-04 in adenocarcinoma, 9.89E-02 in squamous cell carcinoma,
6.04E-02 in Large cell carcinoma, 3.14E-03 in small cell carcinoma
as checked by exact fisher test. The above values demonstrate
statistical significance of the results.
[2923] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: HSSTROL3
seg24F forward primer (SEQ ID NO: 1673); and HSSTROL3 seg24R
reverse primer (SEQ ID NO: 1674).
[2924] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: HSSTROL3 seg24 (SEQ ID NO: 1675).
TABLE-US-01127 Forward Primer (SEQ ID NO: 1673):
ATTTCCATCCTCAACTGGCAGA Reverse Primer (SEQ ID NO: 1674):
TGCCCTGGAACCCACG Amplicon (SEQ ID NO: 1675):
ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCC
AGGGACTTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAG GGCA
Expression of Stromelysin-3 Precursor HSSTROL3 Transcripts which
are Detectable by Amplicon as Depicted in Sequence Name HSSTROL3
seg24 (SEQ ID NO: 1675) in Different Normal Tissues
[2925] Expression of Stromelysin-3 precursor transcripts detectable
by or according to HSSTROL3 seg24 amplicon (SEQ ID NO: 1675) and
HSSTROL3 seg24F (SEQ ID NO: 1673) and HSSTROL3 seg24R (SEQ ID NO:
1674) was measured by real time PCR. In parallel the expression of
four housekeeping genes Ubiquitin (GenBank Accession No. BC000449
(SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and
SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), RPL19 (GenBank Accession
No. NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ ID
NO:1630), TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID
NO:1716); TATA amplicon, SEQ ID NO:1633) was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the lung samples
(Sample Nos. 15-17, Table 2 "Tissue samples in normal panel",
above), to obtain a value of relative expression of each sample
relative to median of the lung samples.
TABLE-US-01128 Forward Primer (SEQ ID NO: 1673):
ATTTCCATCCTCAACTGGCAGA Reverse Primer (SEQ ID NO: 1674):
TGCCCTGGAACCCACG Amplicon (SEQ ID NO: 1675):
ATTTCCATCCTCAACTGGCAGAGATGAGAGCCTGGAGCATTGCAGATGCC
AGGGACTTCACAAATGAAGGCACAGCATGGGAAACCTGCGTGGGTTCCAG GGCA
[2926] The results are demonstrated in FIG. 40, showing the
expression of Stromelysin-3 HSSTROL3 transcripts, which are
detectable by amplicon as depicted in sequence name HSSTROL3 seg24
(SEQ ID NO: 1675), in different normal tissues.
Expression of Homo sapiens Matrix Metalloproteinase 11 (Stromelysin
3) (MMP11) HSSTROL3 Transcripts which are Detectable by Amplicon as
Depicted in Sequence Name HSSTROL3 seg20-21 (SEQ ID NO: 1678) in
Normal and Cancerous Lung Tissues
[2927] Expression of Homo sapiens matrix metalloproteinase 11
(stromelysin 3) (MMP11) transcripts detectable by or according to
seg20-21, HSSTROL3 seg20-21 amplicon (SEQ ID NO: 1678) and primers
HSSTROL3 seg20-21F (SEQ ID NO: 1676) and HSSTROL3 seg20-21R (SEQ ID
NO: 1677) was measured by real time PCR. In parallel the expression
of four housekeeping genes--PBGD (GenBank Accession No. BC019323
(SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[2928] FIG. 71 is a histogram showing over expression of the
above-indicated Homo sapiens matrix metalloproteinase 11
(stromelysin 3) (MMP11) transcripts in cancerous lung samples
relative to the normal samples.
[2929] As is evident from FIG. 71, the expression of Homo sapiens
matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts
detectable by the above amplicon(s) in cancer samples was
significantly higher than in the non-cancerous samples (Sample Nos.
46-50, 90-93, 96-99 Table 2,). Notably an over-expression of at
least 6 fold was found in 11 out of 15 adenocarcinoma samples, 6
out of 16 squamous cell carcinoma samples, 1 out of 4 large cell
carcinoma samples and in 6 out of 8 small cells carcinoma
samples.
[2930] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: HSSTROL3
seg20-21F forward primer (SEQ ID NO: 1676); and HSSTROL3 seg20-21R
reverse primer (SEQ ID NO: 1677).
[2931] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: HSSTROL3 seg20-21 (SEQ ID NO: 1678).
TABLE-US-01129 Forward primer HSSTROL3 seg20-21F (SEQ ID NO: 1676):
TCTGCTGGCCACTGTGACTG Reverse primer HSSTROL3 seg20-21R (SEQ ID NO:
1677): GAAGAAAAAGAGCTCGCCTCG Amplicon HSSTROL3 seg20-21 (SEQ ID NO:
1678): TCTGCTGGCCACTGTGACTGCAGCATATGCCCTCAGCATGTGTCCCTCTC
TCCCACCCCAGCCAGACGCCCCGCCAGATGCCTGTGAGGCCTCCTTTGAC
GCGGTCTCCACCATCCGAGGCGAGCTCTTTTTCTTC
Expression of Homo sapiens Matrix Metalloproteinase 11 (Stromelysin
3) (MMP11) HSSTROL3 Transcripts which are Detectable by Amplicon as
Depicted in Sequence Name HSSTROL3 junc21-27 (SEQ ID NO: 1681) in
Normal and Cancerous Lung Tissues
[2932] Expression of Homo sapiens matrix metalloproteinase 11
(stromelysin 3) (MMP11) transcripts detectable by or according to
junc21-27, HSSTROL3 junc21-27 amplicon (SEQ ID NO: 1681) and
primers HSSTROL3 junc21-27F (SEQ ID NO: 1679) and HSSTROL3
junc21-27R (SEQ ID NO: 1680) was measured by real time PCR. In
parallel the expression of four housekeeping genes--PBGD (GenBank
Accession No. BC019323 (SEQ ID NO:1713); amplicon--PBGD-amplicon,
SEQ ID NO:334), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ
ID NO:1714); amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin
(GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), was measured similarly.
For each RT sample, the expression of the above amplicon was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[2933] FIG. 72 is a histogram showing over expression of the
above-indicated Homo sapiens matrix metalloproteinase 11
(stromelysin 3) (MMP11) transcripts in cancerous lung samples
relative to the normal samples.
[2934] As is evident from FIG. 72, the expression of Homo sapiens
matrix metalloproteinase 11 (stromelysin 3) (MMP11) transcripts
detectable by the above amplicon(s) in cancer samples was
significantly higher than in the non-cancerous samples (Sample Nos.
46-50, 90-93, 96-99 Table 2,). Notably an over-expression of at
least 10 fold was found in 15 out of 15 adenocarcinoma samples, 13
out of 16 squamous cell carcinoma samples, 3 out of 4 large cell
carcinoma samples and in 5 out of 8 small cells carcinoma
samples.
[2935] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: HSSTROL3
junc21-27F forward primer (SEQ ID NO: 1679); and HSSTROL3
junc21-27R reverse primer (SEQ ID NO: 1680).
[2936] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: HSSTROL3 junc21-27 (SEQ ID NO: 1681).
TABLE-US-01130 Forward primer HSSTROL3 junc21-27F (SEQ ID NO:
1679): ACATTTGGTTCTTCCAAGGGACTAC Reverse primer HSSTROL3 junc21-27R
(SEQ ID NO: 1680): TCGATCTCAGAGGGCACCC Amplicon HSSTROL3 junc21-27
(SEQ ID NO: 1681):
ACATTTGGTTCTTCCAAGGGACTACTGGCGTTTCCACCCCAGCACCCGGC
GTGTAGACAGTCCCGTGCCCCGCAGGGCCACTGACTGGAGAGGGGTGCCC TCTGAGATCGA
[2937] FIG. 72 is a histogram showing over expression of the Homo
sapiens matrix metalloproteinase 11 (stromelysin 3) (MMP11)
HSSTROL3 transcripts which are detectable by amplicon as depicted
in sequence name HSSTROL3 junc21-27 (SEQ ID NO:1681) in cancerous
lung samples relative to the normal samples. The transcript
encoding for HSSTROL3_T12 splice variant (SEQ ID NO:130)) was shown
to be specifically differentially overexpressed in lung cancer
tissue samples. The junction HSSTROL3 junc21-27 (SEQ ID NO:1681)
between two nodes is unique to this polynucleotide and hence shows
that this protein would be predicted to be overexpressed in lung
cancer. It should be noted for the sake of completeness that this
junction is present also in one other sequence, HSSTROL3_T12 (SEQ
ID NO:128); however, only SEQ ID NO:130 was verified as being
expressed as a full length sequence. The full length mRNA identical
to SEQ ID NO:130 was published (after the priority date of the
present application) in GenBank with accession number AK075448
[gi:22761543].
[2938] 1. HSSTROL3 P9 (SEQ ID NO:1398) Splice Variant is Detected
in Serum Samples.
[2939] Antibodies were raised against peptides corresponding to
HSSTROL3_P9 (SEQ ID NO:1398) splice variant. Antibodies raised
against HSSTROL3_P9 (SEQ ID NO:1398) splice variant showed that
HSSTROL3_P9 (SEQ ID NO:1398) splice variant protein was found
consistently to be present in one serum sample taken from a patient
with a small cell lung carcinoma and not in any other healthy
subjects, suggesting a differential expression in serum samples
derived from lung cancer patients as compared to healthy
individuals, thereby supporting the utility of HSSTROL3_P9 (SEQ ID
NO:1398) splice variant as a diagnostic agent for lung cancer. The
experiments were performed as described in greater detail
below.
[2940] As a tool for antibody development and ELISA assay
development, both recombinant HSSTROL3_P9 (SEQ ID NO:1398) splice
variant (MMP11.sub.--354) and wild type WT MMP11 (SEQ ID NO:1455)
(MMP11.sub.--488) proteins were produced. The two genes were
originally cloned into mammalian vectors, and then corresponding
DNA fragments were transferred from the mammalian vectors into
bacterial expression vectors. The protein was produced and purified
from bacterial cells.
[2941] 1.1 Cloning and Expression of HSSTROL3_P9 (SEQ ID NO:1398)
and WT MMP11 (SEQ ID NO:1455).
[2942] 1.1.1 Cloning of HSSTROL3 P9 (SEQ ID NO:1398) and WT MMP11
(SEQ ID NO:1455)
[2943] The following sequences were codon optimized to boost
protein expression in mammalian system: the active domain of WT
MMP11 (SEQ ID NO:1455) (amino acids 114-end, (SEQ ID NO:1782)), and
the active domain of HSSTROL3_P9 (SEQ ID NO:1398) (amino acids
98-end, (SEQ ID NO:1783)). In addition, bacterial low usage codons
were eliminated to enable bacterial expression of the variants
using the same sequences.
[2944] The optimized genes were synthesized by GeneArt (Germany) by
using their proprietary gene synthesis technology with the addition
of DNA sequences encoding the His-tag downstream to the ectopic IL6
signal peptide. The His tag protein sequence was added in order to
allow an easier purification of the expressed proteins can. The
resultant DNA sequences of HSSTROL3_P9 (SEQ ID NO: 1783)
(MMP11.sub.--354) and WT MMP11 (SEQ ID NO: 1782) (MMP11.sub.--488)
including the tag sequence are shown in FIG. 86; while the amino
acid sequences are shown in FIG. 87 (SEQ ID NO: 1785 and SEQ ID NO:
1784, respectively). The DNA fragments were cloned into EcoRI/NotI
sites of pIRESpuro3 (Clontech, cat #PT3646-5) (FIG. 88) and the
sequences were verified.
[2945] 1.1.2 Bacterial Cloning and Expression of MMP11 Proteins
[2946] WT MMP11 (MMP11.sub.--488) and HSSTROL3_P9 (MMP11.sub.--354)
inserts, encoding WT MMP11 (MMP11.sub.--488) (SEQ ID NO:1786) and
HSSTROL3_P9 (MMP11.sub.--354) (SEQ ID NO:1787), were isolated from
MMP11.sub.--488 pIRESpuro3 and MMP11.sub.--354 pIRESpuro3,
respectively by double digestion with NcoI and Nod. The sites are
marked in the sequences in FIG. 86, and by arrows in FIG. 89.
[2947] The inserts were ligated to pET28 previously digested with
the same enzymes (plasmid maps and protein sequences are given in
FIGS. 89 and 90 respectively). The ligation mix was transformed
into DH5alpha competent cells. The transformation solutions were
plated on selective LB plates containing Kanamycin. Several
colonies from each transcript clone that grew on the selective
plates were taken for further analysis by re-plating on a selective
plate and by restriction enzyme analysis.
[2948] DNA from positive clones was extracted and transformed into
BL21 codon plus (DE3) RIL competent cells (Stratagene Cat no.
230245). Small scale expression was performed following induction
with 1 mM IPTG at 37.degree. C. for 3 hrs. Expression of the
recombinant proteins was detected in the whole cell lysates, both
by Coomassie staining (FIG. 91) and by Western blot (FIG. 92) using
anti-His antibodies (Serotec, Cat. #MCA1396).
[2949] 1.2. Bacterial Production of HSSTROL3_P9 (SEQ ID NO:1787)
and WT MMP11 (SEQ ID NO:1786).
[2950] Bacterial cultures expressing WT MMP11 (SEQ ID NO:1786) and
HSSTROL3_P9 (SEQ ID NO:1787) (pET28, BL21+codon) were prepared as
described above and 50 .mu.l culture were used to start production.
The cultures were propagated over-night in 50 ml LB medium
supplemented with selection antibiotics (Kanamycin 10 ug/ml,
Chloramphenicol 34 ug/ml), at 37.degree. C., 200 rpm and then
expanded to a final volume of 1 L each. After a few hours, when the
cultures reached OD.sub.600 of 0.5-0.7, induction was carried out
with 1 mM IPTG. Following three hours after induction, upon cells
reaching a density of 1.3-1.4 OD.sub.600, cultures were centrifuged
at 6000 g for 10 min and supernatant was discarded. Cell pellets
were stored at -20.degree. C. until purification.
[2951] 1.3 Purification of MMP11.sub.--354 (HSSTROL3_P9 (SEQ ID
NO:1787)) and MMP11.sub.--488 (WT MMP11) (SEQ ID NO:1786).
[2952] 1.3.1. Purification of HSSTROL3_P9 (MMP11 354) (SEQ ID
NO:1787)
[2953] The bacterial cell pellet of 1 liter culture expressing
HSSTROL3_P9 (MMP11.sub.--354, (SEQ ID NO:1787)) prepared as
described above, was re-suspended in 50 ml of lysis buffer (50 mM
Tris pH 7.5, 100 mM KCl, 0.5% triton x100, 0.1 mg/ml lysozyme) and
incubated for 1 hour at room temperature. The cells were further
disrupted by sonication on ice (Misonix XL2020, microtip). The
inclusion bodies were collected by centrifugation and washed 3
times with 30 ml wash buffer 1 (50 mM tris pH 7.5, 2M NaCl 0.5%
triton) and then twice with 30 ml wash buffer 2 (50 mM tris pH
7.5), by re-suspension and centrifugation as described above.
[2954] Washed inclusion bodies were resuspended in 1/20 original
culture volume of 8M urea buffer (8M urea, 50 mM tris, 10 mM DTT,
pH 8.5) and incubated for 2 hours at RT. The dissolved inclusion
bodies were diluted .times.10 in binding buffer (8M urea, 50 mM
tris, 300 mM NaCl 20 mM imidazole) and incubated for 17 hours at
37.degree. C. with Ni-NTA Superflow beads (Ni-NTA Superflow.RTM.,
IBA) that were equilibrated with 5 column volumes (CV) of WFI
followed by 10 CV of binding buffer with 1 mM DTT. The beads were
packed in XK16 column and washed with binding buffer containing 1
mM DU. The bound protein was eluted with elution buffer (8M urea,
50 mM Tris, 0.3M NaCl, 1 mM DTT, 0.25M imidazole, pH 8.0).
[2955] The eluted protein was diluted x8.3 with binding buffer+1 mM
DTT and refolded gradually by dialysis against buffer containing
decreasing urea concentrations in 50 mM tris pH 8.5, 100 mM NaCl,
10 mM CaCl.sub.2 and 100 .mu.M ZnCl.sub.2. The final buffer pH was
adjusted to 7.4.
[2956] After dialysis the refolded protein was filtered through
0.22 .mu.m filter and concentrated .times.5 on 10,000 MWCO membrane
(Amicon, Cat#PBGC06210). The concentrated protein was centrifuged
to eliminate aggregates.
[2957] A sample of the purified protein was analyzed by SDS-PAGE
stained by Coomassie (not shown). The identity of the proteins was
verified by LC-MS/MS.
[2958] 1.3.2. Purification of WT MMP11(MMP11 488, (SEQ ID
NO:1786))
[2959] The bacterial cell pellet of 1 liter culture expressing WT
MMP11 (MMP11.sub.--488) (SEQ ID NO:1786) prepared, as described
above, was re-suspended in 50 ml of lysis buffer (50 mM Tris pH
7.5, 100 mM KCl, 0.5% triton x100, 0.1 mg/ml lysozyme) and
incubated for 1 hour at room temperature. The cells were further
disrupted by sonication on ice (Misonix XL2020, microtip). The
inclusion bodies were collected by centrifugation and washed 3
times with 30 ml wash buffer 1 (50 mM tris pH 7.5, 2M NaCl 0.5%
triton) and then twice with 30 ml wash buffer 2 (50 mM tris pH
7.5), by re-suspension and centrifugation as described above.
[2960] Washed inclusion bodies were resuspended in 1/20 original
culture volume of 8M urea buffer (8M urea, 50 mM tris, 10 mM DTT,
pH 8.5) and incubated for 2 hours at RT. The dissolved inclusion
bodies were diluted 10.times. in binding buffer (8M urea, 50 mM
tris, 300 mM NaCl 20 mM imidazole) and incubated for 17 hours at
37.degree. C. with Ni-NTA Superflow beads (Ni-NTA Superflow.RTM.,
IBA) that were equilibrated with 5 column volumes (CV) of WFI
followed by 10 CV of binding buffer with 1 mM DTT. The beads were
packed in XK16 column and washed with binding buffer containing 1
mM DTT. The bound protein was eluted with elution buffer (8M urea,
50 mM Tris, 0.3M NaCl, 1 mM DTT, 0.25M imidazole, pH 8.0).
[2961] The eluted protein was treated with 10 mM DTI for 30 min at
room temperature and then diluted gradualy .times.8 with dilution
buffer (0.5M arginine, 50 mM tris pH 8.5, 100 mM NaCl, 5 mM
CaCl.sub.2, 1 .mu.M ZnCl.sub.2, 5% glycerol, 0.5% Tween 20, 1 mM
DTT pH 9). Following dialysis agianst the dilution buffer the
protein was dialysed against the final buffer containing 50 mM Tris
pH 7.4, 100 mM NaCl, 5 mM CaCl.sub.2, 1 .mu.M ZnCl.sub.2, 1 mM
DTT.
[2962] After dialysis the refolded protein was filtered through
0.22 um filter, concentrated .times.3-5 on 10,000 MWCO membrane and
the concentrated protein was centrifuged to eliminate aggregates. A
sample of the purified protein was analyzed by SDS-PAGE stained by
Coomassie (not shown). The identity of the proteins was verified by
LC-MS/MS.
[2963] 2 Antibody Development
[2964] In order to test HSSTROL3_P9 (SEQ ID NO:1398) protein
expression pattern in serum samples of diseased and healthy
individuals, both monoclonal and polyclonal antibodies were
developed that had sufficient binding specificity to permit the
specific analysis of this protein.
[2965] The antibody of interest had to recognize HSSTROL3_P9 (SEQ
ID NO:1398) without recognizing WT MMP11 (SEQ ID NO:1455).
Therefore, serum titers as well as resultant antibodies were tested
against both protein preparations following a successful
recognition of the immunogen.
[2966] 2.1 Peptide Design and Synthesis
[2967] One peptide was selected as immunogen for monoclonal and
polyclonal antibody development for the unique splice variant. The
peptide sequence of HSSTROL3_P9 (SEQ ID NO:1398) unique tail was
used as a template.
[2968] Selected immunogen: The primary sequence of the immunogen
peptide (CGEN6301, SEQ ID NO: 1781) is shown below. The terminal
cysteine residue was used to facilitate coupling via
m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to KLH. Ahx
stand for a 6-aminohexanoic acid. Peptide CGEN6301 (SEQ ID NO:
1781): CKK-Ahx-FFQGTTGVSTPAPGV
[2969] The peptide represents the C terminus of the protein;
therefore the C-terminus of the immunogen was left unblocked. The
peptide immunogen indicated above is overlaied on the primary
sequence of the protein (SEQ ID NO: 1398) is shown in FIG. 93.
[2970] The immunogen peptide was synthesized using a conventional
technology (50 mg; purity.gtoreq.90%). The peptide was conjugated
to Keyhole Limpet Hemocyanin (KLH) and Bovine Serum Albumin (BSA)
using an m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS)
linker.
[2971] 2.2 Rabbit Polyclonal Antibody Development 2.2.1. Rabbit
Immunization and Sera Testing
[2972] Three New Zealand White Rabbits (referred to herein by
number as 8350, 8351 and 8352) were immunized with CGEN6301
conjugated with KLH. Immunization schedule and production bleed
schedules are summarized in Tables 1066 and 1067, respectively.
TABLE-US-01131 TABLE 1066 Summary of rabbit immunization and test
bleed schedule. Scheduled Date Initial Injection Boost #1 Boost #2
Boost #3 (500 .mu.g (250 .mu.g (250 .mu.g (250 .mu.g Rabbit # Pre
Bleed ID/CFA) ID/IFA) SC/IFA) SC/IFA) Test Bleed #1 8350 Jun. 12,
2006 Jun. 16, 2006 Jun. 23, 2006 Jun. 30, 2006 Jul. 14, 2006 Jul.
24, 2006 8351 Jun. 12, 2006 Jun. 16, 2006 Jun. 23, 2006 Jun. 30,
2006 Jul. 14, 2006 Jul. 24, 2006 8352 Jun. 12, 2006 Jun. 16, 2006
Jun. 23, 2006 Jun. 30, 2006 Jul. 14, 2006 * * Rabbit 8352 expired
on Jul. 21, 2006
TABLE-US-01132 TABLE 1067 Summary of rabbit production bleed
schedule. Scheduled Date Rabbit Production Production Production
Production Production Production Production Production Terminal #
Bleed #1 Bleed #2 Bleed #3 Bleed #4 Bleed #5 Bleed #6 Bleed #7
Bleed #8 Bleed 8350 Aug. 3, 2006 Aug. 14, 2006 Aug. 21, 2006 Sep.
4, 2006 Sep. 11, 2006 Sep. 18, 2006 Sep. 25, 2006 Oct. 2, 2006 Nov.
6, 2006 8351 Aug. 3, 2006 Aug. 14, 2006 Aug. 21, 2006 Sep. 4, 2006
Sep. 11, 2006 Sep. 18, 2006 Sep. 25, 2006 Oct. 2, 2006 Nov. 6,
2006
[2973] Production bleeds were collected and antibody titers were
determined by ELISA using CGEN6301 peptide conjugated to BSA,
recombinant HSSTROL3_P9 (SEQ ID NO:1787) splice variant and WT
MMP11 (SEQ ID NO:1786) (not shown). Rabbit 8352 expired on Jul. 21,
2006 therefore; no test bleed and no production bleeds were
collected from this rabbit.
[2974] 2.2.2 Rabbit Polyclonal Antibody Affinity Purification
[2975] Affinity purification was performed on all production bleeds
collected from the two rabbits (8350 and 8351) using a CGEN6301
immunoaffinity resin. Two passes of PBS diluted antiserum (1:1)
were run on immunoaffinity resin prepared by coupling 10 mg of the
CGEN6301 peptide to agarose beads. The purified product was
concentrated to approximately 1 mg/ml and dialyzed against
1.times.PBS. The yield obtained from these purifications is
summarized in Table 1068 below.
TABLE-US-01133 TABLE 1068 Affinity purified antibody yield Lot
Number Rabbit Concentration Volume Total Yield Buffer 18976C 8350
1.20 mg/ml 45.0 ml 54.2 mg 0.02 M Potassium Phosphate, 0.15 M
Sodium Chloride, pH 7.2, 18977C 8351 1.15 mg/ml 75.0 ml 86.3 mg
0.02 M Potassium Phosphate, 0.15 M Sodium Chloride, pH 7.2,
[2976] Purified antibodies were assayed by ELISA for reactivity
towards the immunogen conjugated to BSA, recombinant splice variant
protein and wild type protein. Results are summarized in FIG. 94.
These two antibody preparations showed a good recognition of
HSSTROL3_P9 ((SEQ ID NO:1787) and low recognition of WT MMP11 (SEQ
ID NO:1786). Therefore, both lots were used for Assay
Development.
[2977] Reactivity of the purified antibodies to both the splice
variant and the wild type proteins was also tested by a Western
blot analysis. The results showed good recognition of HSSTROL3_P9
(SEQ ID NO:1787) splice variant and no recognition of the WT MMP11
(SEQ ID NO:1786) protein (see FIGS. 95 and 96).
[2978] 2.3. Mouse Monoclonal Antibody Development
[2979] 2.3.1 Mouse Immunization and Sera Testing
[2980] Twenty Balb/c mice were immunized with CGEN6301 conjugated
to KLH. Immunization and bleeding schedules are summarized in Table
1069.
TABLE-US-01134 TABLE 1069 Summary of Mouse Immunizations, Test
Bleeds and Final Boosting Schedules. Scheduled Date Initial
Injection Boost #1 Boost #2 (100 ug IP/ (50 ug IP/ Test Bleed (50
ug Test Boost #3 Test Bleed Final Boost Peptide # Pre-Bleed CFA)
IFA) #1 IP/IFA) Bleed #2 (50 ug IP/IFA) #3 (50 ug IP) CGEN6301 Jun.
20, Jun. 22, 2006 Jul. 06, 2006 Jul. 17, 2006 Jul. 27, 2006 Aug. 7,
2006 Sep. 19, 2006 Sep. 29, 2006 Aug. 25, 2006 2006 Aug. 26, 2006
Oct. 09, 2006
Test bleeds were collected and antibody titers were determined by
ELISA using CGEN6301 peptide conjugated to BSA, HSSTROL3_P9 (SEQ ID
NO:1787) splice variant and WT MMP11 protein (SEQ ID NO:1786) (data
not shown).
[2981] Out of twenty mice immunized with CGEN6301 peptide, 6 showed
high antibody titers to HSSTROL3_P9 (SEQ ID NO:1787) splice variant
and limited recognition of the WT MMP11 protein (SEQ ID NO:1786).
These were selected for hybridoma production.
[2982] 2.3.2. Cell Fusion and Screening
[2983] Hybridoma cell lines were developed by performing
splenocyte:myeloma fusions using the spleens from two mice for each
fusion. Three fusions in total, were performed using the best mice
responders. The fusion partner used was the SP2/0 Ag 14 (CRL-1581)
myeloma cell line. The splenocytes and cell line were fused using
polyethylene glycol. The fused cells were allowed to grow for 7-10
days prior to screening. The resulting hybridoma clones were
screened by a two step strategy described below: [2984] 1. Primary
Screening Step [2985] a. Direct ELISA using Cgen6301 peptide-BSA
conjugate: Only positive reacting clones with sufficiently high
titers (OD at 450 nm >2) were carried forward. [2986] b. Class
and subclass determination: Positive clones were expanded and
isotyped to determine antibody class and subclass. Only IgG class
antibodies were carried forward. The preferred order of subclass
clones is: IgG.sub.1>IgG.sub.2a>IgG.sub.2b>IgG.sub.3.
[2987] Clones that were approved by the primary screening criteria
were transferred for secondary screening. [2988] 2. Secondary
Screening Step: Direct ELISA using HSSTROL3_P9 (SEQ ID NO:1787)
splice variant protein and WT MMP11 (SEQ ID NO:1786) protein. Only
clones reacting positively with the splice variant and negatively
with the wild type protein were carried forward. Data collected
during the secondary screening of post-fusion products is
summarized in Table 1070 below.
TABLE-US-01135 [2988] TABLE 1070 Summary of Secondary Screening
Results for Post-Fusion Clones. Reactivity in Direct ELISA Peptide
Parental Clone (OD 450 nm) Immunogen Designation Isotype(s)
Peptide-BSA SVr WT CGEN6301 13E1 IgG3 3.404 >4.000 0.125 5A10
IgG3 3.073 >4.000 0.106 7B7 IgG3 2.794 >4.000 0.088 5A8 *
1.900 3.837 0.084 12F6 * 2.101 1.789 0.100 5C6 * 2.337 >4.000
0.130 7G5 * 2.149 2.725 0.099 7G11 IgG1 2.274 2.602 0.115 5F6 IgG3
2.104 3.945 0.120 5D5 IgG3 2.004 >4.000 0.153 5D6 IgG3 2.763
>4.000 0.143 * - Mixed population-parental clones demonstrated
more then one isotype, once determined monoclonal the clones were
re-isotyped
[2989] A total of 11 positive parental clones were identified for
HSSTROL3_P9 (SEQ ID NO:1398) project.
[2990] These were then transferred for expansion and subcloning in
order to prepare monoclonal cell populations.
[2991] 2.3.3. Subcloning and Colony Expansion
[2992] Up to 2 subclones per positive parental clone were obtained
by limiting dilution for each of the 11 clones transferred to this
stage. All subclones generated in this step were evaluated by a
direct ELISA test with CGEN6301 peptide-BSA conjugate, HSSTROL3_P9
(SEQ ID NO:1787) splice variant and WT MMP11 (SEQ ID NO:1786)
proteins.
[2993] Table 1071 shows reactivity of successfully subcloned
parental cell lines produced from splenocyte fusions of animals
injected with CGEN6301. All subclones designated in table 1071 were
cryopreserved for future long term use.
TABLE-US-01136 TABLE 1071 Summary of Secondary Screening Results
for CGEN6301 Peptide Immunizations. Reactivity in Direct ELISA
Peptide Parental Clone Subclone (OD 450 nm) Immunogen Designation
Isotype(s) Designation Peptide-BSA SVr WT CGEN6301 5A10 IgG3/kappa
5A10.HI 3.441 >4.000 0.228 5A10 IgG3/kappa 5A10.H6 3.321
>4.000 0.211 13E1 IgG3/kappa 13E1.G1.F3 3.316 >4.000 0.143
13E1 IgG3/kappa 13E1.G1.G1 3.236 >4.000 0.159 7B7 IgG3/kappa
7B7.C12.E12 2.920 >4.000 0.114 7B7 IgG3/kappa 7B7.C12.F7 2.968
>4.000 0.108 5D6 IgG3/kappa 5D6.E3 3.548 3.906 0.248 5D6
IgG3/kappa 5D6.H4 3.502 3.929 0.290 5D5 IgG3/kappa 5D5.G1 3.613
>4.000 0.295 5D5 IgG3/kappa 5D5.G7 3.502 >4.000 0.290 7G11
IgG1/kappa 7G11.F6.E1 3.418 3.740 0.231 7G11 IgG1/kappa 7G11.F6.H4
3.211 3.746 0.208 5F6 IgG3/kappa 5F6.E9.F4 3.528 >4.000 0.299
5F6 IgG3/kappa 5F6.E9.F5 3.408 >4.000 0.322 5C6 IgG3/kappa
5C6.H5.H8.H 3.578 >4.000 0.282 5C6 IgG3/kappa 5C6.H5.H8.H 3.475
>4.000 0.297
[2994] 2.3.4. Monoclonal Antibody Production and Purification
[2995] Subclones demonstrating high titers to HSSTROL3_P9 (SEQ ID
NO:1787) and the immunogen peptide CGEN6301 low titers to WT MMP11
(SEQ ID NO:1786) were selected for antibody production (Table
1072).
TABLE-US-01137 TABLE 1072 Subclones Selected for Antibody
Production. Peptide Parental Clone Subclone Immunogen Designation
Isotype(s) Designation CGEN6301 13E1 IgG3/kappa 13E1.G1.F3 7G11
IgG1/kappa 7G11.F6.E1
[2996] Subclones listed in Table 1072 were cultured in 2,000 ml
roller bottles for antibody production. Protein A purification was
performed on 200 ml of .times.10 concentrated roller bottle
supernatant diluted with an equal volume of sample buffer. A single
pass was run over a Protein A sepharose column and the eluted
product was dialyzed against PBS. Prior to final vialing each
antibody was filter sterilized (0.22 um).
[2997] Antibody yield and concentration were determined after
purification using conventional methods and are summarized in Table
1073.
TABLE-US-01138 TABLE 1073 Monoclonal Antibody Yield and
Concentration. Protein Yield Peptide Subclone Concentration Volume
Amount Immunogen Designation (mg/ml) (ml) (mg) Lot# Buffer CGEN6301
13E1.G1.F3 2.26 mg/ml 58 ml 131 mg 18944C 0.02 M Potassium
Phosphate, 0.15 M Sodium Chloride, pH 7G11.F6.E1 1.37 mg/ml 68 ml
93 mg 19032C 0.02 M Potassium Phosphate, 0.15 M Sodium Chloride,
pH
[2998] Purified antibodies were assayed by ELISA for reactivity
towards CGEN6301 peptide (SEQ ID NO:1781) conjugated to BSA,
HSSTROL3_P9 (SEQ ID NO:1787) splice variant and WT MMP11 (SEQ ID
NO:1786). Results appear in FIG. 97. FIG. 97 shows that clone
13E1.G1.F3 (lot 18944C) has a higher recognition towards
HSSTROL3_P9 (SEQ ID NO:1787) splice variant and CGEN6301 (SEQ ID
NO:1781) peptide than clone 7G11.F6.E1 (antibody lot 19032).
[2999] 3. HSSTROL3_P9 (SEQ ID NO:1398) Assay Development
[3000] Next the Assay Development stage of HSSTROL3_P9 (SEQ ID
NO:1398) project was performed with serum samples of Non Small Cell
Lung Carcinoma patients and controls (ie patients who were not
suffering from lung cancer).
[3001] Four antibodies, described above, were used for assay
development [3002] Two polyclonal antibodies, (Rockland polyclonals
Rabbit 8350 & Rabbit 8351) developed against a synthetic
peptide CKK-Ahx-FFQGTTGVSTPAPGV (SEQ ID NO:1781) comprising the
unique tail of the HSSTROL3_P9 (SEQ ID NO:1398). [3003] Two
monoclonal antibodies (Rockland monoclonals clone 13E1.G1.F3 and
clone 7G11.F6.E1) developed against a synthetic peptide
CKK-Ahx-FFQGTTGVSTPAPGV (SEQ ID NO:1781) comprising the unique tail
of HSSTROL3_P9 (SEQ ID NO:1398). Three ELISA formats were developed
in order to identify the most sensitive assay format for the
detection of HSSTROL3_P9 (SEQ ID NO:1398) splice variant protein in
serum: [3004] Sandwich ELISA [3005] Antibody capture competitive
ELISA [3006] Antigen capture competitive ELISA
[3007] 3.1. Sandwich ELISA
[3008] In order to find the best sandwich pair, various
combinations of antibodies raised in different hosts were tested
for their ability to detect serial dilutions of HSSTROL3_P9 (SEQ ID
NO:1787) spiked in serum. Antibodies from the same host were not
tested in this format.
[3009] The best sandwich assay format for the detection of
HSSTROL3_P9 (SEQ ID NO:1398) was found to be: Format #1: [3010]
Coat: Mab 13E1.G1.F3 [3011] Detector Rabbit polyclonal (Rb 8351)
[3012] LOD for HSSTROL3_P9 (SEQ ID NO:1787) .about.30 ng/ml
[3013] 3.2 Competitive ELISA
[3014] Two competitive assay formats were developed: antibody
capture and antigen capture, and the best conditions were
determined to each format.
[3015] 3.2.1 Antigen Capture Competitive ELISA
[3016] ELISA plates were coated with HSSTROL3_P9 (SEQ ID NO:1787)
protein and binding to antibody pre-incubated with HSSTROL3_P9 (SEQ
ID NO:1787) protein-spiked serum samples was assessed.
[3017] The best optimized antigen capture assay was: Format #2:
[3018] Coat HSSTROL3_P9 (SEQ ID NO:1787) [3019] Detector Rabbit
polyclonal (Rabbit 8351) [3020] LOD for HSSTROL3_P9 (SEQ ID
NO:1787) .about.70 ng/ml
[3021] 3.2.2. Antibody Capture Competitive ELISA
[3022] ELISA plates were coated with the antibody and its binding
to labeled (biotinylated) HSSTROL3_P9 (SEQ ID NO:1787)
protein-spiked serum samples was assessed. Non-labeled HSSTROL3_P9
(SEQ ID NO:1787) protein was tested as competing antigen; mouse
13E1.G1.F3 and both rabbit antibodies were tested as capture
antibodies. The best optimized antibody capture assay format was:
Format #3: [3023] Coat Rabbit polyclonal (Rb 8351) [3024] Detector
HSSTROL3_P9 (SEQ ID NO:1787) biotin-labeled protein [3025] LOD for
HSSTROL3_P9 (SEQ ID NO:1787) .about.50 ng/ml
[3026] The sandwich ELISA (Format #1) appeared to be somewhat more
sensitive than both competitive formats (Formats #2 & 3).
Therefore, this format was selected for screening the serum
samples.
[3027] 4. Serum Screening
[3028] Serum screening of 50 serum samples from Non Small Cell Lung
Cancer (NSCLC) patients and 50 control sera were tested by using
the above described HSSTROL3_P9 (SEQ ID NO:1398) sandwich
assay.
[3029] 4.1 Serum Samples Screening by Sandwich ELISA (Format
#1)
[3030] The plates were coated overnight with mouse 13E1.G1.F1
antibody. Bound antigen was detected using rabbit 8351 antibodies.
50 sera from NSCLC patients, and 50 age and gender matched control
sera (ie from subjects not suffering from lung cancer) were tested
in this ELISA format. The 50 control serum samples consisted of 36
different samples plus duplicates of 14 of them. The reference
curve was prepared by diluting HSSTROL3_P9 (SEQ ID NO:1787) splice
variant protein into pooled normal serum.
[3031] The results showed that out of 100 samples tested in this
assay only one sample (patient 1388P) was detected.
[3032] In order to verify the results observed in the first serum
screening, a second serum screen was performed using the same
sandwich ELISA format. The same 50 NSCLC patients and 28 out of the
50 control sera samples were assayed. The results observed were
very similar to those obtained in the first serum test: the same
one sample (1388P) was detected. The results of the two serum
screens were therefore consistent.
[3033] The overall results suggest that HSSTROL3_P9 (SEQ ID
NO:1398) is probably present in serum samples from lung cancer
patients, however its concentration is too low to be detected by
this assay format.
Summary
[3034] A collection of monoclonal and polyclonal antibodies
specific for HSSTROL3_P9 (SEQ ID NO:1398) splice variant was
developed. These antibodies were used to test the potential of
HSSTROL3_P9 (SEQ ID NO:1398) to become a diagnostic biomarker for
Non Small Cell Lung Cancer diagnosis. A few ELISA formats were
developed using this antibody collection for the determination of
serum levels of HSSTROL3_P9 (SEQ ID NO:1398) splice variant in
healthy and diseased individuals. The sandwich ELISA format was
selected to test HSSTROL3_P9 (SEQ ID NO:1398) serum levels.
[3035] It appears that this ELISA format is not sufficiently
sensitive to detect expression of HSSTROL3_P9 (SEQ ID NO:1398) in
most of the tested samples. However HSSTROL3_P9 (SEQ ID NO:1398)
splice variant was found consistently to be present in one serum
sample, suggesting that it might be present also in other serum
samples but below the detection limit.
[3036] It is likely that improving assay sensitivity by 10 fold
through the use of antibodies with higher binding affinities or by
the use of novel detection technologies will allow the detection of
CenMMP11 in serum samples. A more sensitive test may reliably
enable the assessment of HSSTROL3_P9 (SEQ ID NO:1398) diagnostic
potential.
Conclusions
[3037] HSSTROL3_P9 (SEQ ID NO:1398) splice variant appears to be a
specific molecular diagnostic marker for lung cancer.
Description for Cluster HUMTREFAC
[3038] Cluster HUMTREFAC features 2 transcript(s) and 7 segment(s)
of interest, the names for which are given in Tables 1074 and 1075,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1076.
TABLE-US-01139 TABLE 1074 Transcripts of interest Transcript Name
Sequence ID No. HUMTREFAC_PEA_2_T4 131 HUMTREFAC_PEA_2_T5 132
TABLE-US-01140 TABLE 1075 Segments of interest Segment Name
Sequence ID No. HUMTREFAC_PEA_2_node_0 903 HUMTREFAC_PEA_2_node_9
904 HUMTREFAC_PEA_2_node_2 905 HUMTREFAC_PEA_2_node_3 906
HUMTREFAC_PEA_2_node_4 907 HUMTREFAC_PEA_2_node_5 908
HUMTREFAC_PEA_2_node_8 909
TABLE-US-01141 TABLE 1076 Proteins of interest Sequence Protein
Name ID No. Corresponding Transcript(s) HUMTREFAC_PEA_2_P7 1399
HUMTREFAC_PEA_2_T5 (SEQ ID NO: 132) HUMTREFAC_PEA_2_P8 1400
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131)
[3039] These sequences are variants of the known protein Trefoil
factor 3 precursor (SwissProt accession identifier TFF3_HUMAN;
known also according to the synonyms Intestinal trefoil factor;
hP1.B), SEQ ID NO: 1456, referred to herein as the previously known
protein.
[3040] Protein Trefoil factor 3 precursor (SEQ ID NO:1456) is known
or believed to have the following function(s): May have a role in
promoting cell migration (motogen). The sequence for protein
Trefoil factor 3 precursor is given at the end of the application,
as "Trefoil factor 3 precursor amino acid sequence". Known
polymorphisms for this sequence are as shown in Table 1077.
TABLE-US-01142 TABLE 1077 Amino acid mutations for Known Protein
SNP position(s) on amino acid sequence Comment 74-76 QEA ->
TRKT
[3041] Protein Trefoil factor 3 precursor (SEQ ID NO:1456)
localization is believed to be Secreted. The following GO
Annotation(s) apply to the previously known protein. The following
annotation(s) were found: defense response; digestion, which are
annotation(s) related to Biological Process; and extracellular,
which are annotation(s) related to Cellular Component.
[3042] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3043] Cluster HUMTREFAC can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the right hand column of the table and the numbers on
the y-axis of FIG. 41 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[3044] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 41 and Table 1078. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: a mixture of malignant tumors from
different tissues, breast malignant tumors, pancreas carcinoma and
prostate cancer.
TABLE-US-01143 TABLE 1078 Normal tissue distribution Name of Tissue
Number adrenal 40 colon 797 epithelial 95 general 39 liver 0 lung
57 lymph nodes 3 breast 0 muscle 3 pancreas 2 prostate 16 stomach 0
Thyroid 257 uterus 54
TABLE-US-01144 TABLE 1079 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 6.4e-01
6.9e-01 7.1e-01 1.1 7.8e-01 0.9 colon 4.6e-01 5.7e-01 9.7e-01 0.5 1
0.4 epithelial 2.4e-02 3.4e-01 9.5e-10 2.0 5.3e-02 1.1 general
2.5e-04 3.9e-02 1.4e-28 3.6 1.9e-10 1.9 liver 1 6.8e-01 1 1.0
6.9e-01 1.4 lung 4.8e-01 7.6e-01 2.2e-03 1.0 1.6e-01 0.5 lymph
nodes 5.1e-01 8.0e-01 2.3e-02 5.0 1.9e-01 2.1 breast 7.6e-02
1.2e-01 3.1e-06 12.0 1.1e-03 6.5 muscle 9.2e-01 4.8e-01 1 0.8
3.9e-01 2.1 pancreas 1.2e-01 2.4e-01 5.7e-03 6.5 2.1e-02 4.6
prostate 1.5e-01 2.7e-01 9.9e-10 8.1 3.1e-07 5.7 stomach 3.0e-01
1.3e-01 5.0e-01 2.0 6.7e-02 2.8 Thyroid 6.4e-01 6.4e-01 9.6e-01 0.5
9.6e-01 0.5 uterus 4.1e-01 7.3e-01 7.5e-02 1.3 4.0e-01 0.8
[3045] As noted above, cluster HUMTREFAC features 2 transcript(s),
which were listed in Table 1074 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Trefoil factor 3
precursor (SEQ ID NO:1456). A description of each variant protein
according to the present invention is now provided.
[3046] Variant protein HUMTREFAC_PEA.sub.--2_P7 (SEQ ID NO:1399)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). The location of the
variant protein was determined according to results from a number
of different software programs and analyses, including analyses
from SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[3047] Variant protein HUMTREFAC_PEA.sub.--2_P7 (SEQ ID NO:1399)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1080, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMTREFAC_PEA.sub.--2_P7 (SEQ ID NO:1399) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-01145 TABLE 1080 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
5 A -> S No 5 A -> T No 14 A -> V Yes 43 L -> M No 60 P
-> S Yes 123 S -> * Yes
[3048] Variant protein HUMTREFAC_PEA.sub.--2_P7 (SEQ ID NO:1399) is
encoded by the following transcript(s): HUMTREFAC_PEA.sub.--2_T5
(SEQ ID NO:132), for which the sequence(s) is/are given at the end
of the application. The coding portion of transcript
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132) is shown in bold; this
coding portion starts at position 278 and ends at position 688. The
transcript also has the following SNPs as listed in Table 1081
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is !mown or not; the presence of known SNPs in
variant protein HUMTREFAC_PEA.sub.--2_P7 (SEQ ID NO:1399) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01146 TABLE 1081 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
233 A -> G Yes 290 G -> A No 290 G -> T No 318 C -> T
Yes 404 C -> A No 404 C -> T No 455 C -> T Yes 645 C ->
A Yes 685 C -> T No
[3049] Variant protein HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131). An alignment is given to
the known protein (Trefoil factor 3 precursor (SEQ ID NO:1456)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[3050] Comparison report between HUMTREFAC_PEA.sub.--2_P8 (SEQ ID
NO:1400) and TFF3 HUMAN (SEQ ID NO:1456):
[3051] 1. An isolated chimeric polypeptide encoding for
HUMTREFAC_PEA2_P8 (SEQ ID NO:1400), comprising a first amino acid
sequence being at least 90% homologous to
MAARALCMLGLVLALLSSSSAEEYVGL corresponding to amino acids 1- 27 of
TFF3_HUMAN (SEQ ID NO:1456), which also corresponds to amino acids
1-27 of HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence WKVHLPKGEGFSSG (SEQ ID NO: 1774) corresponding to amino
acids 28-41 of HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[3052] 2. An isolated polypeptide encoding for a tail of
HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
WKVHLPKGEGFSSG (SEQ ID NO: 1774) in HUMTREFAC_PEA.sub.--2_P8 (SEQ
ID NO:1400).
[3053] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3054] Variant protein HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400)
also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1082, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-01147 TABLE 1082 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
5 A -> S No 5 A -> T No 14 A -> V Yes
[3055] Variant protein HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400) is
encoded by the following transcript(s): HUMTREFAC_PEA.sub.--2_T4
(SEQ ID NO:131), for which the sequence(s) is/are given at the end
of the application. The coding portion of transcript
HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) is shown in bold; this
coding portion starts at position 278 and ends at position 400. The
transcript also has the following SNPs as listed in Table 1083
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HUMTREFAC_PEA.sub.--2_P8 (SEQ ID NO:1400) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01148 TABLE 1083 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
233 A -> G Yes 290 G -> A No 290 G -> T No 318 C -> T
Yes 515 C -> A No 515 C -> T No 566 C -> T Yes 756 C ->
A Yes 796 C -> T No 1265 A -> C No 1266 A -> T No
[3056] As noted above, cluster HUMTREFAC features 7 segment(s),
which were listed in Table 2 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[3057] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--0 (SEQ ID
NO:903) according to the present invention is supported by 188
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) and
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1084 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01149 TABLE 1084 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 1 359 HUMTREFAC_PEA_2_T5 (SEQ
ID NO: 132) 1 359
[3058] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--9 (SEQ ID
NO:904) according to the present invention is supported by 150
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) and
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1085 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01150 TABLE 1085 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 681 1266 HUMTREFAC_PEA_2_T5
(SEQ ID NO: 132) 570 747
[3059] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3060] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--2 (SEQ ID
NO:905) according to the present invention is supported by 4
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131). Table 1086
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01151 TABLE 1086 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 360 470
[3061] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--3 (SEQ ID
NO:906) according to the present invention is supported by 10
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) and
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1087 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01152 TABLE 1087 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 471 514 HUMTREFAC_PEA_2_T5 (SEQ
ID NO: 132) 360 403
[3062] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--4 (SEQ ID
NO:907) according to the present invention is supported by 197
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) and
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1088 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01153 TABLE 1088 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 515 611 HUMTREFAC_PEA_2_T5 (SEQ
ID NO: 132) 404 500
[3063] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--5 (SEQ ID
NO:908) according to the present invention is supported by 187
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131) and
HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1089 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01154 TABLE 1089 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 612 661 HUMTREFAC_PEA_2_T5 (SEQ
ID NO: 132) 501 550
[3064] Segment cluster HUMTREFAC_PEA.sub.--2_node.sub.--8 (SEQ ID
NO:909) according to the present invention can be found in the
following transcript(s): HUMTREFAC_PEA.sub.--2_T4 (SEQ ID NO:131)
and HUMTREFAC_PEA.sub.--2_T5 (SEQ ID NO:132). Table 1090 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01155 TABLE 1090 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HUMTREFAC_PEA_2_T4 (SEQ ID NO: 131) 662 680 HUMTREFAC_PEA_2_T5 (SEQ
ID NO: 132) 551 569
Variant protein alignment to the previously known protein:
TABLE-US-01156 ##STR00757##
Description for Cluster HSS100PCB
[3065] Cluster HSS100PCB features 1 transcript(s) and 3 segment(s)
of interest, the names for which are given in Tables 1091 and 1092,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1093.
TABLE-US-01157 TABLE 1091 Transcripts of interest Transcript Name
Sequence ID No. HSS100PCB_T1 133
TABLE-US-01158 TABLE 1092 Segments of interest Segment Name
Sequence ID No. HSS100PCB_node_3 910 HSS100PCB_node_4 911
HSS100PCB_node_5 912
TABLE-US-01159 TABLE 1093 Proteins of interest Sequence Protein
Name ID No. Corresponding Transcript(s) HSS100PCB_P3 1401
HSS100PCB_T1 (SEQ ID NO: 133)
[3066] These sequences are variants of the known protein S-100P
protein (SwissProt accession identifier S10P_HUMAN), SEQ ID
NO:1457, referred to herein as the previously known protein, which
binds two calcium ions.
[3067] The sequence for protein S-100P protein (SEQ ID NO:1457) is
given at the end of the application, as "S-100P protein amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 1094.
TABLE-US-01160 TABLE 1094 Amino acid mutations for Known Protein
SNP position(s) on amino acid sequence Comment 32 E -> T 44 F
-> E
[3068] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: calcium binding;
protein binding, which are annotation(s) related to Molecular
Function.
[3069] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3070] Cluster HSS100PCB can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the right hand column of the table and the numbers on
the y-axis of FIG. 42 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[3071] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 42 and Table 1095. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: a mixture of malignant tumors from
different tissues.
TABLE-US-01161 TABLE 1095 Normal tissue distribution Name of Tissue
Number bladder 41 colon 37 epithelial 38 general 22 kidney 0 liver
0 lung 18 breast 0 bone marrow 0 ovary 0 pancreas 0 prostate 46
stomach 553 uterus 13
TABLE-US-01162 TABLE 1096 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bladder 3.3e-01
2.9e-01 2.9e-02 2.8 3.5e-02 2.8 colon 3.0e-01 1.9e-01 5.2e-01 1.2
2.4e-01 1.7 epithelial 4.7e-02 1.6e-02 2.0e-01 1.2 6.1e-02 1.3
general 1.1e-03 6.8e-05 1.4e-02 1.5 4.9e-04 1.7 kidney 6.5e-01
7.2e-01 5.8e-01 1.7 7.0e-01 1.4 liver 9.1e-01 4.9e-01 1 1.0 7.7e-02
2.1 lung 6.8e-01 7.3e-01 2.2e-02 2.9 1.3e-01 1.7 breast 2.8e-01
3.2e-01 4.7e-01 2.0 6.8e-01 1.5 bone marrow 1 6.7e-01 1 1.0 2.8e-01
2.8 ovary 2.6e-01 3.0e-01 4.7e-01 2.0 5.9e-01 1.7 pancreas 3.3e-01
4.4e-01 7.6e-02 3.7 1.5e-01 2.8 prostate 9.1e-01 9.3e-01 5.8e-01
0.6 7.6e-01 0.5 stomach 3.7e-01 3.2e-01 1 0.1 1 0.3 uterus 9.4e-01
7.0e-01 1 0.6 4.1e-01 1.1
[3072] As noted above, cluster HSS100PCB features 1 transcript(s),
which were listed in Table 1091 above. These transcript(s) encode
for protein(s) which are variant(s) of protein S-100P protein (SEQ
ID NO:1457). A description of each variant protein according to the
present invention is now provided.
[3073] Variant protein HSS100PCB_P3 (SEQ ID NO:1401) according to
the present invention has an amino acid sequence as given at the
end of the application; it is encoded by transcript(s) HSS100PCB_T1
(SEQ ID NO:133). The location of the variant protein was determined
according to results from a number of different software programs
and analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3074] Variant protein HSS100PCB_P3 (SEQ ID NO:1401) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1097, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:1401)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01163 TABLE 1097 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
1 M -> R Yes 11 M -> L Yes 20 L -> F Yes
[3075] Variant protein HSS100PCB_P3 (SEQ ID NO:1401) is encoded by
the following transcript(s): HSS100PCB_T1 (SEQ ID NO:133), for
which the sequence(s) is/are given at the end of the application.
The coding portion of transcript HSS100PCB_T1 (SEQ ID NO:133) is
shown in bold; this coding portion starts at position 1057 and ends
at position 1533. The transcript also has the following SNPs as
listed in Table 1098 (given according to their position on the
nucleotide sequence, with the alternative nucleic acid listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein HSS100PCB_P3 (SEQ ID NO:1401)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01164 TABLE 1098 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
52 C -> T Yes 107 A -> C Yes 458 C -> T Yes 468 A -> G
Yes 648 C -> T Yes 846 C -> G Yes 882 G -> A Yes 960 C
-> T No 965 C -> T Yes 1058 T -> G Yes 1087 A -> C Yes
1114 C -> T Yes 1968 G -> A Yes 1971 C -> T Yes 2010 C
-> A Yes 2099 G -> No
[3076] As noted above, cluster HSS100PCB features 3 segment(s),
which were listed in Table 1092 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[3077] Segment cluster HSS100PCB_node.sub.--3 (SEQ ID NO:910)
according to the present invention is supported by 16 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSS100PCB_T1 (SEQ ID NO:133). Table 1099 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01165 TABLE 1099 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 133) 1 1133
[3078] Segment cluster HSS100PCB_node.sub.--4 (SEQ ID NO:911)
according to the present invention is supported by 29 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSS100PCB_T1 (SEQ ID NO:133). Table 1100 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01166 TABLE 1100 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 133) 1134 1923
[3079] Segment cluster HSS100PCB_node.sub.--5 (SEQ ID NO:912)
according to the present invention is supported by 141 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HSS100PCB_T1 (SEQ ID NO:133). Table 1101 below describes the
starting and ending position of this segment on each
transcript.
TABLE-US-01167 TABLE 1101 Segment location on transcripts Segment
Segment Transcript name starting position ending position
HSS100PCB_T1 (SEQ ID NO: 133) 1924 2201
Description for Cluster HSU33147
[3080] Cluster HSU33147 features 2 transcript(s) and 5 segment(s)
of interest, the names for which are given in Tables 1102 and 1103,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1104.
TABLE-US-01168 TABLE 1102 Transcripts of interest Transcript Name
Sequence ID No. HSU33147_PEA_1_T1 1464 HSU33147_PEA_1_T2 1465
TABLE-US-01169 TABLE 1103 Segments of interest Segment Name
Sequence ID No. HSU33147_PEA_1_node_0 1276 HSU33147_PEA_1_node_2
1277 HSU33147_PEA_1_node_4 1278 HSU33147_PEA_1_node_7 1279
HSU33147_PEA_1_node_3 1280
TABLE-US-01170 TABLE 1104 Proteins of interest Sequence Protein
Name ID No. Corresponding Transcript(s) HSU33147_PEA_1_P5 1415
HSU33147_PEA_1_T1 (SEQ ID NO: 1464); HSU33147_PEA_1_T2 (SEQ ID NO:
1465)
[3081] These sequences are variants of the known protein
Mammaglobin A precursor (SwissProt accession identifier MGBA_HUMAN;
known also according to the synonyms Mammaglobin 1; Secretoglobin
family 2A member 2), SEQ ID NO: 1416, referred to herein as the
previously known protein.
[3082] The sequence for protein Mammaglobin A precursor (SEQ ID
NO:1416) is given at the end of the application, as "Mammaglobin A
precursor amino acid sequence".
[3083] It has been investigated for clinical/therapeutic use in
humans, for example as a target for an antibody or small molecule,
and/or as a direct therapeutic; available information related to
these investigations is as follows. Potential pharmaceutically
related or therapeutically related activity or activities of the
previously known protein are as follows: Immunostimulant. A
therapeutic role for a protein represented by the cluster has been
predicted. The cluster was assigned this field because there was
information in the drug database or the public databases (e.g.,
described herein above) that this protein, or part thereof, is used
or can be used for a potential therapeutic indication:
Anticancer.
[3084] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: steroid binding,
which are annotation(s) related to Molecular Function.
[3085] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3086] Cluster HSU33147 can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the left hand column of the table and the numbers on
the y-axis of FIG. 43 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[3087] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 43 and Table 1105. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: a mixture of malignant tumors from
different tissues.
TABLE-US-01171 TABLE 1105 Normal tissue distribution Name of Tissue
Number epithelial 6 general 2 lung 0 breast 131
TABLE-US-01172 TABLE 1106 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 epithelial
4.1e-02 6.4e-02 1.5e-12 2.6 2.2e-06 1.5 general 1.6e-02 1.1e-02
1.2e-22 4.4 7.2e-13 2.4 lung 1 6.3e-01 1 1.0 6.2e-01 1.6 breast
8.6e-02 1.1e-01 3.4e-07 1.7 2.6e-03 1.0
[3088] As noted above, cluster HSU33147 features 2 transcript(s),
which were listed in Table 1102 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Mammaglobin A
precursor (SEQ ID NO:1416). A description of each variant protein
according to the present invention is now provided.
[3089] Variant protein HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
HSU33147_PEA.sub.--1_T1 (SEQ ID NO:1464). An alignment is given to
the known protein (Mammaglobin A precursor (SEQ ID NO:1416)) at the
end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[3090] Comparison report between HSU33147_PEA.sub.--1_P5 (SEQ ID
NO:1415) and MGBA_HUMAN (SEQ ID NO:1416):
[3091] 1. An isolated chimeric polypeptide encoding for
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), comprising a first amino
acid sequence being at least 90% homologous to
MKLLMVLMLAALSQHCYAGSGCPLLENVISKTINPQVSKTEYKELLQEFIDDNATTNAIDELKECFLNQTD
ETLSNVE corresponding to amino acids 1-78 of MGBA_HUMAN (SEQ ID
NO:1416), which also corresponds to amino acids 1-78 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), and a second amino acid
sequence being at least 90% homologous to QLIYDSSLCDLF
corresponding to amino acids 82-93 of MGBA_HUMAN (SEQ ID NO:1416),
which also corresponds to amino acids 79-90 of
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[3092] 2. An isolated chimeric polypeptide encoding for an edge
portion of HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise EQ, having a structure as follows: a
sequence starting from any of amino acid numbers 78-x to 78; and
ending at any of amino acid numbers 79+((n-2)-x), in which x varies
from 0 to n-2.
[3093] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3094] The glycosylation sites of variant protein
HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415), as compared to the known
protein Mammaglobin A precursor (SEQ ID NO:1416), are described in
Table 1107 (given according to their position(s) on the amino acid
sequence in the first column; the second column indicates whether
the glycosylation site is present in the variant protein; and the
last column indicates whether the position is different on the
variant protein).
TABLE-US-01173 TABLE 1107 Glycosylation site(s) Position(s) on
known amino Position in acid sequence Present in variant protein?
variant protein? 68 yes 68 53 yes 53
[3095] Variant protein HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415) is
encoded by the following transcript(s): HSU33147_PEA.sub.--1_T1
(SEQ ID NO:1464), for which the sequence(s) is/are given at the end
of the application. The coding portion of transcript
HSU33147_PEA.sub.--1_T1 (SEQ ID NO:1464) is shown in bold; this
coding portion starts at position 72 and ends at position 341. The
transcript also has the following SNPs as listed in Table 1108
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein HSU33147_PEA.sub.--1_P5 (SEQ ID NO:1415) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01174 TABLE 1108 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
84 A -> C No 124 C -> No 396 A -> G No
[3096] As noted above, cluster HSU33147 features 5 segment(s),
which were listed in Table 1103 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[3097] Segment cluster HSU33147_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1276) according to the present invention is supported by 38
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HSU33147_PEA.sub.--1_T1 (SEQ ID NO:1464) and
HSU33147_PEA.sub.--1_T2 (SEQ ID NO:1465). Table 1109 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01175 TABLE 1109 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSU33147_PEA_1_T1 (SEQ ID NO: 1464) 1 126 HSU33147_PEA_1_T2 (SEQ ID
NO: 1465) 1 126
[3098] Segment cluster HSU33147_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:1277) according to the present invention is supported by 44
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HSU33147_PEA.sub.--1_T1 (SEQ ID NO:1464) and
HSU33147_PEA.sub.--1_T2 (SEQ ID NO:1465). Table 1110 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01176 TABLE 1110 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSU33147_PEA_1_T1 (SEQ ID NO: 1464) 127 305 HSU33147_PEA_1_T2 (SEQ
ID NO: 1465) 127 305
[3099] Segment cluster HSU33147_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1278) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HSU33147_PEA.sub.--1_T2 (SEQ ID NO:1465). Table 1111
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01177 TABLE 1111 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSU33147_PEA_1_T2 (SEQ ID NO: 1465) 315 907
[3100] Segment cluster HSU33147_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:1279) according to the present invention is supported by 35
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): HSU33147_PEA.sub.--1_T1 (SEQ ID NO:1464). Table 1112
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01178 TABLE 1112 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSU33147_PEA_1_T1 (SEQ ID NO: 1464) 306 516
[3101] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3102] Segment cluster HSU33147_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:1280) according to the present invention can be found in the
following transcript(s): HSU33147_PEA.sub.--1_T2 (SEQ ID NO:1465).
Table 1113 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01179 TABLE 1113 Segment location on transcripts Segment
Segment starting ending Transcript name position position
HSU33147_PEA_1_T2 (SEQ ID NO: 1465) 306 314
Variant protein alignment to the previously known protein:
TABLE-US-01180 ##STR00758##
Description for Cluster R20779
[3103] Cluster R20779 features 1 transcript(s) and 24 segment(s) of
interest, the names for which are given in Tables 1114 and 1115,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1116.
TABLE-US-01181 TABLE 1114 Transcripts of interest Transcript Name
Sequence ID No. R20779_T7 134
TABLE-US-01182 TABLE 1115 Segments of interest Segment Name
Sequence ID No. R20779_node_0 913 R20779_node_2 914 R20779_node_7
915 R20779_node_9 916 R20779_node_18 917 R20779_node_21 918
R20779_node_24 919 R20779_node_27 920 R20779_node_28 921
R20779_node_30 922 R20779_node_31 923 R20779_node_32 924
R20779_node_1 925 R20779_node_3 926 R20779_node_10 927
R20779_node_11 928 R20779_node_14 929 R20779_node_17 930
R20779_node_19 931 R20779_node_20 932 R20779_node_22 933
R20779_node_23 934 R20779_node_25 935 R20779_node_29 936
TABLE-US-01183 TABLE 1116 Proteins of interest Protein Name
Sequence ID No. Corresponding Transcript(s) R20779_P2 1402
R20779_T7 (SEQ ID NO: 134)
[3104] These sequences are variants of the known protein
Stanniocalcin 2 precursor (SwissProt accession identifier
STC2_HUMAN; known also according to the synonyms STC-2;
Stanniocalcin-related protein; STCRP; STC-related protein), SEQ ID
NO:1458, referred to herein as the previously known protein.
[3105] Protein Stanniocalcin 2 precursor (SEQ ID NO:1458) is known
or believed to have the following function(s): Has an
anti-hypocalcemic action on calcium and phosphate homeostasis. The
sequence for protein Stanniocalcin 2 precursor is given at the end
of the application, as "Stanniocalcin 2 precursor amino acid
sequence". Protein Stanniocalcin 2 precursor localization is
believed to be Secreted (Potential).
[3106] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: cell surface
receptor linked signal transduction; cell-cell signaling;
nutritional response pathway, which are annotation(s) related to
Biological Process; hormone, which are annotation(s) related to
Molecular Function; and extracellular, which are annotation(s)
related to Cellular Component.
[3107] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3108] Cluster 820779 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 44 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[3109] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 44 and Table 1117. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues and lung malignant
tumors.
TABLE-US-01184 TABLE 1117 Normal tissue distribution Name of Tissue
Number bone 825 brain 0 colon 0 epithelial 32 general 38 kidney 22
liver 9 lung 11 lymph nodes 0 breast 215 muscle 35 ovary 36
pancreas 4 prostate 80 skin 99 stomach 0 uterus 4
TABLE-US-01185 TABLE 1118 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 bone 5.9e-01
7.4e-01 1 0.2 1 0.1 brain 2.5e-02 1.6e-02 2.2e-01 6.0 3.5e-02 8.0
colon 1.7e-01 1.7e-01 1 1.3 7.7e-01 1.5 epithelial 1.7e-01 1.5e-03
5.9e-01 1.0 2.0e-04 2.0 general 2.4e-02 6.2e-07 7.6e-01 0.8 4.6e-05
1.6 kidney 4.3e-01 2.7e-01 6.2e-01 1.3 1.5e-01 2.0 liver 8.3e-01
7.6e-01 1 0.8 3.3e-01 1.6 lung 1.2e-01 1.4e-03 1.9e-01 2.9 1.6e-05
7.7 lymph nodes 1 3.1e-01 1 1.0 1 1.4 breast 6.8e-01 6.8e-01
6.9e-01 0.8 3.6e-01 0.8 muscle 9.2e-01 4.8e-01 1 0.3 1.4e-03 1.4
ovary 8.4e-01 7.1e-01 9.0e-01 0.7 8.6e-01 0.8 pancreas 9.3e-01
6.8e-01 1 0.7 1.5e-01 2.0 prostate 9.1e-01 5.0e-01 9.8e-01 0.4
5.7e-01 0.7 skin 6.3e-01 7.5e-01 7.1e-01 0.8 9.5e-01 0.3 stomach 1
4.5e-01 1 1.0 5.1e-01 1.8 uterus 7.1e-01 2.6e-01 4.4e-01 1.7
4.1e-01 1.8
[3110] As noted above, cluster R20779 features 1 transcript(s),
which were listed in Table 1114 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Stanniocalcin 2
precursor (SEQ ID NO:1458). A description of each variant protein
according to the present invention is now provided.
[3111] Variant protein R20779_P2 (SEQ ID NO:1402) according to the
present invention has an amino acid sequence as given at the end of
the application; it is encoded by transcript(s) R20779_T7 (SEQ ID
NO:134). An alignment is given to the known protein (Stanniocalcin
2 precursor (SEQ ID NO:1458)) at the end of the application. One or
more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[3112] Comparison report between R20779_P2 (SEQ ID NO:1402) and
STC2_HUMAN (SEQ ID NO:1458):
[3113] 1. An isolated chimeric polypeptide encoding for R20779_P2
(SEQ ID NO:1402), comprising a first amino acid sequence being at
least 90% homologous to
MCAERLGQFMTLALVLATFDPARGTDATNPPEGPQDRSSQQKGRLSLQNTAEIQHCLVNAGDVGCGVFE
CFENNSCEIRGLHGICMTFLHNAGKFDAQGKSFIKDALKCKAHALRHRFGCISRKCPAIREMVSQLQRECY
LKHDLCAAAQENTRVIVEMIHFKDLLLHE corresponding to amino acids 1-169 of
STC2_HUMAN (SEQ ID NO:1458), which also corresponds to amino acids
1-169 of R20779_P2 (SEQ ID NO:1402), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
CYKIEITMPKRRKVKLRD (SEQ ID NO: 270) corresponding to amino acids
170-187 of R20779_P2 (SEQ ID NO:1402), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[3114] 2. An isolated polypeptide encoding for a tail of R20779_P2
(SEQ ID NO:1402), comprising a polypeptide being at least 70%,
optionally at least about 80%, preferably at least about 85%, more
preferably at least about 90% and most preferably at least about
95% homologous to the sequence CYKIEITMPKRRKVKLRD (SEQ ID NO: 270)
in R20779_P2 (SEQ ID NO:1402).
[3115] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3116] Variant protein R20779_P2 (SEQ ID NO:1402) also has the
following non-silent SNPs (Single Nucleotide Polymorphisms) as
listed in Table 1119, (given according to their position(s) on the
amino acid sequence, with the alternative amino acid(s) listed; the
last column indicates whether the SNP is known or not; the presence
of known SNPs in variant protein R20779_P2 (SEQ ID NO:1402)
sequence provides support for the deduced sequence of this variant
protein according to the present invention).
TABLE-US-01186 TABLE 1119 Amino acid mutations SNP position(s) on
amino acid sequence Alternative amino acid(s) Previously known SNP?
16 L -> No 98 Q -> No 171 Y -> C Yes 177 M -> V Yes
[3117] The glycosylation sites of variant protein R20779_P2 (SEQ ID
NO:1402), as compared to the known protein Stanniocalcin 2
precursor (SEQ ID NO:1458), are described in Table 1120 (given
according to their position(s) on the amino acid sequence in the
first column; the second column indicates whether the glycosylation
site is present in the variant protein; and the last column
indicates whether the position is different on the variant
protein).
TABLE-US-01187 TABLE 1120 Glycosylation site(s) Position(s) on
known amino Position in acid sequence Present in variant protein?
variant protein? 73 yes 73
[3118] Variant protein R20779_P2 (SEQ ID NO:1402) is encoded by the
following transcript(s): R20779_T7 (SEQ ID NO:134), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R20779_T7 (SEQ ID NO:134) is shown in bold;
this coding portion starts at position 1397 and ends at position
1957. The transcript also has the following SNPs as listed in Table
1121 (given according to their position on the nucleotide sequence,
with the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R20779_P2 (SEQ ID NO:1402) sequence provides
support for the deduced sequence of this variant protein according
to the present invention).
TABLE-US-01188 TABLE 1121 Nucleic acid SNPs SNP position on
nucleotide sequence Alternative nucleic acid Previously known SNP?
1442 T -> No 1690 G -> No 1732 C -> T Yes 1867 G -> T
Yes 1908 A -> G Yes 1925 A -> G Yes 1968 G -> A Yes 2087 C
-> T No 2138 C -> T Yes 2270 C -> No 2443 A -> No 2478
G -> No 2479 C -> A No 2616 C -> A No 2941 C -> No 3196
-> A No 3479 T -> G Yes 4290 C -> T Yes 4358 G -> A Yes
5363 G -> A No
[3119] As noted above, cluster R20779 features 24 segment(s), which
were listed in Table 1115 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[3120] Segment cluster R20779_node.sub.--0 (SEQ ID NO:913)
according to the present invention is supported by 31 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1122 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01189 TABLE 1122 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1 1298
[3121] Segment cluster R20779_node.sub.--2 (SEQ ID NO:914)
according to the present invention is supported by 55 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1123 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01190 TABLE 1123 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1337 1506
[3122] Segment cluster R20779_node.sub.--7 (SEQ ID NO:915)
according to the present invention is supported by 63 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1124 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01191 TABLE 1124 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1548 1690
[3123] Segment cluster R20779_node.sub.--9 (SEQ ID NO:916)
according to the present invention is supported by 66 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1125 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01192 TABLE 1125 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1691 1838
[3124] Segment cluster R20779_node.sub.--18 (SEQ ID NO:917)
according to the present invention is supported by 61 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1126 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01193 TABLE 1126 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2009 2176
[3125] Segment cluster R20779_node.sub.--21 (SEQ ID NO:918)
according to the present invention is supported by 106 libraries.
The number of libraries was determined as'previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1127 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01194 TABLE 1127 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2219 2796
[3126] Segment cluster R20779_node.sub.--24 (SEQ ID NO:919)
according to the present invention is supported by 100 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1128 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01195 TABLE 1128 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2977 3667
[3127] Segment cluster R20779_node.sub.--27 (SEQ ID NO:920)
according to the present invention is supported by 26 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1129 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01196 TABLE 1129 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 3673 3803
[3128] Segment cluster R20779_node.sub.--28 (SEQ ID NO:921)
according to the present invention is supported by 31 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1130 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01197 TABLE 1130 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 3804 4050
[3129] Segment cluster R20779_node.sub.--30 (SEQ ID NO:922)
according to the present invention is supported by 34 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1131 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01198 TABLE 1131 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 4068 4193
[3130] Segment cluster R20779_node.sub.--31 (SEQ ID NO:923)
according to the present invention is supported by 46 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1132 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01199 TABLE 1132 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 4194 4424
[3131] Segment cluster R20779_node.sub.--32 (SEQ ID NO:924)
according to the present invention is supported by 88 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1133 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01200 TABLE 1133 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 4425 5503
[3132] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3133] Segment cluster R20779_node.sub.--1 (SEQ ID NO:925)
according to the present invention is supported by 27 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1134 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01201 TABLE 1134 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1299 1336
[3134] Segment cluster R20779_node.sub.--3 (SEQ ID NO:926)
according to the present invention is supported by 52 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1135 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01202 TABLE 1135 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1507 1547
[3135] Segment cluster R20779_node.sub.--1 (SEQ ID NO:927)
according to the present invention can be found in the following
transcript(s): R20779_T7 (SEQ ID NO:134). Table 1136 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01203 TABLE 1136 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1839 1849
[3136] Segment cluster R20779_node.sub.--11 (SEQ ID NO:928)
according to the present invention is supported by 58 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1137 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01204 TABLE 1137 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1850 1902
[3137] Segment cluster R20779_node.sub.--14 (SEQ ID NO:929)
according to the present invention is supported by 1 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s): R20779_T7 (SEQ
ID NO:134). Table 1138 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01205 TABLE 1138 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1903 1975
[3138] Segment cluster R20779_node.sub.--17 (SEQ ID NO:930)
according to the present invention is supported by 54 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1139 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01206 TABLE 1139 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 1976 2008
[3139] Segment cluster R20779_node.sub.--19 (SEQ ID NO:931)
according to the present invention can be found in the following
transcript(s): R20779_T7 (SEQ ID NO:134). Table 1140 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01207 TABLE 1140 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2177 2188
[3140] Segment cluster R20779_node.sub.--20 (SEQ ID NO:932)
according to the present invention is supported by 53 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1141 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01208 TABLE 1141 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2189 2218
[3141] Segment cluster R20779_node.sub.--22 (SEQ ID NO:933)
according to the present invention is supported by 76 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1142 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01209 TABLE 1142 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2797 2899
[3142] Segment cluster R20779_node.sub.--23 (SEQ ID NO:934)
according to the present invention is supported by 81 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s): R20779_T7
(SEQ ID NO:134). Table 1143 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01210 TABLE 1143 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 2900 2976
[3143] Segment cluster R20779_node.sub.--25 (SEQ ID NO:935)
according to the present invention can be found in the following
transcript(s): R20779_T7 (SEQ ID NO:134). Table 1144 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01211 TABLE 1144 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 3668 3672
[3144] Segment cluster R20779_node.sub.--29 (SEQ ID NO:936)
according to the present invention can be found in the following
transcript(s): R20779_T7 (SEQ ID NO:134). Table 1145 below
describes the starting and ending position of this segment on each
transcript.
TABLE-US-01212 TABLE 1145 Segment location on transcripts Segment
Segment Transcript name starting position ending position R20779_T7
(SEQ ID NO: 134) 4051 4067
Variant protein alignment to the previously known protein:
TABLE-US-01213 ##STR00759## ##STR00760##
Description for Cluster R38144
[3145] Cluster R38144 features 6 transcript(s) and 24 segment(s) of
interest, the names for which are given in Tables 1146 and 1147,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1148.
TABLE-US-01214 TABLE 1146 Transcripts of interest Transcript Name
Sequence ID No. R38144_PEA_2_T6 135 R38144_PEA_2_T10 136
R38144_PEA_2_T13 137 R38144_PEA_2_T15 138 R38144_PEA_2_T19 139
R38144_PEA_2_T27 140
TABLE-US-01215 TABLE 1147 Segments of interest Segment Name
Sequence ID No. R38144_PEA_2_node_21 937 R38144_PEA_2_node_26 938
R38144_PEA_2_node_29 939 R38144_PEA_2_node_31 940
R38144_PEA_2_node_46 941 R38144_PEA_2_node_47 942
R38144_PEA_2_node_49 943 R38144_PEA_2_node_0 944
R38144_PEA_2_node_1 945 R38144_PEA_2_node_4 946 R38144_PEA_2_node_5
947 R38144_PEA_2_node_7 948 R38144_PEA_2_node_11 949
R38144_PEA_2_node_14 950 R38144_PEA_2_node_15 951
R38144_PEA_2_node_16 952 R38144_PEA_2_node_19 953
R38144_PEA_2_node_20 954 R38144_PEA_2_node_36 955
R38144_PEA_2_node_37 956 R38144_PEA_2_node_43 957
R38144_PEA_2_node_44 958 R38144_PEA_2_node_45 959
R38144_PEA_2_node_51 960
TABLE-US-01216 TABLE 1148 Proteins of interest Protein Name
Sequence ID No. Corresponding Transcript(s) R38144_PEA_2_P6 1403
R38144_PEA_2_T6 (SEQ ID NO: 135) R38144_PEA_2_P13 1404
R38144_PEA_2_T13 (SEQ ID NO: 137) R38144_PEA_2_P15 1405
R38144_PEA_2_T15 (SEQ ID NO: 138) R38144_PEA_2_P19 1406
R38144_PEA_2_T19 (SEQ ID NO: 139) R38144_PEA_2_P24 1407
R38144_PEA_2_T27 (SEQ ID NO: 140) R38144_PEA_2_P36 1408
R38144_PEA_2_T10 (SEQ ID NO: 136)
[3146] These sequences are variants of the known protein Putative
alpha-mannosidase C20orf31 precursor (SwissProt accession
identifier CT31_HUMAN; known also according to the synonyms EC
3.2.1), SEQ ID NO:1459, referred to herein as the previously known
protein.
[3147] The sequence for protein Putative alpha-mannosidase C20orf31
precursor (SEQ ID NO:1459) is given at the end of the application,
as "Putative alpha-mannosidase C20orf31 precursor amino acid
sequence". Known polymorphisms for this sequence are as shown in
Table 1149.
TABLE-US-01217 TABLE 1149 Amino acid mutations for Known Protein
SNP position(s) on amino acid sequence Comment 456 A -> T. /FTId
= VAR_012165. 511 S -> C
[3148] Protein Putative alpha-mannosidase C20orf31 precursor (SEQ
ID NO:1459) localization is believed to be Secreted
(Potential).
[3149] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: carbohydrate
metabolism; N-linked glycosylation, which are annotation(s) related
to Biological Process; mannosyl-oligosaccharide
1,2-alpha-mannosidase; calcium binding; hydrolase, acting on
glycosyl bonds, which are annotation(s) related to Molecular
Function; and membrane, which are annotation(s) related to Cellular
Component.
[3150] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3151] Cluster 838144 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 45 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[3152] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 45 and Table 1150. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, lung
malignant tumors, skin malignancies and gastric carcinoma.
TABLE-US-01218 TABLE 1150 Normal tissue distribution Name of Tissue
Number Adrenal 40 Bladder 41 Bone 38 Brain 16 Colon 37 Epithelial
18 General 31 head and neck 50 Kidney 26 Liver 4 Lung 11 lymph
nodes 47 Breast 52 Ovary 7 Pancreas 20 Prostate 0 Skin 13 Stomach 0
Uterus 0
TABLE-US-01219 TABLE 1151 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Adrenal 9.2e-01
6.9e-01 1 0.5 7.8e-01 0.9 Bladder 7.6e-01 8.1e-01 8.1e-01 0.9
9.0e-01 0.7 Bone 6.6e-01 8.5e-01 1 0.6 1 0.6 Brain 8.0e-02 6.0e-02
4.7e-02 3.0 1.6e-02 3.0 colon 7.7e-01 7.5e-01 1 0.5 3.5e-01 0.8
epithelial 2.0e-01 4.8e-03 1.7e-01 1.4 2.7e-16 5.2 general 3.9e-01
2.2e-02 7.8e-01 0.9 2.1e-19 2.9 head and neck 3.4e-01 5.6e-01
4.6e-01 1.4 7.5e-01 0.9 kidney 8.3e-01 7.7e-01 4.4e-01 1.4 8.5e-02
1.6 liver 9.1e-01 6.0e-01 1 0.9 1.1e-01 1.8 lung 1.6e-02 1.5e-02
9.5e-02 3.8 1.6e-05 6.6 lymph nodes 7.1e-01 7.8e-01 1 0.3 1.2e-04
1.0 breast 9.1e-01 9.1e-01 1 0.5 9.7e-01 0.6 ovary 5.0e-01 2.9e-01
4.7e-01 1.7 7.0e-02 2.2 pancreas 7.2e-01 4.2e-01 8.1e-01 0.8
3.0e-02 1.8 prostate 7.9e-01 5.7e-01 3.0e-01 2.5 1.8e-04 3.0 skin
9.2e-01 8.7e-02 1 0.5 3.0e-05 4.1 stomach 3.0e-01 5.5e-02 2.5e-01
3.0 9.2e-04 6.1 uterus 2.1e-01 9.4e-02 4.4e-01 2.0 5.1e-01 1.9
[3153] As noted above, cluster R38144 features 6 transcript(s),
which were listed in Table 1146 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Putative
alpha-mannosidase C20orf31 precursor (SEQ ID NO:1459). A
description of each variant protein according to the present
invention is now provided.
[3154] Variant protein R38144_PEA.sub.--2_P6 (SEQ ID NO:1403)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T6 (SEQ ID NO:135). An alignment is given to the
known protein (Putative alpha-mannosidase C20orf31 precursor (SEQ
ID NO:1459)) at the end of the application. One or more alignments
to one or more previously published protein sequences are given at
the end of the application. A brief description of the relationship
of the variant protein according to the present invention to each
such aligned protein is as follows:
[3155] Comparison report between R38144_PEA.sub.--2_P6 (SEQ ID
NO:1403) and CT31_HUMAN (SEQ ID NO:1459):
[3156] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLPTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGG
LPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFAT
corresponding to amino acids 1-412 of CT31_HUMAN (SEQ ID NO:1459),
which also corresponds to amino acids 1-412 of
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV (SEQ ID NO: 268)
corresponding to amino acids 413-449 of R38144_PEA.sub.--2_P6 (SEQ
ID NO:1403), wherein said first amino acid sequence and second
amino acid sequence are contiguous and in a sequential order.
[3157] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
LASFSHMSDQRSARPQAGQPHGVVLPGRDCEIPLPPV (SEQ ID NO: 268) in
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403).
[3158] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3159] Variant protein R38144_PEA.sub.--2_P6 (SEQ ID NO:1403) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1152, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P6
(SEQ ID NO:1403) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01220 TABLE 1152 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 54 A -> V Yes 55 F -> L Yes 73 S -> I Yes 87
I -> No 145 P -> No 145 P -> A No 164 A -> G No 164 A
-> No 203 A -> G No 203 A -> No 211 D -> No 236 G ->
No 265 V -> G No 285 K -> No 294 D -> N No 305 G -> E
No 323 Q -> R No 346 F -> No
[3160] The glycosylation sites of variant protein
R38144_PEA.sub.--2_P6 (SEQ ID NO:1403), as compared to the known
protein Putative alpha-mannosidase C20orf31 precursor (SEQ ID
NO:1459), are described in Table 1153 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-01221 TABLE 1153 Glycosylation site(s) Position(s) on
known amino acid Present in Position in sequence variant protein?
variant protein? 450 no 289 yes 289 112 yes 112 90 yes 90
[3161] Variant protein R38144_PEA.sub.--2_P6 (SEQ ID NO:1403) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T6 (SEQ
ID NO:135), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T6 (SEQ ID NO:135) is shown in bold; this coding
portion starts at position 91 and ends at position 1437. The
transcript also has the following SNPs as listed in Table 1154
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P6 (SEQ ID NO:1403) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01222 TABLE 1154 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 251 C -> T Yes 253 T -> C Yes 308 G -> T
Yes 312 T -> C No 350 T -> No 523 C -> No 523 C -> G No
581 C -> No 581 C -> G No 698 C -> No 698 C -> G No 723
C -> No 798 C -> No 798 C -> G No 849 -> C No 849 ->
G No 884 T -> G No 901 -> C No 901 -> T No 943 A -> No
970 G -> A No 1004 G -> A No 1058 A -> G No 1126 T ->
No 1218 C -> T Yes 1392 A -> G No 1425 T -> C No 1481 G
-> A Yes 1560 C -> T No 1566 C -> No 1644 G -> A Yes
1646 A -> T No 1763 A -> No 1763 A -> C No 1781 C -> T
Yes 1799 C -> No 1799 C -> G No 1844 T -> G No 1855 A
-> C Yes
[3162] Variant protein R38144_PEA.sub.--2_P13 (SEQ ID NO:1404)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T13 (SEQ ID NO:137). An alignment is given to
the known protein (Putative alpha-mannosidase C20orf31 precursor
(SEQ ID NO:1459)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3163] Comparison report between R38144_PEA.sub.--2_P13 (SEQ ID
NO:1404) and CT31_HUMAN (SEQ ID NO:1459):
[3164] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P13 (SEQ ID NO:1404), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQ corresponding to amino
acids 1-323 of CT31_HUMAN (SEQ ID NO:1459), which also corresponds
to amino acids 1-323 of R38144_PEA.sub.--2_P13 (SEQ ID NO:1404),
and a second amino acid sequence being at least 70%, optionally at
least 80%, preferably at least 85%, more preferably at least 90%
and most preferably at least 95% homologous to a polypeptide having
the sequence NLLKAQCTSTVPRGIPPS (SEQ ID NO: 269) corresponding to
amino acids 324-341 of R38144_PEA.sub.--2_P13 (SEQ ID NO:1404),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[3165] 2. An isolated polypeptide encoding for a tail of
R38144PEA.sub.--2_P13 (SEQ ID NO:1404), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
NLLKAQCTSTVPRGIPPS (SEQ ID NO: 269) in R38144_PEA.sub.--2_P13 (SEQ
ID NO:1404).
[3166] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignaiP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3167] Variant protein R38144_PEA.sub.--2_P13 (SEQ ID NO:1404) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1155, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P13
(SEQ ID NO:1404) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01223 TABLE 1155 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 54 A -> V Yes 55 F -> L Yes 73 S -> I Yes 87
I -> No 145 P -> No 145 P -> A No 164 A -> G No 164 A
-> No 203 A -> G No 203 A -> No 211 D -> No 236 G ->
No 265 V -> G No 285 K -> No 294 D -> N No 305 G -> E
No 323 Q -> R No 328 A -> V Yes
[3168] The glycosylation sites of variant protein
R38144_PEA.sub.--2_P13 (SEQ ID NO:1404), as compared to the known
protein Putative alpha-mannosidase C20orf31 precursor (SEQ ID
NO:1459), are described in Table 1156 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-01224 TABLE 1156 Glycosylation site(s) Position(s) on
known amino acid Present in Position sequence variant protein? in
variant protein? 450 no 289 yes 289 112 yes 112 90 yes 90
[3169] Variant protein R38144_PEA.sub.--2_P13 (SEQ ID NO:1404) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T13 (SEQ ID NO:137) is shown in bold; this
coding portion starts at position 91 and ends at position 1113. The
transcript also has the following SNPs as listed in Table 1157
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P13 (SEQ ID NO:1404) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01225 TABLE 1157 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 251 C -> T Yes 253 T -> C Yes 308 G -> T
Yes 312 T -> C No 350 T -> No 523 C -> No 523 C -> G No
581 C -> No 581 C -> G No 698 C -> No 698 C -> G No 723
C -> No 798 C -> No 798 C -> G No 849 -> C No 849 ->
G No 884 T -> G No 901 -> C No 901 -> T No 943 A -> No
970 G -> A No 1004 G -> A No 1058 A -> G No 1073 C -> T
Yes 1222 A -> G No 1255 T -> C No 1311 G -> A Yes 1390 C
-> T No 1396 C -> No 1474 G -> A Yes 1476 A -> T No
1593 A -> No 1593 A -> C No 1611 C -> T Yes 1629 C ->
No 1629 C -> G No 1674 T -> G No 1685 A -> C Yes
[3170] Variant protein R38144_PEA.sub.--2_P15 (SEQ ID NO:1405)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T15 (SEQ ID NO:138). An alignment is given to
the known protein (Putative alpha-mannosidase C20orf31 precursor
(SEQ ID NO:1459)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3171] Comparison report between R38144_PEA.sub.--2_P15 (SEQ ID
NO:1405) and CT31_HUMAN (SEQ ID NO:1459):
[3172] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LE corresponding to amino acids 1-282 of CT31_HUMAN (SEQ ID
NO:1459), which also corresponds to amino acids 1-282 of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence PHWRH
(SEQ ID NO: 270) corresponding to amino acids 283-287 of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[3173] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence PHWRH (SEQ
ID NO: 270) in R38144_PEA.sub.--2_P15 (SEQ ID NO:1405).
[3174] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3175] Variant protein R38144_PEA.sub.--2_P15 (SEQ ID NO:1405) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1158, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P15
(SEQ ID NO:1405) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01226 TABLE 1158 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 54 A -> V Yes 55 F -> L Yes 73 S -> I Yes 87
I -> No 145 P -> No 145 P -> A No 164 A -> G No 164 A
-> No 203 A -> G No 203 A -> No 211 D -> No 236 G ->
No 265 V -> G No
[3176] The glycosylation sites of variant protein
R38144_PEA.sub.--2_P15 (SEQ ID NO:1405), as compared to the known
protein Putative alpha-mannosidase C20orf31 precursor (SEQ ID
NO:1459), are described in Table 1159 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-01227 TABLE 1159 Glycosylation site(s) Position(s) on
known amino acid Present Position sequence in variant protein? in
variant protein? 450 no 289 no 112 yes 112 90 yes 90
[3177] Variant protein R38144_PEA.sub.--2_P15 (SEQ ID NO:1405) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T15 (SEQ
ID NO:138), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T15 (SEQ ID NO:138) is shown in bold; this
coding portion starts at position 91 and ends at position 951. The
transcript also has the following SNPs as listed in Table 1160
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P15 (SEQ ID NO:1405) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01228 TABLE 1160 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 251 C -> T Yes 253 T -> C Yes 308 G -> T
Yes 312 T -> C No 350 T -> No 523 C -> No 523 C -> G No
581 C -> No 581 C -> G No 698 C -> No 698 C -> G No 723
C -> No 798 C -> No 798 C -> G No 849 -> C No 849 ->
G No 884 T -> G No 901 -> C No 901 -> T No 1001 T -> No
1093 C -> T Yes 1242 A -> G No 1275 T -> C No 1331 G ->
A Yes 1410 C -> T No 1416 C -> No 1494 G -> A Yes 1496 A
-> T No 1613 A -> No 1613 A -> C No 1631 C -> T Yes
1649 C -> No 1649 C -> G No 1694 T -> G No 1705 A -> C
Yes
[3178] Variant protein R38144_PEA.sub.--2_P19 (SEQ ID NO:1406)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). An alignment is given to
the known protein (Putative alpha-mannosidase C20orf31 precursor
(SEQ ID NO:1459)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3179] Comparison report between R38144_PEA.sub.--2_P19 (SEQ ID
NO:1406) and CT31_HUMAN (SEQ ID NO:1459):
[3180] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIRVVGGLLSAHLLSKKAGVEVE
AGWPCSGPLLRMAEEAARKLLPAFQTPTGMPYGTVNLLHGVNPGETPVTCTAGIGTFIVEFATLSSLTGDP
VFEDVARVALMRLWESRSDIGLVGNHIDVLTGKWVAQDAGIGAGVDSYFEYLVKGAILLQDKKLMAMF
LEYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGG
LPEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFAT
corresponding to amino acids 1-412 of CT31_HUMAN (SEQ ID NO:1459),
which also corresponds to amino acids 1-412 of
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
KRSRSVAQAGVQWCDHDSPQP (SEQ ID NO: 270) corresponding to amino acids
413-433 of R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[3181] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
KRSRSVAQAGVQWCDHDSPQP (SEQ ID NO: 270) in R38144_PEA.sub.--2_P19
(SEQ ID NO:1406).
[3182] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3183] Variant protein R38144_PEA.sub.--2_P19 (SEQ ID NO:1406) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1161, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P19
(SEQ ID NO:1406) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01229 TABLE 1161 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 54 A -> V Yes 55 F -> L Yes 73 S -> I Yes 87
I -> No 145 P -> No 145 P -> A No 164 A -> G No 164 A
-> No 203 A -> G No 203 A -> No 211 D -> No 236 G ->
No 265 V -> G No 285 K -> No 294 D -> N No 305 G -> E
No 323 Q -> R No 346 F -> No
[3184] The glycosylation sites of variant protein
R38144_PEA.sub.--2_P19 (SEQ ID NO:1406), as compared to the known
protein Putative alpha-mannosidase C20orf31 precursor (SEQ ID
NO:1459), are described in Table 1162(given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-01230 TABLE 1162 Glycosylation site(s) Position(s) on
known amino acid Present Position sequence in variant protein? in
variant protein? 450 no 289 yes 289 112 yes 112 90 yes 90
[3185] Variant protein R38144_PEA.sub.--2_P19 (SEQ ID NO:1406) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T19 (SEQ
ID NO:139), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) is shown in bold; this
coding portion starts at position 91 and ends at position 1389. The
transcript also has the following SNPs as listed in Table 1163
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P19 (SEQ ID NO:1406) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01231 TABLE 1163 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 251 C -> T Yes 253 T -> C Yes 308 G -> T
Yes 312 T -> C No 350 T -> No 523 C -> No 523 C -> G No
581 C -> No 581 C -> G No 698 C -> No 698 C -> G No 723
C -> No 798 C -> No 798 C -> G No 849 -> C No 849 ->
G No 884 T -> G No 901 -> C No 901 -> T No 943 A -> No
970 G -> A No 1004 G -> A No 1058 A -> G No 1126 T ->
No 1218 C -> T Yes 1446 C -> Yes
[3186] Variant protein R38144_PEA.sub.--2_P24 (SEQ ID NO:1407)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). An alignment is given to
the known protein (Putative alpha-mannosidase C20orf31 precursor
(SEQ ID NO:1459)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3187] Comparison report between R38144_PEA.sub.--2_P24 (SEQ ID
NO:1407) and CT31_HUMAN (SEQ ID NO:1459):
[3188] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYRERVKAMFYHAYDSYLENAFPFDELRPLTCDGHDT
WGSFSLTLIDALDTLLILGNVSEFQRVVEVLQDSVDFDIDVNASVFETNIR corresponding
to amino acids 1-121 of CT31_HUMAN (SEQ ID NO:1459), which also
corresponds to amino acids 1-121 of R38144_PEA.sub.--2_P24 (SEQ ID
NO:1407), and a second amino acid sequence being at least 90%
homologous to
EYNKAIRNYTRFDDWYLWVQMYKGTVSMPVFQSLEAYWPGLQSLIGDIDNAMRTFLNYYTVWKQFGGL
PEFYNIPQGYTVEKREGYPLRPELIESAMYLYRATGDPTLLELGRDAVESIEKISKVECGFATIKDLRDHKL
DNRMESFFLAETVKYLYLLFDPTNFIHNNGSTFDAVITPYGECILGAGGYIFNTEAHPIDPAALHCCQRLKE
EQWEVEDLMREFYSLKRSRSKFQKNTVSSGPWEPPARPGTLFSPENHDQARERKPAKQKVPLLSCPSQPFT
SKLALLGQVFLDSS corresponding to amino acids 282-578 of CT31_HUMAN
(SEQ ID NO:1459), which also corresponds to amino acids 122-418 of
R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), wherein said first amino
acid sequence and second amino acid sequence are contiguous and in
a sequential order.
[3189] 2. An isolated chimeric polypeptide encoding for an edge
portion of R38144_PEA.sub.--2_P24 (SEQ ID NO:1407), comprising a
polypeptide having a length "n", wherein n is at least about 10
amino acids in length, optionally at least about 20 amino acids in
length, preferably at least about 30 amino acids in length, more
preferably at least about 40 amino acids in length and most
preferably at least about 50 amino acids in length, wherein at
least two amino acids comprise RE, having a structure as follows: a
sequence starting from any of amino acid numbers 121-x to 121; and
ending at any of amino acid numbers 122+((n-2)-x), in which x
varies from 0 to n-2.
[3190] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3191] Variant protein R38144_PEA.sub.--2_P24 (SEQ ID NO:1407) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1164, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P24
(SEQ ID NO:1407) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01232 TABLE 1164 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 54 A -> V Yes 55 F -> L Yes 73 S -> I Yes 87
I -> No 125 K -> No 134 D -> N No 145 G -> E No 163 Q
-> R No 186 F -> No 266 E -> G No 277 L -> P No 296 A
-> T Yes 322 P -> L No 324 A -> No 350 R -> Q Yes 351 S
-> C No 390 K -> No 390 K -> Q No 396 L -> F Yes 402 P
-> No 402 P -> A No 417 S -> A No
[3192] The glycosylation sites of variant protein R38144_PEA2_P24
(SEQ ID NO:1407), as compared to the known protein Putative
alpha-mannosidase C20orf31 precursor (SEQ ID NO:1459), are
described in Table 1165 (given according to their position(s) on
the amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-01233 TABLE 1165 Glycosylation site(s) Position(s) on
known amino acid Present Position sequence in variant protein? in
variant protein? 450 yes 290 289 yes 129 112 yes 112 90 yes 90
[3193] Variant protein R38144_PEA.sub.--2_P24 (SEQ ID NO:1407) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T27 (SEQ
ID NO:140), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T27 (SEQ ID NO:140) is shown in bold; this
coding portion starts at position 91 and ends at position 1344. The
transcript also has the following SNPs as listed in Table 1166
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P24 (SEQ ID NO:1407) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01234 TABLE 1166 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 251 C -> T Yes 253 T -> C Yes 308 G -> T
Yes 312 T -> C No 350 T -> No 463 A -> No 490 G -> A No
524 G -> A No 578 A -> G No 646 T -> No 738 C -> T Yes
887 A -> G No 920 T -> C No 976 G -> A Yes 1055 C -> T
No 1061 C -> No 1139 G -> A Yes 1141 A -> T No 1258 A
-> No 1258 A -> C No 1276 C -> T Yes 1294 C -> No 1294
C -> G No 1339 T -> G No 1350 A -> C Yes
[3194] Variant protein R38144_PEA.sub.--2_P36 (SEQ ID NO:1408)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R38144_PEA.sub.--2_T10 (SEQ ID NO:136). An alignment is given to
the known protein (Putative alpha-mannosidase C20orf31 precursor
(SEQ ID NO:1459); SEQ ID NO:1459) at the end of the application.
One or more alignments to one or more previously published protein
sequences are given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to each such aligned protein is as
follows:
[3195] Comparison report between R38144_PEA.sub.--2_P36 (SEQ ID
NO:1408) and AAH16184 (SEQ ID NO: 1460):
[3196] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR corresponding to amino acids
1-36 of AAH16184 (SEQ ID NO:1460), which also corresponds to amino
acids 1-36 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) corresponding to
amino acids 37-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[3197] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) in R38144_PEA.sub.--2_P36
(SEQ ID NO:1408).
[3198] Comparison report between R38144_PEA.sub.--2_P36 (SEQ ID
NO:1408) and AAQ88943 (SEQ ID NO:1461):
[3199] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHY corresponding to amino acids
1-35 of AAQ88943 (SEQ ID NO:1461), which also corresponds to amino
acids 1-35 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence RFWGMSQNSKEWLKCSRTAWTLILM corresponding to amino acids
36-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[3200] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
RFWGMSQNSKEWLKCSRTAWTLILM in R38144_PEA.sub.--2_P36 (SEQ ID
NO:1408).
[3201] Comparison report between R38144_PEA.sub.--2_P36 (SEQ ID
NO:1408) and CT31_HUMAN (SEQ ID NO:1459):
[3202] 1. An isolated chimeric polypeptide encoding for
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a first amino
acid sequence being at least 90% homologous to
MPFRLLIPLGLLCALLPQHHGAPGPDGSAPDPAHYR corresponding to amino acids
1-36 of CT31_HUMAN (SEQ ID NO:1459), which also corresponds to
amino acids 1-36 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), and a
second amino acid sequence being at least 70%, optionally at least
80%, preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) corresponding to
amino acids 37-60 of R38144_PEA.sub.--2_P36 (SEQ ID NO:1408),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[3203] 2. An isolated polypeptide encoding for a tail of
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
FWGMSQNSKEWLKCSRTAWTLILM (SEQ ID NO: 272) in R38144_PEA.sub.--2_P36
(SEQ ID NO:1408).
[3204] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3205] Variant protein R38144_PEA.sub.--2_P36 (SEQ ID NO:1408) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1167, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R38144_PEA.sub.--2_P36
(SEQ ID NO:1408) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01235 TABLE 1167 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
10 G -> No 37 F -> No
[3206] The glycosylation sites of variant protein
R38144_PEA.sub.--2_P36 (SEQ ID NO:1408), as compared to the known
protein Putative alpha-mannosidase C20orf31 precursor (SEQ ID
NO:1459), are described in Table 1168 (given according to their
position(s) on the amino acid sequence in the first column; the
second column indicates whether the glycosylation site is present
in the variant protein; and the last column indicates whether the
position is different on the variant protein).
TABLE-US-01236 TABLE 1168 Glycosylation site(s) Position(s) on
known amino acid sequence Present in variant protein? 450 no 289 no
112 no 90 no
[3207] Variant protein R38144_PEA.sub.--2_P36 (SEQ ID NO:1408) is
encoded by the following transcript(s): R38144_PEA.sub.--2_T10 (SEQ
ID NO:136), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R38144_PEA.sub.--2_T10 (SEQ ID NO:136) is shown in bold; this
coding portion starts at position 91 and ends at position 270. The
transcript also has the following SNPs as listed in Table 1169
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R38144_PEA.sub.--2_P36 (SEQ ID NO:1408) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01237 TABLE 1169 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
120 C -> No 199 T -> No 372 C -> No 372 C -> G No 430 C
-> No 430 C -> G No 547 C -> No 547 C -> G No 572 C
-> No 647 C -> No 647 C -> G No 698 -> C No 698 -> G
No 733 T -> G No 750 -> C No 750 -> T No 792 A -> No
819 G -> A No 853 G -> A No 907 A -> G No 975 T -> No
1067 C -> T Yes 1216 A -> G No 1249 T -> C No 1305 G ->
A Yes 1384 C -> T No 1390 C -> No 1468 G -> A Yes 1470 A
-> T No 1587 A -> No 1587 A -> C No 1605 C -> T Yes
1623 C -> No 1623 C -> G No 1668 T -> G No 1679 A -> C
Yes
[3208] As noted above, cluster R38144 features 24 segment(s), which
were listed in Table 1147 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[3209] Segment cluster R38144_PEA.sub.--2_node.sub.--21 (SEQ ID
NO:937) according to the present invention is supported by 108
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1170 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01238 TABLE 1170 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R38144_PEA_2_T6 626 792 (SEQ ID NO: 135) R38144_PEA_2_T10 475 641
(SEQ ID NO: 136) R38144_PEA_2_T13 626 792 (SEQ ID NO: 137)
R38144_PEA_2_T15 626 792 (SEQ ID NO: 138) R38144_PEA_2_T19 626 792
(SEQ ID NO: 139)
[3210] Segment cluster R38144_PEA.sub.--2_node.sub.--26 (SEQ ID
NO:938) according to the present invention is supported by 98
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1171 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01239 TABLE 1171 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R38144_PEA_2_T6 793 934 (SEQ ID NO: 135) R38144_PEA_2_T10 642 783
(SEQ ID NO: 136) R38144_PEA_2_T13 793 934 (SEQ ID NO: 137)
R38144_PEA_2_T15 793 934 (SEQ ID NO: 138) R38144_PEA_2_T19 793 934
(SEQ ID NO: 139)
[3211] Segment cluster R38144_PEA.sub.--2_node.sub.--29 (SEQ ID
NO:939) according to the present invention is supported by 98
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1172 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01240 TABLE 1172 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R38144_PEA_2_T6 935 1059 (SEQ ID NO: 135) R38144_PEA_2_T10 784 908
(SEQ ID NO: 136) R38144_PEA_2_T13 935 1059 (SEQ ID NO: 137)
R38144_PEA_2_T19 935 1059 (SEQ ID NO: 139) R38144_PEA_2_T27 455 579
(SEQ ID NO: 140)
[3212] Segment cluster R38144_PEA.sub.--2_node.sub.--31 (SEQ ID
NO:940) according to the present invention is supported by 95
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T15 (SEQ
ID NO:138), R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1173 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01241 TABLE 1173 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R38144_PEA_2_T6 1060 1204 (SEQ ID NO: 135) R38144_PEA_2_T10 909
1053 (SEQ ID NO: 136) R38144_PEA_2_T15 935 1079 (SEQ ID NO: 138)
R38144_PEA_2_T19 1060 1204 (SEQ ID NO: 139) R38144_PEA_2_T27 580
724 (SEQ ID NO: 140)
[3213] Segment cluster R38144_PEA.sub.--2_node.sub.--46 (SEQ ID
NO:941) according to the present invention is supported by 147
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1174 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01242 TABLE 1174 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R38144_PEA_2_T6 1373 1544 (SEQ ID NO: 135) R38144_PEA_2_T10 1197
1368 (SEQ ID NO: 136) R38144_PEA_2_T13 1203 1374 (SEQ ID NO: 137)
R38144_PEA_2_T15 1223 1394 (SEQ ID NO: 138) R38144_PEA_2_T27 868
1039 (SEQ ID NO: 140)
[3214] Segment cluster R38144_PEA.sub.--2_node.sub.--47 (SEQ ID
NO:942) according to the present invention is supported by 147
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1175 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01243 TABLE 1175 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1545 1919 R38144_PEA_2_T10 (SEQ ID
NO: 136) 1369 1743 R38144_PEA_2_T13 (SEQ ID NO: 137) 1375 1749
R38144_PEA_2_T15 (SEQ ID NO: 138) 1395 1769 R38144_PEA_2_T27 (SEQ
ID NO: 140) 1040 1414
[3215] Segment cluster R38144_PEA.sub.--2_node.sub.--49 (SEQ ID
NO:943) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1176
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01244 TABLE 1176 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T19 (SEQ ID NO: 139) 1327 1448
[3216] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3217] Segment cluster R38144_PEA.sub.--2_node.sub.--0 (SEQ ID
NO:944) according to the present invention is supported by 101
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138),
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and R38144_PEA.sub.--2_T27
(SEQ ID NO:140). Table 1177 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01245 TABLE 1177 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1 105 R38144_PEA_2_T10 (SEQ ID NO:
136) 1 105 R38144_PEA_2_T13 (SEQ ID NO: 137) 1 105 R38144_PEA_2_T15
(SEQ ID NO: 138) 1 105 R38144_PEA_2_T19 (SEQ ID NO: 139) 1 105
R38144_PEA_2_T27 (SEQ ID NO: 140) 1 105
[3218] Segment cluster R38144_PEA.sub.--2_node.sub.--1 (SEQ ID
NO:945) according to the present invention is supported by 105
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138),
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and R38144_PEA.sub.--2_T27
(SEQ ID NO:140). Table 1178 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01246 TABLE 1178 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 106 197 R38144_PEA_2_T10 (SEQ ID
NO: 136) 106 197 R38144_PEA_2_T13 (SEQ ID NO: 137) 106 197
R38144_PEA_2_T15 (SEQ ID NO: 138) 106 197 R38144_PEA_2_T19 (SEQ ID
NO: 139) 106 197 R38144_PEA_2_T27 (SEQ ID NO: 140) 106 197
[3219] Segment cluster R38144_PEA.sub.--2_node.sub.--4 (SEQ ID
NO:946) according to the present invention is supported by 107
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T13 (SEQ ID NO:137), R38144_PEA.sub.--2 T15 (SEQ
ID NO:138), R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1179 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01247 TABLE 1179 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 198 299 R38144_PEA_2_T13 (SEQ ID
NO: 137) 198 299 R38144_PEA_2_T15 (SEQ ID NO: 138) 198 299
R38144_PEA_2_T19 (SEQ ID NO: 139) 198 299 R38144_PEA_2_T27 (SEQ ID
NO: 140) 198 299
[3220] Segment cluster R38144_PEA.sub.--2_node.sub.--5 (SEQ ID
NO:947) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T13 (SEQ ID NO:137), R38144_PEA.sub.--2_T15 (SEQ
ID NO:138), R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1180 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01248 TABLE 1180 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 300 308 R38144_PEA_2_T13 (SEQ ID
NO: 137) 300 308 R38144_PEA_2_T15 (SEQ ID NO: 138) 300 308
R38144_PEA_2_T19 (SEQ ID NO: 139) 300 308 R38144_PEA_2_T27 (SEQ ID
NO: 140) 300 308
[3221] Segment cluster R38144_PEA.sub.--2_node.sub.--7 (SEQ ID
NO:948) according to the present invention is supported by 92
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T13 (SEQ ID NO:137), R38144_PEA.sub.--2_T15 (SEQ
ID NO:138), R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1181 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01249 TABLE 1181 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 309 348 R38144_PEA_2_T13 (SEQ ID
NO: 137) 309 348 R38144_PEA_2_T15 (SEQ ID NO: 138) 309 348
R38144_PEA_2_T19 (SEQ ID NO: 139) 309 348 R38144_PEA_2_T27 (SEQ ID
NO: 140) 309 348
[3222] Segment cluster R38144_PEA.sub.--2_node.sub.--11 (SEQ ID
NO:949) according to the present invention is supported by 106
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138),
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and R38144_PEA.sub.--2_T27
(SEQ ID NO:140). Table 1182 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01250 TABLE 1182 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 349 454 R38144_PEA_2_T10 (SEQ ID
NO: 136) 198 303 R38144_PEA_2_T13 (SEQ ID NO: 137) 349 454
R38144_PEA_2_T15 (SEQ ID NO: 138) 349 454 R38144_PEA_2_T19 (SEQ ID
NO: 139) 349 454 R38144_PEA_2_T27 (SEQ ID NO: 140) 349 454
[3223] Segment cluster R38144_PEA.sub.--2_node.sub.--14 (SEQ ID
NO:950) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1183 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01251 TABLE 1183 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 455 460 R38144_PEA_2_T10 (SEQ ID
NO: 136) 304 309 R38144_PEA_2_T13 (SEQ ID NO: 137) 455 460
R38144_PEA_2_T15 (SEQ ID NO: 138) 455 460 R38144_PEA_2_T19 (SEQ ID
NO: 139) 455 460
[3224] Segment cluster R38144_PEA_node.sub.--11 (SEQ ID NO:951)
according to the present invention is supported by 105 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
R38144_PEA.sub.--2_T6 (SEQ ID NO:135), R38144_PEA.sub.--2_T10 (SEQ
ID NO:136), R38144_PEA.sub.--2_T13 (SEQ ID NO:137),
R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and R38144_PEA.sub.--2_T19
(SEQ ID NO:139). Table 1184 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01252 TABLE 1184 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 461 487 R38144_PEA_2_T10 (SEQ ID
NO: 136) 310 336 R38144_PEA_2_T13 (SEQ ID NO: 137) 461 487
R38144_PEA_2_T15 (SEQ ID NO: 138) 461 487 R38144_PEA_2_T19 (SEQ ID
NO: 139) 461 487
[3225] Segment cluster R38144_PEA.sub.--2_node_l 6 (SEQ ID NO:952)
according to the present invention is supported by 106 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
R38144_PEA.sub.--2_T6 (SEQ ID NO:135), R38144_PEA.sub.--2_T10 (SEQ
ID NO:136), R38144_PEA.sub.--2_T13 (SEQ ID NO:137),
R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and R38144_PEA.sub.--2_T19
(SEQ ID NO:139). Table 1185 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01253 TABLE 1185 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 488 580 R38144_PEA_2_T10 (SEQ ID
NO: 136) 337 429 R38144_PEA_2_T13 (SEQ ID NO: 137) 488 580
R38144_PEA_2_T15 (SEQ ID NO: 138) 488 580 R38144_PEA_2_T19 (SEQ ID
NO: 139) 488 580
[3226] Segment cluster R38144_PEA.sub.--2_node.sub.--19 (SEQ ID
NO:953) according to the present invention is supported by 93
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1186 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01254 TABLE 1186 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 581 615 R38144_PEA_2_T10 (SEQ ID
NO: 136) 430 464 R38144_PEA_2_T13 (SEQ ID NO: 137) 581 615
R38144_PEA_2_T15 (SEQ ID NO: 138) 581 615 R38144_PEA_2_T19 (SEQ ID
NO: 139) 581 615
[3227] Segment cluster R38144_PEA.sub.--2_node.sub.--20 (SEQ ID
NO:954) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1187 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01255 TABLE 1187 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 616 625 R38144_PEA_2_T10 (SEQ ID
NO: 136) 465 474 R38144_PEA_2_T13 (SEQ ID NO: 137) 616 625
R38144_PEA_2_T15 (SEQ ID NO: 138) 616 625 R38144_PEA_2_T19 (SEQ ID
NO: 139) 616 625
[3228] Segment cluster R38144_PEA.sub.--2_node.sub.--36 (SEQ ID
NO:955) according to the present invention is supported by 95
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138),
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and R38144_PEA.sub.--2_T27
(SEQ ID NO:140). Table 1188 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01256 TABLE 1188 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1205 1293 R38144_PEA_2_T10 (SEQ ID
NO: 136) 1054 1142 R38144_PEA_2_T13 (SEQ ID NO: 137) 1060 1148
R38144_PEA_2_T15 (SEQ ID NO: 138) 1080 1168 R38144_PEA_2_T19 (SEQ
ID NO: 139) 1205 1293 R38144_PEA_2_T27 (SEQ ID NO: 140) 725 813
[3229] Segment cluster R38144_PEA.sub.--2_node.sub.--37 (SEQ ID
NO:956) according to the present invention is supported by 97
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138),
R38144_PEA.sub.--2_T19 (SEQ ID NO:139) and R38144_PEA.sub.--2_T27
(SEQ ID NO:140). Table 1213 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01257 TABLE 1213 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1294 1326 R38144_PEA_2_T10 (SEQ ID
NO: 136) 1143 1175 R38144_PEA_2_T13 (SEQ ID NO: 137) 1149 1181
R38144_PEA_2_T15 (SEQ ID NO: 138) 1169 1201 R38144_PEA_2_T19 (SEQ
ID NO: 139) 1294 1326 R38144_PEA_2_T27 (SEQ ID NO: 140) 814 846
[3230] Segment cluster R38144_PEA.sub.--2_node.sub.--43 (SEQ ID
NO:957) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135).
Table 1189 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01258 TABLE 1189 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1327 1346
[3231] Segment cluster R38144_PEA.sub.--2_node.sub.--44 (SEQ ID
NO:958) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135).
Table 1190 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01259 TABLE 1190 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1347 1351
[3232] Segment cluster R38144_PEA.sub.--2_node.sub.--45 (SEQ ID
NO:959) according to the present invention can be found in the
following transcript(s): R38144_PEA.sub.--2_T6 (SEQ ID NO:135),
R38144_PEA.sub.--2_T10 (SEQ ID NO:136), R38144_PEA.sub.--2_T13 (SEQ
ID NO:137), R38144_PEA.sub.--2_T15 (SEQ ID NO:138) and
R38144_PEA.sub.--2_T27 (SEQ ID NO:140). Table 1191 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01260 TABLE 1191 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T6 (SEQ ID NO: 135) 1352 1372 R38144_PEA_2_T10 (SEQ ID
NO: 136) 1176 1196 R38144_PEA_2_T13 (SEQ ID NO: 137) 1182 1202
R38144_PEA_2_T15 (SEQ ID NO: 138) 1202 1222 R38144_PEA_2_T27 (SEQ
ID NO: 140) 847 867
[3233] Segment cluster R38144_PEA.sub.--2_node.sub.--51 (SEQ ID
NO:960) according to the present invention is supported by 1
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R38144_PEA.sub.--2_T19 (SEQ ID NO:139). Table 1192
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01261 TABLE 1192 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R38144_PEA_2_T19 (SEQ ID NO: 139) 1449 1522
Variant protein alignment to the previously known protein:
TABLE-US-01262 ##STR00761## ##STR00762## ##STR00763## ##STR00764##
##STR00765## ##STR00766## ##STR00767## ##STR00768## ##STR00769##
##STR00770## ##STR00771## ##STR00772## ##STR00773##
##STR00774##
Description for Cluster HUMOSTRO
[3234] Cluster HUMOSTRO features 3 transcript(s) and 30 segment(s)
of interest, the names for which are given in Tables 1193 and 1194,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1195.
TABLE-US-01263 TABLE 1193 Transcripts of interest Transcript Name
Sequence ID No. HUMOSTRO_PEA_1_PEA_1_T14 141
HUMOSTRO_PEA_1_PEA_1_T16 142 HUMOSTRO_PEA_1_PEA_1_T30 143
TABLE-US-01264 TABLE 1194 Segments of interest Segment Name
Sequence ID No. HUMOSTRO_PEA_1_PEA_1_node_0 961
HUMOSTRO_PEA_1_PEA_1_node_10 962 HUMOSTRO_PEA_1_PEA_1_node_16 963
HUMOSTRO_PEA_1_PEA_1_node_23 964 HUMOSTRO_PEA_1_PEA_1_node_31 965
HUMOSTRO_PEA_1_PEA_1_node_43 966 HUMOSTRO_PEA_1_PEA_1_node_3 967
HUMOSTRO_PEA_1_PEA_1_node_5 968 HUMOSTRO_PEA_1_PEA_1_node_7 969
HUMOSTRO_PEA_1_PEA_1_node_8 970 HUMOSTRO_PEA_1_PEA_1_node_15 971
HUMOSTRO_PEA_1_PEA_1_node_17 972 HUMOSTRO_PEA_1_PEA_1_node_20 973
HUMOSTRO_PEA_1_PEA_1_node_21 974 HUMOSTRO_PEA_1_PEA_1_node_22 975
HUMOSTRO_PEA_1_PEA_1_node_24 976 HUMOSTRO_PEA_1_PEA_1_node_26 977
HUMOSTRO_PEA_1_PEA_1_node_27 978 HUMOSTRO_PEA_1_PEA_1_node_28 979
HUMOSTRO_PEA_1_PEA_1_node_29 980 HUMOSTRO_PEA_1_PEA_1_node_30 981
HUMOSTRO_PEA_1_PEA_1_node_32 982 HUMOSTRO_PEA_1_PEA_1_node_34 983
HUMOSTRO_PEA_1_PEA_1_node_36 984 HUMOSTRO_PEA_1_PEA_1_node_37 985
HUMOSTRO_PEA_1_PEA_1_node_38 986 HUMOSTRO_PEA_1_PEA_1_node_39 987
HUMOSTRO_PEA_1_PEA_1_node_40 988 HUMOSTRO_PEA_1_PEA_1_node_41 989
HUMOSTRO_PEA_1_PEA_1_node_42 990
TABLE-US-01265 TABLE 1195 Proteins of interest Sequence Protein
Name ID No. Corresponding Transcript(s) HUMOSTRO_PEA_1_PEA_1_P21
1627 HUMOSTRO_PEA_1_PEA_1_T14 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_P25 1628 HUMOSTRO_PEA_1_PEA_1_T16 (SEQ ID NO:
142) HUMOSTRO_PEA_1_PEA_1_P30 1629 HUMOSTRO_PEA_1_PEA_1_T30 (SEQ ID
NO: 143)
[3235] These sequences are variants of the known protein
Osteopontin precursor (SwissProt accession identifier OSTP_HUMAN;
known also according to the synonyms Bone sialoprotein 1; Urinary
stone protein; Secreted phosphoprotein 1; SPP-1; Nephropontin;
Uropontin), SEQ ID NO:1462, referred to herein as the previously
known protein.
[3236] Protein Osteopontin precursor (SEQ ID NO:1462) is known or
believed to have the following function(s): Binds tightly to
hydroxyapatite. Appears to form an integral part of the mineralized
matrix. Probably important to cell-matrix interaction. Acts as a
cytokine involved in enhancing production of interferon-gamma and
interleukin-12 and reducing production of interleukin-10 and is
essential in the pathway that leads to type I immunity (By
similarity). The sequence for protein Osteopontin precursor is
given at the end of the application, as "Osteopontin precursor
amino acid sequence". Known polymorphisms for this sequence are as
shown in Table 1196.
TABLE-US-01266 TABLE 1196 Amino acid mutations for Known Protein
SNP position(s) on amino acid sequence Comment 301 R -> H (in
dbSNP: 4660). /FTId = VAR_014717. 188 D -> H 237 T -> A
275-278 SHEF -> GNSL
[3237] Protein Osteopontin precursor (SEQ ID NO:1462) localization
is believed to be Secreted.
[3238] The previously known protein also has the following
indication(s) and/or potential therapeutic use(s): Regeneration,
bone. It has been investigated for clinical/therapeutic use in
humans, for example as a target for an antibody or small molecule,
and/or as a direct therapeutic; available information related to
these investigations is as follows. Potential pharmaceutically
related or therapeutically related activity or activities of the
previously known protein are as follows: Bone formation stimulant.
A therapeutic role for a protein represented by the cluster has
been predicted. The cluster was assigned this field because there
was information in the drug database or the public databases (e.g.,
described herein above) that this protein, or part thereof, is used
or can be used for a potential therapeutic indication:
Musculoskeletal.
[3239] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: ossification;
anti-apoptosis; inflammatory response; cell-matrix adhesion;
cell-cell signaling, which are annotation(s) related to Biological
Process; defense/immunity protein; cytokine; integrin ligand;
protein binding; growth factor; apoptosis inhibitor, which are
annotation(s) related to Molecular Function; and extracellular
matrix, which are annotation(s) related to Cellular Component.
[3240] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3241] Cluster HUMOSTRO can be used as a diagnostic marker
according to overexpression of transcripts of this cluster in
cancer. Expression of such transcripts in normal tissues is also
given according to the previously described methods. The term
"number" in the right hand column of the table and the numbers on
the y-axis of FIG. 46 refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[3242] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 46 and Table 1197. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues, lung malignant tumors,
breast malignant tumors, ovarian carcinoma and skin
malignancies.
TABLE-US-01267 TABLE 1197 Normal tissue distribution Name of Tissue
Number Adrenal 4 Bladder 0 Bone 897 Brain 506 Colon 69 Epithelial
548 General 484 head and neck 50 Kidney 5618 Liver 4 Lung 10 lymph
nodes 75 Breast 8 bone marrow 62 Muscle 37 Ovary 40 Pancreas 845
Prostate 48 Skin 13 Stomach 73 Thyroid 0 Uterus 168
TABLE-US-01268 TABLE 1198 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Adrenal 1.5e-01
2.1e-01 2.0e-02 4.6 4.4e-02 3.6 Bladder 1.2e-01 9.2e-02 5.7e-02 4.1
2.1e-02 4.3 Bone 4.9e-01 7.4e-01 4.1e-06 0.6 5.4e-01 0.4 Brain
6.6e-01 7.0e-01 3.2e-01 0.6 1 0.4 Colon 2.7e-01 4.0e-01 3.1e-01 1.5
5.2e-01 1.1 Epithelial 2.0e-07 1.6e-03 9.8e-01 0.7 1 0.5 General
1.2e-06 1.2e-02 7.9e-01 0.8 1 0.6 head and neck 3.4e-01 5.0e-01 1
0.7 1 0.7 Kidney 6.8e-01 7.4e-01 1 0.2 1 0.1 Liver 3.3e-01 2.5e-01
1 1.8 2.3e-01 2.6 Lung 4.3e-04 4.6e-03 2.1e-30 15.0 2.8e-27 23.5
lymph nodes 6.7e-01 8.7e-01 8.1e-01 0.7 9.9e-01 0.3 Breast 2.3e-01
3.0e-01 1.9e-04 6.2 4.1e-03 4.3 bone marrow 7.5e-01 7.8e-01 1 0.3
2.0e-02 1.2 Muscle 4.0e-02 7.5e-02 1.1e-01 4.6 5.1e-01 1.5 Ovary
4.7e-02 8.4e-02 1.9e-05 5.4 8.3e-04 3.7 Pancreas 5.0e-02 3.3e-01 1
0.3 1 0.2 Prostate 8.5e-01 9.0e-01 8.9e-01 0.7 9.5e-01 0.6 Skin
1.6e-01 1.6.sup.e-01 1.2e-10 12.6 5.2e-04 4.1 Stomach 1.5e-01
6.3.sup.e-01 5.0e-01 1.2 9.4e-01 0.6 Thyroid 2.9e-01 2.9e-01
5.9e-02 2.0 5.9e-02 2.0 Uterus 6.1e-02 5.7.sup.e-01 1.1e-01 1.3
7.0e-01 0.7
[3243] As noted above, cluster HUMOSTRO features 3 transcript(s),
which were listed in Table 1193 above. These transcript(s) encode
for protein(s) which are variant(s) of protein Osteopontin
precursor (SEQ ID NO:1462). A description of each variant protein
according to the present invention is now provided.
[3244] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID
NO:1627) according to the present invention has an amino acid
sequence as given at the end of the application; it is encoded by
transcript(s) HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141).
An alignment is given to the known protein (Osteopontin precursor
(SEQ ID NO:1462)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3245] Comparison report between
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627) and
OSTP_HUMAN (SEQ ID NO:1462):
[3246] 1. An isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ
corresponding to amino acids 1-58 of OSTP_HUMAN (SEQ ID NO:1462),
which also corresponds to amino acids 1-58 of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), and a second
amino acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence VFLNFS (SEQ ID NO: 261) corresponding to amino acids 59-64
of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), wherein
said first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[3247] 2. An isolated polypeptide encoding for a tail of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VFLNFS (SEQ ID NO: 261) in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21
(SEQ ID NO:1627).
[3248] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because of manual inspection of known
protein localization and/or gene structure.
[3249] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID
NO:1627) also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1199, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01269 TABLE 1199 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
7 C -> W No 31 Q -> R No 47 D -> V Yes 49 S -> P No
[3250] The glycosylation sites of variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627), as compared
to the known protein Osteopontin precursor (SEQ ID NO:1462), are
described in Table 1200 (given according to their position(s) on
the amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-01270 TABLE 1200 Glycosylation site(s) Position(s) on
known amino acid sequence Present in variant protein? 79 no 106
no
[3251] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID
NO:1627) is encoded by the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID
NO:141) is shown in bold; this coding portion starts at position
199 and ends at position 390. The transcript also has the following
SNPs as listed in Table 1201 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P21 (SEQ ID NO:1627) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01271 TABLE 1201 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
136 A -> G Yes 154 T -> No 159 G -> T Yes 219 C -> G No
274 -> G No 290 A -> G No 338 A -> T Yes 343 T -> C No
413 G -> C Yes 707 C -> T Yes 708 C -> A Yes 715 A -> G
Yes 730 A -> C No 730 A -> G No 746 T -> C Yes 767 C ->
T No 779 G -> A Yes 866 -> G No 869 T -> No 889 -> A No
891 A -> C No 891 A -> G No 905 T -> C No 910 -> G No
910 -> T No 997 A -> G No 1026 G -> C No 1042 -> G No
1042 -> T No 1071 A -> No 1071 A -> C No 1098 A -> No
1105 C -> T No 1124 -> G No 1135 G -> A Yes 1136 T ->
No 1136 T -> G No 1173 A -> C No 1173 A -> G No 1179 A
-> G No 1214 C -> T Yes 1246 T -> No 1246 T -> A No
1359 A -> No 1359 A -> G No 1362 T -> No 1365 C -> T
Yes 1366 G -> A Yes 1408 A -> C No 1418 A -> C No 1433 A
-> C No 1456 A -> C No 1524 T -> A No 1524 T -> C No
1547 A -> G Yes 1553 T -> No 1574 -> G No 1654 A -> C
Yes 1691 A -> G No 1703 A -> C Yes 1755 A -> C No 1764 T
-> No
[3252] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID
NO:1628) according to the present invention has an amino acid
sequence as given at the end of the application; it is encoded by
transcript(s) HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142).
An alignment is given to the known protein (Osteopontin precursor
(SEQ ID NO:1462)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3253] Comparison report between
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628) and
OSTP_HUMAN (SEQ ID NO:1462):
[3254] 1. An isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31
of OSTP_HUMAN (SEQ ID NO:1462), which also corresponds to amino
acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID
NO:1628), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence H corresponding to amino acids
32-32 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628),
wherein said first amino acid sequence and second amino acid
sequence are contiguous and in a sequential order.
[3255] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3256] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID
NO:1628) also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1202, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01272 TABLE 1202 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
7 C -> W No 31 Q -> R No
[3257] The glycosylation sites of variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628), as compared
to the known protein Osteopontin precursor (SEQ ID NO:1462), are
described in Table 1203 (given according to their position(s) on
the amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-01273 TABLE 1203 Glycosylation site(s) Position(s) on
known amino acid sequence Present in variant protein? 79 no 106
no
[3258] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID
NO:1628) is encoded by the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID
NO:142) is shown in bold; this coding portion starts at position
199 and ends at position 294. The transcript also has the following
SNPs as listed in Table 1204 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P25 (SEQ ID NO:1628) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01274 TABLE 1204 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
136 A -> G Yes 154 T -> No 159 G -> T Yes 219 C -> G No
274 -> G No 290 A -> G No 419 C -> T Yes 454 G -> C Yes
527 A -> T Yes 532 T -> C No 630 C -> T Yes 631 C -> A
Yes 638 A -> G Yes 653 A -> C No 653 A -> G No 669 T ->
C Yes 690 C -> T No 702 G -> A Yes 789 -> G No 792 T ->
No 812 -> A No 814 A -> C No 814 A -> G No 828 T -> C
No 833 -> G No 833 -> T No 920 A -> G No 949 G -> C No
965 -> G No 965 -> T No 994 A -> No 994 A -> C No 1021
A -> No 1028 C -> T No 1047 -> G No 1058 G -> A Yes
1059 T -> No 1059 T -> G No 1096 A -> C No 1096 A -> G
No 1102 A -> G No 1137 C -> T Yes 1169 T -> No 1169 T
-> A No 1282 A -> No 1282 A -> G No 1285 T -> No 1288 C
-> T Yes 1289 G -> A Yes 1331 A -> C No 1341 A -> C No
1356 A -> C No 1379 A -> C No 1447 T -> A No 1447 T ->
C No 1470 A -> G Yes 1476 T -> No 1497 -> G No 1577 A
-> C Yes 1614 A -> G No 1626 A -> C Yes 1678 A -> C No
1687 T -> No
[3259] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID
NO:1629) according to the present invention has an amino acid
sequence as given at the end of the application; it is encoded by
transcript(s) HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143).
An alignment is given to the known protein (Osteopontin precursor
(SEQ ID NO:1462)) at the end of the application. One or more
alignments to one or more previously published protein sequences
are given at the end of the application. A brief description of the
relationship of the variant protein according to the present
invention to each such aligned protein is as follows:
[3260] Comparison report between
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629) and
OSTP_HUMAN (SEQ ID NO:1462):
[3261] 1. An isolated chimeric polypeptide encoding for
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), comprising a
first amino acid sequence being at least 90% homologous to
MRIAVICFCLLGITCAIPVKQADSGSSEEKQ corresponding to amino acids 1-31
of OSTP_HUMAN (SEQ ID NO:1462), which also corresponds to amino
acids 1-31 of HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID
NO:1629), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence VSIFYVFI
[3262] (SEQ ID NO: 262) corresponding to amino acids 32-39 of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), wherein said
first amino acid sequence and second amino acid sequence are
contiguous and in a sequential order.
[3263] 2. An isolated polypeptide encoding for a tail of
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), comprising a
polypeptide being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
VSIFYVFI (SEQ ID NO: 262) in HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30
(SEQ ID NO:1629).
[3264] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3265] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID
NO:1629) also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1205, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01275 TABLE 1205 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
7 C -> W No 31 Q -> R No
[3266] The glycosylation sites of variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629), as compared
to the known protein Osteopontin precursor (SEQ ID NO:1462), are
described in Table 1206 (given according to their position(s) on
the amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-01276 TABLE 1206 Glycosylation site(s) Position(s) on
known amino acid sequence Present in variant protein? 79 no 106
no
[3267] Variant protein HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID
NO:1629) is encoded by the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID
NO:143) is shown in bold; this coding portion starts at position
199 and ends at position 315. The transcript also has the following
SNPs as listed in Table 1207 (given according to their position on
the nucleotide sequence, with the alternative nucleic acid listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_P30 (SEQ ID NO:1629) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01277 TABLE 1207 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
136 A -> G Yes 154 T -> No 159 G -> T Yes 219 C -> G No
274 -> G No 290 A -> G No
[3268] As noted above, cluster HUMOSTRO features 30 segment(s),
which were listed in Table 1194 above and for which the sequence(s)
are given at the end of the application. These segment(s) are
portions of nucleic acid sequence(s) which are described herein
separately because they are of particular interest. A description
of each segment according to the present invention is now
provided.
[3269] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--0 (SEQ ID NO:961)
according to the present invention is supported by 333 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141),
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143). Table 1208
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01278 TABLE 1208 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1 184 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1 184 (SEQ ID NO: 142)
HUMOSTRO_PEA_1_PEA_1_T30 1 184 (SEQ ID NO: 143)
[3270] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--10 (SEQ ID NO:962)
according to the present invention is supported by 4 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1209
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01279 TABLE 1209 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T16 292 480 (SEQ ID NO: 142)
[3271] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--16 (SEQ ID NO:963)
according to the present invention is supported by 6 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141). Table 1210
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01280 TABLE 1210 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 373 638 (SEQ ID NO: 141)
[3272] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--23 (SEQ ID NO:964)
according to the present invention is supported by 334 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1211
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01281 TABLE 1211 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 804 967 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 727 890 (SEQ ID NO: 142)
[3273] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--31 (SEQ ID NO:965)
according to the present invention is supported by 350 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1212
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01282 TABLE 1212 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1164 1393 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1087 1316 (SEQ ID NO: 142)
[3274] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--43 (SEQ ID NO:966)
according to the present invention is supported by 192 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1213
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01283 TABLE 1213 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1810 1846 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1733 1769 (SEQ ID NO: 142)
[3275] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3276] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--3 (SEQ ID NO:967)
according to the present invention is supported by 353 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141),
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143). Table 1214
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01284 TABLE 1214 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 185 210 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 185 210 (SEQ ID NO: 142)
HUMOSTRO_PEA_1_PEA_1_T30 185 210 (SEQ ID NO: 143)
[3277] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--5 (SEQ ID NO:968)
according to the present invention is supported by 353 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141),
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143). Table 1215
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01285 TABLE 1215 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 211 252 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 211 252 (SEQ ID NO: 142)
HUMOSTRO_PEA_1_PEA_1_T30 211 252 (SEQ ID NO: 143)
[3278] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--7 (SEQ ID NO:969)
according to the present invention is supported by 357 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141),
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143). Table 1216
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01286 TABLE 1216 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 253 291 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 253 291 (SEQ ID NO: 142)
HUMOSTRO_PEA_1_PEA_1_T30 253 291 (SEQ ID NO: 143)
[3279] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--8 (SEQ ID NO:970)
according to the present invention is supported by 1 libraries. The
number of libraries was determined as previously described. This
segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T30 (SEQ ID NO:143). Table 1217
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01287 TABLE 1217 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T30 292 378 (SEQ ID NO: 143)
[3280] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--15 (SEQ ID NO:971)
according to the present invention is supported by 366 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1218
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01288 TABLE 1218 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 292 372 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 481 561 (SEQ ID NO: 142)
[3281] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--17 (SEQ ID NO:972)
according to the present invention is supported by 261 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1219
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01289 TABLE 1219 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 639 680 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 562 603 (SEQ ID NO: 142)
[3282] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--20 (SEQ ID NO:973)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1220 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01290 TABLE 1220 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 681 688 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 604 611 (SEQ ID NO: 142)
[3283] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--21 (SEQ ID NO:974)
according to the present invention is supported by 315 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1221
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01291 TABLE 1221 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 689 738 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 612 661 (SEQ ID NO: 142)
[3284] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--22 (SEQ ID NO:975)
according to the present invention is supported by 322 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1222
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01292 TABLE 1222 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 739 803 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 662 726 (SEQ ID NO: 142)
[3285] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--24 (SEQ ID NO:976)
according to the present invention is supported by 270 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1223
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01293 TABLE 1223 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 968 1004 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 891 927 (SEQ ID NO: 142)
[3286] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--26 (SEQ ID NO:977)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1224 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01294 TABLE 1224 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1005 1022 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 928 945 (SEQ ID NO: 142)
[3287] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--27 (SEQ ID NO:978)
according to the present invention is supported by 260 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1225
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01295 TABLE 1225 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1023 1048 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 946 971 (SEQ ID NO: 142)
[3288] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--28 (SEQ ID NO:979)
according to the present invention is supported by 273 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1226
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01296 TABLE 1226 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1049 1100 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 972 1023 (SEQ ID NO: 142)
[3289] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--29 (SEQ ID NO:980)
according to the present invention is supported by 272 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1227
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01297 TABLE 1227 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1101 1151 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1024 1074 (SEQ ID NO: 142)
[3290] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--30 (SEQ ID NO:981)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1228 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01298 TABLE 1228 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1152 1163 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1075 1086 (SEQ ID NO: 142)
[3291] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--32 (SEQ ID NO:982)
according to the present invention is supported by 293 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1229
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01299 TABLE 1229 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1394 1427 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1317 1350 (SEQ ID NO: 142)
[3292] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--34 (SEQ ID NO:983)
according to the present invention is supported by 301 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1230
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01300 TABLE 1230 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1428 1468 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1351 1391 (SEQ ID NO: 142)
[3293] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--36 (SEQ ID NO:984)
according to the present invention is supported by 292 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1231
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01301 TABLE 1231 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1469 1504 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1392 1427 (SEQ ID NO: 142)
[3294] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--37 (SEQ ID NO:985)
according to the present invention is supported by 295 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1232
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01302 TABLE 1232 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1505 1623 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1428 1546 (SEQ ID NO: 142)
[3295] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--38 (SEQ ID NO:986)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1233 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01303 TABLE 1233 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1624 1634 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1547 1557 (SEQ ID NO: 142)
[3296] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--39 (SEQ ID NO:987)
according to the present invention is supported by 268 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1234
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01304 TABLE 1234 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1635 1725 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1558 1648 (SEQ ID NO: 142)
[3297] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--40 (SEQ ID NO:988)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1235 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01305 TABLE 1235 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1726 1743 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1649 1666 (SEQ ID NO: 142)
[3298] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--41 (SEQ ID NO:989)
according to the present invention can be found in the following
transcript(s): HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141)
and HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table
1236 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01306 TABLE 1236 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1744 1749 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1667 1672 (SEQ ID NO: 142)
[3299] Segment cluster
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_node.sub.--42 (SEQ ID NO:990)
according to the present invention is supported by 224 libraries.
The number of libraries was determined as previously described.
This segment can be found in the following transcript(s):
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T14 (SEQ ID NO:141) and
HUMOSTRO_PEA.sub.--1_PEA.sub.--1_T16 (SEQ ID NO:142). Table 1237
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01307 TABLE 1237 Segment location on transcripts Segment
Segment ending Transcript name starting position position
HUMOSTRO_PEA_1_PEA_1_T14 1750 1809 (SEQ ID NO: 141)
HUMOSTRO_PEA_1_PEA_1_T16 1673 1732 (SEQ ID NO: 142)
Variant protein alignment to the previously known protein:
TABLE-US-01308 ##STR00775## ##STR00776## ##STR00777##
Description for Cluster R11723
[3300] Cluster R11723 features 6 transcript(s) and 26 segment(s) of
interest, the names for which are given in Tables 1238 and 1239,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1240.
TABLE-US-01309 TABLE 1238 Transcripts of interest Transcript Name
Sequence ID No. R11723_PEA_1_T15 144 R11723_PEA_1_T17 145
R11723_PEA_1_T19 146 R11723_PEA_1_T20 147 R11723_PEA_1_T5 148
R11723_PEA_1_T6 149
TABLE-US-01310 TABLE 1239 Segments of interest Segment Name
Sequence ID No. R11723_PEA_1_node_13 991 R11723_PEA_1_node_16 992
R11723_PEA_1_node_19 993 R11723_PEA_1_node_2 994
R11723_PEA_1_node_22 995 R11723_PEA_1_node_31 996
R11723_PEA_1_node_10 997 R11723_PEA_1_node_11 998
R11723_PEA_1_node_15 999 R11723_PEA_1_node_18 1000
R11723_PEA_1_node_20 1001 R11723_PEA_1_node_21 1002
R11723_PEA_1_node_23 1003 R11723_PEA_1_node_24 1004
R11723_PEA_1_node_25 1005 R11723_PEA_1_node_26 1006
R11723_PEA_1_node_27 1007 R11723_PEA_1_node_28 1008
R11723_PEA_1_node_29 1009 R11723_PEA_1_node_3 1010
R11723_PEA_1_node_30 1011 R11723_PEA_1_node_4 1012
R11723_PEA_1_node_5 1013 R11723_PEA_1_node_6 1014
R11723_PEA_1_node_7 1015 R11723_PEA_1_node_8 1016
TABLE-US-01311 TABLE 1240 Proteins of interest Protein Name
Sequence ID No. R11723_PEA_1_P2 1409 R11723_PEA_1_P6 1410
R11723_PEA_1_P7 1411 R11723_PEA_1_P13 1412 R11723_PEA_1_P10
1413
[3301] Cluster R11723 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 47 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[3302] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 47 and Table 1241. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues and kidney malignant
tumors.
TABLE-US-01312 TABLE 1241 Normal tissue distribution Name of Tissue
Number Adrenal 0 Brain 30 Epithelial 3 General 17 head and neck 0
Kidney 0 Lung 0 Breast 0 Ovary 0 Pancreas 10 Skin 0 Uterus 0
TABLE-US-01313 TABLE 1242 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Adrenal 4.2e-01
4.6e-01 4.6e-01 2.2 5.3e-01 1.9 Brain 2.2e-01 2.0e-01 1.2e-02 2.8
5.0e-02 2.0 Epithelial 3.0e-05 6.3e-05 1.8e-05 6.3 3.4e-06 6.4
General 7.2e-03 4.0e-02 1.3e-04 2.1 1.1e-03 1.7 head and neck 1
5.0e-01 1 1.0 7.5e-01 1.3 Kidney 1.5e-01 2.4e-01 4.4e-03 5.4
2.8e-02 3.6 Lung 1.2e-01 1.6e-01 1 1.6 1 1.3 Breast 5.9e-01 4.4e-01
1 1.1 6.8e-01 1.5 Ovary 1.6e-02 1.3e-02 1.0e-01 3.8 7.0e-02 3.5
Pancreas 5.5e-01 2.0e-01 3.9e-01 1.9 1.4e-01 2.7 Skin 1 4.4e-01 1
1.0 1.9e-02 2.1 Uterus 1.5e-02 5.4e-02 1.9e-01 3.1 1.4e-01 2.5
[3303] As noted above, contig R11723 features 6 transcript(s),
which were listed in Table 1238 above. A description of each
variant protein according to the present invention is now
provided.
[3304] Variant protein R11723_PEA.sub.--1_P2 (SEQ ID NO:1409)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). The location of the variant
protein was determined according to results from a number of
different software programs and analyses, including analyses from
SignalP and other specialized programs. The variant protein is
believed to be located as follows with regard to the cell:
secreted. The protein localization is believed to be secreted
because both signal-peptide prediction programs predict that this
protein has a signal peptide, and neither trans-membrane region
prediction program predicts that this protein has a trans-membrane
region.
[3305] Variant protein R11723_PEA.sub.--1.sub.--1_P2 (SEQ ID
NO:1409) also has the following non-silent SNPs (Single Nucleotide
Polymorphisms) as listed in Table 1243, (given according to their
position(s) on the amino acid sequence, with the alternative amino
acid(s) listed; the last column indicates whether the SNP is known
or not; the presence of known SNPs in variant protein
R11723_PEA.sub.--1_P2 (SEQ ID NO:1409) sequence provides support
for the deduced sequence of this variant protein according to the
present invention).
TABLE-US-01314 TABLE 1243 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
107 H -> P Yes 70 G -> No 70 G -> C No
[3306] Variant protein R11723_PEA.sub.--1_P2 (SEQ ID NO:1409) is
encoded by the following transcript(s): R11723_PEA.sub.--1_T6 (SEQ
ID NO:149), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R11723_PEA.sub.--1_T6 (SEQ ID NO:149) is shown in bold; this coding
portion starts at position 1716 and ends at position 2051. The
transcript also has the following SNPs as listed in Table 1244
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last colunm indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R11723_PEA.sub.--1_P2 (SEQ ID NO:1409) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01315 TABLE 1244 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
1231 C -> T Yes 1278 G -> C Yes 1923 G -> No 1923 G ->
T No 2035 A -> C Yes 2048 A -> C No 2057 A -> G Yes
[3307] Variant protein R11723_PEA.sub.--1_P6 (SEQ ID NO:1410)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R11723_PEA.sub.--1_T15 (SEQ ID NO:144). One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[3308] Comparison report between R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410) and Q8IXM0 (SEQ ID NO:1707):
[3309] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO: 1741)
corresponding to amino acids 1-110 of R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410), and a second amino acid sequence being at least 90%
homologous to
MYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDDRAEVEKRLREGEEDHVRPEVGPRPVVLG
FGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSMRTQ corresponding to amino
acids 1-112 of Q8IXM0 (SEQ ID NO:1707), which also corresponds to
amino acids 111-222 of R11723_PEA.sub.--1_P6 (SEQ ID NO:1410),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[3310] 2. An isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAGSPCRGLAPGREEQRALHKAGAVGGGVR (SEQ ID NO: 1741) of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410).
[3311] Comparison report between R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410) and Q96AC2 (SEQ ID NO: 1708):
[3312] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 1-83 of Q96AC2 (SEQ ID
NO:1708), which also corresponds to amino acids 1-83 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3313] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[3314] Comparison report between R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410) and Q8N2G4 (SEQ ID NO: 1709):
[3315] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 1-83 of Q8N2G4 (SEQ ID
NO:1709), which also corresponds to amino acids 1-83 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3316] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[3317] Comparison report between R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410) and BAC85518 (SEQ ID NO: 1710):
[3318] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAGIMYRKS
CASSAACLIASAG corresponding to amino acids 24-106 of BAC85518 (SEQ
ID NO:1710), which also corresponds to amino acids 1-83 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEKHSM
RTQ (SEQ ID NO: 1742) corresponding to amino acids 84-222 of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3319] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P6 (SEQ ID NO:1410), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SPCRGLAPGREEQRALHKAGAVGGGVRMYAQALLVVGVLQRQAAAQHLHEHPPKLLRGHRVQERVDD
RAEVEKRLREGEEDHVRPEVGPRPVVLGFGRSHDPPNLVGHPAYGQCHNNQPWADTSRRERQRKEHSM
RTQ (SEQ ID NO: 1742) in R11723_PEA.sub.--1_P6 (SEQ ID
NO:1410).
[3320] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3321] Variant protein R11723_PEA.sub.--1_P6 (SEQ ID NO:1410) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1245, (given according to their 1271 position(s)
on the amino acid sequence, with the alternative amino acid(s)
listed; the last column indicates whether the SNP is known or not;
the presence of known SNPs in variant protein R11723_PEA.sub.--1_P6
(SEQ ID NO:1410) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01316 TABLE 1245 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
180 G -> No 180 G -> C No 217 H -> P Yes
[3322] Variant protein R11723_PEA.sub.--1_P6 (SEQ ID NO:1410) is
encoded by the following transcript(s): R11723_PEA.sub.--1_T15 (SEQ
ID NO:144), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R11723_PEA.sub.--1_T15 (SEQ ID NO:144) is shown in bold; this
coding portion starts at position 434 and ends at position 1099.
The transcript also has the following SNPs as listed in Table 1246
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R11723_PEA.sub.--1_P6 (SEQ ID NO:1410) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01317 TABLE 1246 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
971 G -> No 971 G -> T No 1083 A -> C Yes 1096 A -> C
No 1105 A -> G Yes
[3323] Variant protein R11723_PEA.sub.--1_P7 (SEQ ID NO:1411)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R11723_PEA.sub.--1_T17 (SEQ ID NO:145). One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[3324] Comparison report between R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411) and Q96AC2 (SEQ ID NO:1708):
[3325] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 1-64 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-64 of R11723_PEA.sub.--1_P7 (SEQ
ID NO:1411), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3326] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[3327] Comparison report between R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411) and Q8N2G4 (SEQ ID NO:1709):
[3328] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 1-64 of Q8N2G4 (SEQ ID NO:1709), which
also corresponds to amino acids 1-64 of R11723_PEA.sub.--1_P7 (SEQ
ID NO:1411), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3329] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[3330] Comparison report between R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411) and BAC85273:
[3331] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MWVLG (SEQ ID NO: 1744) corresponding to amino acids 1-5
of R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), second amino acid
sequence being at least 90% homologous to
IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 22-80 of BAC85273, which also
corresponds to amino acids 6-64 of R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ
ID NO: 1743) corresponding to amino acids 65-93 of R11723_PEA_P7
(SEQ ID NO:1411), wherein said first, second and third amino acid
sequences are contiguous and in a sequential order.
[3332] 2. An isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MWVLG (SEQ
ID NO: 1744) of R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[3333] 3. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[3334] Comparison report between R11723_PEA.sub.--1_P7 (SEQ ID
NO:1411) and BAC85518 (SEQ ID NO:1710):
[3335] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSAG
corresponding to amino acids 24-87 of BAC85518 (SEQ ID NO:1710),
which also corresponds to amino acids 1-64 of R11723_PEA.sub.--1_P7
(SEQ ID NO:1411), and a second amino acid sequence being at least
70%, optionally at least 80%, preferably at least 85%, more
preferably at least 90% and most preferably at least 95% homologous
to a polypeptide having the sequence SHCVTRLECSGTISAHCNLCLPGSNDHPT
(SEQ ID NO: 1743) corresponding to amino acids 65-93 of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3336] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
SHCVTRLECSGTISAHCNLCLPGSNDHPT (SEQ ID NO: 1743) in
R11723_PEA.sub.--1_P7 (SEQ ID NO:1411).
[3337] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3338] Variant protein R11723_PEA.sub.--1_P7 (SEQ ID NO:1411) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1247, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R11723_PEA.sub.--1_P7
(SEQ ID NO:1411) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01318 TABLE 1247 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
67 C -> S Yes
[3339] Variant protein R11723_PEA.sub.--1_P7 (SEQ ID NO:1411) is
encoded by the following transcript(s): R11723_PEA.sub.--1_T17 (SEQ
ID NO:145), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R11723_PEA.sub.--1_T17 (SEQ ID NO:145) is shown in bold; this
coding portion starts at position 434 and ends at position 712. The
transcript also has the following SNPs as listed in Table 1248
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R11723_PEA.sub.--1_P7 (SEQ ID NO:1411) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01319 TABLE 1248 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
625 G -> T Yes 633 G -> C Yes 1303 C -> T Yes
[3340] Variant protein R11723_PEA.sub.--1_P13 (SEQ ID NO:1412)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R11723_PEA.sub.--1_T19 (SEQ ID NO:146). One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[3341] Comparison report between R11723_PEA.sub.--1_P13 (SEQ ID
NO:1412) and Q96AC2 (SEQ ID NO:1708):
[3342] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P13 (SEQ ID NO:1412), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P13 (SEQ
ID NO:1412), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:
1745) corresponding to amino acids 64-84 of R11723_PEA.sub.--1_P13
(SEQ ID NO:1412), wherein said first and second amino acid
sequences are contiguous and in a sequential order.
[3343] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P13 (SEQ ID NO:1412), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO: 1745) in R11723_PEA.sub.--1_P13
(SEQ ID NO:1412).
[3344] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3345] Variant protein R11723_PEA.sub.--1_P13 (SEQ ID NO:1412) is
encoded by the following transcript(s): R11723_PEA.sub.--1_T19 (SEQ
ID NO:146) and R11723_PEA.sub.--1_T5 (SEQ ID NO:148), for which the
sequence(s) is/are given at the end of the application. The coding
portion of transcript R11723_PEA_LT19 (SEQ ID NO:146) is shown in
bold; this coding portion starts at position 434 and ends at
position 685. The transcript also has the following SNPs as listed
in Table 1249 (given according to their position on the nucleotide
sequence, with the alternative nucleic acid listed; the last column
indicates whether the SNP is known or not; the presence of known
SNPs in variant protein R11723_PEA.sub.--1_P13 (SEQ ID NO:1412)
sequence provides support for the deducted sequence of this variant
protein according to the present invention).
TABLE-US-01320 TABLE 1249 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
778 G -> T Yes 786 G -> C Yes 1456 C -> T Yes
[3346] Variant protein R11723_PEA.sub.--1_P10 (SEQ ID NO:1413)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R11723_PEA.sub.--1_T20 (SEQ ID NO:147). One or more alignments to
one or more previously published protein sequences are given at the
end of the application. A brief description of the relationship of
the variant protein according to the present invention to each such
aligned protein is as follows:
[3347] Comparison report between R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413) and Q96AC2 (SEQ ID NO:1708):
[3348] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:1708), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P10 (SEQ
ID NO:1413), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3349] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[3350] Comparison report between R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413) and Q8N2G4 (SEQ ID NO:1709):
[3351] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 1-63 of Q8N2G4 (SEQ ID NO:1709), which
also corresponds to amino acids 1-63 of R11723_PEA.sub.--1_P10 (SEQ
ID NO:1413), and a second amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3352] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[3353] Comparison report between R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413) and BAC85273:
[3354] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 70%, optionally at least 80%,
preferably at least 85%, more preferably at least 90% and most
preferably at least 95% homologous to a polypeptide having the
sequence MWVLG (SEQ ID NO: 1744) corresponding to amino acids 1-5
of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), second amino acid
sequence being at least 90% homologous to
IAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 22-79 of BAC85273, which also
corresponds to amino acids 6-63 of R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413), and a third amino acid sequence being at least 70%,
optionally at least 80%, preferably at least 85%, more preferably
at least 90% and most preferably at least 95% homologous to a
polypeptide having the sequence DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID
NO: 1746) corresponding to amino acids 64-90 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[3355] 2. An isolated polypeptide encoding for a head of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence MWVLG (SEQ
ID NO: 1744) of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[3356] 3. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413).
[3357] Comparison report between R11723_PEA.sub.--1_P10 (SEQ ID
NO:1413) and BAC85518 (SEQ ID NO:1710):
[3358] 1. An isolated chimeric polypeptide encoding for
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a first amino
acid sequence being at least 90% homologous to
MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEVMEQSA
corresponding to amino acids 24-86 of BAC85518 (SEQ ID NO:1710),
which also corresponds to amino acids 1-63 of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) corresponding to
amino acids 64-90 of R11723_PEA.sub.--1_P10 (SEQ ID NO:1413),
wherein said first and second amino acid sequences are contiguous
and in a sequential order.
[3359] 2. An isolated polypeptide encoding for a tail of
R11723_PEA.sub.--1_P10 (SEQ ID NO:1413), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
DRVSLCHEAGVQWNNFSTLQPLPPRLK (SEQ ID NO: 1746) in
R11723PEA.sub.--1_P10 (SEQ ID NO:1413).
[3360] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3361] Variant protein R11723_PEA.sub.--1_P10 (SEQ ID NO:1413) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1250, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R11723_PEA.sub.--1_P10
(SEQ ID NO:1413) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01321 TABLE 1250 Amino acid mutations SNP position(s) on
Alternative Previously amino acid sequence amino acid(s) known SNP?
66 V -> F Yes
[3362] Variant protein R11723_PEA.sub.--1_P10 (SEQ ID NO:1413) is
encoded by the following transcript(s): R11723_PEA.sub.--1_T20 (SEQ
ID NO:147), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R11723_PEA.sub.--1_T20 (SEQ ID NO:147) is shown in bold; this
coding portion starts at position 434 and ends at position 703. The
transcript also has the following SNPs as listed in Table 1251
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R11723_PEA.sub.--1_P10 (SEQ ID NO:1413) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01322 TABLE 1251 Nucleic acid SNPs SNP position on
Alternative Previously nucleotide sequence nucleic acid known SNP?
629 G -> T Yes 637 G -> C Yes 1307 C -> T Yes
[3363] As noted above, cluster R11723 features 26 segment(s), which
were listed in Table 1239 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[3364] Segment cluster R11723_PEA.sub.--1_node.sub.--13 (SEQ ID
NO:991) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T19 (SEQ ID NO:146),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1252 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01323 TABLE 1252 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R11723_PEA_1_T19 (SEQ ID NO: 146) 624 776 R11723_PEA_1_T5 (SEQ ID
NO: 148) 624 776 R11723_PEA_1_T6 (SEQ ID NO: 149) 658 810
[3365] Segment cluster R11723_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:992) according to the present invention is supported by 3
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T17 (SEQ ID NO:145),
R11723_PEA.sub.--1_T19 (SEQ ID NO:146) and R11723_PEA.sub.--1_T20
(SEQ ID NO:147). Table 1253 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01324 TABLE 1253 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R11723_PEA_1_T17 (SEQ ID NO: 145) 624 1367 R11723_PEA_1_T19 (SEQ ID
NO: 146) 777 1520 R11723_PEA_1_T20 (SEQ ID NO: 147) 628 1371
[3366] Segment cluster R11723_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:993) according to the present invention is supported by 45
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1254 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01325 TABLE 1254 Segment location on transcripts Segment
starting Segment ending Transcript name position position
R11723_PEA_1_T5 (SEQ ID NO: 148) 835 1008 R11723_PEA_1_T6 (SEQ ID
NO: 149) 869 1042
[3367] Segment cluster R11723_PEA.sub.--1_node.sub.--2 (SEQ ID
NO:994) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID ON:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1255 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01326 TABLE 1255 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 1 309 R11723_PEA_1_T17 (SEQ ID
NO: 145) 1 309 R11723_PEA_1_T19 (SEQ ID NO: 146) 1 309
R11723_PEA_1_T20 (SEQ ID NO: 147) 1 309 R11723_PEA_1_T5 (SEQ ID NO:
148) 1 309 R11723_PEA_1_T6 (SEQ ID NO: 149) 1 309
[3368] Segment cluster R11723_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:995) according to the present invention is supported by 65
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1256 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01327 TABLE 1256 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R11723_PEA_1_T5 (SEQ ID NO: 148) 1083 1569 R11723_PEA_1_T6 (SEQ ID
NO: 149) 1117 1603
[3369] Segment cluster R11723_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:996) according to the present invention is supported by 70
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1257 below describes the starting and ending
position of this segment on each transcript (it should be noted
that these transcripts show alternative polyadenylation).
TABLE-US-01328 TABLE 1257 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 1060 1295 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1978 2213 R11723_PEA_1_T6 (SEQ ID NO: 149) 2012 2247
[3370] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3371] Segment cluster R11723_PEA.sub.--1_node.sub.--10 (SEQ ID
NO:997) according to the present invention is supported by 38
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1258 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01329 TABLE 1258 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 486 529 R11723_PEA_1_T17 (SEQ ID
NO: 145) 486 529 R11723_PEA_1_T19 (SEQ ID NO: 146) 486 529
R11723_PEA_1_T20 (SEQ ID NO: 147) 486 529 R11723_PEA_1_T5 (SEQ ID
NO: 148) 486 529 R11723_PEA_1_T6 (SEQ ID NO: 149) 520 563
[3372] Segment cluster R11723_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:998) according to the present invention is supported by 42
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1259 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01330 TABLE 1259 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 530 623 R11723_PEA_1_T17 (SEQ ID
NO: 145) 530 623 R11723_PEA_1_T19 (SEQ ID NO: 146) 530 623
R11723_PEA_1_T20 (SEQ ID NO: 147) 530 623 R11723_PEA_1_T5 (SEQ ID
NO: 148) 530 623 R11723_PEA_1_T6 (SEQ ID NO: 149) 564 657
[3373] Segment cluster R11723_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:999) according to the present invention can be found in the
following transcript(s): R11723_PEA.sub.--1_T20 (SEQ ID NO:147).
Table 1260 below describes the starting and ending position of this
segment on each transcript.
TABLE-US-01331 TABLE 1260 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T20 (SEQ ID NO: 147) 624 627
[3374] Segment cluster R11723_PEA.sub.--1_node.sub.--18 (SEQ ID
NO:1000) according to the present invention is supported by 40
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1261 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01332 TABLE 1261 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 624 681 R11723_PEA_1_T5 (SEQ ID
NO: 148) 777 834 R11723_PEA_1_T6 (SEQ ID NO: 149) 811 868
[3375] Segment cluster R11723_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:1001) according to the present invention can be found in the
following transcript(s): R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1262 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01333 TABLE 1262 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R11723_PEA_1_T5 (SEQ ID NO: 148) 1009 1019 R11723_PEA_1_T6 (SEQ ID
NO: 149) 1043 1053
[3376] Segment cluster R11723_PEA.sub.--1_node.sub.--21 (SEQ ID NO:
1002) according to the present invention is supported by 36
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1263 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01334 TABLE 1263 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R11723_PEA_1_T5 (SEQ ID NO: 148) 1020 1082 R11723_PEA_1_T6 (SEQ ID
NO: 149) 1054 1116
[3377] Segment cluster R11723_PEA.sub.--1_node.sub.--23 (SEQ ID
NO:1003) according to the present invention is supported by 39
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1264 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01335 TABLE 1264 Segment location on transcripts Segment
Segment ending Transcript name starting position position
R11723_PEA_1_T5 (SEQ ID NO: 148) 1570 1599 R11723_PEA_1_T6 (SEQ ID
NO: 149) 1604 1633
[3378] Segment cluster R11723_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:1004) according to the present invention is supported by 51
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1265 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01336 TABLE 1265 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 682 765 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1600 1683 R11723_PEA_1_T6 (SEQ ID NO: 149) 1634 1717
[3379] Segment cluster R11723_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:1005) according to the present invention is supported by 54
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1266 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01337 TABLE 1266 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 766 791 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1684 1709 R11723_PEA_1_T6 (SEQ ID NO: 149) 1718 1743
[3380] Segment cluster R11723_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:1006) according to the present invention is supported by 62
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1267 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01338 TABLE 1267 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 792 904 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1710 1822 R11723_PEA_1_T6 (SEQ ID NO: 149) 1744 1856
[3381] Segment cluster R11723_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:1007) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1268 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01339 TABLE 1268 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 905 986 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1823 1904 R11723_PEA_1_T6 (SEQ ID NO: 149) 1857 1938
[3382] Segment cluster R11723_PEA.sub.--1_node.sub.--28 (SEQ ID
NO:1008) according to the present invention can be found in the
following transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1269 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01340 TABLE 1269 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 987 1010 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1905 1928 R11723_PEA_1_T6 (SEQ ID NO: 149) 1939 1962
[3383] Segment cluster R11723_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:1009) according to the present invention is supported by 69
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1270 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01341 TABLE 1270 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 1011 1038 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1929 1956 R11723_PEA_1_T6 (SEQ ID NO: 149) 1963 1990
[3384] Segment cluster R11723_PEA.sub.--1_node.sub.--3 (SEQ ID
NO:1010) according to the present invention can be found in the
following transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1271 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01342 TABLE 1271 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 310 319 R11723_PEA_1_T17 (SEQ ID
NO: 145) 310 319 R11723_PEA_1_T19 (SEQ ID NO: 146) 310 319
R11723_PEA_1_T20 (SEQ ID NO: 147) 310 319 R11723_PEA_1_T5 (SEQ ID
NO: 148) 310 319 R11723_PEA_1_T6 (SEQ ID NO: 149) 310 319
[3385] Segment cluster R11723_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:1011) according to the present invention can be found in the
following transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1272 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01343 TABLE 1272 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 1039 1059 R11723_PEA_1_T5 (SEQ ID
NO: 148) 1957 1977 R11723_PEA_1_T6 (SEQ ID NO: 149) 1991 2011
[3386] Segment cluster R11723_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1012) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T.sub.5 (SEQ ID NO:148) and
R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1273 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01344 TABLE 1273 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 320 371 R11723_PEA_1_T17 (SEQ ID
NO: 145) 320 371 R11723_PEA_1_T19 (SEQ ID NO: 146) 320 371
R11723_PEA_1_T20 (SEQ ID NO: 147) 320 371 R11723_PEA_1_T5 (SEQ ID
NO: 148) 320 371 R11723_PEA_1_T6 (SEQ ID NO: 149) 320 371
[3387] Segment cluster R11723_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1013) according to the present invention is supported by 26
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1274 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01345 TABLE 1274 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T15 (SEQ ID NO: 144) 372 414 R11723_PEA_1_T17 (SEQ ID
NO: 145) 372 414 R11723_PEA_1_T19 (SEQ ID NO: 146) 372 414
R11723_PEA_1_T20 (SEQ ID NO: 147) 372 414 R11723_PEA_1_T5 (SEQ ID
NO: 148) 372 414 R11723_PEA_1_T6 (SEQ ID NO: 149) 372 414
[3388] Segment cluster R11723_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1014) according to the present invention is supported by 27
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1275 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01346 TABLE 1275 Segment location on transcripts Segment
starting Segment Transcript name position ending position
R11723_PEA_1_T19 (SEQ ID NO: 146) 415 446 R11723_PEA_1_T20 (SEQ ID
NO: 147) 415 446 R11723_PEA_1_T5 (SEQ ID NO: 148) 415 446
R11723_PEA_1_T6 (SEQ ID NO: 149) 415 446
[3389] Segment cluster R11723_PEA.sub.--1_node.sub.--7 (SEQ ID
NO:1015) according to the present invention is supported by 29
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T15 (SEQ ID NO:144),
R11723_PEA.sub.--1_T17 (SEQ ID NO:145), R11723_PEA.sub.--1_T19 (SEQ
ID NO:146), R11723_PEA.sub.--1_T20 (SEQ ID NO:147),
R11723_PEA.sub.--1_T5 (SEQ ID NO:148) and R11723_PEA.sub.--1_T6
(SEQ ID NO:149). Table 1276 below describes the starting and ending
position of this segment on each transcript.
TABLE-US-01347 TABLE 1276 Segment location on transcripts Segment
Segment starting ending Transcript name position position
R11723_PEA_1_T15 (SEQ ID NO: 144) 447 485 R11723_PEA_1_T17 (SEQ ID
NO: 145) 447 485 R11723_PEA_1_T19 (SEQ ID NO: 146) 447 485
R11723_PEA_1_T20 (SEQ ID NO: 147) 447 485 R11723_PEA_1_T5 (SEQ ID
NO: 148) 447 485 R11723_PEA_1_T6 (SEQ ID NO: 149) 447 485
[3390] Segment cluster R11723_PEA.sub.--1_node.sub.--8 (SEQ ID
NO:1016) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R11723_PEA.sub.--1_T6 (SEQ ID NO:149). Table 1277
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01348 TABLE 1277 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R11723_PEA_1_T6 (SEQ ID 486 519 NO: 149)
Variant protein alignment to the previously known protein:
TABLE-US-01349 ##STR00778## ##STR00779## ##STR00780## ##STR00781##
##STR00782## ##STR00783## ##STR00784## ##STR00785## ##STR00786##
##STR00787## ##STR00788## ##STR00789## ##STR00790##
[3391] It should be noted that the nucleotide transcript sequence
of known protein (PSEC, also referred to herein as the "wild type"
or WT protein) feature at least one SNP that appears to affect the
coding region, in addition to certain silent SNPs. This SNP does
not have an effect on the R11723_PEA.sub.--1_T5 (SEQ ID NO:148)
splice variant sequence): "G.fwdarw." resulting in a missing
nucleotide (affects amino acids from position 91 onwards). The
missing nucleotide creates a frame shift, resulting in a new
protein. This SNP was not previously identified and is supported by
5 ESTs out of .about.70 ESTs in this exon.
[3392] It should be noted that the variants of this cluster are
variants of the hypothetical protein PSEC0181 (referred to herein
as "PSEC"). Furthermore, use of the known protein (WT protein) for
detection of lung cancer, alone or in combination with one or more
variants of this cluster and/or of any other cluster and/or of any
known marker, also comprises an embodiment of the present
invention.
Expression of R11723 Transcripts which are Detectable by Amplicon
as Depicted in Sequence Name R11723 seg13 (SEQ ID NO: 1684) in
Normal and Cancerous Lung Tissues
[3393] Expression of transcripts detectable by or according to
R11723 seg13, R11723 seg13 amplicon (SEQ ID NO: 1684), and R11723
seg13F (SEQ ID NO: 1682), and R11723 seg13R (SEQ ID NO: 1683),
primers was measured by real time PCR. In parallel the expression
of four housekeeping genes PBGD (GenBank Accession No. BC019323
(SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2
"Tissue samples in testing panel", above), to obtain a value of
fold up-regulation for each sample relative to median of the normal
PM samples.
[3394] FIG. 48 is a histogram showing over expression of the
above-indicated transcripts in cancerous lung samples relative to
the normal samples. The number and percentage of samples that
exhibit at least 5 fold over-expression, out of the total number of
samples tested is indicated in the bottom.
[3395] As is evident from FIG. 48, the expression of transcripts
detectable by the above amplicon(s) in cancer samples was higher
than in the non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99
Table 2 "Tissue samples in testing panel"). Notably an
over-expression of at least 5 fold was found in 10 out of 15
adenocarcinoma samples, and in 4 out of 8 small cells carcinoma
samples.
[3396] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: R11723 seg13F
forward primer (SEQ ID NO: 1682); and R11723 seg13R reverse primer
(SEQ ID NO: 1683).
[3397] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: R11723 seg13 (SEQ ID NO: 1684).
TABLE-US-01350 R11723seg13F, (SEQ ID NO: 1682)
ACACTAAAAGAACAAACACCTTGCTC R11723seg13R, (SEQ ID NO: 1683)
TCCTCAGAAGGCACATGAAAGA R11723seg13-amplicon,: (SEQ ID NO: 1684)
ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAG
CAGTTGACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTC TGAGGA
Expression of R11723 Transcripts which are Detectable by Amplicon
as Depicted in Sequence Name R11723seg13 (SEQ ID NO: 1684) in
Different Normal Tissues
[3398] Expression of R11723 transcripts detectable by or according
to R11723seg13 amplicon (SEQ ID NO: 1684), and R11723seg13F (SEQ ID
NO: 1682), R11723seg13R (SEQ ID NO: 1683), was measured by real
time PCR. In parallel the expression of four housekeeping genes
RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:1715);
RPL19 amplicon, SEQ ID NO:1630), TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO:1716); TATA amplicon, SEQ ID NO:1633),
UBC (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the ovary samples (Sample Nos. 18-20,
Table 2 "Tissue samples in normal panel" above), to obtain a value
of relative expression of each sample relative to median of the
ovary samples.
TABLE-US-01351 R11723seg13F, (SEQ ID NO: 1682)
ACACTAAAAGAACAAACACCTTGCTC R11723seg13R, (SEQ ID NO: 1683)
TCCTCAGAAGGCACATGAAAGA R11723seg13-amplicon,: (SEQ ID NO: 1684)
ACACTAAAAGAACAAACACCTTGCTCTTCGAGATGAGACATTTTGCCAAG
CAGTTGACCACTTAGTTCTCAAGAAGCAACTATCTCTTTCATGTGCCTTC TGAGGA
The results are presented in FIG. 49, showing the expression of
R11723 transcripts which are detectable by amplicon as depicted in
sequence name R11723seg13 (SEQ ID NO: 1684) in different normal
tissues.
Expression of R11723 Transcripts, which are Detectable by Amplicon
as Depicted in Sequence Name R11723 junc11-18 (SEQ ID NO: 1687) in
Normal and Cancerous Lung Tissues
[3399] Expression of transcripts detectable by or according to
junc11-18, R11723 junc11-18 amplicon (SEQ ID NO: 1687) and R11723
junc11-18F (SEQ ID NO: 1685) and R11723 junc11-18R (SEQ ID NO:
1686) primers was measured by real time PCR (this junction is found
in the known protein sequence or "wild type" (WT) sequence, also
termed herein the PSEC sequence). In parallel the expression of
four housekeeping genes PBGD (GenBank Accession No. BC019323 (SEQ
ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), SDHA (GenBank Accession
No. NM.sub.--004168 (SEQ ID NO:1712); amplicon--SDHA-amplicon, SEQ
ID NO:331), and Ubiquitin (GenBank Accession No. BC000449 (SEQ ID
NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID NO:328) was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above: "Tissue samples in lung cancer testing panel"), to obtain a
value of fold up-regulation for each sample relative to median of
the normal PM samples.
[3400] FIG. 50 is a histogram showing over expression of the
above-indicated transcripts in cancerous lung samples relative to
the normal samples. Values represent the average of duplicate
experiments. Error bars indicate the minimal and maximal values
obtained.
[3401] As is evident from FIG. 50, the expression of transcripts
detectable by the above amplicon in cancer samples was higher than
in the non-cancerous samples (Sample Nos. 47-50, 90-93, 96-99 Table
2 "Tissue samples in lung cancer testing panel"). Notably an
over-expression of at least 5 fold was found in 11 out of 15
adenocarcinoma samples, 4 out of 16 squamous cell carcinoma
samples, 1 out of 4 large cell carcinoma samples and in 5 out of 8
small cells carcinoma samples.
[3402] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: R11723
junc11-18F forward primer (SEQ ID NO: 1685); and R11723 junc11-18R
reverse primer (SEQ ID NO: 1686).
[3403] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: R11723 junc11-18 (SEQ ID NO: 1687).
TABLE-US-01352 R11723junc11-18F (SEQ ID NO: 1685)
AGTGATGGAGCAAAGTGCCG R11723 junc11-18R (SEQ ID NO: 1686)
CAGCAGCTGATGCAAACTGAG R11723 junc11-18-amplicon (SEQ ID NO: 1687)
AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCAT
CAGCGGCCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCA
GGGAAACTGAACTCAGTTTGCATCAGCTGCTG
[3404] Expression of R11723 Transcripts, which were Detected by
Amplicon as Depicted in the Sequence Name R11723 junc11-18 (SEQ ID
NO: 1687) in Different Normal Tissues
Expression of R11723 transcripts detectable by or according to
R11723seg13 amplicon (SEQ ID NO: 1687) and R11723 junc11-18F (SEQ
ID NO: 1685), R11723 junc11-18R(SEQ ID NO: 1686) was measured by
real time PCR. In parallel the expression of four housekeeping
genes RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID
NO:1715); RPL19 amplicon, SEQ ID NO:1630), TATA box (GenBank
Accession No. NM.sub.--003194 (SEQ ID NO:1716); TATA amplicon, SEQ
ID NO:1633), UBC (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the ovary samples (Sample Nos. 18-20
Table 3 above), to obtain a value of relative expression of each
sample relative to median of the ovary samples.
TABLE-US-01353 R11723junc11-18F (SEQ ID NO: 1685)
AGTGATGGAGCAAAGTGCCG R11723 junc11-18R (SEQ ID NO: 1686)
CAGCAGCTGATGCAAACTGAG R11723 junc11-18-amplicon (SEQ ID NO: 1687)
AGTGATGGAGCAAAGTGCCGGGATCATGTACCGCAAGTCCTGTGCATCAT
CAGCGGCCTGTCTCATCGCCTCTGCCGGGTACCAGTCCTTCTGCTCCCCA
GGGAAACTGAACTCAGTTTGCATCAGCTGCTG
The results are demonstrated in FIG. 73, showing the expression of
R11723 transcripts, which were detected by amplicon as depicted in
the sequence name R11723 junc11-18 (SEQ ID NO: 1687) in different
normal tissues. Cloning of this Variant
Full Length Validation
[3405] RNA Preparation
[3406] Human adult papillary adenocarcinoma ovary RNA pool (lot
#ILS1408) was obtained from ABS (http://www.absbioreagents,
Wilmington, Del. 19801, USA com). Total RNA samples were treated
with DNaseI (Ambion Cat #1906).
RT PCR
[3407] RT Preparation
[3408] Purified RNA (1 ug) was mixed with 150 ng Random Hexamer
primers (Invitrogen Cat #48190-011) and 500 uM dNTP (Takara, Cat
#B9501-1) in a total volume of 15.6 ul DEPC-H.sub.2O (Beit Haemek,
Cat #01-852-1A). The mixture was incubated for 5 min at 65.degree.
C. and then quickly chilled on ice. Thereafter, 5 ul of 5.times.
Superscript II first strand buffer (Invitrogen, Cat #Y00146), 2.4
ul 0.1M DTT (Invitrogen, Cat #Y00147) and 40 units RNasin (Promega,
Cat #N251A) were added, and the mixture was incubated for 2 min at
42.degree. C. Then, 1 ul (200 units) of SuperscriptII (Invitrogen,
Cat #18064-022) was added and the reaction was incubated for 50 min
at 42.degree. C. and then inactivated at 70.degree. C. for 15 min.
The resulting cDNA was diluted 1:20 in TE buffer (10 mM Tris pH=8,
1 mM EDTA pH=8).
[3409] PCR Amplification and Analysis
[3410] cDNA (5 ul), prepared as described above, was used as a
template in PCR reactions. The amplification was done using
AccuPower PCR PreMix (Bioneer, Korea, Cat #K2016), under the
following conditions: 1 ul--of each primer (10 uM)
TABLE-US-01354 PSECfor-TGCTGTCGCCTCCTCTGATG (SEQ ID NO: 1777)
PSECrev-CCTCAGAAGGCACATGAAAG (SEQ ID NO: 1778)
plus 13 ul--H.sub.2O were added into AccuPower PCR PreMix tube with
a reaction program of 5 minutes at 94.degree. C.; 35 cycles of: [30
seconds at 94.degree. C., 30 seconds at 52.degree. C., 40 seconds
at 72.degree. C.] and 10 minutes at 72.degree. C. At the end of the
PCR amplification, products were analyzed on agarose gels stained
with ethidium bromide and visualized with UV light. PCR product was
extracted from the gel using QiaQuick.TM. gel extraction kit
(Qiagen.TM., Cat #28706). The extracted DNA product (FIG. 79) was
sequenced by direct sequencing using the gene specific primers from
above (Hy-Labs, Israel), resulting in the expected sequence of PSEC
variant R11723_PEA.sub.--1 T5 (SEQ ID NO:148) (FIG. 80).
[3411] It was concluded that the predicted PSEC variant
R11723_PEA.sub.--1 T5 (SEQ ID NO:148) is indeed a naturally
expressed variant in an adult papillary adenocarcinoma ovary human
tissue as shown in FIG. 79.
[3412] Cloning of PSEC variant R11723_PEA.sub.--1 T5 (SEQ ID
NO:148) into bacterial expression vector
[3413] The PSEC splice variant R11723_PEA.sub.--1 T5 (SEQ ID
NO:148) coding sequence was prepared for cloning by PCR
amplification using the fragment described above as template and
Platinum Pfx DNA polymerase (Invitrogen Cat #11708021) under the
following conditions: 5 ul--Amplification .times.10 buffer
(Invitrogen Cat #11708021); 2 ul--PCR product from above; 1
ul--dNTPs (10 mM each); 1 .mu.l MgSO4 (50 mM) 5 ul enhancer
solution (Invitrogen Cat #11708021); 33 ul--H.sub.2O; 1 ul--of each
primer (10 uM) and 1.25 units of Taq polymerase [Platinum Pfx DNA
polymerase (Invitrogen Cat #11708021)] in a total reaction volume
of 50 ul with a reaction program of 3 minutes at 94.degree. C.; 29
cycles of: [30 seconds at 94.degree. C., 30 seconds at 58.degree.
C., 40 seconds at 68.degree. C.] and 7 minutes at 68.degree. C. The
Primers listed below include specific sequences of the nucleotide
sequence corresponding to the splice variant and NheI and HindIII
restriction sites.
TABLE-US-01355 (SEQ ID NO: 1779) PSEC
NheIfor-ATAGCTAGCATGTGGGTCCTAGGCATCGCGG (SEQ ID NO: 1780) PSEC
HindIIIrev-CCCAAGCTTCTAAGTGGTCAACTGCTTGGC
[3414] The PCR product was then double digested with NheI and
HindIII (New England Biolabs (UK) LTD) (FIG. 81), and inserted into
pRSET-A (Invitrogen, Cat #V351-20), previously digested with the
same enzymes, in-frame to an N-terminal 6His-tag, to give HisPSEC
T5 pRSET (FIG. 82). The coding sequence encodes for a protein
having the 6His-tag at the N' end (6His residues in a row at one
end of the protein), and 8 additional amino acids encoded by the
pRSET vector.
[3415] The sequence of the PSEC insert in the final plasmid, as
well as its flanking regions, were verified by sequencing and found
to be identical to the desired sequences. The complete sequence of
His PSEC T5 pRESTA, including the sequenced regions, is shown in
FIG. 84.
[3416] FIG. 83 shows the translated sequence of PSEC variant
R11723_PEA.sub.--1 T5 (SEQ ID NO:148).
Bacterial Culture and Induction of Protein Expression
[3417] HisPSEC pRSETA DNA was transformed into competent DH5a cells
(Invitrogen Cat #18258-012). Ampicillin resistant transformants
were screened and positive clones were further analyzed by
restriction enzyme digestion and sequence verification.
[3418] In order to express the recombinant protein, HisPSEC pRSETA
DNA was further transformed into competent BL21Gold cells
(Stratagene Cat #230134) and BL21star (Invitrogen Cat #44-0054).
Ampicillin resistant transformants were screened and positive
clones were selected.
[3419] Bacterial cells containing the HisPSEC T5 pRSET vector or
empty pRSET vector (as negative control) were grown in LB medium,
supplemented with Ampicillin (50 ug/ml) and chloramphenicol (34
ug/ml), until O.D. 600 nm reached 0.55. This value was reached in
about 3 hours. 1 mM IPTG (Roche, Cat #724815) was added and the
cells were grown at 37.degree. C. overnight. 1 ml aliquots of each
culture were removed for gel analysis at time zero, 3 hrs after
induction and following overnight incubation (T0, T3 and TO/N,
respectively).
Expression Results
[3420] The time course of small-scale expression of PSEC in
BL21Gold is demonstrated in FIG. 85. The expression of a
recombinant protein with the appropriate molecular weight (9.2 kDa)
was visualized by Western Blot with anti-His antibodies (BD
Clontech, Ref 631212, FIG. 85), but not by Coomassie staining (data
not shown). Similar expression pattern was obtained with BL21 star
as well (data not shown).
[3421] These results show that the protein encoded by PSEC variant
R11723_PEA.sub.--1 T5 (SEQ ID NO:148) is indeed expressed in
bacterial cells.
Description for Cluster R16276
[3422] Cluster R16276 features 1 transcript(s) and 5 segment(s) of
interest, the names for which are given in Tables 1278 and 1279,
respectively, the sequences themselves are given at the end of the
application. The selected protein variants are given in table
1280.
TABLE-US-01356 TABLE 1278 Transcripts of interest Transcript Name
Sequence ID No. R16276_PEA_1_T6 150
TABLE-US-01357 TABLE 1279 Segments of interest Segment Name
Sequence ID No. R16276_PEA_1_node_0 1017 R16276_PEA_1_node_6 1018
R16276_PEA_1_node_1 1019 R16276_PEA_1_node_4 1020
R16276_PEA_1_node_5 1021
TABLE-US-01358 TABLE 1280 Proteins of interest Protein Name
Sequence ID No. Corresponding Transcript(s) R16276_PEA_1_P7 1414
R16276_PEA_1_T6 (SEQ ID NO: 150)
[3423] These sequences are variants of the known protein NOV
protein homolog precursor (SwissProt accession identifier
NOV_HUMAN; known also according to the synonyms NovH;
Nephroblastoma overexpressed gene protein homolog), SEQ ID NO:1463,
referred to herein as the previously known protein.
[3424] Protein NOV protein homolog precursor (SEQ ID NO:1463) is
known or believed to have the following function(s):
Immediate-early protein, likely to play a role in cell growth
regulation (By similarity). The sequence for protein NOV protein
homolog precursor is given at the end of the application, as "NOV
protein homolog precursor amino acid sequence". Known polymorphisms
for this sequence are as shown in Table 1281.
TABLE-US-01359 TABLE 1281 Amino acid mutations for Known Protein
SNP position(s) on amino acid sequence Comment 97 N -> K
[3425] Protein NOV protein homolog precursor (SEQ ID NO:1463)
localization is believed to be Secreted.
[3426] The following GO Annotation(s) apply to the previously known
protein. The following annotation(s) were found: regulation of cell
growth, which are annotation(s) related to Biological Process;
insulin-like growth factor binding; growth factor, which are
annotation(s) related to Molecular Function; and extracellular,
which are annotation(s) related to Cellular Component.
[3427] The GO assignment relies on information from one or more of
the SwissProt/TremB1 Protein knowledgebase, available from <dot
expasy dot ch/sprot/>; or Locuslink, available from <dot ncbi
dot nlm dot nih dot gov/projects/LocusLink/>.
[3428] Cluster R16276 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 51 refer to weighted expression of ESTs in each category, as
"parts per million" (ratio of the expression of ESTs for a
particular cluster to the expression of all ESTs in that category,
according to parts per million).
[3429] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 51 and Table 1282. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: lung malignant tumors.
TABLE-US-01360 TABLE 1282 Normal tissue distribution Name of Tissue
Number Adrenal 977 Bone 32 Brain 24 Colon 0 Epithelial 63 General
43 Kidney 24 Liver 341 Lung 0 Breast 0 Muscle 20 Ovary 0 Pancreas 0
Prostate 24 Skin 13 Stomach 146 Uterus 0
TABLE-US-01361 TABLE 1283 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 Adrenal 5.9e-01
6.2e-01 1 0.2 9.9e-01 0.2 Bone 5.5e-01 7.3e-01 1 0.8 1 0.6 Brain
2.8e-01 4.4e-01 6.8e-01 0.9 8.9e-01 0.6 Colon 2.6e-01 3.3e-01
4.9e-01 2.0 5.9e-01 1.7 Epithelial 2.6e-01 2.9e-01 9.7e-01 0.6 1
0.5 General 4.1e-01 6.8e-01 9.4e-01 0.7 1 0.5 Kidney 8.3e-01
7.7e-01 6.2e-01 1.2 5.3e-01 1.4 Liver 9.1e-01 7.5e-01 1 0.1 1 0.1
Lung 2.3e-02 9.1e-02 8.0e-04 10.5 2.1e-02 5.1 Breast 5.9e-01
6.7e-01 6.9e-01 1.5 8.2e-01 1.2 Muscle 5.2e-01 6.1e-01 2.7e-01 3.2
6.3e-01 1.2 Ovary 6.2e-01 6.5e-01 6.8e-01 1.5 7.7e-01 1.3 Pancreas
3.3e-01 4.4e-01 4.2e-01 2.4 5.3e-01 1.9 Prostate 9.3e-01 9.4e-01 1
0.5 9.4e-01 0.6 Skin 9.2e-01 6.8e-01 1 0.5 4.1e-01 1.1 Stomach
5.0e-01 7.3e-01 5.0e-01 0.6 9.7e-01 0.4 Uterus 2.4e-01 1.6e-01
2.9e-01 2.5 4.1e-01 2.0
[3430] As noted above, cluster R16276 features 1 transcript(s),
which were listed in Table 1278 above. These transcript(s) encode
for protein(s) which are variant(s) of protein NOV protein homolog
precursor (SEQ ID NO:1463). A description of each variant protein
according to the present invention is now provided.
[3431] Variant protein R16276_PEA.sub.--1_P7 (SEQ ID NO:1414)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
R16276_PEA.sub.--1_T6 (SEQ ID NO:150). An alignment is given to the
known protein (NOV protein homolog precursor (SEQ ID NO:1463)) at
the end of the application. One or more alignments to one or more
previously published protein sequences are given at the end of the
application. A brief description of the relationship of the variant
protein according to the present invention to each such aligned
protein is as follows:
[3432] Comparison report between R16276_PEA.sub.--1_P7 (SEQ ID
NO:1414) and NOV_HUMAN (SEQ ID NO:1463):
[3433] 1. An isolated chimeric polypeptide encoding for
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a first amino
acid sequence being at least 90% homologous to
MQSVQSTSFCLRKQCLCLTFLLLHLLGQVAATQRCPPQCPG corresponding to amino
acids 1-41 of NOV_HUMAN (SEQ ID NO:1463), which also corresponds to
amino acids 1-41 of R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), a
bridging amino acid Q corresponding to amino acid 42 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), a second amino acid
sequence being at least 90% homologous to
CPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICT
corresponding to amino acids 43-103 of NOV_HUMAN (SEQ ID NO:1463),
which also corresponds to amino acids 43-103 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), and a third amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence GNPAPSAV
(SEQ ID NO: 1748) corresponding to amino acids 104-111 of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), wherein said first amino
acid sequence, bridging amino acid, second amino acid sequence and
third amino acid sequence are contiguous and in a sequential
order.
[3434] 2. An isolated polypeptide encoding for a tail of
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence GNPAPSAV
(SEQ ID NO: 1748) in R16276_PEA.sub.--1_P7 (SEQ ID NO:1414).
[3435] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3436] Variant protein R16276_PEA.sub.--1_P7 (SEQ ID NO:1414) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1284, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein R16276_PEA.sub.--1_P7
(SEQ ID NO:1414) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01362 TABLE 1284 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
42 Q -> R Yes
[3437] The glycosylation sites of variant protein
R16276_PEA.sub.--1_P7 (SEQ ID NO:1414), as compared to the known
protein NOV protein homolog precursor (SEQ ID NO:1463), are
described in Table 1285 (given according to their position(s) on
the amino acid sequence in the first column; the second column
indicates whether the glycosylation site is present in the variant
protein; and the last column indicates whether the position is
different on the variant protein).
TABLE-US-01363 TABLE 1285 Glycosylation site(s) Position(s) on
known amino Present in acid sequence variant protein? Position in
variant protein? 280 no 97 yes 97
[3438] Variant protein R16276_PEA.sub.--1_P7 (SEQ ID NO:1414) is
encoded by the following transcript(s): R16276_PEA.sub.--1_T6 (SEQ
ID NO:150), for which the sequence(s) is/are given at the end of
the application. The coding portion of transcript
R16276_PEA.sub.--1_T6 (SEQ ID NO:150) is shown in bold; this coding
portion starts at position 445 and ends at position 777. The
transcript also has the following SNPs as listed in Table 1286
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein R16276_PEA.sub.--1_P7 (SEQ ID NO:1414) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01364 TABLE 1286 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
371 G -> No 430 A -> G No 569 A -> G Yes 729 C -> A Yes
827 G -> T Yes
[3439] As noted above, cluster R16276 features 5 segment(s), which
were listed in Table 2 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[3440] Segment cluster R16276_PEA.sub.--1_node.sub.--0 (SEQ ID
NO:1017) according to the present invention is supported by 35
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R16276_PEA.sub.--1_T6 (SEQ ID NO:150). Table 1287
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01365 TABLE 1287 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R16276_PEA_1_T6 (SEQ ID NO: 1 438 150)
[3441] Segment cluster R16276_PEA.sub.--1_node.sub.--6 (SEQ ID
NO:1018) according to the present invention is supported by 2
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R16276_PEA.sub.--1_T6 (SEQ ID NO:150). Table 1288
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01366 TABLE 1288 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R16276_PEA_1_T6 (SEQ ID NO: 755 876 150)
[3442] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3443] Segment cluster R16276_PEA.sub.--1_node.sub.--1 (SEQ ID
NO:1019) according to the present invention is supported by 37
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R16276_PEA.sub.--1_T6 (SEQ ID NO:150). Table 1289
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01367 TABLE 1289 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R16276_PEA_1_T6 (SEQ ID NO: 439 528 150)
[3444] Segment cluster R16276_PEA.sub.--1_node.sub.--4 (SEQ ID
NO:1020) according to the present invention is supported by 38
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R16276_PEA.sub.--1_T6 (SEQ ID NO:150). Table 1290
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01368 TABLE 1290 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R16276_PEA_1_T6 (SEQ ID NO: 529 639 150)
[3445] Segment cluster R16276_PEA.sub.--1_node.sub.--5 (SEQ ID
NO:1021) according to the present invention is supported by 37
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): R16276_PEA.sub.--1_T6 (SEQ ID NO:150). Table 1291
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01369 TABLE 1291 Segment location on transcripts Segment
Segment Transcript name starting position ending position
R16276_PEA_1_T6 (SEQ ID NO: 640 754 150)
Variant protein alignment to the previously known protein:
TABLE-US-01370 ##STR00791##
[3446] Combined expression of 6 sequences H61775seg8 (SEQ ID NO:
1636), HUMGRP5E junc3-7 (SEQ ID NO: 1648), M85491Seg24 (SEQ ID NO:
1639), Z21368 junc17-21 (SEQ ID NO: 1642), HSSTROL3seg24 (SEQ ID
NO: 1675) and Z25299seg20 (SEQ ID NO: 1669) in normal and cancerous
lung tissues.
[3447] Expression of immunoglobulin superfamily, member 9,
gastrin-releasing peptide, Ephrin type-B receptor 2 precursor,
SUL1_HUMAN, Stromelysin-3 precursor (EC 3.4.24.-) (Matrix
metalloproteinase-11) (MMP-11) (ST3) (SL-3) and Secretory leukocyte
protease inhibitor Acid-stable proteinase inhibitor transcripts
detectable by or according to H61775seg8 (SEQ ID NO: 1636),
HUMGRP5E junc3-7 (SEQ ID NO: 1648), M85491Seg24 (SEQ ID NO: 1639),
Z21368 junc17-21 (SEQ ID NO: 1642), HSSTROL3seg24 (SEQ ID NO: 1675)
and Z25299seg20 amplicons (SEQ ID NO: 1669) and H61775seg8F2 (SEQ
ID NO: 1634), H61775seg8R2 (SEQ ID NO: 1635), HUMGRP5E junc3-7F
(SEQ ID NO: 1646), HUMGRP5E junc3-7R (SEQ ID NO: 1647),
M85491Seg24F (SEQ ID NO: 1637), M85491Seg24R (SEQ ID NO: 1638),
Z21368 junc17-21F (SEQ ID NO: 1640), Z21368 junc17-21R (SEQ ID NO:
1641), HSSTROL3seg24F (SEQ ID NO: 1673), HSSTROL3seg24R (SEQ ID NO:
1674), Z25299seg20F (SEQ ID NO: 1667), Z25299seg20R (SEQ ID NO:
1668) primers was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334),
HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), Ubiquitin (GenBank
Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicons was
normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample of
each amplicon was then divided by the median of the quantities of
the normal post-mortem (PM) samples detected for the same amplicon
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samplesin
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples. The
reciprocal of this ratio was calculated for Z25299seg20 (SEQ ID NO:
1669), to obtain a value of fold down-regulation for each sample
relative to median of the normal PM samples.
[3448] FIGS. 52-53 are histograms showing differential expression
of the above-indicated transcripts in cancerous lung samples
relative to the normal samples. The number and percentage of
samples that exhibit at least 5 fold differential of at least one
of the sequences, out of the total number of samples tested is
indicated in the bottom.
[3449] As is evident from FIGS. 52-53, differential expression of
at least 5 fold in at least one of the sequences was found in 15
out of 15 adenocarcinoma samples, 14 out of 16 squamous cell
carcinoma samples, 4 out of 4 large cell carcinoma samples and in 8
out of 8 small cell carcinoma samples.
[3450] Statistical analysis was applied to verify the significance
of these results, as described below. Threshold of 5 fold
differential expression of at least one of the amplicons was found
to differentiate between cancer and normal samples with P value of
7.82E-06 in adenocarcinoma, 2.63E-04 in squamous cell carcinoma,
8.24E-03 in large cell adenocarcinoma and 3.57E-04 in small cell
carcinoma as checked by exact fisher test.
[3451] The above values demonstrate statistical significance of the
results.
Description for Cluster H53626
[3452] Cluster H53626 features 2 transcript(s) and 20 segment(s) of
interest, the names for which are given in Tables 1292 and 1293,
respectively, the sequences themselves are given at the end of the
application.
TABLE-US-01371 TABLE 1292 Transcripts of interest Transcript Name
SEQ ID NO: H53626_PEA_1_T15 16 H53626_PEA_1_T16 17
TABLE-US-01372 TABLE 1293 Segments of interest Segment Name SEQ ID
NO: H53626_PEA_1_node_15 18 H53626_PEA_1_node_22 19
H53626_PEA_1_node_25 306 H53626_PEA_1_node_26 307
H53626_PEA_1_node_27 308 H53626_PEA_1_node_34 309
H53626_PEA_1_node_35 310 H53626_PEA_1_node_36 311
H53626_PEA_1_node_11 312 H53626_PEA_1_node_12 313
H53626_PEA_1_node_16 314 H53626_PEA_1_node_19 315
H53626_PEA_1_node_20 316 H53626_PEA_1_node_24 317
H53626_PEA_1_node_28 318 H53626_PEA_1_node_29 319
H53626_PEA_1_node_30 320 H53626_PEA_1_node_31 321
H53626_PEA_1_node_32 322 H53626_PEA_1_node_33 323
TABLE-US-01373 TABLE 1294 Proteins of interest Transcript Name SEQ
ID NO: H53626_PEA_1_P4 324 H53626_PEA_1_P5 325
[3453] Cluster H53626 can be used as a diagnostic marker according
to overexpression of transcripts of this cluster in cancer.
Expression of such transcripts in normal tissues is also given
according to the previously described methods. The term "number" in
the right hand column of the table and the numbers on the y-axis of
FIG. 76 below refer to weighted expression of ESTs in each
category, as "parts per million" (ratio of the expression of ESTs
for a particular cluster to the expression of all ESTs in that
category, according to parts per million).
[3454] Overall, the following results were obtained as shown with
regard to the histograms in FIG. 76 and Table 1295. This cluster is
overexpressed (at least at a minimum level) in the following
pathological conditions: epithelial malignant tumors, a mixture of
malignant tumors from different tissues and myosarcoma.
TABLE-US-01374 TABLE 1295 Normal tissue distribution Name of Tissue
Number adrenal 4 bone 233 brain 33 colon 0 epithelial 12 general 17
head and neck 0 kidney 8 lung 25 breast 8 muscle 0 ovary 7 pancreas
10 prostate 8 skin 0 stomach 73 Thyroid 0 uterus 0
TABLE-US-01375 TABLE 1296 P values and ratios for expression in
cancerous tissue Name of Tissue P1 P2 SP1 R3 SP2 R4 adrenal 6.4e-01
4.2e-01 2.1e-01 3.1 1.3e-02 4.1 bone 5.8e-01 8.1e-01 9.8e-01 0.3
1.0e+00 0.3 brain 2.2e-01 2.6e-01 8.1e-01 0.8 8.9e-01 0.6 colon
2.3e-01 1.4e-01 1.5e+00 1.2 4.6e-01 1.9 epithelial 8.3e-02 4.8e-03
6.4e-02 1.5 6.6e-08 4.1 general 2.4e-03 1.5e-05 1.1e-03 1.6 2.0e-12
3.1 head and neck 2.1e-01 3.3e-01 0.0e+00 0.0 0.0e+00 0.0 kidney
7.3e-01 5.8e-01 5.8e-01 1.3 5.7e-02 2.0 lung 8.3e-01 5.5e-01
7.9e-01 0.8 3.2e-02 2.1 breast 6.5e-01 2.7e-01 6.9e-01 1.2 7.8e-02
1.9 muscle 1.5e+00 2.9e-01 1.5e+00 1.0 3.5e-03 4.1 ovary 6.7e-01
5.6e-01 1.5e-01 1.7 7.0e-02 2.7 pancreas 2.3e-01 2.0e-01 3.9e-01
1.9 8.2e-02 2.3 prostate 9.0e-01 9.0e-01 6.7e-01 1.1 1.8e-01 1.9
skin 1.5e+00 4.4e-01 1.5e+00 1.0 6.4e-01 1.6 stomach 9.0e-01
3.4e-01 1.0e+00 0.3 6.1e-01 0.9 Thyroid 2.4e-01 2.4e-01 1.5e+00 1.1
1.5e+00 1.1 uterus 2.1e-01 2.4e-01 2.9e-01 2.5 2.6e-01 2.2
[3455] As noted above, contig H53626 features 2 transcript(s),
which were listed in Table 1292 above. A description of each
variant protein according to the present invention is now
provided.
[3456] Variant protein H53626_PEA.sub.--1_P4 (SEQ ID NO:324)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
H53626_PEA.sub.--1_T15 (SEQ ID NO:16). The alignment to the wild
type protein is given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to the wild type protein is as follows:
[3457] Comparison report between H53626_PEA.sub.--1_P4 (SEQ ID
NO:324) and wild type Q8N441 (SEQ ID NO:1699):
[3458] 1. An isolated chimeric polypeptide encoding for
H53626_PEA.sub.--1_P4 (SEQ ID NO:324), comprising a first amino
acid sequence being at least 90% homologous to
MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI
HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA
SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK
NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCKVRSDVKPVIQ
WLKRVEYGAEGRHNSTIDVGGQKFVVLPTGDVWSRPDGSYLNKLLITRARQDDAGMYICLGANTMGYSF
RSAFLTVLP corresponding to amino acids 1-357 of Q8N441 (SEQ ID
NO:1699), which also corresponds to amino acids 1-357 of
H53626_PEA.sub.--1_P4 (SEQ ID NO:324), second amino acid sequence
being at least 70%, optionally at least 80%, preferably at least
85%, more preferably at least 90% and most preferably at least 95%
homologous to a polypeptide having the sequence
GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMGLGCSPGLCVGVP
LPTSFPLALA (SEQ ID NO: 1775) corresponding to amino acids 358-437
of H53626_PEA.sub.--1_P4 (SEQ ID NO:324), and a third amino acid
sequence being at least 90% homologous to
DPKPPGPPVASSSSATSLPWPVVIGIPAGAVFILGTLLLWLCQAQKKPCTPAPAPPLPGHRPPGTARDRSGD
KDLPSLAALSAGPGVGLCEEHGSPAAPQHLLGPGPVAGPKLYPKLYTDIHTHTHTHSHTHSHVEGKVHQH
IHYQC corresponding to amino acids 358-504 of Q8N441 (SEQ ID
NO:1699), which also corresponds to amino acids 438-584 of
H53626_PEA.sub.--1_P4 (SEQ ID NO:324), wherein said first, second
and third amino acid sequences are contiguous and in a sequential
order.
[3459] 2. An isolated polypeptide encoding for an edge portion of
H53626_PEA.sub.--1_P4 (SEQ ID NO:324), comprising an amino acid
sequence being at least 70%, optionally at least about 80%,
preferably at least about 85%, more preferably at least about 90%
and most preferably at least about 95% homologous to the sequence
encoding for
GARLPRHATPCWCPDPPPGPGVPPTGWGPTLPSRAVLARSSAEGGQPRGTVSTAPGMGLGCSPGLCVG
LPTSFPLALA (SEQ ID NO: 1775), corresponding to
H53626_PEA.sub.--1_P4 (SEQ ID NO:324).
[3460] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: membrane. The protein localization is
believed to be membrane because although both signal-peptide
prediction programs agree that this protein has a signal peptide,
both trans-membrane region prediction programs predict that this
protein has a trans-membrane region downstream of this signal
peptide.
[3461] Variant protein H53626PEA.sub.--1_P4 (SEQ ID NO:324) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1297, (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein H53626_PEA.sub.--1_P4
(SEQ ID NO:324) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01376 TABLE 1297 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
193 R -> L Yes 300 G -> No 319 Y -> H No 442 P -> Q Yes
504 R -> L Yes 521 G -> No 544 P -> L Yes 573 E -> G
No
[3462] Variant protein H53626_PEA.sub.--1_P4 (SEQ ID NO:324) is
encoded by the following transcript(s): H53626_PEA.sub.--1_T15 (SEQ
ID NO:16), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
H53626_PEA.sub.--1_T15 (SEQ ID NO:16) is shown in bold; this coding
portion starts at position 17 and ends at position 1771. The
transcript also has the following SNPs as listed in Table 1298
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein H53626_PEA.sub.--1_P4 (SEQ ID NO:324) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01377 TABLE 1298 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
76 G -> A Yes 340 G -> T No 1647 C -> T Yes 1734 A -> G
No 1797 G -> No 1948 A -> G Yes 2193 C -> T Yes 2308 C
-> T Yes 2333 C -> G Yes 2648 C -> T Yes 2649 G -> A
Yes 2765 C -> T Yes 594 G -> T Yes 2972 G -> A Yes 3027 C
-> G Yes 907 T -> C Yes 916 C -> No 971 T -> C No 1135
G -> A Yes 1341 C -> A Yes 1527 G -> T Yes 1579 C ->
No
[3463] Variant protein H53626_PEA.sub.--1_P5 (SEQ ID NO:325)
according to the present invention has an amino acid sequence as
given at the end of the application; it is encoded by transcript(s)
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). The alignment to the wild
type protein is given at the end of the application. A brief
description of the relationship of the variant protein according to
the present invention to the wild type protein is as follows:
[3464] Comparison report between H53626_PEA.sub.--1_P5 (SEQ ID
NO:325) and wild type Q9H4D7 (SEQ ID NO:1700):
[3465] 1. An isolated chimeric polypeptide encoding for
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), comprising a first amino
acid sequence being at least 90% homologous to
MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI
HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA
SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK
NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK
corresponding to amino acids 1-269 of Q9H4D7 (SEQ ID NO:1700),
which also corresponds to amino acids 1-269 of
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRG-
RPATAAE
TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRA-
RSTS
TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA
CMHTHARTRAP (SEQ ID NO: 1776) corresponding to amino acids 270-490
of H53626_PEA.sub.--1_P5 (SEQ ID NO:325), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3466] 2. An isolated polypeptide encoding for a tail of
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCCFARPRRSRAPPRLPLPCLGTARRGRPATAAE
TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTS
TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA
CMHTHARTRAP (SEQ ID NO: 1776) in H53626_PEA.sub.--1_P5 (SEQ ID
NO:325).
[3467] Comparison report between H53626_PEA.sub.--1_P5 (SEQ ID
NO:325) and wild type Q8N441 (SEQ ID NO:1699):
[3468] 1. An isolated chimeric polypeptide encoding for
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), comprising a first amino
acid sequence being at least 90% homologous to
MTPSPLLLLLLPPLLLGAFPPAAAARGPPKMADKVVPRQVARLGRTVRLQCPVEGDPPPLTMWTKDGRTI
HSGWSRFRVLPQGLKVKQVEREDAGVYVCKATNGFGSLSVNYTLVVLDDISPGKESLGPDSSSGGQEDPA
SQQWARPRFTQPSKMRRRVIARPVGSSVRLKCVASGHPRPDITWMKDDQALTRPEAAEPRKKKWTLSLK
NLRPEDSGKYTCRVSNRAGAINATYKVDVIQRTRSKPVLTGTHPVNTTVDFGGTTSFQCK
corresponding to amino acids 1-269 of Q8N441 (SEQ ID NO:1699),
which also corresponds to amino acids 1-269 of
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), and a second amino acid
sequence being at least 70%, optionally at least 80%, preferably at
least 85%, more preferably at least 90% and most preferably at
least 95% homologous to a polypeptide having the sequence
TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRG-
RPATAAE
TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRA-
RSTS
TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA
CMHTHARTRAP (SEQ ID NO: 1776) corresponding to amino acids 270-490
of H53626_PEA.sub.--1_P5 (SEQ ID NO:325), wherein said first and
second amino acid sequences are contiguous and in a sequential
order.
[3469] 2. An isolated polypeptide encoding for a tail of
H53626_PEA.sub.--1_P5 (SEQ ID NO:325), comprising a polypeptide
being at least 70%, optionally at least about 80%, preferably at
least about 85%, more preferably at least about 90% and most
preferably at least about 95% homologous to the sequence
TQNRQGHLWPPRPRPLACRGPWSSASQPALSSSWAPCSCGFARPRRSRAPPRLPLPCLGTARRGRPATAAE
TRTFPRWPPSALALVWGCVRSMGLRQPPSTYWAQAQLLALSCTPNSTQTSTHTHTHTLTHTHTWRARSTS
TSTISARRHRICSGHGGAGQTGRLGGWRTELQTKAGDPWRGGMASTPGSLCVRHSPWTHTHRHTHYLDA
CMHTHARTRAP (SEQ ID NO: 1776) in H53626_PEA.sub.--1_P5 (SEQ ID
NO:325).
[3470] The location of the variant protein was determined according
to results from a number of different software programs and
analyses, including analyses from SignalP and other specialized
programs. The variant protein is believed to be located as follows
with regard to the cell: secreted. The protein localization is
believed to be secreted because both signal-peptide prediction
programs predict that this protein has a signal peptide, and
neither trans-membrane region prediction program predicts that this
protein has a trans-membrane region.
[3471] Variant protein H53626_PEA.sub.--1_P5 (SEQ ID NO:325) also
has the following non-silent SNPs (Single Nucleotide Polymorphisms)
as listed in Table 1299 (given according to their position(s) on
the amino acid sequence, with the alternative amino acid(s) listed;
the last column indicates whether the SNP is known or not; the
presence of known SNPs in variant protein H53626_PEA.sub.--1_P5
(SEQ ID NO:325) sequence provides support for the deduced sequence
of this variant protein according to the present invention).
TABLE-US-01378 TABLE 1299 Amino acid mutations SNP position(s) on
amino acid Alternative sequence amino acid(s) Previously known SNP?
193 R -> L Yes 274 Q -> K Yes 336 A -> S Yes 353 A ->
No 376 Q -> * Yes 405 R -> G No 426 G -> No 476 Y -> C
Yes
[3472] Variant protein H53626_PEA.sub.--1_P5 (SEQ ID NO:325) is
encoded by the following transcript(s): H53626_PEA.sub.--1_T16 (SEQ
ID NO:17), for which the sequence(s) is/are given at the end of the
application. The coding portion of transcript
H53626_PEA.sub.--1_T16 (SEQ ID NO:17) is shown in bold; this coding
portion starts at position 17 and ends at position 1489. The
transcript also has the following SNPs as listed in Table 1300
(given according to their position on the nucleotide sequence, with
the alternative nucleic acid listed; the last column indicates
whether the SNP is known or not; the presence of known SNPs in
variant protein H53626_PEA.sub.--1_P5 (SEQ ID NO:325) sequence
provides support for the deduced sequence of this variant protein
according to the present invention).
TABLE-US-01379 TABLE 1300 Nucleic acid SNPs SNP position on
nucleotide Alternative sequence nucleic acid Previously known SNP?
76 G -> A Yes 340 G -> T No 1688 C -> T Yes 1803 C -> T
Yes 1828 C -> G Yes 2143 C -> T Yes 2144 G -> A Yes 2260 C
-> T Yes 2467 G -> A Yes 2522 C -> G Yes 594 G -> T Yes
836 C -> A Yes 1022 G -> T Yes 1074 C -> No 1142 C -> T
Yes 1229 A -> G No 1292 G -> No 1443 A -> G Yes
[3473] As noted above, cluster H53626 features 20 segment(s), which
were listed in Table 1293 above and for which the sequence(s) are
given at the end of the application. These segment(s) are portions
of nucleic acid sequence(s) which are described herein separately
because they are of particular interest. A description of each
segment according to the present invention is now provided.
[3474] Segment cluster H53626_PEA.sub.--1_node.sub.--15 (SEQ ID
NO:18) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1301 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01380 TABLE 1301 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 96 343 H53626_PEA_1_T16 (SEQ ID
NO: 17) 96 343
[3475] Segment cluster H53626_PEA.sub.--1_node.sub.--22 (SEQ ID
NO:19) according to the present invention is supported by 42
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1302 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01381 TABLE 1302 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 450 734 H53626_PEA_1_T16 (SEQ ID
NO: 17) 450 734
[3476] Segment cluster H53626_PEA.sub.--1_node.sub.--25 (SEQ ID
NO:306) according to the present invention is supported by 41
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16). Table 1303
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01382 TABLE 1303 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 824 1088
[3477] Segment cluster H53626_PEA.sub.--1_node.sub.--26 (SEQ ID
NO:307) according to the present invention is supported by 5
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16). Table 1304
below describes the starting and ending position of this segment on
each transcript.
TABLE-US-01383 TABLE 1304 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 1089 1328
[3478] Segment cluster H53626_PEA.sub.--1_node.sub.--27 (SEQ ID
NO:308) according to the present invention is supported by 106
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1305 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01384 TABLE 1305 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 1329 2228 H53626_PEA_1_T16 (SEQ ID
NO: 17) 824 1723
[3479] Segment cluster H53626_PEA.sub.--1_node.sub.--34 (SEQ ID
NO:309) according to the present invention is supported by 121
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1306 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01385 TABLE 1306 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2507 2977 H53626_PEA_1_T16 (SEQ ID
NO: 17) 2002 2472
[3480] Segment cluster H53626_PEA.sub.--1_node.sub.--35 (SEQ ID
NO:310) according to the present invention is supported by 85
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1307 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01386 TABLE 1307 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2978 3148 H53626_PEA_1_T16 (SEQ ID
NO: 17) 2473 2643
[3481] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment, shown in
Table 1308.
TABLE-US-01387 TABLE 1308 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference NA
[3482] Segment cluster H53626_PEA.sub.--1_node.sub.--36 (SEQ ID
NO:311) according to the present invention is supported by 69
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1309 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01388 TABLE 1309 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 3149 3322 H53626_PEA_1_T16 (SEQ ID
NO: 17) 2644 2817
[3483] Microarray (chip) data is also available for this segment as
follows. As described above with regard to the cluster itself,
various oligonucleotides were tested for being differentially
expressed in various disease conditions, particularly cancer. The
following oligonucleotides were found to hit this segment, shown in
Table 1310.
TABLE-US-01389 TABLE 1310 Oligonucleotides related to this segment
Oligonucleotide name Overexpressed in cancers Chip reference NA
[3484] According to an optional embodiment of the present
invention, short segments related to the above cluster are also
provided. These segments are up to about 120 by in length, and so
are included in a separate description.
[3485] Segment cluster H53626_PEA.sub.--1_node.sub.--11 (SEQ ID
NO:312) according to the present invention is supported by 12
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1311 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01390 TABLE 1311 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 1 55 H53626_PEA_1_T16 (SEQ ID NO:
17) 1 55
[3486] Segment cluster H53626_PEA.sub.--1_node.sub.--12 (SEQ ID
NO:313) according to the present invention is supported by 11
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1312 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01391 TABLE 1312 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 56 95 H53626_PEA_1_T16 (SEQ ID NO:
17) 56 95
[3487] Segment cluster H53626_PEA.sub.--1_node.sub.--16 (SEQ ID
NO:314) according to the present invention can be found in the
following transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1313 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01392 TABLE 1313 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 344 368 H53626_PEA_1_T16 (SEQ ID
NO: 17) 344 368
[3488] Segment cluster H53626_PEA.sub.--1_node.sub.--19 (SEQ ID
NO:315) according to the present invention is supported by 25
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1314 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01393 TABLE 1314 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 369 419 H53626_PEA_1_T16 (SEQ ID
NO: 17) 369 419
[3489] Segment cluster H53626_PEA.sub.--1_node.sub.--20 (SEQ ID
NO:316) according to the present invention is supported by 27
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1315 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01394 TABLE 1315 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 420 449 H53626_PEA_1_T16 (SEQ ID
NO: 17) 420 449
[3490] Segment cluster H53626_PEA.sub.--1_node.sub.--24 (SEQ ID
NO:317) according to the present invention is supported by 34
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1316 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01395 TABLE 1316 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 735 823 H53626_PEA_1_T16 (SEQ ID
NO: 17) 735 823
[3491] Segment cluster H53626_PEA.sub.--1_node.sub.--28 (SEQ ID
NO:318) according to the present invention is supported by 66
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1317 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01396 TABLE 1317 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2229 2306 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1724 1801
[3492] Segment cluster H53626_PEA.sub.--1_node.sub.--29 (SEQ ID
NO:319) according to the present invention is supported by 73
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1318 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01397 TABLE 1318 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2307 2396 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1802 1891
[3493] Segment cluster H53626_PEA.sub.--1_node.sub.--30 (SEQ ID
NO:320) according to the present invention is supported by 71
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1319 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01398 TABLE 1319 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2397 2442 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1892 1937
[3494] Segment cluster H53626_PEA.sub.--1_node.sub.--31 (SEQ ID
NO:321) according to the present invention is supported by 67
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1320 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01399 TABLE 1320 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2443 2469 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1938 1964
[3495] Segment cluster H53626_PEA.sub.--1_node.sub.--32 (SEQ ID
NO:322) according to the present invention is supported by 65
libraries. The number of libraries was determined as previously
described. This segment can be found in the following
transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1321 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01400 TABLE 1321 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2470 2498 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1965 1993
[3496] Segment cluster H53626_PEA.sub.--1_node.sub.--33 (SEQ ID
NO:323) according to the present invention can be found in the
following transcript(s): H53626_PEA.sub.--1_T15 (SEQ ID NO:16) and
H53626_PEA.sub.--1_T16 (SEQ ID NO:17). Table 1322 below describes
the starting and ending position of this segment on each
transcript.
TABLE-US-01401 TABLE 1322 Segment location on transcripts Segment
Segment starting ending Transcript name position position
H53626_PEA_1_T15 (SEQ ID NO: 16) 2499 2506 H53626_PEA_1_T16 (SEQ ID
NO: 17) 1994 2001
Variant protein alignment to the previously known protein:
TABLE-US-01402 ##STR00792## ##STR00793## ##STR00794## ##STR00795##
##STR00796## ##STR00797## ##STR00798##
Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1
(FGFRL1) H53626 Transcripts, which are Detectable by Amplicon as
Depicted in Sequence Name H53626 junc24-27F1R3 (SEQ ID NO: 1690) in
Normal and Cancerous Lung Tissues
[3497] Expression of Homo sapiens fibroblast growth factor
receptor-like 1 (FGFRL1) transcripts detectable by or according to
junc24-27, H53626 junc24-27F1R3 amplicon (SEQ ID NO: 1690) and
H53626 junc24-27F1 (SEQ ID NO: 1688) and H53626 junc24-27R3 (SEQ ID
NO: 1689) primers was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334),
HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), UBC (GenBank Accession
No. BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331), was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[3498] FIG. 74 is a histogram showing over expression of the
above-indicated Homo sapiens fibroblast growth factor receptor-like
1 (FGFRL1) transcripts in cancerous lung samples relative to the
normal samples.
[3499] As is evident from FIG. 74, the expression of Homo sapiens
fibroblast growth factor receptor-like 1 (FGFRL1) transcripts
detectable by the above amplicon(s) was higher in several cancer
samples than in the non-cancerous samples (Sample Nos. 46-50,
90-93, 96-99 Table 2). Notably an over-expression of at least 5
fold was found in 7 out of 15 adenocarcinoma samples.
[3500] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: H53626
junc24-27F1 forward primer (SEQ ID NO: 1688); and H53626
junc24-27R3 reverse primer (SEQ ID NO: 1689).
[3501] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: H53626 junc24-27F1R3 (SEQ ID NO: 1690).
TABLE-US-01403 Forward primer (SEQ ID NO: 1688):
GTCCTTCCAGTGCAAGACCCA Reverse primer (SEQ ID NO: 1689):
TGGGCCTGGCAAAGCC Amplicon (SEQ ID NO: 1690):
GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTC
GTCCTCGGCCACTAGCCTGCCGTGGCCCGTGGTCATCGGCATCCCAGCCG
GCGCTGTCTTCATCCTGGGCACCCTGCTCCTGTGGCTTTGCCAGGCCCA
Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1
(FGFRL1) H53626 Transcripts, which are Detectable by Amplicon as
Depicted in Sequence Name H53626 seg25 (SEQ ID NO: 1693) in Normal
and Cancerous Lung Tissues
[3502] Expression of Homo sapiens fibroblast growth factor
receptor-like 1 (FGFRL1) transcripts detectable by or according to
seg25, H53626 seg25 amplicon (SEQ ID NO: 1693) and H53626 seg25F
(SEQ ID NO: 1691) and H53626 seg25R (SEQ ID NO: 1692) primers was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--PBGD-amplicon, SEQ ID NO:334), HPRT1 (GenBank
Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--HPRT1-amplicon, SEQ ID NO:1297), UBC (GenBank Accession
No. BC000449 (SEQ ID NO:1711); amplicon--Ubiquitin-amplicon, SEQ ID
NO:328) and SDHA (GenBank Accession No. NM.sub.--004168 (SEQ ID
NO:1712); amplicon--SDHA-amplicon, SEQ ID NO:331), was measured
similarly. For each RT sample, the expression of the above amplicon
was normalized to the geometric mean of the quantities of the
housekeeping genes. The normalized quantity of each RT sample was
then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
above), to obtain a value of fold up-regulation for each sample
relative to median of the normal PM samples.
[3503] As is evident from FIG. 75, the expression of Homo sapiens
fibroblast growth factor receptor-like 1 (FGFRL1) transcripts
detectable by the above amplicon(s) was higher in a few cancer
samples than in the non-cancerous samples (Sample Nos. 46-50,
90-93, 96-99 Table 2). Notably an over-expression of at least 5
fold was found in 3 out of 15 adenocarcinoma samples.
[3504] Primer pairs are also optionally and preferably encompassed
within the present invention; for example, for the above
experiment, the following primer pair was used as a non-limiting
illustrative example only of a suitable primer pair: H53626 seg25F
forward primer (SEQ ID NO: 1691); and H53626 seg25R reverse primer
(SEQ ID NO: 1692).
[3505] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: H53626 seg25 (SEQ ID NO: 1693).
TABLE-US-01404 Forward primer (SEQ ID NO: 1691);
CCGACGGCTCCTACCTCAA Reverse primer (SEQ ID NO: 1692):
GGAAGCTGTAGCCCATGGTGT Amplicon (SEQ ID NO: 1693):
CCGACGGCTCCTACCTCAATAAGCTGCTCATCACCCGTGCCCGCCAGGAC
GATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTT CC
Expression of Homo sapiens Fibroblast Growth Factor Receptor-Like 1
(FGFRL1) H53626 Transcripts, which are Detectable by Amplicon as
Depicted in Sequence Name H53626 seg25 (SEQ ID NO: 1693) in
Different Normal Tissues
[3506] Expression of Homo sapiens fibroblast growth factor
receptor-like 1 (FGFRL1) transcripts detectable by or according to
H53626 seg25 amplicon (SEQ ID NO: 1693) and H53626 seg25F (SEQ ID
NO: 1691) and H53626 seg25R (SEQ ID NO: 1692) was measured by real
time PCR. In parallel the expression of four housekeeping genes:
RPL19 (GenBank Accession No. NM.sub.--000981 (SEQ ID NO:1715);
RPL19 amplicon, SEQ ID NO:1630), TATA box (GenBank Accession No.
NM.sub.--003194 (SEQ ID NO:1716); TATA amplicon, SEQ ID NO:1633),
UBC (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the lung samples (Sample Nos. 15-17
Table 3 above), to obtain a value of relative expression of each
sample relative to median of the lung samples.
TABLE-US-01405 Forward primer (SEQ ID NO: 1691);
CCGACGGCTCCTACCTCAA Reverse primer (SEQ ID NO: 1692):
GGAAGCTGTAGCCCATGGTGT Amplicon (SEQ ID NO: 1693):
CCGACGGCTCCTACCTCAATAAGCTGCTCATCACCCGTGCCCGCCAGGAC
GATGCGGGCATGTACATCTGCCTTGGCGCCAACACCATGGGCTACAGCTT CC
[3507] The results are demonstrated in FIG. 77, showing the
expression of of Homo sapiens fibroblast growth factor
receptor-like 1 (FGFRL1) H53626 transcripts, which are detectable
by amplicon as depicted in sequence name H53626 seg25 (SEQ ID NO:
1693) in different normal tissues.
Expression of Homo sapiens Fibroblast Growth Factor Receptor-like 1
(FGFRL1) H53626 Transcripts which are Detectable by Amplicon as
Depicted in Sequence Name H53626 junc24-27F1R3 (SEQ ID NO: 1690) in
Different Normal Tissues
[3508] Expression of Homo sapiens fibroblast growth factor
receptor-like 1 (FGFRL1) transcripts detectable by or according to
H53626 junc24-27F1R3 amplicon (SEQ ID NO: 1690) and H53626
junc24-27F1 (SEQ ID NO: 1688) and H53626 junc24-27R3 (SEQ ID NO:
1689) was measured by real time PCR. In parallel the expression of
four housekeeping genes--RPL19 (GenBank Accession No.
NM.sub.--000981 (SEQ ID NO:1715); RPL19 amplicon, SEQ ID NO:1630),
TATA box (GenBank Accession No. NM.sub.--003194 (SEQ ID NO:1716);
TATA amplicon, SEQ ID NO:1633; primers SEQ ID NOs 1631 and 1632),
UBC (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--Ubiquitin-amplicon, SEQ ID NO:328) and SDHA (GenBank
Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SDHA-amplicon, SEQ ID NO:331) was measured similarly. For
each RT sample, the expression of the above amplicon was normalized
to the geometric mean of the quantities of the housekeeping genes.
The normalized quantity of each RT sample was then divided by the
median of the quantities of the lung samples (Sample Nos. 15-17
Table 3 above), to obtain a value of relative expression of each
sample relative to median of the lung samples.
TABLE-US-01406 Forward primer (SEQ ID NO: 1688):
GTCCTTCCAGTGCAAGACCCA Reverse primer (SEQ ID NO: 1689):
TGGGCCTGGCAAAGCC Amplicon (SEQ ID NO: 1690):
GTCCTTCCAGTGCAAGACCCAAAACCGCCAGGGCCACCTGTGGCCTCCTC
GTCCTCGGCCACTAGCCTGCCGTGGCCCGTGGTCATCGGCATCCCAGCCG
GCGCTGTCTTCATCCTGGGCACCCTGCTCCTGTGGCTTTGCCAGGCCCA
[3509] The results are demonstrated in FIG. 78, showing the
expression of Homo sapiens fibroblast growth factor receptor-like 1
(FGFRL1) H53626 transcripts, which are detectable by amplicon as
depicted in sequence name H53626 junc24-27F1R3 (SEQ ID NO: 1690) in
different normal tissues.
Expression of Trophinin Associated Protein (Tastin) [T86235]
Transcripts which are Detectable by Amplicon as Depicted in SEQ ID
NO:1480 in Normal and Cancerous Lung Tissues
[3510] Expression of trophinin associated protein (tastin)
transcripts detectable by SEQ ID NO:1480 (e.g., variant no. 23-26
31, 32--represented by SEQ IDs 1485-1488, 1609, 1610) was measured
by real time PCR. In parallel the expression of four housekeeping
genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--SEQ ID NO:1471), HPRT1 (GenBank Accession No.
NM.sub.--000194 (SEQ ID NO:1714); amplicon--SEQ ID NO:1468),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--SEQ ID NO:1474) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SEQ ID NO:1477), was
measured similarly. For each RT sample, the expression of SEQ ID
NO:1480 was normalized to the geometric mean of the quantities of
the housekeeping genes. The normalized quantity of each RT sample
was then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel", above), to obtain a value of
fold up-regulation for each sample relative to median of the normal
PM samples.
[3511] FIG. 54a is a histogram showing over expression of the
above-indicated trophinin associated protein (tastin) transcripts
in cancerous lung samples relative to the normal samples. The
number and percentage of samples that exhibit at least 5 fold
over-expression, out of the total number of samples tested is
indicated in the bottom.
[3512] As is evident from FIG. 54a, the expression of trophinin
associated protein (tastin) transcripts detectable by SEQ ID
NO:1480 in cancer samples was significantly higher than in the
non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99 Table 2,
"Tissue samples in testing panel"). Notably an over-expression of
at least 5 fold was found in 6 out of 15 adenocarcinoma samples, 8
out of 16 squamous cell carcinoma samples, 2 out of 4 large cell
carcinoma samples and in 8 out of 8 small cells carcinoma
samples.
[3513] Statistical analysis was applied to verify the significance
of these results, as described below.
[3514] The P value for the difference in the expression levels of
trophinin associated protein (tastin) transcripts detectable by SEQ
ID NO:1480 in lung cancer samples versus the normal lung samples
was determined by T test as 1.61E-04.
[3515] Threshold of 5 fold overexpression was found to
differentiate between cancer and normal samples with P value of
1.49E-02 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[3516] According to the present invention, trophinin associated
protein (tastin) is a non-limiting example of a marker for
diagnosing lung cancer. The trophinin associated protein (tastin)
marker of the present invention, can be used alone or in
combination, for various uses, including but not limited to,
prognosis, prediction, screening, early diagnosis, therapy
selection and treatment monitoring of lung cancer. Although
optionally any method may be used to detected overexpression and/or
differential expression of this marker, preferably a NAT-based
technology is used. Therefore, optionally and preferably, any
nucleic acid molecule capable of selectively hybridizing to
trophinin associated protein (tastin) as previously defined is also
encompassed within the present invention. Primer pairs are also
optionally and preferably encompassed within the present invention;
for example, for the above experiment, the following primer pair
was used as a non-limiting illustrative example only of a suitable
primer pair: trophinin associated protein (tastin)-TAA-seg
44-forward primer (SEQ ID NO: 1478):
AGACTCCAACCCACAGCCC; and trophinin associated protein
(tastin)--TAA-seg 44-Reverse primer (SEQ ID NO: 1479):
CAGCTCAGCCAACCTTGCA.
[3517] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: trophinin associated protein (tastin) amplicon, SEQ ID
NO: 1480:
AGACTCCAACCCACAGCCCAGCTGTGGCTGCACAGTGAGCCTGATGGGAGGTGGGGAACAGGGACA
GGGGGCCACCTGGGCTTCTTCACAGAGAGGTCAGCAGGAAGGCTTGGCTACAGTGCAAGGTTGGCTG
AGCTG
[3518] According to other preferred embodiments of the present
invention, trophinin associated protein (tastin) or a fragment
thereof comprises a biomarker for detecting lung cancer. Optionally
and more preferably, trophinin associated protein (tastin) splice
variants, as depicted in SEQ ID NO: 1485-1488, 1609, 1610 (e.g.,
variant no. 23-26, 31, 32), or a fragment thereof comprise a
biomarker for detecting lung cancer. Optionally and more
preferably, the fragment of trophinin associated protein (tastin)
comprises segment_TAA-44--SEQ ID NO: 1507. Also optionally and more
preferably, any suitable method may be used for detecting a
fragment such as trophinin associated protein (tastin) _segment_
TAA-44--SEQ ID no 1507 for example. Most preferably, NAT-based
technology used, such as any nucleic acid molecule capable of
specifically hybridizing with the fragment. Optionally and most
preferably, a primer pair is used for obtaining the fragment.
[3519] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to trophinin associated protein (tastin) as described
above, including but not limited to SEQ ID NOs: 1492-1501, 1612.
Any oligopeptide or peptide relating to such an amino acid sequence
or fragment thereof may optionally also (additionally or
alternatively) be used as a biomarker, including but not limited to
the unique amino acid sequences of these proteins that are depicted
in SEQ ID Nos: 1508-1511, 1613. The present invention also
optionally encompasses antibodies capable of recognizing, and/or
being elicited by, such oligopeptides or peptides.
[3520] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to trophinin
associated protein (tastin) as described above, optionally for any
application.
[3521] Expression of Trophinin Associated Protein (Tastin) [T86235]
Transcripts which are Detectable by Oligonucleotides as Depicted in
SEQ ID NOs:1512-1514 in Normal and Cancerous Lung Tissues
[3522] Expression of trophinin associated protein (tastin) [T86235]
transcripts detectable by oligonucleotides SEQ ID NOs: 1512-1514
(e.g., variants no. 8-10, 22, 23, 26, 27, 29-31, 33--represented by
SEQ IDs 1481-1485, 1488-1491, 1609, 1611) was measured with
oligonucleotide-based micro-arrays. The segments detected by the
above oligonucleotides as depicted in SEQ ID NOs: 1512-1514 are for
example nucleotide sequences as depicted in SEQ IDs 1503, 1504,
1506.
[3523] The results of image intensities for each feature were
normalized according to the ninetieth percentile of the image
intensities of all the features on the chip. Then, feature image
intensities for replicates of the same oligonucleotide on the chip
and replicates of the same sample were averaged. Outlying results
were discarded. For every oligonucleotide (SEQ ID NOs: 1512-1514)
the averaged intensity determined for every sample was divided by
the averaged intensity of all the normal samples (Sample Nos.
48,50, 90-92, 96-99, Table 2, "Tissue samples in testing panel",
above), to obtain a value of fold up-regulation for each sample
relative to the averaged normal samples. These data are presented
in a histogram in FIG. 54b. As is evident from FIG. 54b, the
expression of trophinin associated protein (tastin) [T86235]
transcripts detectable with oligonucleotides according to SEQ ID
NOs: 1512-1514 in cancer samples was significantly higher than in
the normal samples.
[3524] According to the present invention, trophinin associated
protein (tastin) is a non-limiting example of a marker for
diagnosing lung cancer. Although optionally any method may be used
to detected overexpression and/or differential expression of this
marker, preferably a NAT-based technology is used. Therefore,
optionally and preferably, any nucleic acid molecule capable of
selectively hybridizing to trophinin associated protein (tastin) as
previously defined is also encompassed within the present
invention. Oligonucleotides are also optionally and preferably
encompassed within the present invention; for example, for the
above experiment, the following oligonucleotides were used as a
non-limiting illustrative example only of a suitable
oligonucleotides: SEQ ID NOs: 1512-1514
TABLE-US-01407 (SEQ ID NO: 1512)
CATGGTAACACGGCCTCCATGGCTGAGTAGGGGACTAGGAAGGGTAAAAG (SEQ ID NO:
1513) TGTACATCTAGGGCCTCTCAGTTAGGGGCTTCAATCCATTCCTCATGAGG (SEQ ID
NO: 1514) TGTGAACACAAGAGGTCCTCACCTCACTGTGAGCTGCACACCTGCCCTGC
[3525] According to other preferred embodiments of the present
invention, trophinin associated protein (tastin) or a fragment
thereof comprises a biomarker for detecting lung cancer. Optionally
and more preferably, trophinin associated protein (tastin) splice
variants, as depicted in SEQ ID NO: 1481-1485, 1488-1491, 1609,
1611 (e.g., variant no. 8-10, 22, 23, 26, 27, 29-31, 33), or a
fragment thereof comprise a biomarker for detecting lung cancer.
Optionally and more preferably, the fragment of trophinin
associated protein (tastin) comprises segment_TAA-14, 35 and
42--SEQ ID no. 1503, 1504, 1506. Also optionally and more
preferably, any suitable method may be used for detecting a
fragment such as trophinin associated protein (tastin)
_segment_TAA-14, 35 and 42--SEQ ID NOs 1503, 1504 and 1506 for
example. Most preferably, NAT-based technology used, such as any
nucleic acid molecule capable of specifically hybridizing with the
fragment. Optionally and most preferably, a primer pair is used for
obtaining the fragment.
[3526] According to other preferred embodiments of the present
invention, trophinin associated protein (tastin) splice variants
containing the unique segments as depicted in SEQ ID Nos 1502 and
1505, for example as these included in variants 9 and 29 (SEQ ID
NOs: 1482 and 1490, respectively), are useful as biomarkers for
detecting lung cancer.
[3527] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to trophinin
associated protein (tastin) as described above, optionally for any
application.
Expression of Homeo Box C10 (HOXC10) [N31842] Transcripts which are
Detectable by Amplicon as Depicted in SEQ ID NO:1517 in Normal and
Cancerous Lung Tissues
[3528] Expression of Homeo box C10 (HOXC10) transcripts detectable
by SEQ ID NO: 1517 (e.g., variant no. 3, represented by SEQ ID
1519) was measured by real time PCR. In parallel the expression of
four housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ
ID NO:1713); amplicon--SEQ ID NO:1471), HPRT1 (GenBank Accession
No. NM.sub.--000194 (SEQ ID NO:1714); amplicon--SEQ ID NO:3),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--SEQ ID NO:9) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SEQ ID NO:1477), was
measured similarly. For each RT sample, the expression of SEQ ID
NO:1517 was normalized to the geometric mean of the quantities of
the housekeeping genes. The normalized quantity of each RT sample
was then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel", above), to obtain a value of
fold up-regulation for each sample relative to median of the normal
PM samples.
[3529] FIG. 55 is a histogram showing over expression of the
above-indicated Homeo box C10 (HOXC10) transcripts in cancerous
lung samples relative to the normal samples. The number and
percentage of samples that exhibit at least 20 fold
over-expression, out of the total number of samples tested is
indicated in the bottom.
[3530] As is evident from FIG. 55, the expression of Homeo box C10
(HOXC10) transcripts detectable by SEQ ID NO: 1517 in cancer
samples was significantly higher than in the non-cancerous samples
(Sample Nos. 46-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel"). Notably an over-expression of at least 20 fold was
found in 6 out of 15 adenocarcinoma samples, 9 out of 16 squamous
cell carcinoma samples, and in 3 out of 4 large cell carcinoma
samples.
[3531] Statistical analysis was applied to verify the significance
of these results, as described below. The P value for the
difference in the expression levels of Homeo box C10 (HOXC10)
transcripts detectable by SEQ ID NO: 1517 in lung cancer samples
versus the normal lung samples was determined by T test as
4.43E-03. Threshold of 20 fold overexpression was found to
differentiate between cancer and normal samples with P value of
2.88E-02 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[3532] According to the present invention, Homeo box C10 (HOXC10)
is a non-limiting example of a marker for diagnosing lung cancer.
The Homeo box C10 (HOXC10) marker of the present invention, can be
used alone or in combination, for various uses, including but not
limited to, prognosis, prediction, screening, early diagnosis,
therapy selection and treatment monitoring of lung cancer. Although
optionally any method may be used to detected overexpression and/or
differential expression of this marker, preferably a NAT-based
technology is used. Therefore, optionally and preferably, any
nucleic acid molecule capable of selectively hybridizing to Homeo
box C10 (HOXC10) as previously defined is also encompassed within
the present invention. Primer pairs are also optionally and
preferably encompassed within the present invention; for example,
for the above experiment, the following primer pair was used as a
non-limiting illustrative example only of a suitable primer pair:
Homeo box C10 (HOXC10)-forward primer (SEQ ID NO: 1515):
GCGAAACGCGATTTGTTGTT; and Homeo box C10 (HOXC10)-Reverse primer
(SEQ ID NO:1516): CATCTGGAGGAGGGAGGGA.
[3533] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Homeo box C10 (HOXC10) amplicon (SEQ ID NO:1517):
GCGAAACGCGATTTGTTGTTTGTGGGTCTGATTTGTGCGTGCGGCTTGGGCTCCTGCGGCTTTTGGCTC
GGCCGGGGGCCTTGGGCAGCGAGGCTGGAGCCGGAAGAGGTGGAGGTGAAGGGCTGCCCGCCACGT
CCCTCCCTCCCTCCAGATG.
[3534] According to other preferred embodiments of the present
invention, Homeo box C10 (HOXC10) or a fragment thereof comprises a
biomarker for detecting lung cancer. Optionally and more
preferably, Homeo box C10 (HOXC10) splice variants, as depicted in
SEQ ID NO:54 (e.g., variant no. 3), or a fragment thereof comprise
a biomarker for detecting lung cancer. Optionally and more
preferably, the fragment of Homeo box C10 (HOXC10) comprises
segment_TAA-seg 6 (SEQ ID NO: 1526). Also optionally and more
preferably, any suitable method may be used for detecting a
fragment such as Homeo box C10 (HOXC10) _segment_ TAA-seg 6 (SEQ ID
NO:1526) for example. Most preferably, NAT-based technology used,
such as any nucleic acid molecule capable of specifically
hybridizing with the fragment. Optionally and most preferably, a
primer pair is used for obtaining the fragment.
[3535] According to other preferred embodiments of the present
invention, Homeo box C10 (HOXC10) splice variants containing the
unique segments as depicted in SEQ ID NOs: 1524 and 1525, for
example transcripts as depicted in SEQ ID NO: 1515, 1519 and 1520,
comprise a biomarker for detecting lung cancer.
[3536] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to trophinin associated protein (tastin) as described
above, including but not limited to SEQ ID NOs: 1521 and 1522. Any
oligopeptide or peptide relating to such an amino acid sequence or
fragment thereof may optionally also (additionally or
alternatively) be used as a biomarker, including but not limited to
the unique amino acid sequence of the protein SEQ ID NO: 1522, as
depicted in SEQ ID NO:1523. The present invention also optionally
encompasses antibodies capable of recognizing, and/or being
elicited by, such oligopeptides or peptides.
[3537] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to trophinin
associated protein (tastin) as described above, optionally for any
application.
Expression of Nucleolar Protein 4 (NOL4)-[T06014] Transcripts which
are Detectable by Amplicon as Depicted in SEQ IDs NO:1529 in Normal
and Cancerous Lung Tissues
[3538] Expression of Nucleolar protein 4 (NOL4) transcripts
detectable by SEQ ID NOs:1529 (e.g., variant no. 3, 11 and 12,
represented by SEQ IDs 1533, 1537, 1538) was measured by real time
PCR. In parallel the expression of four housekeeping genes--PBGD
(GenBank Accession No. BC019323 (SEQ ID NO:1713); amplicon--SEQ ID
NO:1471), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID
NO:1714); amplicon--SEQ ID NO:1468), Ubiquitin (GenBank Accession
No. BC000449 (SEQ ID NO:1711); amplicon--SEQ ID NO:1474) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SEQ ID NO:1477), was measured similarly. For each RT
sample, the expression of SEQ ID NO:1529 was normalized to the
geometric mean of the quantities of the housekeeping genes. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, above, "Tissue samples
in testing panel"), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[3539] FIGS. 56a and b are histograms showing over expression of
the above-indicated Nucleolar protein 4 (NOL4) transcripts in
cancerous lung samples relative to the normal samples. The number
and percentage of samples that exhibit at least 200 fold or 6 fold
over-expression, out of the total number of samples tested is
indicated in the bottom of FIGS. 56a and 56b respectively.
[3540] As is evident from FIG. 56a, the expression of Nucleolar
protein 4 (NOL4) transcripts detectable by SEQ ID NO: 1529 in the
samples originate from small cell carcinoma of the lung was
significantly higher than in the non-cancerous samples (Sample Nos.
46-50, 90-93, 96-99, Table 2, "Tissue samples in testing panel").
Notably an over-expression of at least 200 fold was found in 8 out
of 8 small cell carcinoma samples. As is evident from FIG. 56b,
over expression of at least 6 fold was observed also in 2 out of 15
adenocarcinoma samples, 3 out of 16 squamous cell carcinoma
samples.
[3541] Statistical analysis was applied to verify the significance
of these results, as described below.
[3542] The P value for the difference in the expression levels of
Nucleolar protein 4 (NOL4) transcripts detectable by SEQ ID NO:1529
in lung cancer samples versus the normal lung samples was
determined by T test as 1.36E-02.
[3543] Threshold of 6 fold overexpression was found to
differentiate between cancer and normal samples with P value of
2.52E-02 as checked by exact fisher test.
[3544] The P value for the difference in the expression levels of
Nucleolar protein 4 (NOL4) transcripts detectable by SEQ ID NO:1529
in lung small cell carcinoma samples versus the normal lung samples
was determined by T test as 3.86E-03.
Threshold of 200 fold overexpression was found to differentiate
between small cell carcinoma and normal lung samples with P value
of 7.94E-06 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[3545] According to the present invention, Nucleolar protein 4
(NOL4) is a non-limiting example of a marker for diagnosing lung
cancer. The Nucleolar protein 4 (NOL4) marker of the present
invention, can be used alone or in combination, for various uses,
including but not limited to, prognosis, prediction, screening,
early diagnosis, therapy selection and treatment monitoring of lung
cancer. Although optionally any method may be used to detected
overexpression and/or differential expression of this marker,
preferably a NAT-based technology is used. Therefore, optionally
and preferably, any nucleic acid molecule capable of selectively
hybridizing to Nucleolar protein 4 (NOL4) as previously defined is
also encompassed within the present invention. Primer pairs are
also optionally and preferably encompassed within the present
invention; for example, for the above experiment, the following
primer pair was used as a non-limiting illustrative example only of
a suitable primer pair: Nucleolar protein 4 (NOL4)-TAA-seg1-forward
primer (SEQ ID NO:1527): CTCGCTCCCTTGCTCACAC; and Nucleolar protein
4 (NOL4)-TAA-seg1-Reverse primer (SEQ ID NO:1528):
AAAGGGAAAGCGGGATGTTT.
[3546] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Nucleolar protein 4 (NOL4) amplicon (SEQ ID NO:1529):
CTCGCTCCCTTGCTCACACACACGCACACACTCAGCCTGGCCGAGCAGGAGCCACTGACCATTTTGCAAGTGT-
CAGG ACCAGCTACAGCGCGGTGGGCGCAAACATCCCGCTTTCCCTTT.
[3547] According to other preferred embodiments of the present
invention, Nucleolar protein 4 (NOL4) or a fragment thereof
comprises a biomarker for detecting lung cancer. Optionally and
more preferably, Nucleolar protein 4 (NOL4) splice variants, as
depicted in SEQ ID NO:1529 (e.g., variants nos. 3, 11 and 12), or a
fragment thereof comprise a biomarker for detecting lung cancer.
Optionally and more preferably, the fragment of Nucleolar protein 4
(NOL4) comprises segment_TAA-seg-1 (SEQ ID NO: 1552). Also
optionally and more preferably, any suitable method may be used for
detecting a fragment such as Nucleolar protein 4 (NOL4)_segment_
TAA-seg-1 (SEQ ID NO: 1552) for example. Most preferably, NAT-based
technology used, such as any nucleic acid molecule capable of
specifically hybridizing with the fragment. Optionally and most
preferably, a primer pair is used for obtaining the fragment.
[3548] According to other preferred embodiments of the present
invention, Nucleolar protein 4 (NOL4) splice variants containing
the unique segments as depicted in SEQ ID NOs: 1554 and 1555, for
example transcripts as depicted in SEQ ID NOs: 1534-1536 and
1539-1541, comprises a biomarker for detecting lung cancer.
[3549] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to Nucleolar protein 4 (NOL4) as described above,
including but not limited to SEQ ID Nos: 1542, 1547 and 1543; 1548,
1545, 1546, and 1549-1551. Any oligopeptide or peptide relating to
such an amino acid sequence or fragment thereof may optionally also
(additionally or alternatively) be used as a biomarker, including
but not limited to the unique amino acid sequence of the protein
SEQ ID NO: 1543, 1546, 1549 as depicted in SEQ ID NO:1544.
[3550] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3551] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to Nucleolar
protein 4 (NOL4) as described above, optionally for any
application.
Expression of Nucleolar Protein 4 (NOL4)-[T06014] Transcripts which
are Detectable by Amplicon as Depicted in SEQ IDs NO:1532 in Normal
and Cancerous Lung Tissues
[3552] Expression of Nucleolar protein 4 (NOL4) transcripts
detectable by SEQ ID NOs:1532 (e.g., variant no. 3, 11 and 12,
represented by SEQ IDs 1533, 1537, 1538) was measured by real time
PCR. In parallel the expression of four housekeeping genes--PBGD
(GenBank Accession No. BC019323 (SEQ ID NO:1713); amplicon--SEQ ID
NO:1471), HPRT1 (GenBank Accession No. NM.sub.--000194 (SEQ ID
NO:1714); amplicon--SEQ ID NO:1468), Ubiquitin (GenBank Accession
No. BC000449 (SEQ ID NO:1711); amplicon--SEQ ID NO:1474) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SEQ ID NO: 1481), was measured similarly. For each RT
sample, the expression of SEQ ID NO:1532 was normalized to the
geometric mean of the quantities of the housekeeping genes. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[3553] FIGS. 57a and b are histograms showing over expression of
the above-indicated Nucleolar protein 4 (NOL4) transcripts in
cancerous lung samples relative to the normal samples. The number
and percentage of samples that exhibit at least 400 fold or 6 fold
over-expression, out of the total number of samples tested is
indicated in the bottom of FIGS. 57a and b respectively.
[3554] As is evident from FIG. 57a, the expression of Nucleolar
protein 4 (NOL4) transcripts detectable by SEQ ID NO:1532 in the
samples originate from small cell carcinoma of the lung was
significantly higher than in the non-cancerous samples (Sample Nos.
46-50, 90-93, 96-99, Table 2, "Tissue samples in testing panel").
Notably an over-expression of at least 400 fold was found in 8 out
of 8 small cell carcinoma samples. As is evident from FIG. 4b, over
expression of at least 6 fold was observed also in 4 out of 15
adenocarcinoma samples, 3 out of 16 squamous cell carcinoma
samples.
[3555] Statistical analysis was applied to verify the significance
of these results, as described below.
[3556] The P value for the difference in the expression levels of
Nucleolar protein 4 (NOL4) transcripts detectable by SEQ ID NO:1532
in lung cancer samples versus the normal lung samples was
determined by T test as 1.70E-02.
[3557] Threshold of 6 fold overexpression was found to
differentiate between cancer and normal samples with P value of
1.80E-02 as checked by exact fisher test.
[3558] The P value for the difference in the expression levels of
Nucleolar protein 4 (NOL4) transcripts detectable by SEQ ID NO:1532
in lung small cell carcinoma samples versus the normal lung samples
was determined by T test as 7.08E-03.
Threshold of 400 fold overexpression was found to differentiate
between small cell carcinoma and normal lung samples with P value
of 1.03E-04 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[3559] According to the present invention, Nucleolar protein 4
(NOL4) is a non-limiting example of a marker for diagnosing lung
cancer. The Nucleolar protein 4 (NOL4) marker of the present
invention, can be used alone or in combination, for various uses,
including but not limited to, prognosis, prediction, screening,
early diagnosis, therapy selection and treatment monitoring of lung
cancer. Although optionally any method may be used to detected
overexpression and/or differential expression of this marker,
preferably a NAT-based technology is used. Therefore, optionally
and preferably, any nucleic acid molecule capable of selectively
hybridizing to Nucleolar protein 4 (NOL4) as previously defined is
also encompassed within the present invention. Primer pairs are
also optionally and preferably encompassed within the present
invention; for example, for the above experiment, the following
primer pair was used as a non-limiting illustrative example only of
a suitable primer pair: Nucleolar protein 4 (NOL4)-TAA-seg
3-forward primer (SEQ ID NO: 1530): ACATCCCCCTGGAACGGAT; and
Nucleolar protein 4 (NOL4)-TAA-seg 3-Reverse primer (SEQ ID
NO:1531): CAGAAATTAGCAAAGCATTGATGG.
[3560] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Nucleolar protein 4 (NOL4) amplicon (SEQ ID NO: 1532):
ACATCCCCCTGGAACGGATATCTGTTTGGGGCACTACAATCTATCCTGTAGAACTATGGCCAAATCTC
CATCAATGCTTTGCTAATTTCTG.
[3561] According to other preferred embodiments of the present
invention, Nucleolar protein 4 (NOL4) or a fragment thereof
comprises a biomarker for detecting lung cancer. Optionally and
more preferably, Nucleolar protein 4 (NOL4) splice variants, as
depicted in SEQ ID NO:1533, 1537, 1538 (e.g., variants nos. 3, 11,
12), or a fragment thereof comprise a biomarker for detecting lung
cancer. Optionally and more preferably, the fragment of Nucleolar
protein 4 (NOL4) comprises segment_TAA-seg-3 (SEQ ID NO: 1553).
Also optionally and more preferably, any suitable method may be
used for detecting a fragment such as Nucleolar protein 4
(NOL4)_segment_ TAA-seg-3 (SEQ ID NO: 1553) for example. Most
preferably, NAT-based technology used, such as any nucleic acid
molecule capable of specifically hybridizing with the fragment.
Optionally and most preferably, a primer pair is used for obtaining
the fragment.
[3562] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to Nucleolar protein 4 (NOL4) as described above,
including but not limited to SEQ ID NOs: SEQ ID Nos: 1542, 1547 and
1548. Any oligopeptide or peptide relating to such an amino acid
sequence or fragment thereof may optionally also (additionally or
alternatively) be used as a biomarker.
[3563] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3564] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof corresponding to Nucleolar
protein 4 (NOL4) as described above, optionally for any
application.
Expression of AA281370 Transcripts which are Detectable by Amplicon
as Depicted in SEQ ID NO:1558 in Normal and Cancerous Lung
Tissues
[3565] AA281370 gene was identified by a computational process
described above as over expressed in lung cancer. The AA281370
encoded proteins (SEQ ID NO: 1563, 1564) contain several WD40
domains, which are found in a number of eukaryotic proteins that
cover a wide variety of functions, including adaptor/regulatory
modules in signal transduction, pre-mRNA processing and
cytoskeleton assembly. As is demonstrated in FIG. 63, the WD40
domain region of AA281370 encoded protein, depicted in SEQ ID NO:
1564, has several similarities that might suggest involvement in
signal transduction MAPK pathway. For example, the region of the
AA281370 polypeptide SEQ ID NO: 1564 located between amino acids at
positions 40-790 has 75% homology to the WD40 domain region of
mouse Mapkbp1 protein (gi|47124622) (FIG. 63a); and the amino acids
at positions 40-886 of the AA281370 polypeptide SEQ ID NO: 1564 has
70% homology to rat JNK-binding protein JNKBP1 (gi|34856717) (FIG.
63b).
[3566] Expression of AA281370 transcripts detectable by SEQ ID NO:
1558 (e.g., variant no. 0, 1, 4 and 5, represented in SEQ IDs
1559-1562) was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--SEQ ID NO:1471), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--SEQ ID NO:1468), Ubiquitin (GenBank Accession No.
BC000449 (SEQ ID NO:1711); amplicon--SEQ ID NO:1474) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SEQ ID NO:1477), was measured similarly. For each RT
sample, the expression of SEQ ID NO:1558 was normalized to the
geometric mean of the quantities of the housekeeping genes. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[3567] FIG. 58 is a histogram showing over expression of the
above-indicated AA281370 transcripts in cancerous lung samples
relative to the normal samples. The number and percentage of
samples that exhibit at least 6 fold over-expression, out of the
total number of samples tested is indicated in the bottom.
[3568] As is evident from FIGS. 58, the expression of AA281370
transcripts detectable by SEQ ID NO:1558 in cancer samples was
significantly higher than in the non-cancerous samples (Sample Nos.
46-50, 90-93, 96-99, Table 2, "Tissue samples in testing panel").
Notably an over-expression of at least 6 fold was found in 8 out of
8 small cell carcinoma, 2 out of 16 squamous cell carcinoma
samples, and in 1 out of 4 large cell carcinoma samples.
[3569] Statistical analysis was applied to verify the significance
of these results, as described below.
[3570] The P value for the difference in the expression levels of
AA281370 transcripts detectable by SEQ ID NO:1558 in lung cancer
samples versus the normal lung samples was determined by T test as
8.58E-07.
[3571] Threshold of 6 fold overexpression was found to
differentiate between cancer and normal samples with P value of
4.81E-02 as checked by exact fisher test. The above values
demonstrate statistical significance of the results.
[3572] According to the present invention, AA281370 transcripts are
a non-limiting example of a marker for diagnosing lung cancer. The
AA281370 marker of the present invention, can be used alone or in
combination, for various uses, including but not limited to,
prognosis, prediction, screening, early diagnosis, therapy
selection and treatment monitoring of lung cancer. Although
optionally any method may be used to detected overexpression and/or
differential expression of this marker, preferably a NAT-based
technology is used. Therefore, optionally and preferably, any
nucleic acid molecule capable of selectively hybridizing to
AA281370 as previously defined is also encompassed within the
present invention. Primer pairs are also optionally and preferably
encompassed within the present invention; for example, for the
above experiment, the following primer pair was used as a
non-limiting illustrative example only of a suitable primer pair:
AA281370-forward primer (SEQ ID NO: 1556):
GGTTCGGATGGACTACACTTTGTC; and AA281370-Reverse primer (SEQ ID NO:
1557): CCACGTACTTCTGGGTGATGTC.
[3573] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: AA281370-amplicon (SEQ ID NO: 1558):
GGTTCGGATGGACTACACTTTGTCCGTACCCACCACGTAGCAGAGAAAACCACCTTGTATGACATGGA
CATTGACATCACCCAGAAGTACGTGG.
[3574] According to other preferred embodiments of the present
invention, AA281370 or a fragment thereof comprises a biomarker for
detecting lung cancer. Optionally and more preferably, AA281370
splice variants, as depicted in SEQ ID NO:1558 (e.g., variants no:
0, 1, 4 and 5), or a fragment thereof comprise a biomarker for
detecting lung cancer. Optionally and more preferably, the fragment
of AA281370 comprises segment_TAA seg 10 SEQ ID NO: 1567, Also
optionally and more preferably, any suitable method may be used for
detecting a fragment such as AA281370_segment_TAA seg 10 SEQ ID NO:
1567 for example. Most preferably, NAT-based technology used, such
as any nucleic acid molecule capable of specifically hybridizing
with the fragment. Optionally and most preferably, a primer pair is
used for obtaining the fragment.
[3575] According to other preferred embodiments, the present
invention also optionally and preferably encompasses AA281370
splice variants containing the unique segments as depicted in SEQ
ID NO: 1568, for example transcripts 4 and 5, as depicted in SEQ ID
NOs: 1561 and 1562, comprises a biomarker for detecting lung
cancer.
[3576] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to AA281370 as described above, including but not
limited to SEQ ID NOs: 1563-1566. Any oligopeptide or peptide
relating to such an amino acid sequence or fragment thereof may
optionally also (additionally or alternatively) be used as a
biomarker, including but not limited to the unique amino acid
sequence of the proteins SEQ ID NOs: 1563-1566, as depicted in SEQ
ID NOs: 1569, 1570 and 1571.
[3577] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3578] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to AA281370 as
described above, optionally for any application.
Expression of Sulfatase 1 (SULF1)-[221368], Transcripts which are
Detectable by Amplicon as Depicted in SEQ ID NO:1574 in Normal and
Cancerous Lung Tissues
[3579] SULF1 is a secreted protein which is found in the
extracellular matrix. It is known to be downregulated in many
epithelial cancer types.
[3580] Expression of Sulfatase 1 (SULF1) transcripts detectable by
SEQ ID NO:1574 (e.g., variant no. 13 and 14, represented in SEQ ID
1578, 1579) was measured by real time PCR. In parallel the
expression of four housekeeping genes--PBGD (GenBank Accession No.
BC019323 (SEQ ID NO:1713); amplicon--SEQ ID NO:1471), HPRT1
(GenBank Accession No. NM.sub.--000194 (SEQ ID NO:1714);
amplicon--SEQ ID NO:1468), Ubiquitin (GenBank Accession No.
BC000449 (SEQ ID NO:1711); amplicon--SEQ ID NO:1474) and SDHA
(GenBank Accession No. NM.sub.--004168 (SEQ ID NO:1712);
amplicon--SEQ ID NO:1477), was measured similarly. For each RT
sample, the expression of SEQ ID NO: 1574 was normalized to the
geometric mean of the quantities of the housekeeping genes. The
normalized quantity of each RT sample was then divided by the
median of the quantities of the normal post-mortem (PM) samples
(Sample Nos. 47-50, 90-93, 96-99, Table 2, "Tissue samples in
testing panel", above), to obtain a value of fold up-regulation for
each sample relative to median of the normal PM samples.
[3581] FIG. 59 is a histogram showing over expression of the
above-indicated Sulfatase 1 (SULF1) transcripts in cancerous lung
samples relative to the normal samples. The number and percentage
of samples that exhibit at least 8 fold over-expression, out of the
total number of samples tested is indicated in the bottom.
[3582] As is evident from FIG. 59, the expression of Sulfatase 1
(SULF1) transcripts detectable by SEQ ID NO: 1574 in cancer samples
originate from non-cell carcinoma was significantly higher than in
the non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99, Table
2, "Tissue samples in testing panel"). Notably an over-expression
of at least 8 fold was found in 11 out of 15 adenocarcinoma
samples, 11 out of 16 squamous cell carcinoma samples, and in 4 out
of 4 large cell carcinoma samples.
[3583] Statistical analysis was applied to verify the significance
of these results, as described below.
[3584] The P value for the difference in the expression levels of
Sulfatase 1 (SULF1) transcripts detectable by SEQ ID NO: 1574 in
lung cancer samples versus the normal lung samples was determined
by T test as 3.18E-07. Threshold of 8 fold overexpression was found
to differentiate between cancer and normal samples with P value of
1.18E-04 as checked by exact fisher test.
[3585] The above values demonstrate statistical significance of the
results.
[3586] According to the present invention, Sulfatase 1 (SULF1) is a
non-limiting example of a marker for diagnosing lung cancer. The
Sulfatase 1 (SULF1) marker of the present invention, can be used
alone or in combination, for various uses, including but not
limited to, prognosis, prediction, screening, early diagnosis,
therapy selection and treatment monitoring of lung cancer. Although
optionally any method may be used to detected overexpression and/or
differential expression of this marker, preferably a NAT-based
technology is used. Therefore, optionally and preferably, any
nucleic acid molecule capable of selectively hybridizing to
Sulfatase 1 (SULF1) as previously defined is also encompassed
within the present invention. Primer pairs are also optionally and
preferably encompassed within the present invention; for example,
for the above experiment, the following primer pair was used as a
non-limiting illustrative example only of a suitable primer pair:
Sulfatase 1 (SULF1)-forward primer (SEQ ID NO: 1572):
ACTCACTCAGAGACTAACACAAAGGAAG; and Sulfatase 1 (SULF1)-Reverse
primer (SEQ ID NO: 1573): AGTATGGGAAGAATTTACTGGTCACA.
[3587] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: Sulfatase 1 (SULF1)-amplicon (SEQ ID NO: 1574):
ACTCACTCAGAGACTAACACAAAGGAAGTAATTTCTTACCTGGTCATTATTTAGTCTACAATAAGTTC
ATCCTTCTTCAGTGTGACCAGTAAATTCTTCCCATACT.
[3588] According to other preferred embodiments of the present
invention, Sulfatase 1 (SULF1) or a fragment thereof comprises a
biomarker for detecting lung cancer. Optionally and more
preferably, Sulfatase 1 (SULF1) splice variants, as depicted in SEQ
ID NO:1578, 1579 (e.g., variants no: 13 and 14), or a fragment
thereof comprise a biomarker for detecting lung cancer. Optionally
and more preferably, the fragment of Sulfatase 1 (SULF1) comprises
segment_TAA seg 5--SEQ ID NO: 1587. Also optionally and more
preferably, any suitable method may be used for detecting a
fragment such as Sulfatase 1 (SULF1) _segment_ TAA seg 5--SEQ ID
NO: 1587 for example. Most preferably, NAT-based technology used,
such as any nucleic acid molecule capable of specifically
hybridizing with the fragment. Optionally and most preferably, a
primer pair is used for obtaining the fragment.
[3589] According to other preferred embodiments of the present
invention, Sulfatase 1 (SULF1) splice variants containing the
unique segments as depicted in SEQ ID NOs: 1588-1591, for example
transcripts as depicted in SEQ ID NOs: 1575-1577, comprises a
biomarker for detecting lung cancer.
[3590] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to Sulfatase 1 (SULF1) as described above, including
but not limited to SEQ ID NOs:1586, 1580, 1582, 1584. Any
oligopeptide or peptide relating to such an amino acid sequence or
fragment thereof may optionally also (additionally or
alternatively) be used as a biomarker, including but not limited to
the unique amino acid sequence of the protein SEQ ID NO: 1580,
1582, 1584, as depicted in SEQ ID NO: 1581, 1583, 1585,
respectively.
[3591] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3592] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to Nucleolar
protein 4 (NOL4) as described above, optionally for any
application.
Expression of SRY (Sex Determining Region Y)-box 2
(SOX2))-[HUMHMGBOX], Transcripts which are Detectable by the
Amplicon as Depicted in SEQ ID NO:1594 in Normal and Cancerous Lung
Tissues
[3593] Expression of SOX2 transcripts detectable by SEQ ID NO:1594
(e.g., variant no. 0 represented by SEQ ID 1595) was measured by
real time PCR. In parallel the expression of four housekeeping
genes--PBGD (GenBank Accession No. BC019323 (SEQ ID NO:1713);
amplicon--SEQ ID NO:1471), HPRT1 (GenBank Accession No.
NM.sub.--000194 (SEQ ID NO:1714); amplicon--SEQ ID NO:1468),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--SEQ ID NO:1474) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SEQ ID NO: 1477), was
measured similarly. For each RT sample, the expression of SEQ ID
NO: 1594 was normalized to the geometric mean of the quantities of
the housekeeping genes. The normalized quantity of each RT sample
was then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel", above), to obtain a value of
fold up-regulation for each sample relative to median of the normal
PM samples.
[3594] FIG. 60 is a histogram showing over expression of the
above-indicated SOX2 transcripts in cancerous lung samples relative
to the normal samples. The number and percentage of samples that
exhibit at least 5 fold over-expression, out of the total number of
samples tested is indicated in the bottom.
[3595] As is evident from FIG. 60, the expression of SOX2
transcripts detectable by SEQ ID NO: 1594 in cancer samples
originate from lung carcinoma was significantly higher than in the
non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel"). Notably an over-expression of
at least 5 fold was found in 4 out of 15 adenocarcinoma samples, 10
out of 16 squamous cell carcinoma samples, in 2 out of 4 large cell
carcinoma, and in 7 out of 8 small cell carcinoma samples.
[3596] Statistical analysis was applied to verify the significance
of these results, as described below.
[3597] The P value for the difference in the expression levels of
SOX2 transcripts detectable by SEQ ID NO: 1594 in lung cancer
samples versus the normal lung samples was determined by T test as
4.38E-05.
Threshold of 5 fold overexpression was found to differentiate
between cancer and normal samples with P value of 8.09E-04 as
checked by exact fisher test.
[3598] The above values demonstrate statistical significance of the
results.
[3599] According to the present invention, SOX2 is a non-limiting
example of a marker for diagnosing lung cancer. The SOX2 marker of
the present invention, can be used alone or in combination, for
various uses, including but not limited to, prognosis, prediction,
screening, early diagnosis, therapy selection and treatment
monitoring of lung cancer. Although optionally any method may be
used to detected overexpression and/or differential expression of
this marker, preferably a NAT-based technology is used. Therefore,
optionally and preferably, any nucleic acid molecule capable of
selectively hybridizing to SOX2 as previously defined is also
encompassed within the present invention. Primer pairs are also
optionally and preferably encompassed within the present invention;
for example, for the above experiment, the following primer pair
was used as a non-limiting illustrative example only of a suitable
primer pair: SOX2-forward primer (SEQ ID NO: 1592): GGCGGCGGCAGGAT;
and SOX2-Reverse primer (SEQ ID NO: 1593): GTCGGGAGCGCAGGG.
[3600] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: SOX2--amplicon (SEQ ID NO: 1594):
GGCGGCGGCAGGATCGGCCAGAGGAGGAGGGAAGCGCTTTTTTTGATCCTGATTCCAGTTTGCCTCTC
TCTTTTTTTCCCCCAAATTATTCTTCGCCTGATTTTCCTCGCGGAGCCCTGCGCTCCCGAC.
[3601] According to other preferred embodiments of the present
invention, SOX2 or a fragment thereof comprises a biomarker for
detecting lung cancer. Optionally and more preferably, SOX2 splice
variants, as depicted in SEQ ID NO:1595 (e.g., variants no: 0), or
a fragment thereof comprise a biomarker for detecting lung cancer.
Optionally and more preferably, the fragment of SOX2 comprises
segment_TAA seg 2--SEQ ID NO: 1597. Also optionally and more
preferably, any suitable method may be used for detecting a
fragment such as SOX2 _segment_ TAA seg 2--SEQ ID NO: 1597 for
example. Most preferably, NAT-based technology used, such as any
nucleic acid molecule capable of specifically hybridizing with the
fragment. Optionally and most preferably, a primer pair is used for
obtaining the fragment.
[3602] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to SOX2 as described above, including but not limited
to SEQ ID NOs: SEQ ID NO: 1596. Any oligopeptide or peptide
relating to such an amino acid sequence or fragment thereof may
optionally also (additionally or alternatively) be used as a
biomarker.
[3603] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3604] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to SOX2 as
described above, optionally for any application.
Expression of Plakophilin 1 (Ectodermal Dysplasia/Skin Fragility
Syndrome) (PKP1)--[HSB6PR], Transcripts which are Detectable by the
Amplicon as Depicted in SEQ ID NO:1600 in Normal and Cancerous Lung
Tissues
[3605] Expression of PKP1 transcripts detectable by SEQ ID NO:1600
(e.g., variant no. 0, 5 and 6-represented by SEQ IDs 1601-1603) was
measured by real time PCR. In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--SEQ ID NO:1471), HPRT1 (GenBank Accession No.
NM.sub.--000194 (SEQ ID NO:1714); amplicon--SEQ ID NO:1468),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--SEQ ID NO:1474) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SEQ ID NO: 1477), was
measured similarly. For each RT sample, the expression of SEQ ID
NO: 1600 was normalized to the geometric mean of the quantities of
the housekeeping genes. The normalized quantity of each RT sample
was then divided by the median of the quantities of the normal
post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel" above), to obtain a value of fold
up-regulation for each sample relative to median of the normal PM
samples.
[3606] FIG. 61 is a histogram showing over expression of the
above-indicated PKP1 transcripts in cancerous lung samples relative
to the normal samples. The number and percentage of samples that
exhibit at least 7 fold over-expression, out of the total number of
samples tested is indicated in the bottom.
[3607] As is evident from FIG. 61, the expression of PKP1
transcripts detectable by SEQ ID NO: 1600 in cancer samples
originate from lung carcinoma was significantly higher than in the
non-cancerous samples (Sample Nos. 46-50, 90-93, 96-99, Table 2,
"Tissue samples in testing panel"). Notably an over-expression of
at least 7 fold was found in 11 out of 16 squamous cell carcinoma
samples, and in 1 out of 4 large cell carcinoma.
[3608] Statistical analysis was applied to verify the significance
of these results, as described below.
[3609] The P value for the difference in the expression levels of
PKP I transcripts detectable by SEQ ID NO: 1600 in lung cancer
samples versus the normal lung samples was determined by T test as
3.18E-03.
[3610] Threshold of 7 fold overexpression was found to
differentiate between cancer and normal samples with P value of
3.50E-02 as checked by exact fisher test.
[3611] The above values demonstrate statistical significance of the
results.
[3612] According to the present invention, PKP1 is a non-limiting
example of a marker for diagnosing lung cancer. The PKP1 marker of
the present invention, can be used alone or in combination, for
various uses, including but not limited to, prognosis, prediction,
screening, early diagnosis, therapy selection and treatment
monitoring of lung cancer. Although optionally any method may be
used to detected overexpression and/or differential expression of
this marker, preferably a NAT-based technology is used. Therefore,
optionally and preferably, any nucleic acid molecule capable of
selectively hybridizing to PKP1 as previously defined is also
encompassed within the present invention. Primer pairs are also
optionally and preferably encompassed within the present invention;
for example, for the above experiment, the following primer pair
was used as a non-limiting illustrative example only of a suitable
primer pair: PKP1-forward primer (SEQ ID NO: 1598):
CCCCAGACTCTGTGCACTTCA; and PKP1-Reverse primer (SEQ ID NO: 1599):
TGGGCTCTGCTCTGTCTTAGTGTA
[3613] The present invention also preferably encompasses any
amplicon obtained through the use of any suitable primer pair; for
example, for the above experiment, the following amplicon was
obtained as a non-limiting illustrative example only of a suitable
amplicon: PKP1-amplicon (SEQ ID NO: 1600):
CCCCAGACTCTGTGCACTTCAGACCAGCAGCAGCAGGAGGGCTCCCGAGGGCCTTATGAGAAAACCT
GTGTGGACATCCCTTGGTGTACACTAAGACAGAGCAGAGCCCA
[3614] According to other preferred embodiments of the present
invention, PKP1 or a fragment thereof comprises a biomarker for
detecting lung cancer. Optionally and more preferably, PKP1 splice
variants, as depicted in SEQ ID NO: 1601-1603 (e.g., variants no:
0, 5 and 6), or a fragment thereof comprise a biomarker for
detecting lung cancer. Optionally and more preferably, the fragment
of PKP1 comprises segment_TAA seg 34-SEQ ID NO: 1608. Also
optionally and more preferably, any suitable method may be used for
detecting a fragment such as PKP1_segment_ TAA seg 34-SEQ ID NO:
1608 for example. Most preferably, NAT-based technology used, such
as any nucleic acid molecule capable of specifically hybridizing
with the fragment. Optionally and most preferably, a primer pair is
used for obtaining the fragment.
[3615] According to other preferred embodiments of the present
invention, PKP1 splice variants containing the unique
segment.sub.--8 as depicted in SEQ ID NO: 1607, for example variant
6, as depicted in SEQ ID NO: 1603, are suitable as biomarkers for
detecting lung cancer.
[3616] According to still other preferred embodiments, the present
invention optionally and preferably encompasses any amino acid
sequence or fragment thereof encoded by a nucleic acid sequence
corresponding to PKP1 as described above, including but not limited
to SEQ ID NOs: 1604-1606. Any oligopeptide or peptide relating to
such an amino acid sequence or fragment thereof may optionally also
(additionally or alternatively) be used as a biomarker.
[3617] The present invention also optionally encompasses antibodies
capable of recognizing, and/or being elicited by, such
oligopeptides or peptides.
[3618] The present invention also optionally and preferably
encompasses any nucleic acid sequence or fragment thereof, or amino
acid sequence or fragment thereof, corresponding to PKP1 as
described above, optionally for any application.
[3619] Combined Expression of 12 Sequences (SEQ ID NO: 1480, 1517,
1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622, 1625) in
Normal and Cancerous Lung Tissues.
[3620] Expression of several transcripts detectable by SEQ ID NOs:
1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619, 1622,
1625 was measured by real time PCR (the expression of each SEQ ID
was checked separately). In parallel the expression of four
housekeeping genes--PBGD (GenBank Accession No. BC019323 (SEQ ID
NO:1713); amplicon--SEQ ID NO:1471), HPRT1 (GenBank Accession No.
NM.sub.--000194 (SEQ ID NO:1714); amplicon--SEQ ID NO:1468),
Ubiquitin (GenBank Accession No. BC000449 (SEQ ID NO:1711);
amplicon--SEQ ID NO:1474) and SDHA (GenBank Accession No.
NM.sub.--004168 (SEQ ID NO:1712); amplicon--SEQ ID NO: 1477), was
measured similarly. For each RT sample, the expression of SEQ ID
NOs: 1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619,
1622, 1625 was normalized to the geometric mean of the quantities
of the housekeeping genes. The normalized quantity of each RT
sample was then divided by the median of the quantities of the
normal post-mortem (PM) samples (Sample Nos. 47-50, 90-93, 96-99,
Table 2, "Tissue samples in testing panel", above), to obtain a
value of fold up-regulation for each sample relative to median of
the normal PM samples.
[3621] FIG. 62 is a histogram showing over expression of the
above-indicated transcripts in cancerous lung samples relative to
the normal samples. The number and percentage of samples that
exhibit at least 10 fold over-expression of at least one of the SEQ
IDs, out of the total number of samples tested is indicated in the
bottom.
[3622] As is evident from FIG. 62, an over-expression of at least
10 fold in at least one of the SEQ IDs was found in 15 out of 15
adenocarcinoma samples, 15 out of 16 squamous cell carcinoma
samples, 4 out of 4 large cell carcinoma samples, and in 8 out of 8
small-cell samples.
[3623] Statistical analysis was applied to verify the significance
of these results, as described below. Threshold of 10 fold
overexpression of at least one of the amplicons as depicted in SEQ
ID NOs: 1480, 1517, 1529, 1532, 1558, 1574, 1594, 1600, 1616, 1619,
1622, 1625, was found to differentiate between cancer and normal
samples with P value of 2.37E-08 as checked by exact fisher
test.
[3624] The above values demonstrate statistical significance of the
results.
Kits and Diagnostic Assays and Methods
[3625] The markers described with regard to any of Examples above
can be used alone, in combination with other markers described
above, and/or with other entirely different markers, including but
not limited to UbcH10 (see U.S. Patent Application Nos: 60/535,904
and 60/572,122; attorney refs: 27080 and 28045, filed on Jan. 13
and May 19 2004, respectively), Troponin (see U.S. Patent
Application No: 60/539,129; attorney ref: 26940), Sim2 (see PCT
Application No. WO 2004/012847), PE-10 (SP-A), TTF-1, Cytokeratin
5/6, to aid in the diagnosis of lung cancer. All of these
applications are hereby incorporated by reference as if fully set
forth herein. These markers can be used in combination with other
markers for a number of uses, including but not limited to,
prognosis, prediction, screening, early diagnosis, therapy
selection and treatment monitoring of lung cancer, and also
optionally including staging of the disease. Used together, they
may provide more information for the diagnostician, increasing the
percentage of true positive and true negative diagnoses and
decreasing the percentage of false positive or false negative
diagnoses, as compared to the results obtained with a single marker
alone.
[3626] Assays and methods according to the present invention, as
described above, include but are not limited to, immunoassays,
hybridization assays and NAT-based assays. The combination of the
markers of the present invention with other markers described
above, and/or with other entirely different markers to aid in the
diagnosis of lung cancer could be carried out as a mix of NAT-based
assays, immunoassays and hybridization assays. According to
preferred embodiments of the present invention, the assays are
NAT-based assays, as described for example with regard to the
Examples above.
[3627] In yet another aspect, the present invention provides kits
for aiding a diagnosis of lung cancer, wherein the kits can be used
to detect the markers of the present invention. For example, the
kits can be used to detect any one or combination of markers
described above, which markers are differentially present in
samples of a lung cancer patients and normal patients. The kits of
the invention have many applications. For example, the kits can be
used to differentiate if a subject has a small cell lung cancer,
non-small cell lung cancer, adenocarcinoma,
bronchoalveolar-alveolar, squamous cell or large cell carcinomas or
has a negative diagnosis, thus aiding a lung cancer diagnosis. In
another example, the kits can be used to identify compounds that
modulate expression of the markers in in vitro lung cells or in
vivo animal models for lung cancer.
[3628] In one embodiment, a kit comprises: (a) a substrate
comprising an adsorbent thereon, wherein the adsorbent is suitable
for binding a marker, and (b) a washing solution or instructions
for making a washing solution, wherein the combination of the
adsorbent and the washing solution allows detection of the marker
as previously described.
[3629] Optionally, the kit can further comprise instructions for
suitable operational parameters in the form of a label or a
separate insert. For example, the kit may have standard
instructions informing a consumer/kit user how to wash the probe
after a sample of seminal plasma or other tissue sample is
contacted on the probe.
[3630] In another embodiment, a kit comprises (a) an antibody that
specifically binds to a marker; and (b) a detection reagent. Such
kits can be prepared from the materials described above.
[3631] In either embodiment, the kit may optionally further
comprise a standard or control information, and/or a control amount
of material, so that the test sample can be compared with the
control information standard and/or control amount to determine if
the test amount of a marker detected in a sample is a diagnostic
amount consistent with a diagnosis of lung cancer.
[3632] It is appreciated that certain features of the invention,
which are, for clarity, described in the context of separate
embodiments, may also be provided in combination in a single
embodiment. Conversely, various features of the invention, which
are, for brevity, described in the context of a single embodiment,
may also be provided separately or in any suitable
subcombination.
[3633] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the spirit and broad scope of the appended claims. All
publications, patents and patent applications mentioned in this
specification are herein incorporated in their entirety by
reference into the specification, to the same extent as if each
individual publication, patent or patent application was
specifically and individually indicated to be incorporated herein
by reference. In addition, citation or identification of any
reference in this application shall not be construed as an
admission that such reference is available as prior art to the
present invention.
Sequence CWU 0 SQTB SEQUENCE LISTING The patent application
contains a lengthy "Sequence Listing" section. A copy of the
"Sequence Listing" is available in electronic form from the USPTO
web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20100068736A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
0 SQTB SEQUENCE LISTING The patent application contains a lengthy
"Sequence Listing" section. A copy of the "Sequence Listing" is
available in electronic form from the USPTO web site
(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20100068736A1).
An electronic copy of the "Sequence Listing" will also be available
from the USPTO upon request and payment of the fee set forth in 37
CFR 1.19(b)(3).
* * * * *
References