U.S. patent application number 15/809162 was filed with the patent office on 2018-04-12 for method of diagnosing neoplasms.
This patent application is currently assigned to CLINICAL GENOMICS PTY. LTD.. The applicant listed for this patent is CLINICAL GENOMICS PTY. LTD., COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION. Invention is credited to Robert DUNNE, Lawrence Charles LAPOINTE, Trevor John LOCKETT, William J. WILSON, Graeme P. YOUNG.
Application Number | 20180100200 15/809162 |
Document ID | / |
Family ID | 40578971 |
Filed Date | 2018-04-12 |
United States Patent
Application |
20180100200 |
Kind Code |
A1 |
LAPOINTE; Lawrence Charles ;
et al. |
April 12, 2018 |
METHOD OF DIAGNOSING NEOPLASMS
Abstract
The present invention relates generally to nucleic acid
molecules, the RNA and protein expression profiles of which are
indicative of the onset, predisposition to the onset and/or
progression of a neoplasm. More particularly, the present invention
is directed to nucleic acid molecules, the expression profiles of
which are indicative of the onset and/or progression of a large
intestine neoplasm, such as an adenoma or an adenocarcinoma. The
expression profiles of the present invention are useful in a range
of applications including, but not limited to, those relating to
the diagnosis and/or monitoring of colorectal neoplasms, such as
colorectal adenocarcinomas. Accordingly, in a related aspect the
present invention is directed to a method of screening a subject
for the onset, predisposition to the onset and/or progression of a
neoplasm by screening for modulation in the expression profile of
one or more nucleic acid molecule markers.
Inventors: |
LAPOINTE; Lawrence Charles;
(West Pennant Hills, AU) ; DUNNE; Robert;
(Darlington, AU) ; YOUNG; Graeme P.; (Malvern,
AU) ; LOCKETT; Trevor John; (Denistone, AU) ;
WILSON; William J.; (Hornsby Heights, AU) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CLINICAL GENOMICS PTY. LTD.
COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH
ORGANISATION |
North Ryde
Campbell |
|
AU
AU |
|
|
Assignee: |
CLINICAL GENOMICS PTY. LTD.
North Ryde
AU
COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH
ORGANISATION
Campbell
AU
|
Family ID: |
40578971 |
Appl. No.: |
15/809162 |
Filed: |
November 10, 2017 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
15381895 |
Dec 16, 2016 |
|
|
|
15809162 |
|
|
|
|
14540583 |
Nov 13, 2014 |
|
|
|
15381895 |
|
|
|
|
12739580 |
Jul 28, 2010 |
|
|
|
PCT/AU2008/001571 |
Oct 23, 2008 |
|
|
|
14540583 |
|
|
|
|
60982114 |
Oct 23, 2007 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 2800/06 20130101;
C12Q 2600/112 20130101; G01N 33/57446 20130101; C12Q 2600/158
20130101; C12Q 1/6886 20130101; C12Q 2600/16 20130101 |
International
Class: |
C12Q 1/68 20060101
C12Q001/68; G01N 33/574 20060101 G01N033/574 |
Claims
1. A method of screening for the onset or predisposition to the
onset of a large intestine neoplasm or monitoring the progress of a
neoplasm in an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from: (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs: 205513_at; and/or (ii) TCN1 in a biological sample
from said individual wherein a higher level of expression of the
genes or transcripts of group (i) and/or group (ii) relative to
control levels is indicative of a neoplastic large intestine cell
or a cell predisposed to the onset of a neoplastic state.
2. The method according to claim 1 wherein said control level is a
non-neoplastic level.
3. The method according to claim 1 wherein said neoplastic cell is
an adenoma or an adenocarcinoma.
4. The method according to claim 1 wherein said cell is a
colorectal cell.
5. The method according to claim 1 wherein said biological sample
is a faecal sample, enema wash, surgical resection, tissue biopsy
or blood sample.
6. The method according to claim 1 wherein said level of expression
is mRNA expression or protein expression.
7. The method according to claim 1 wherein said biological sample
is a fecal sample, enema wash, surgical resection, tissue biopsy or
blood sample.
8. The method according to claim 1 wherein said individual is a
human.
Description
FIELD OF THE INVENTION
[0001] The present invention relates generally to nucleic acid
molecules, the RNA and protein expression profiles of which are
indicative of the onset, predisposition to the onset and/or
progression of a neoplasm. More particularly, the present invention
is directed to nucleic acid molecules, the expression profiles of
which are indicative of the onset and/or progression of a large
intestine neoplasm, such as an adenoma or an adenocarcinoma. The
expression profiles of the present invention are useful in a range
of applications including, but not limited to, those relating to
the diagnosis and/or monitoring of colorectal neoplasms, such as
colorectal adenocarcinomas. Accordingly, in a related aspect the
present invention is directed to a method of screening a subject
for the onset, predisposition to the onset and/or progression of a
neoplasm by screening for modulation in the expression profile of
one or more nucleic acid molecule markers.
INCORPORATION BY REFERENCE OF SEQUENCE LISTING
[0002] The Sequence Listing in the ASCII text file, named as
26139ABC_SeqListing.txt of 146 KB, created on November 9, 2017 and
submitted to the United States Patent and Trademark Office via
EFS-Web, is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0003] Bibliographic details of the publications referred to by
author in this specification are collected alphabetically at the
end of the description.
[0004] The reference in this specification to any prior publication
(or information derived from it), or to any matter which is known,
is not, and should not be taken as an acknowledgment or admission
or any form of suggestion that that prior publication (or
information derived from it) or known matter forms part of the
common general knowledge in the field of endeavour to which this
specification relates.
[0005] Adenomas are benign tumours, or neoplasms, of epithelial
origin which are derived from glandular tissue or exhibit clearly
defined glandular structures. Some adenomas show recognisable
tissue elements, such as fibrous tissue (fibroadenomas) and
epithelial structure, while others, such as bronchial adenomas,
produce active compounds that might give rise to clinical
syndromes.
[0006] Adenomas may progress to become an invasive neoplasm and are
then termed adenocarcinomas. Accordingly, adenocarcinomas are
defined as malignant epithelial tumours arising from glandular
structures, which are constituent parts of many organs of the body.
The term adenocarcinoma is also applied to tumours showing a
glandular growth pattern. These tumours may be sub-classified
according to the substances that they produce, for example mucus
secreting and serous adenocarcinomas, or to the microscopic
arrangement of their cells into patterns, for example papillary and
follicular adenocarcinomas. These carcinomas may be solid or cystic
(cystadenocarcinomas). Each organ may produce tumours showing a
variety of histological types, for example the ovary may produce
both mucinous and cystadenocarcinoma.
[0007] Adenomas in different organs behave differently. In general,
the overall chance of carcinoma being present within an adenoma
(i.e. a focus of cancer having developed within a benign lesion) is
approximately 5%. However, this is related to size of an adenoma.
For instance, in the large bowel (colon and rectum specifically)
occurrence of a cancer within an adenoma is rare in adenomas of
less than 1 centimetre. Such a development is estimated at 40 to
50% in adenomas which are greater than 4 centimetres and show
certain histopathological change such as villous change, or high
grade dysplasia. Adenomas with higher degrees of dysplasia have a
higher incidence of carcinoma. In any given colorectal adenoma, the
predictors of the presence of cancer now or the future occurrence
of cancer in the organ include size (especially greater than 9 mm)
degree of change from tubular to villous morphology, presence of
high grade dysplasia and the morphological change described as
"serrated adenoma". In any given individual, the additional
features of increasing age, familial occurrence of colorectal
adenoma or cancer, male gender or multiplicity of adenomas, predict
a future increased risk for cancer in the organ--so-called risk
factors for cancer. Except for the presence of adenomas and its
size, none of these is objectively defined and all those other than
number and size are subject to observer error and to confusion as
to precise definition of the feature in question. Because such
factors can be difficult to assess and define, their value as
predictors of current or future risk for cancer is imprecise.
[0008] Once a sporadic adenoma has developed, the chance of a new
adenoma occurring is approximately 30% within 26 months.
[0009] Colorectal adenomas represent a class of adenomas which are
exhibiting an increasing incidence, particularly in more affluent
countries. The causes of adenoma, and of progression to
adenocarcinoma, are still the subject of intensive research. To
date it has been speculated that in addition to genetic
predisposition, environmental factors (such as diet) play a role in
the development of this condition. Most studies indicate that the
relevant environmental factors relate to high dietary fat, low
fibre, low vegetable intake, smoking, obesity, physical inactivity
and high refined carbohydrates.
[0010] Colonic adenomas are localised areas of dysplastic
epithelium which initially involve just one or several crypts and
may not protrude from the surface, but with increased growth in
size, usually resulting from an imbalance in proliferation and/or
apoptosis, they may protrude. Adenomas can be classified in several
ways. One is by their gross appearance and the major descriptors
include degrees of protrusion: flat sessile (i.e. protruding but
without a distinct stalk) or pedunculated (i.e. having a stalk).
Other gross descriptors include actual size in the largest
dimension and actual number in the colon/rectum. While small
adenomas (less than say 5 or 10 millimetres) exhibit a smooth tan
surface, pedunculated and especially larger adenomas tend to have a
cobblestone or lobulated red-brown surface. Larger sessile adenomas
may exhibit a more delicate villous surface. Another set of
descriptors include the histopathological classification; the prime
descriptors of clinical value include degree of dysplasia (low or
high), whether or not a focus of invasive cancer is present, degree
of change from tubular gland formation to villous gland formation
(hence classification is tubular, villous or tubulovillous),
presence of admixed hyperplastic change and of so-called "serrated"
adenomas and its subgroups. Adenomas can be situated at any site in
the colon and/or rectum although they tend to be more common in the
rectum and distal colon. All of these descriptors, with the
exception of number and size, are relatively subjective and subject
to interobserver disagreement.
[0011] The various descriptive features of adenomas are of value
not just to ascertain the neoplastic status of any given adenomas
when detected, but also to predict a person's future risk of
developing colorectal adenomas or cancer. Those features of an
adenoma or number of adenomas in an individual that point to an
increased future risk for cancer or recurrence of new adenomas
include: size of the largest adenoma (especially 10 mm or larger),
degree of villous change (especially at least 25% such change and
particularly 100% such change), high grade dysplasia, number (3 or
more of any size or histological status) or presence of serrated
adenoma features. None except size or number is objective and all
are relatively subjective and subject to interobserver
disagreement. These predictors of risk for future neoplasia (hence
"risk") are vital in practice because they are used to determine
the rate and need for and frequency of future colonoscopic
surveillance. More accurate risk classification might thus reduce
workload of colonoscopy, make it more cost-effective and reduce the
risk of complications from unnecessary procedures.
[0012] Adenomas are generally asymptomatic, therefore rendering
difficult their diagnosis and treatment at a stage prior to when
they might develop invasive characteristics and so became cancer.
It is technically impossible to predict the presence or absence of
carcinoma based on the gross appearance of adenomas, although
larger adenomas are more likely to show a region of malignant
change than are smaller adenomas. Sessile adenomas exhibit a higher
incidence of malignancy than pedunculated adenomas of the same
size. Some adenomas result in blood loss which might be observed or
detectable in the stools; while sometimes visible by eye, it is
often, when it occurs, microscopic or "occult". Larger adenomas
tend to bleed more than smaller adenomas. However, since blood in
the stool, whether overt or occult, can also be indicative of
non-adenomatous conditions, the accurate diagnosis of adenoma is
rendered difficult without the application of highly invasive
procedures such as colonoscopy combined with tissue acquisition by
either removal (i.e. polypectomy) or biopsy and subsequent
histopathological analysis.
[0013] Accordingly, there is an on-going need to elucidate the
causes of adenoma and to develop more informative diagnostic
protocols or aids to diagnosis that enable one to direct
colonoscopy at people more likely to have adenomas. These adenomas
may be high risk, advanced or neither of these. Furthermore, it can
be difficult after colonoscopy to be certain that all adenomas have
been removed, especially in a person who has had multiple adenomas.
An accurate screening test may minimise the need to undertake an
early second colonoscopy to ensure that the colon has been cleared
of neoplasms. Accordingly, the identification of molecular markers
for adenomas would provide means for understanding the cause of
adenomas and cancer, improving diagnosis of adenomas including
development of useful screening tests, elucidating the histological
stage of an adenoma, characterising a patient's future risk for
colorectal neoplasia on the basis of the molecular state of an
adenoma and facilitating treatment of adenomas.
[0014] To date, research has focused on the identification of gene
mutations which lead to the development of colorectal neoplasms. In
work leading up to the present invention, however, it has been
determined that changes in expression profiles of genes which are
also expressed in healthy individuals are indicative of the
development of neoplasms of the large intestine, such as adenomas
and adenocarcinomas. It has been further determined that in
relation to neoplasms of the large intestine, diagnosis can be made
based on screening for one or more of a panel of these
differentially expressed genes. In a related aspect, it has still
further been determined that to the extent that neoplastic tissue
has been identified either by the method of the invention or by
some other method, the present invention provides still further
means of characterising that tissue as an adenoma or a cancer. In
yet another aspect, it has been determined that a proportion of
these genes are characterised by gene expression which occurs in
the context of a neoplastic state but not in the context of a
non-neoplastic state, thereby facilitating the development of
qualitative analyses which do not require a relative analysis to be
performed against a non-neoplastic or normal control reference
level. Accordingly, the inventors have identified a panel of genes
which facilitate the diagnosis of adenocarcinoma and adenoma
development and/or the monitoring of conditions characterised by
the development of these types of neoplasms.
SUMMARY OF THE INVENTION
[0015] Throughout this specification and the claims which follow,
unless the context requires otherwise, the word "comprise", and
variations such as "comprises" and "comprising", will be understood
to imply the inclusion of a stated integer or step or group of
integers or steps but not the exclusion of any other integer or
step or group of integers or steps.
[0016] As used herein, the term "derived from" shall be taken to
indicate that a particular integer or group of integers has
originated from the species specified, but has not necessarily been
obtained directly from the specified source. Further, as used
herein the singular forms of "a", "and" and "the" include plural
referents unless the context clearly dictates otherwise.
[0017] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs.
[0018] The subject specification contains amino acid and nucleotide
sequence information prepared using the programme PatentIn Version
3.4, presented herein after the bibliography. Each amino acid and
nucleotide sequence is identified in the sequence listing by the
numeric indicator <210 > followed by the sequence identifier
(eg. <210>1, <210>2, etc). The length, type of sequence
(amino acid, DNA, etc.) and source organism for each sequence is
indicated by information provided in the numeric indicator fields
<211>m <212> and <213>, respectively. Amino acid
and nucleotide sequences referred to in the specification are
identified by the indicator SEQ ID NO: followed by the sequence
identifier (eg. SEQ ID NO:1, SEQ ID NO: 2, etc). The sequence
identifier referred to in the specification correlates to the
information provided in numeric indicator field <400> in the
sequence listing, which is followed by the sequence identifier (eg.
<400>1, <400>2, etc). That is SEQ ID NO: 1 as detailed
in the specification correlates to the sequence indicated as
<400>1 in the sequence listing.
[0019] One aspect of the present invention is directed to a method
of screening for the onset or predisposition to the onset of a
large intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00001 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 201328_at 221577_x_at 205828_at
201341_at 221922_at 205886_at 201416_at 60474_at 205890_s_at
201417_at 222696_at 205910_s_at 201468_s_at 223447_at 205941_s_at
201506_at 223970_at 206224_at 201563_at 225541_at 206976_s_at
201656_at 225835_at 207173_x_at 201925_s_at 226360_at 207457_s_at
201926_s_at 227174_at 208079_s_at 202286_s_at 227475_at 208712_at
202718_at 228303_at 209218_at 202831_at 228653_at 209309_at
202833_s_at 228754_at 209752_at 202935_s_at 228915_at 209773_s_at
202936_s_at 229215_at 209774_x_at 203124_s_at 231832_at 209792_s_at
203256_at 231941_s_at 209875_s_at 203313_s_at 232176_at 209955_s_at
203510_at 232252_at 210052_s_at 203860_at 232481_s_at 210511_s_at
203895_at 234331_s_at 210559_s_at 203896_s_at 235210_s_at
210766_s_at 203961_at 235976_at 211506_s_at 203962_s_at 236894_at
212281_s_at 204259_at 238017_at 212344_at 204351_at 238021_s_at
212353_at 204401_at 238984_at 212354_at 204404_at 241031_at
213905_x_at 204855_at 200660_at 214022_s_at 204885_s_at 200832_s_at
214974_x_at 205174_s_at 200903_s_at 215091_s_at 205366_s_at
201014_s_at 217430_x_at 205470_s_at 201112_s_at 217996_at 205513_at
201195_s_at 218507_at 205765_at 201261_x_at 218963_s_at 205825_at
201292_at 218984_at 205927_s_at 201338_x_at 219787_s_at 205983_at
201479_at 219911_s_at 206239_s_at 201577_at 221729_at 206286_s_at
201601_x_at 221730_at 207158_at 201666_at 221731_x_at 207850_at
202310_s_at 221923_s_at 209369_at 202311_s_at 37892_at 210445_at
202404_s_at 222449_at 210519_s_at 202431_s_at 222450_at 211429_s_at
202504_at 222549_at 212063_at 202779_s_at 222608_s_at 212070_at
202859_x_at 223062_s_at 212190_at 202954_at 224428_s_at 212531_at
202998_s_at 224646_x_at 212942_s_at 203083_at 224915_x_at 213880_at
203213_at 225295_at 213975_s_at 203878_s_at 225520_at 214235_at
204051_s_at 225664_at 214651_s_at 204127_at 225681_at 217523_at
204170_s_at 225767_at 217867_x_at 204320_at 225799_at 218086_at
204470_at 225806_at 218211_s_at 204475_at 226227_x_at 218704_at
204580_at 226237_at 218796_at 204620_s_at 226311_at 218872_at
204702_s_at 226777_at 219630_at 205361_s_at 226835_s_at 219682_s_at
205476_at 227140_at 219727_at 205479_s_at 229802_at 219955_at
205713_s_at 231766_s_at 219956_at 205815_at 232151_at; and/or
200665_s_at (ii) FOXQ1 RNF43 CDCA7 LOXL2 MMP1 CCL20 TDGF1 AZGP1
TCN1 CTSE MTHFD1L MYC MMP7 MSLN ANLN COMP WDR72 TIMP1 H19 AURKA
INHBA PCSK1 FAP PAICS COL11A1 CST1 DACH1 PUS7 GDF15 BGN VCAN ZNRF3
CTHRC1 AXIN2 SQLE CCND1 COL1A1 MET REG3A CSE1L LGR5 SOX9 TESC PFDN4
DUSP27 TMEPAI UBE2C C20orf42 SERPINB5 CDH11 TMEM97 SLC11A2 ASCL2
MMP11 TRIM29 NFE2L3 SULF1 CXCL1 KLK11 CEL SLC6A6 QPCT LY6G6D NLF1
TACSTD2 PDZK1IP1 SLC7A5 NPDC1 NEBL CD55 FABP6 ENC1 PCCA ECT2
SLITRK6 SERPINE2 FLJ37644 COL12A1 MLPH UBE2S KRT23 L1TD1 HOXA9
TOP2A CXCL3 WDR51B TBX3 CDC2 MMP3 HOXB6 BACE2 RFC3 SFRP4 FAM84A
GPX2 LILRB1 UBD COL5A2 TPX2 NPM1 SCD MMP12 KCNN4 RDHE2 DPEP1 SORD
LOC541471 PLAU LCN2 PSAT1 CYP3A5 HSPH1 PLCB4 CXCL5 ANXA3 GTF3A
SPINK1 IGFBP2 CYP3A5P2 KLK10 DUOX2 TGIF1 C14orf94 GPSM2 SOX4 CXCL2
RP5-875H10.1 NME1 THBS2 SLCO4A1 RPL22L1 MUC20 CLDN1 CKS2 APOBEC1
RPESP REG1B PHLDA1 HIG2 RRM2 CDH3 SERPINA1 COL10A1 DKC1 SPARC
COL1A2 AHCY CD44 IL8
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a neoplastic large
intestine cell or a cell predisposed to the onset of a neoplastic
state.
[0020] In another aspect there is provided a method of screening
for the onset or predisposition to the onset of a large intestine
neoplasm in an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from: [0021] (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: [0022] 225681_at; 227140_at; and/or [0023]
(ii) CTHRC1 in a biological sample from said individual wherein a
higher level of expression of the genes or transcripts of group (i)
and/or group (ii) relative to control levels is indicative of a
neoplastic large intestine cell or a cell predisposed to the onset
of a neoplastic state.
[0024] In yet another aspect there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from: [0025] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0026] 227475_at
[0027] 204475_at [0028] 202859_x_at [0029] 202404_s_at; and/or
[0030] (ii) FOXQ1, MMP1, IL8, COL1A2 in a biological sample from
said individual wherein a higher level of expression of the genes
or transcripts of group (i) and/or group (ii) relative to control
levels is indicative of a neoplastic large intestine cell or a cell
predisposed to the onset of a neoplastic state.
[0031] In still another aspect there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from: [0032] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0033] 205513_at,
204259_at, 227174_at, 210511_s_at, 37892_at; and/or [0034] (ii)
TCN1, MMP7, WDR72, INHBA, COL11A1 in a biological sample from said
individual wherein a higher level of expression of the genes or
transcripts of group (i) and/or group (ii) relative to control
levels is indicative of a neoplastic large intestine cell or a cell
predisposed to the onset of a neoplastic state.
[0035] Preferably, said control level is a non-neoplastic
level.
[0036] In still yet another aspect there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00002 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 221577_x_at 212942_s_at 202310_s_at
213880_at 232252_at 204855_at 229215_at 212354_at 228754_at
202286_s_at 203962_s_at 203860_at 202935_s_at 218963_s_at 207850_at
205828_at 204051_s_at 205890_s_at 200832_s_at 205983_at 212531_at;
and/or (ii) LGR5 GDF15 COL1A1 ASCL2 DUSP27 SERPINB5 TACSTD2 SULF1
SLC6A6 FLJ37644 NEBL PCCA MMP3 KRT23 CXCL3 SCD SFRP4 UBD DPEP1
LCN2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a neoplastic large
intestine cell or a cell predisposed to the onset of a neoplastic
state.
[0037] In a further aspect the present invention is directed to a
method of screening for the onset or predisposition to the onset of
a large intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00003 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 201328_at 205825_at 219956_at
201468_s_at 205927_s_at 221922_at 201656_at 206239_s_at 223447_at
201925_s_at 207158_at 223970_at 201926_s_at 210445_at 225835_at
202718_at 210519_s_at 226360_at 202831_at 211429_s_at 228303_at
202833_s_at 212063_at 228653_at 203124_s_at 213975_s_at 228915_at
203313_s_at 214235_at 231832_at 203860_at 214651_s_at 231941_s_at
203895_at 217523_at 232176_at 203896_s_at 217867_x_at 232481_s_at
204401_at 218086_at 234331_s_at 204885_s_at 218211_s_at 235210_s_at
205174_s_at 218796_at 235976_at 205366_s_at 219630_at 236894_at
205470_s_at 219682_s_at 238017_at 205513_at 219727_at 238984_at
205765_at 219955_at; 241031_at; and/or (ii) APOBEC1 HOXB6 QPCT
BACE2 IGFBP2 RDHE2 C20orf42 ITGA6 REG4 CD44 KCNN4 RETNLB CD55 KLK11
RP5-875H10.1 CTSE L1TD1 RPESP CYP3A5 LILRB1 SERPINA1 CYP3A5P2 MLPH
SLC11A2 DACH1 MSLN SLC12A2 DUOX2 MUC20 SLITRK6 ETS2 NLF1 SPINK1
FABP6 NPDC1 TBX3 FAM84A NQO1 TCN1 GALNT6 PCCA TGIF1 GPSM2 PCSK1
WDR51B GPX2 PDZK1IP1 ZNRF3 HOXA9 PLCB4
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of an adenoma cell or
a cell predisposed to the onset of an adenoma state.
[0038] In another further aspect of the present invention there is
provided a method of screening for the onset or predisposition to
the onset of a large intestine neoplasm in an individual, said
method comprising measuring the level of expression of one or more
genes or transcripts selected from:
TABLE-US-00004 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 200660_at 205476_at 217430_x_at
200665_s_at 205479_s_at 217996_at 200832_s_at 205713_s_at 218507_at
200903_s_at 205815_at 218963_s_at 201014_s_at 205828_at 218984_at
201112_s_at 205886_at 219787_s_at 201195_s_at 205890_s_at
219911_s_at 201261_x_at 205910_s_at 221729_at 201292_at 205941_s_at
221730_at 201338_x_at 206224_at 221731_x_at 201479_at 206976_s_at
221923_s_at 201577_at 207173_x_at 37892_at 201601_x_at 207457_s_at
222449_at 201666_at 208079_s_at 222450_at 202310_s_at 208712_at
222549_at 202311_s_at 209218_at 222608_s_at 202403_s_at 209309_at
223062_s_at 202404_s_at 209752_at 224428_s_at 202431_s_at
209773_s_at 224646_x_at 202504_at 209774_x_at 224915_x_at
202779_s_at 209792_s_at 225295_at 202859_x_at 209875_s_at 225520_at
202954_at 209955_s_at 225664_at 202998_s_at 210052_s_at 225681_at
203083_at 210511_s_at 225767_at 203213_at 210559_s_at 225799_at
203878_s_at 210766_s_at 225806_at 204051_s_at 211506_s_at
226227_x_at 204127_at 212281_s_at 226237_at 204170_s_at 212344_at
226311_at 204320_at 212353_at 226777_at 204470_at 212354_at
226835_s_at 204475_at 213905_x_at 227140_at 204580_at 214022_s_at
229802_at 204620_s_at 214974_x_at 231766_s_at 204702_s_at
215091_s_at; 232151_at; and/or 205361_s_at (ii) AHCY DKC1 PSAT1
ANLN ECT2 PUS7 AURKA FAP REG1A AZGP1 GTF3A REG1B BGN H19 REG3A
C14orf94 HIG2 RFC3 C20orf199 HSPH1 RRM2 CCL20 IFITM1 S100A11 CCND1
IL8 SCD CDC2 INHBA SFRP4 CDCA7 KLK10 SLC39A10 CDH11 KRT23 SLC7A5
CEL LOC541471 SLCO4A1 CKS2 LOXL2 SPARC CLDN1 LY6G6D SPP1 COL10A1
MMP1 SQLE COL11A1 MMP11 SULF1 COL12A1 MMP12 THBS2 COL1A1 MMP3 TIMP1
COL1A2 MTHFD1L TMEM97 COL5A2 MYC TMEPAI COL8A1 NFE2L3 TOP2A COMP
NME1 TPX2 CSE1L NPM1 TRIM29 CST1 PAICS UBD CTHRC1 PFDN4 UBE2C CXCL1
PHLDA1 UBE2S CXCL2 PLAU VCAN CXCL5
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a cancer cell or a
cell predisposed to the onset of a cancerous state.
[0039] In yet another further aspect there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00005 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 202286_s_at 235976_at 209309_at
204259_at 236894_at 211506_s_at 204885_s_at 214974_x_at 205174_s_at
238984_at 219787_s_at 205825_at 241031_at 37892_at 207850_at
202311_s_at 222608_s_at 213880_at 204320_at 223062_s_at 217523_at
204475_at 225806_at 227174_at 204702_s_at 226237_at 228915_at
205910_s_at 227140_at 232252_at 206224_at 229802_at; and/or (ii)
MMP1 PCSK1 ANLN MMP7 CST1 DACH1 LGR5 QPCT COL11A1 WDR72 ECT2
C14orf94 COL11A1 SLITRK6 AZGP1 COL1A1 L1TD1 REG4 DUSP27 KIAA1199
NFE2L3 NLF1 PSAT1 CEL IL8 CXCL5 CD44 TACSTD2 CXCL3 COL8A1 MSLN
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of a neoplastic
cell or a cell predisposed to the onset of a neoplastic state.
[0040] Yet another aspect of the present invention provides a
method of screening for the onset or predisposition to the onset of
a large intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00006 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 204885_s_at 217523_at 236894_at
205174_s_at 228915_at 238984_at 205825_at 235976_at 241031_at;
and/or (ii) CD44 MSLN QPCT DACH1 NLF1 REG4 L1TD1 PCSK1 SLITRK6
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of an adenoma cell
or a cell predisposed to the onset of an adenoma state.
[0041] In yet still another aspect there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00007 (i) the gene, or genes detected by Affymetrix
probeset IDs: 202311_s_at 209309_at 223062_s_at 204320_at
211506_s_at 225806_at 204475_at 214974_x_at 226237_at 204702_s_at
219787_s_at 227140_at 205910_s_at 37892_at 229802_at; and/or
206224_at 222608_s_at (ii) ANLN COL1A1 IL8 AZGP1 COL8A1 MMP1
C14orf94 CST1 NFE2L3 CEL CXCL5 PSAT1 COL11A1 ECT2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of a cancer cell
or a cell predisposed to the onset of a cancerous state.
[0042] In still yet another aspect of the present invention, there
is provided a method of characterising a neoplastic cell or
cellular population, which cell or cellular population is derived
from the large intestine of an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00008 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 200884_at 214234_s_at 226248_s_at
203240_at 214235_at 226302_at 203963_at 214433_s_at 227676_at
204508_s_at 215125_s_at 227719_at 204607_at 215867_x_at 227725_at
204811_s_at 217109_at 228232_s_at 204895_x_at 217110_s_at 229070_at
204897_at 218211_s_at 231832_at 205259_at 219543_at 232176_at
205765_at 219955_at 232481_s_at 205927_s_at 221841_s_at 235976_at
208063_s_at 221874_at 236894_at 208937_s_at 223969_s_at 237521_x_at
210107_at 223970_at 242601_at 213106_at; and/or (ii) CLCA1 CTSE
ATP8B1 FCGBP C6orf105 CACNA2D2 HMGCS2 CKB KLF4 RETNLB ATP8A1
CYP3A5P2 L1TD1 MUC4 CAPN9 SLITRK6 UGT1A1 NR3C2 VSIG2 SELENBP1 PBLD
LOC253012 PTGER4 CA12 ST6GALNAC1 MLPH WDR51B ID1 KIAA1324 FAM3D
CYP3A5
in said cell or cellular population wherein a higher level of
expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal cancer cell level is indicative
of an adenoma cell or a cell predisposed to the onset of an adenoma
state.
[0043] In another aspect there is provided a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00009 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 200600_at 204006_s_at 213428_s_at
200665_s_at 204051_s_at 213524_s_at 200832_s_at 204122_at
213869_x_at 200974_at 204320_at 213905_x_at 200986_at 204475_at
214247_s_at 201058_s_at 204620_s_at 215049_x_at 201069_at
205479_s_at 215076_s_at 201105_at 205547_s_at 215646_s_at 201141_at
205828_at 216442_x_at 201147_s_at 207173_x_at 217430_x_at
201150_s_at 207191_s_at 217762_s_at 201162_at 208747_s_at
217763_s_at 201163_s_at 208782_at 217764_s_at 201185_at 208788_at
218468_s_at 201261_x_at 208850_s_at 218469_at 201289_at 208851_s_at
218559_s_at 201426_s_at 209101_at 218638_s_at 201438_at 209156_s_at
219087_at 201616_s_at 209218_at 221011_s_at 201645_at 209395_at
221729_at 201667_at 209396_s_at 221730_at 201744_s_at 209596_at
221731_x_at 201792_at 209875_s_at 37892_at 201842_s_at 209955_s_at
223122_s_at 201852_x_at 210095_s_at 223235_s_at 201859_at
210495_x_at 224560_at 201893_x_at 210511_s_at 224694_at 202237_at
210764_s_at 224724_at 202238_s_at 210809_s_at 225664_at 202283_at
211161_s_at 225681_at 202291_s_at 211571_s_at 225710_at 202310_s_at
211719_x_at 225799_at 202311_s_at 211813_x_at 226237_at 202403_s_at
211896_s_at 226311_at 202404_s_at 211959_at 226694_at 202450_s_at
211964_at 226777_at 202620_s_at 211966_at 226930_at 202766_s_at
211980_at 227099_s_at 202859_x_at 211981_at 227140_at 202878_s_at
212077_at 227566_at 202917_s_at 212344_at 229218_at 202998_s_at
212353_at 229802_at 203083_at 212354_at 231579_s_at 203325_s_at
212464_s_at 231766_s_at 203382_s_at 212488_at 231879_at 203477_at
212489_at 232458_at 203570_at 212667_at 233555_s_at 203645_s_at
213125_at 234994_at 203878_s_at; and/or (ii) COL1A2 LGALS1 SRGN
CTHRC1 ELOVL5 LBH FN1 MGP CTGF POSTN MMP2 TNC SPP1 LOXL2 G0S2 MMP1
MYL9 SQLE SPARC DCN EFEMP1 LUM CALD1 APOE GREM1 FBN1 MSN IL8 MMP3
IGFBP3 IGFBP5 IGFBP7 SERPINF1 SFRP2 FSTL1 ISLR SULF1 COL4A2 HNT
ASPN VCAN COL5A1 COL6A3 SMOC2 OLFML2B COL8A1 HTRA1 KIAA1913 COL12A1
CYR61 PALM2-AKAP2 COL5A2 FAP SERPING1 CDH11 VIM TYROBP THBS2 TIMP2
ACTA2 COL15A1 SCD COL3A1 COL11A1 TIMP3 PLOD2 S100A8 AEBP1 MMP11
FNDC1 GJA1 CD163 SFRP4 NNMT FCGR3B INHBA COL1A1 PLAU COL6A2 SULF2
MAFB ANTXR1 COL6A1 LOC541471 GPNMB SPON2 LOC387763 BGN CTSK CHI3L1
TAGLN MXRA5 THY1 COL4A1 C1S LOXL1 RAB31 DKK3 CD93
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal adenoma cell level is
indicative of a cancer or a cell predisposed to the onset of a
cancerous state.
[0044] In a further aspect there is provided a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
[0045] (i) the gene or genes detected by Affymetrix probeset IDs:
[0046] 210107_at; and/or [0047] (ii) CLCA1 in a biological sample
from said individual wherein a higher level of expression of the
genes or transcripts of group (i) and/or group (ii) relative to a
gastrointestinal cancer control level is indicative of an adenoma
cell or a cell predisposed to the onset of an adenoma state.
[0048] In another aspect there is provided a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00010 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 203240_at 219955_at 242601_at 204607_at
232481_s_at 227725_at 223969_s_at 228232_s_at; and/or (ii) FCGBP
L1TD1 LOC253012 HMGCS2 SLITRK6 ST6GALNAC1 RETNLB VSIG2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal cancer control level is
indicative of an adenoma cell or a cell predisposed to the onset of
an adenoma state.
[0049] A further aspect of the present invention is directed to a
method of characterising a cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
[0050] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs: [0051] 202404_s_at, 210809_s_at, 227140_at,
225681_at, 209875_s_at, 204475_at, 212464_s_at; and/or, [0052] (ii)
COL1A2, FN1, SPP1, CTHRC1, POSTN, MMP1 in a biological sample from
said individual wherein a higher level of expression of the genes
or transcripts of group (i) and/or (ii) relative to a
gastrointestinal adenoma control level is indicative of a cancer or
a cell predisposed to the onset of a cancerous state.
[0053] In yet another further aspect the present invention is
directed to a method of characterising a cell or cellular
population, which cell or cellular population is derived from the
large intestine of an individual, said method comprising measuring
the level of expression of one or more genes or transcripts
selected from: [0054] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs: [0055] 200665_s_at, 218468_s_at,
211959_at, 201744_s_at, 202859_x_at; and/or, [0056] (ii) SPARC,
GREM1, IGFBP5, LUM, IL8, in a biological sample from said
individual wherein a higher level of expression of the genes or
transcripts of group (i) and/or (ii) relative to a gastrointestinal
adenoma control level is indicative of a cancer or a cell
predisposed to the onset of a cancerous state.
[0057] In still yet another further aspect the present invention is
directed to a method of characterising a cell or cellular
population, which cell or cellular population is derived from the
large intestine of an individual, said method comprising measuring
the level of expression of one or more genes or transcripts
selected from:
TABLE-US-00011 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 223122_s_at 207173_x_at 210511_s_at
212353_at 203083_at 209156_s_at 219087_at 203477_at 224694_at
201438_at 37892_at 201141_at 226237_at 202917_s_at 213905_x_at
225664_at 226930_at 205547_s_at 221730_at 204051_s_at; and/or (ii)
SFRP2 CDH11 INHBA SULF1 THBS2 COL6A2 ASPN COL15A1 ANTXR1 COL6A3
COL11A1 GPNMB COL8A1 S100A8 BGN COL12A1 FNDC1 TAGLN COL5A2
SFRP4
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to a gastrointestinal adenoma control level is indicative
of a cancer or a cell predisposed to the onset of a cancerous
state.
[0058] Yet another aspect of the present invention provides a
method of characterising a neoplastic cell or cellular population,
which cell or cellular population is derived from the large
intestine of an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from:
TABLE-US-00012 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 235976_at 236894_at; and/or (ii)
SLITRK6 L1TD1
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to neoplastic tissue background levels is indicative of an
adenoma cell or a cell predisposed to the onset of an adenoma
state.
[0059] In still another aspect the present invention provides a
method of characterising a neoplastic cell or cellular population,
which cell or cellular population is derived from the large
intestine of an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from: [0060] (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: [0061] 202311_s_at, 209396_s_at,
226237_at, 204320_at, 215646_s_at, 227140_at, 204475_at, 37892_at,
229802_at, 209395_at; and/or [0062] (ii) COL1A1, VCAN, CHI3L1,
MMP1, COL8A1, COL11A1 in a biological sample from said individual
wherein a higher level of expression of the genes or transcripts of
group (i) and/or (ii) relative to neoplastic tissue background
neoplastic cell levels is indicative of a cancer or a cell
predisposed to the onset of a cancerous state.
[0063] A related aspect of the present invention provides a
molecular array, which array comprises a plurality of: [0064] (i)
nucleic acid molecules comprising a nucleotide sequence
corresponding to any one or more of the neoplastic marker genes
hereinbefore described or a sequence exhibiting at least 80%
identity thereto or a functional derivative, fragment, variant or
homologue of said nucleic acid molecule; or [0065] (ii) nucleic
acid molecules comprising a nucleotide sequence capable of
hybridising to any one or more of the sequences of (i) under medium
stringency conditions or a functional derivative, fragment, variant
or homologue of said nucleic acid molecule; or [0066] (iii) nucleic
acid probes or oligonucleotides comprising a nucleotide sequence
capable of hybridising to any one or more of the sequences of (i)
under medium stringency conditions or a functional derivative,
fragment, variant or homologue of said nucleic acid molecule; or
[0067] (iv) probes capable of binding to any one or more of the
proteins encoded by the nucleic acid molecules of (i) or a
derivative, fragment or, homologue thereof
[0068] wherein the level of expression of said marker genes of (i)
or proteins of (iv) is indicative of the neoplastic state of a cell
or cellular subpopulation derived from the large intestine.
BRIEF DESCRIPTION OF THE DRAWINGS
[0069] FIG. 1 is a graphical representation of nuclear factor
(erythroid-derived-2)-like 2. Blk=normal, grn=inflamed,
red=adenoma,blue=cancer
[0070] FIG. 2 is a graphical representation of SLIT and NTRK-like
family, member 6 (left) and LINE1 type transposase domain
containing 1 (right).
[0071] FIG. 3 is a graphical representation of collagen type XI,
alpha 1.
[0072] FIG. 4 is an image of the immunohistochemical staining for
MSLN in a normal tissue shows mild staining in the cytoplasm of the
colonocytes.
[0073] FIG. 5 is an image of the immunohistochemical staining for
MSLN in a representative cancer tissue shows moderate staining in
the cytoplasm of the colonic epithelia.
[0074] FIG. 6 is an image of the immunohistochemical staining of
MSLN in a moderately differentiated adenoma shows strong staining
in the multilayered colonic epithelium.
[0075] FIG. 7 is a graphical representation depicting Probeset
205828_at Expression profile across 68 clinical specimens
comprising 30 non-disease controls (black), 19 adenomas (red) and
19 adenocarcinoma (green).
[0076] FIG. 8 is a graphical representation of the measurement of
MMP3 expression in protein extract from 27 clinical stool
specimens. Protein extraction was performed on 27 clinical stool
specimens comprising 6 non-disease controls (circle), 10 adenoma
(triangle) and 11 adenocarcinoma (cross) emulsified using a PBS pH
7.4 solution containing 0.05% Tween-20 and 1.times. Protease
Inhibitor Cocktail (Roche). Proteins were further solubilised by 30
minutes incubation in an ultrasonic water bath. Solubilised
proteins were isolated by centrifugation and endogenous levels of
MMP3 in the resulting protein extracts were using measured using a
commercially available Luminex bead-based suspension immunoassay as
recommended by manufacturer (R&D Systems).
[0077] FIG. 9 is a graphical representation of Affymetrix probeset
ID 205828 at which is known to hybrising to transcripts of the MMP3
gene depicting a gene expression profile in 68 clinical specimens
comprising 30 non-disease controls (black), 19 adenomas (red) and
19 cancers (green).
[0078] FIG. 10 is a schematic representation of predicted RNA
variants derived from hCG_1815491. cDNA clones derived from map
region 8579310 to 8562303 on human chromosome 16 were used to
locate exon sequences. Arrows: Oligo nucleotide primer sets were
designed to allow measurement of individual RNA variants by PCR.
Primers covering splice junctions are shown as spanning intron
sequences which is not included in the actual oligonucleotide
primer sequence.
DETAILED DESCRIPTION OF THE INVENTION
[0079] The present invention is predicated, in part, on the
elucidation of gene expression profiles which characterise large
intestine cellular populations in terms of their neoplastic state
and, more particularly, whether they are malignant or
pre-malignant. This finding has now facilitated the development of
routine means of screening for the onset or predisposition to the
onset of a large intestine neoplasm or characterising cellular
populations derived from the large intestine based on screening for
upregulation of the expression of these molecules, relative to
control expression patterns and levels. To this end, in addition to
assessing expression levels of the subject genes relative to normal
or non-neoplastic levels, it has been determined that a proportion
of these genes are expressed only in the diseased state, thereby
facilitating the development of a simple qualitative test based on
requiring assessment only relative to test background levels.
[0080] In accordance with the present invention, it has been
determined that the genes detailed above are modulated, in terms of
differential changes to their levels of expression, depending on
whether the cell expressing that gene is neoplastic or not. It
should be understood that reference to a gene "expression product"
or "expression of a gene" is a reference to either a transcription
product (such as primary RNA or mRNA) or a translation product such
as protein. These genes and their expression products, whether they
be RNA transcripts or encoded proteins, are collectively referred
to as "neoplastic markers".
[0081] Accordingly, one aspect of the present invention is directed
to a method of screening for the onset or predisposition to the
onset of a large intestine neoplasm in an individual, said method
comprising measuring the level of expression of one or more genes
or transcripts selected from:
TABLE-US-00013 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 201328_at 221577_x_at 205828_at 201341_at
221922_at 205886_at 201416_at 60474_at 205890_s_at 201417_at
222696_at 205910_s_at 201468_s_at 223447_at 205941_s_at 201506_at
223970_at 206224_at 201563_at 225541_at 206976_s_at 201656_at
225835_at 207173_x_at 201925_s_at 226360_at 207457_s_at 201926_s_at
227174_at 208079_s_at 202286_s_at 227475_at 208712_at 202718_at
228303_at 209218_at 202831_at 228653_at 209309_at 202833_s_at
228754_at 209752_at 202935_s_at 228915_at 209773_s_at 202936_s_at
229215_at 209774_x_at 203124_s_at 231832_at 209792_s_at 203256_at
231941_s_at 209875_s_at 203313_s_at 232176_at 209955_s_at 203510_at
232252_at 210052_s_at 203860_at 232481_s_at 210511_s_at 203895_at
234331_s_at 210559_s_at 203896_s_at 235210_s_at 210766_s_at
203961_at 235976_at 211506_s_at 203962_s_at 236894_at 212281_s_at
204259_at 238017_at 212344_at 204351_at 238021_s_at 212353_at
204401_at 238984_at 212354_at 204404_at 241031_at 213905_x_at
204855_at 200660_at 214022_s_at 204885_s_at 200832_s_at 214974_x_at
205174_s_at 200903_s_at 215091_s_at 205366_s_at 201014_s_at
217430_x_at 205470_s_at 201112_s_at 217996_at 205513_at 201195_s_at
218507_at 205765_at 201261_x_at 218963_s_at 205825_at 201292_at
218984_at 205927_s_at 201338_x_at 219787_s_at 205983_at 201479_at
219911_s_at 206239_s_at 201577_at 221729_at 206286_s_at 201601_x_at
221730_at 207158_at 201666_at 221731_x_at 207850_at 202310_s_at
221923_s_at 209369_at 202311_s_at 37892_at 210445_at 202404_s_at
222449_at 210519_s_at 202431_s_at 222450_at 211429_s_at 202504_at
222549_at 212063_at 202779_s_at 222608_s_at 212070_at 202859_x_at
223062_s_at 212190_at 202954_at 224428_s_at 212531_at 202998_s_at
224646_x_at 212942_s_at 203083_at 224915_x_at 213880_at 203213_at
225295_at 213975_s_at 203878_s_at 225520_at 214235_at 204051_s_at
225664_at 214651_s_at 204127_at 225681_at 217523_at 204170_s_at
225767_at 217867_x_at 204320_at 225799_at 218086_at 204470_at
225806_at 218211_s_at 204475_at 226227_x_at 218704_at 204580_at
226237_at 218796_at 204620_s_at 226311_at 218872_at 204702_s_at
226777_at 219630_at 205361_s_at 226835_s_at 219682_s_at 205476_at
227140_at 219727_at 205479_s_at 229802_at 219955_at 205713_s_at
231766_s_at 219956_at 205815_at 232151_at; and/or 200665_s_at (ii)
CTHRC1 CDCA7 LOXL2 FOXQ1 RNF43 TDGF1 AZGP1 MMP1 CCL20 MTHFD1L MYC
TCN1 CTSE ANLN COMP MMP7 MSLN H19 AURKA WDR72 TIMP1 FAP PAICS INHBA
PCSK1 DACH1 PUS7 COL11A1 CST1 VCAN ZNRF3 GDF15 BGN SQLE CCND1
COL1A1 AXIN2 REG3A CSE1L LGR5 MET TESC PFDN4 DUSP27 SOX9 UBE2C
C20orf42 SERPINB5 TMEPAI TMEM97 SLC11A2 ASCL2 CDH11 TRIM29 NFE2L3
SULF1 MMP11 KLK11 CEL SLC6A6 CXCL1 LY6G6D NLF1 TACSTD2 QPCT SLC7A5
NPDC1 NEBL PDZK1IP1 FABP6 ENC1 PCCA CD55 SLITRK6 SERPINE2 FLJ37644
ECT2 MLPH UBE2S KRT23 COL12A1 HOXA9 TOP2A CXCL3 L1TD1 TBX3 CDC2
MMP3 WDR51B BACE2 RFC3 SFRP4 HOXB6 GPX2 LILRB1 UBD FAM84A TPX2 NPM1
SCD COL5A2 KCNN4 RDHE2 DPEP1 MMP12 LOC541471 PLAU LCN2 SORD CYP3A5
HSPH1 PLCB4 PSAT1 ANXA3 GTF3A SPINK1 CXCL5 CYP3A5P2 KLK10 DUOX2
IGFBP2 C14orf94 GPSM2 SOX4 TGIF1 RP5-875H10.1 NME1 THBS2 CXCL2
RPL22L1 MUC20 CLDN1 SLCO4A1 APOBEC1 RPESP REG1B CKS2 HIG2 RRM2 CDH3
PHLDA1 COL10A1 DKC1 SPARC SERPINA1 AHCY CD44 COL1A2 IL8
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a neoplastic large
intestine cell or a cell predisposed to the onset of a neoplastic
state.
[0082] Reference to "large intestine" should be understood as a
reference to a cell derived from one of the six anatomical regions
of the large intestine, which regions commence after the terminal
region of the ileum, these being: [0083] (i) the cecum; [0084] (ii)
the ascending colon; [0085] (iii) the transverse colon; [0086] (iv)
the descending colon; [0087] (v) the sigmoid colon; and [0088] (vi)
the rectum.
[0089] Reference to "neoplasm" should be understood as a reference
to a lesion, tumour or other encapsulated or unencapsulated mass or
other form of growth which comprises neoplastic cells. A
"neoplastic cell" should be understood as a reference to a cell
exhibiting abnormal growth. The term "growth" should be understood
in its broadest sense and includes reference to proliferation. In
this regard, an example of abnormal cell growth is the uncontrolled
proliferation of a cell. Another example is failed apoptosis in a
cell, thus prolonging its usual life span. The neoplastic cell may
be a benign cell or a malignant cell. In a preferred embodiment,
the subject neoplasm is an adenoma or an adenocarcinoma. Without
limiting the present invention to any one theory or mode of action,
an adenoma is generally a benign tumour of epithelial origin which
is either derived from epithelial tissue or exhibits clearly
defined epithelial structures. These structures may take on a
glandular appearance. It can comprise a malignant cell population
within the adenoma, such as occurs with the progression of a benign
adenoma to a malignant adenocarcinoma.
[0090] Preferably, said neoplastic cell is an adenoma or
adenocarcinoma and even more preferably a colorectal adenoma or
adenocarcinoma.
[0091] Each of the genes and transcripts detailed in sub-paragraphs
(i) and (ii), above, would be well known to the person of skill in
the art, as would their encoded proteins. The identification of the
expression products of these genes and transcripts as markers of
neoplasia occurred by virtue of differential expression analysis
using Affymetrix HGU133A or HGU133B gene chips. To this end, each
gene chip is characterised by approximately 45,000 probe sets which
detect the RNA transcribed from the genome. On average,
approximately 11 probe pairs detect overlapping or consecutive
regions of the RNA transcript. In general, the genes from which the
RNA transcripts described herein are identified by the Affymetrix
probesets are well known and characterised genes. However, to the
extent that some of the probesets detect RNA transcripts which are
not yet defined, these transcripts are indicated as "the gene,
genes or transcripts detected by Affymetrix probe x". In some cases
a number of genes and/or transcripts may be detectable by a single
probeset. It should be understood, however, that this is not
intended as a limitation as to how the expression level of the
subject gene or transcript can be detected. In the first instance,
it would be understood that the subject gene transcript is also
detectable by other probesets which would be present on the
Affymetrix gene chip. The reference to a single probesets is merely
included as an identifier of the gene transcript of interest. In
terms of actually screening for the transcript, however, one may
utilise a probe or probeset directed to any region of the
transcript and not just to the 3' terminal 600 bp transcript region
to which the Affymetrix probesets are often directed.
[0092] Reference to each of the genes and transcripts detailed
above and their transcribed and translated expression products
should therefore be understood as a reference to all forms of these
molecules and to fragments or variants thereof. As would be
appreciated by the person of skill in the art, some genes are known
to exhibit allelic variation between individuals. Accordingly, the
present invention should be understood to extend to such variants
which, in terms of the present diagnostic applications, achieve the
same outcome despite the fact that minor genetic variants between
the actual nucleic acid sequences may exist between individuals or
that within one individual there may exist two or more splice
variants of one subject gene. The present invention should
therefore be understood to extend to all forms of RNA (eg mRNA,
primary RNA transcript, miRNA, etc), cDNA and peptide isoforms
which arise from alternative splicing or any other mutation,
polymorphic or allelic variation. It should also be understood to
include reference to any subunit polypeptides such as precursor
forms which may be generated, whether existing as a monomer,
multimer, fusion protein or other complex.
[0093] For example, in one embodiment of the invention, the subject
gene is CDH3. Analysis of the AceView Database reveals that there
exist 12 CDH3 alternative mRNA transcripts. Nine are generated by
alternative splicing while three are unspliced forms. In terms of
the genes encompassed by the present invention, means for
determining the existence of such variants and characterising same,
are described in Example 6. To the extent that the genes of the
present invention are described by reference to an Affymetrix
probeset, Table 9 provides details of the nucleic acid sequence to
which each probeset is directed. Based on this information, the
skilled person could, as a matter of routine procedure, identify
the gene in respect of which that sequence forms part. A typical
protocol for doing this is also outlined in Example 6.
[0094] It should be understood that the "individual" who is the
subject of testing may be any human or non-human mammal. Examples
of non-human mammals includes primates, livestock animals (e.g.
horses, cattle, sheep, pigs, donkeys), laboratory test animals
(e.g. mice, rats, rabbits, guinea pigs), companion animals (e.g.
dogs, cats) and captive wild animals (e.g. deer, foxes). Preferably
the mammal is a human.
[0095] The method of the present invention is predicated on the
comparison of the level of the neoplastic markers of a biological
sample with the control levels of these markers. The "control
level" may be either a "normal level", which is the level of marker
expressed by a corresponding large intestine cell or cellular
population which is not neoplastic, or the background level which
is detectable in a negative control sample.
[0096] The normal (or "non-neoplastic") level may be determined
using tissues derived from the same individual who is the subject
of testing. However, it would be appreciated that this may be quite
invasive for the individual concerned and it is therefore likely to
be more convenient to analyse the test results relative to a
standard result which reflects individual or collective results
obtained from individuals other than the patient in issue. This
latter form of analysis is in fact the preferred method of analysis
since it enables the design of kits which require the collection
and analysis of a single biological sample, being a test sample of
interest. The standard results which provide the normal level may
be calculated by any suitable means which would be well known to
the person of skill in the art. For example, a population of normal
tissues can be assessed in terms of the level of the neoplastic
markers of the present invention, thereby providing a standard
value or range of values against which all future test samples are
analysed. It should also be understood that the normal level may be
determined from the subjects of a specific cohort and for use with
respect to test samples derived from that cohort. Accordingly,
there may be determined a number of standard values or ranges which
correspond to cohorts which differ in respect of characteristics
such as age, gender, ethnicity or health status. Said "normal
level" may be a discrete level or a range of levels. An increase in
the expression level of the subject genes relative to normal levels
is indicative of the tissue being neoplastic.
[0097] Without limiting the present invention to any one theory or
mode of action, although each of the genes hereinbefore described
is differentially expressed, either singly or in combination, as
between neoplastic versus non-neoplastic cells of the large
intestine, and is therefore diagnostic of the existence of a large
intestine neoplasm, the expression of some of these genes was found
to exhibit particularly significant levels of sensitivity,
specificity and positive and negative predictive value.
Accordingly, in a preferred embodiment one would screen for and
assess the expression level of one or more of these genes. To this
end, and without limiting the present invention to any one theory
or mode of action, the following markers were determined to be
expressed in neoplastic tissue at a level of 3, 4, 5 or 7 fold
greater than non-neoplastic tissue when assessed by virtue of the
method exemplified herein.
TABLE-US-00014 Gene, genes or transcripts detected Fold Increase by
Affymetrix Probe No: Gene 7 225681_at CTHRC1 227140_at 5 227475_at
FOXQ1 204475_at MMP1 202859_x_at IL8 202404_s_at COL1A2 4 205513_at
TCN1 204259_at MMP7 227174_at WDR72 210511_s_at INHBA 37892_at
COL11A1 3 221577_x_at GDF15 202310_s_at COL1A1 213880_at LGR5
232252_at DUSP27 204855_at SERPINB5 229215_at ASCL2 212354_at SULF1
228754_at SLC6A6 202286_s_at TACSTD2 203962_s_at NEBL 203860_at
PCCA 202935_s_at FLJ37644 218963_s_at KRT23 207850_at CXCL3
205828_at MMP3 204051_s_at SFRP4 205890_s_at UBD 200832_s_at SCD
205983_at DPEP1 212531_at LCN2
[0098] There is therefore more particularly provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from: [0099] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0100] 225681_at;
227140_at; and/or [0101] (ii) CTHRC1 in a biological sample from
said individual wherein a higher level of expression of the genes
or transcripts of group (i) and/or group (ii) relative to control
levels is indicative of a neoplastic large intestine cell or a cell
predisposed to the onset of a neoplastic state.
[0102] Preferably, said control level is a non-neoplastic
level.
[0103] In another embodiment, there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from: [0104] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0105] 227475_at,
204475_at, 202859_x_at, 202404_s_at; and/or [0106] (ii) FOXQ1,
MMP1, IL8, COL1A2 in a biological sample from said individual
wherein a higher level of expression of the genes or transcripts of
group (i) and/or group (ii) relative to control levels is
indicative of a neoplastic large intestine cell or a cell
predisposed to the onset of a neoplastic state.
[0107] Preferably, said control level is a non-neoplastic
level.
[0108] In yet another embodiment there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from: [0109] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0110] 205513_at,
204259_at, 227174_at, 210511_s_at, 37892_at; and/or [0111] (ii)
TCN1, MMP1, WDR72, INHBA, COL11A1 in a biological sample from said
individual wherein a higher level of expression of the genes or
transcripts of group (i) and/or group (ii) relative to control
levels is indicative of a neoplastic large intestine cell or a cell
predisposed to the onset of a neoplastic state.
[0112] Preferably, said control level is a non-neoplastic
level.
[0113] In still yet another preferred embodiment, there is provided
a method of screening for the onset or predisposition to the onset
of a large intestine neoplasm in an individual, said method
comprising measuring the level of expression of one or more genes
or transcripts selected from:
TABLE-US-00015 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 221577_x_at 232252_at 202310_s_at
213880_at 212354_at 204855_at 229215_at 203962_s_at 228754_at
202286_s_at 218963_s_at 203860_at 202935_s_at 204051_s_at 207850_at
205828_at 205983_at 205890_s_at 200832_s_at 212531_at; and/or (ii)
LGR5 GDF15 COL1A1 ASCL2 DUSP27 SERPINB5 TACSTD2 SULF1 SLC6A6
FLJ37644 NEBL PCCA MMP3 KRT23 CXCL3 SCD SFRP4 UBD DPEP1 LCN2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a neoplastic large
intestine cell or a cell predisposed to the onset of a neoplastic
state.
[0114] Preferably, said control level is a non-neoplastic
level.
[0115] According to these aspects of the present invention, said
large intestine tissue is preferably colorectal tissue.
[0116] The detection method of the present invention can be
performed on any suitable biological sample. To this end, reference
to a "biological sample" should be understood as a reference to any
sample of biological material derived from an animal such as, but
not limited to, cellular material, biofluids (eg. blood), faeces,
tissue biopsy specimens, surgical specimens or fluid which has been
introduced into the body of an animal and subsequently removed
(such as, for example, the solution retrieved from an enema wash).
The biological sample which is tested according to the method of
the present invention may be tested directly or may require some
form of treatment prior to testing. For example, a biopsy or
surgical sample may require homogenisation prior to testing or it
may require sectioning for in situ testing of the qualitative
expression levels of individual genes. Alternatively, a cell sample
may require permeabilisation prior to testing. Further, to the
extent that the biological sample is not in liquid form, (if such
form is required for testing) it may require the addition of a
reagent, such as a buffer, to mobilise the sample.
[0117] To the extent that the neoplastic marker gene expression
product is present in a biological sample, the biological sample
may be directly tested or else all or some of the nucleic acid or
protein material present in the biological sample may be isolated
prior to testing. In yet another example, the sample may be
partially purified or otherwise enriched prior to analysis. For
example, to the extent that a biological sample comprises a very
diverse cell population, it may be desirable to enrich for a
sub-population of particular interest. It is within the scope of
the present invention for the target cell population or molecules
derived therefrom to be treated prior to testing, for example,
inactivation of live virus or being run on a gel. It should also be
understood that the biological sample may be freshly harvested or
it may have been stored (for example by freezing) prior to testing
or otherwise treated prior to testing (such as by undergoing
culturing).
[0118] The choice of what type of sample is most suitable for
testing in accordance with the method disclosed herein will be
dependent on the nature of the situation. Preferably, said sample
is a faecal (stool) sample, enema wash, surgical resection, tissue
biopsy or blood sample.
[0119] In a related aspect, it has been determined that certain of
the markers hereinbefore defined are more indicative of adenoma
development versus cancer development or vice versa. This is an
extremely valuable finding since it enables one to more
specifically characterise the likely nature of a neoplasm which is
detected by virtue of the method of the present invention.
[0120] Accordingly, in a related aspect the present invention is
directed to a method of screening for the onset or predisposition
to the onset of a large intestine neoplasm in an individual, said
method comprising measuring the level of expression of one or more
genes or transcripts selected from:
TABLE-US-00016 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 201328_at 205825_at 219956_at 201468_s_at
205927_s_at 221922_at 201656_at 206239_s_at 223447_at 201925_s_at
207158_at 223970_at 201926_s_at 210445_at 225835_at 202718_at
210519_s_at 226360_at 202831_at 211429_s_at 228303_at 202833_s_at
212063_at 228653_at 203124_s_at 213975_s_at 228915_at 203313_s_at
214235_at 231832_at 203860_at 214651_s_at 231941_s_at 203895_at
217523_at 232176_at 203896_s_at 217867_x_at 232481_s_at 204401_at
218086_at 234331_s_at 204885_s_at 218211_s_at 235210_s_at
205174_s_at 218796_at 235976_at 205366_s_at 219630_at 236894_at
205470_s_at 219682_s_at 238017_at 205513_at 219727_at 238984_at
205765_at 219955_at; 241031_at; and/or (ii) APOBEC1 HOXB6 QPCT
BACE2 IGFBP2 RDHE2 C20orf42 ITGA6 REG4 CD44 KCNN4 RETNLB CD55 KLK11
RP5-875H10.1 CTSE L1TD1 RPESP CYP3A5 LILRB1 SERPINA1 CYP3A5P2 MLPH
SLC11A2 DACH1 MSLN SLC12A2 DUOX2 MUC20 SLITRK6 ETS2 NLF1 SPINK1
FABP6 NPDC1 TBX3 FAM84A NQO1 TCN1 GALNT6 PCCA TGIF1 GPSM2 PCSK1
WDR51B GPX2 PDZK1IP1 ZNRF3 HOXA9 PLCB4
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of an adenoma cell or
a cell predisposed to the onset of an adenoma state.
[0121] In another preferred embodiment of this aspect of the
present invention there is provided a method of screening for the
onset or predisposition to the onset of a large intestine neoplasm
in an individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00017 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 200660_at 205476_at 217430_x_at
200665_s_at 205479_s_at 217996_at 200832_s_at 205713_s_at 218507_at
200903_s_at 205815_at 218963_s_at 201014_s_at 205828_at 218984_at
201112_s_at 205886_at 219787_s_at 201195_s_at 205890_s_at
219911_s_at 201261_x_at 205910_s_at 221729_at 201292_at 205941_s_at
221730_at 201338_x_at 206224_at 221731_x_at 201479_at 206976_s_at
221923_s_at 201577_at 207173_x_at 37892_at 201601_x_at 207457_s_at
222449_at 201666_at 208079_s_at 222450_at 202310_s_at 208712_at
222549_at 202311_s_at 209218_at 222608_s_at 202403_s_at 209309_at
223062_s_at 202404_s_at 209752_at 224428_s_at 202431_s_at
209773_s_at 224646_x_at 202504_at 209774_x_at 224915_x_at
202779_s_at 209792_s_at 225295_at 202859_x_at 209875_s_at 225520_at
202954_at 209955_s_at 225664_at 202998_s_at 210052_s_at 225681_at
203083_at 210511_s_at 225767_at 203213_at 210559_s_at 225799_at
203878_s_at 210766_s_at 225806_at 204051_s_at 211506_s_at
226227_x_at 204127_at 212281_s_at 226237_at 204170_s_at 212344_at
226311_at 204320_at 212353_at 226777_at 204470_at 212354_at
226835_s_at 204475_at 213905_x_at 227140_at 204580_at 214022_s_at
229802_at 204620_s_at 214974_x_at 231766_s_at 204702_s_at
215091_s_at; 232151_at; and/or 205361_s_at (ii) AHCY DKC1 PSAT1
ANLN ECT2 PUS7 AURKA FAP REG1A AZGP1 GTF3A REG1B BGN H19 REG3A
C14orf94 HIG2 RFC3 C20orf199 HSPH1 RRM2 CCL20 IFITM1 S100A11 CCND1
IL8 SCD CDC2 INHBA SFRP4 CDCA7 KLK10 SLC39A10 CDH11 KRT23 SLC7A5
CEL LOC541471 SLCO4A1 CKS2 LOXL2 SPARC CLDN1 LY6G6D SPP1 COL10A1
MMP1 SQLE COL11A1 MMP11 SULF1 COL12A1 MMP12 THBS2 COL1A1 MMP3 TIMP1
COL1A2 MTHFD1L TMEM97 COL5A2 MYC TMEPAI COL8A1 NFE2L3 TOP2A COMP
NME1 TPX2 CSE1L NPM1 TRIM29 CST1 PAICS UBD CTHRC1 PFDN4 UBE2C CXCL1
PHLDA1 UBE2S CXCL2 PLAU VCAN CXCL5
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to control levels is indicative of a cancer cell or a
cell predisposed to the onset of a cancerous state.
[0122] According to these aspects, said control levels are
preferably non-neoplastic levels and said large intestine tissue is
colorectal tissue. Even more preferably, said biological sample is
a stool sample or blood sample.
[0123] In a related aspect, it has been determined that a
subpopulation of the markers of the present invention are not only
expressed at levels higher than normal levels, their expression
pattern is uniquely characterised by the fact that expression
levels above that of background control levels are not detectable
in non-neoplastic tissue. This determination has therefore enabled
the development of qualitative screening systems which are simply
designed to detect marker expression relative to a control
background level. In accordance with this aspect of the present
invention, said "control level" is therefore the "background
level". Preferably, said background level is of the chosen testing
methodology.
[0124] According to this aspect, there is therefore provided a
method of screening for the onset or predisposition to the onset of
a large intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00018 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 202286_s_at 235976_at 209309_at 204259_at
236894_at 211506_s_at 204885_s_at 214974_x_at 205174_s_at 238984_at
219787_s_at 205825_at 241031_at 37892_at 207850_at 202311_s_at
222608_s_at 213880_at 204320_at 223062_s_at 217523_at 204475_at
225806_at 227174_at 204702_s_at 226237_at 228915_at 205910_s_at
227140_at 232252_at 206224_at 229802_at; and/or (ii) MMP1 PCSK1
ANLN MMP7 CST1 DACH1 LGR5 QPCT COL11A1 WDR72 ECT2 C14orf94 COL11A1
SLITRK6 AZGP1 COL1A1 L1TD1 REG4 DUSP27 KIAA1199 NFE2L3 NLF1 PSAT1
CEL IL8 CXCL5 CD44 TACSTD2 CXCL3 COL8A1 MSLN
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of a neoplastic
cell or a cell predisposed to the onset of a neoplastic state.
[0125] In a most preferred embodiment, said genes or transcripts
are selected from:
TABLE-US-00019 (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: 227140_at 227174_at 241031_at 204475_at
37892_at 211506_s_at 204259_at 202311_s_at 202286_s_at 213880_at
232252_at 226237_at; and/or (ii) MMP1 COL11A1 IL8 MMP7 COL1A1
TACSTD2 LGR5 DUSP27 COL8A1 WDR72 NLF1
[0126] Preferably, said neoplasm is an adenoma or an adenocarcinoma
and said gastrointestinal tissue is colorectal tissue.
[0127] In yet another embodiment, it has been determined that a
further subpopulation of these markers are more characteristic of
adenoma development, while others are more characteristic of cancer
development. Accordingly, there is provided a convenient means of
qualitatively obtaining indicative information in relation to the
characteristics of the subject neoplasm.
[0128] According to this embodiment there is provided a method of
screening for the onset or predisposition to the onset of a large
intestine neoplasm in an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00020 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 204885_s_at 217523_at 236894_at
205174_s_at 228915_at 238984_at 205825_at 235976_at 241031_at;
and/or (ii) CD44 MSLN QPCT DACH1 NLF1 REG4 L1TD1 PCSK1 SLITRK6
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of an adenoma cell
or a cell predisposed to the onset of an adenoma state.
[0129] In yet still another preferred embodiment there is provided
a method of screening for the onset or predisposition to the onset
of a large intestine neoplasm in an individual, said method
comprising measuring the level of expression of one or more genes
or transcripts selected from:
TABLE-US-00021 the gene or genes detected by Affymetrix probeset
IDs: (i) 202311_s_at 209309_at 223062_s_at 204320_at 211506_s_at
225806_at 204475_at 214974_x_at 226237_at 204702_s_at 219787_s_at
227140_at 205910_s_at 37892_at 229802_at; and/or 206224_at
222608_s_at (ii) ANLN COL1A1 IL8 AZGP1 COL8A1 MMP1 C14orf94 CST1
NFE2L3 CEL CXCL5 PSAT1 COL11A1 ECT2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to background levels is indicative of a cancer cell
or a cell predisposed to the onset of a cancerous state.
[0130] Preferably, said large intestine tissue is colorectal
tissue.
[0131] More preferably, said biological sample is a blood sample or
stool sample.
[0132] As detailed hereinbefore, the present invention is designed
to screen for a neoplastic cell or cellular population, which is
located in the large intestine. Accordingly, reference to "cell or
cellular population" should be understood as a reference to an
individual cell or a group of cells. Said group of cells may be a
diffuse population of cells, a cell suspension, an encapsulated
population of cells or a population of cells which take the form of
tissue.
[0133] Reference to "expression" should be understood as a
reference to the transcription and/or translation of a nucleic acid
molecule. In this regard, the present invention is exemplified with
respect to screening for neoplastic marker expression products
taking the form of RNA transcripts (eg primary RNA or mRNA).
Reference to "RNA" should be understood to encompass reference to
any form of RNA, such as primary RNA or mRNA. Without limiting the
present invention in any way, the modulation of gene transcription
leading to increased or decreased RNA synthesis will also correlate
with the translation of some of these RNA transcripts (such as
mRNA) to produce a protein product. Accordingly, the present
invention also extends to detection methodology which is directed
to screening for modulated levels or patterns of the neoplastic
marker protein products as an indicator of the neoplastic state of
a cell or cellular population. Although one method is to screen for
mRNA transcripts and/or the corresponding protein product, it
should be understood that the present invention is not limited in
this regard and extends to screening for any other form of
neoplastic marker expression product such as, for example, a
primary RNA transcript. It is well within the skill of the person
of skill in the art to determine the most appropriate screening
target for any given situation. To this end, the genes which are
known to encode an expression product which is either secreted by
the cell or membrane bound is detailed in the table, below. It
would be appreciated that screening for neoplastic markers which
are secreted or membrane bound may provide particular advantages in
terms of the design of a diagnostic screening product.
TABLE-US-00022 The gene or genes detected by Affymetrix probe Nos:
200600_at 203961_at 212077_at 224724_at 200832_s_at 203962_s_at
212281_s_at 224915_x_at 200903_s_at 204006_s_at 212344_at 225295_at
200974_at 204122_at 212353_at 225520_at 201058_s_at 204127_at
212354_at 225541_at 201069_at 204170_s_at 212942_s_at 225664_at
201105_at 204320_at 213125_at 225710_at 201112_s_at 204351_at
213524_s_at 225767_at 201195_s_at 204401_at 213869_x_at 225799_at
201328_at 204404_at 213880_at 225806_at 201341_at 204702_s_at
214022_s_at 225835_at 201416_at 204885_s_at 214235_at 226227_x_at
201417_at 205361_s_at 214651_s_at 226311_at 201426_s_at 205366_s_at
215049_x_at 226360_at 201468_s_at 205547_s_at 217523_at 226694_at
201479_at 205765_at 217762_s_at 226777_at 201563_at 205825_at
217763_s_at 226835_s_at 201601_x_at 205890_s_at 217764_s_at
227099_s_at 201616_s_at 205927_s_at 217867_x_at 227140_at 201656_at
205941_s_at 217996_at 227174_at 201667_at 205983_at 218086_at
227475_at 201925_s_at 206286_s_at 218211_s_at 227566_at 201926_s_at
206976_s_at 218559_s_at 228303_at 202237_at 207158_at 218704_at
228653_at 202238_s_at 207173_x_at 218796_at 228754_at 202286_s_at
207191_s_at 218872_at 228915_at 202431_s_at 208079_s_at 218963_s_at
229215_at 202450_s_at 208712_at 218984_at 229802_at 202504_at
208782_at 219630_at 231766_s_at 202620_s_at 208788_at 219682_s_at
231832_at 202779_s_at 208850_s_at 219727_at 231879_at 202831_at
208851_s_at 219787_s_at 232151_at 202878_s_at 209156_s_at
219911_s_at 232176_at 202917_s_at 209218_at 219955_at 232252_at
202935_s_at 209369_at 219956_at 232481_s_at 202936_s_at 209596_at
221011_s_at 233555_s_at 202954_at 209773_s_at 221922_at 234331_s_at
203124_s_at 209955_s_at 221923_s_at 234994_at 203213_at 210052_s_at
222449_at 235210_s_at 203256_at 210445_at 222450_at 235976_at
203313_s_at 210519_s_at 222549_at 236894_at 203382_s_at 210559_s_at
222608_s_at 238017_at 203645_s_at 210766_s_at 223062_s_at 241031_at
203860_at 211964_at 223235_s_at 37892_at 203878_s_at 211966_at
224428_s_at 60474_at 203895_at 212063_at 224646_x_at S100A11
203896_s_at 212070_at 224694_at S100A8 ACTA2 DUOX2 LOC541471 S100P
AHCY DUSP27 MAFB SCD ANLN ECT2 MLPH SLC11A2 ANTXR1 ELOVL5 MMP11
SLC12A2 ANXA3 ENC1 MMP2 SLC39A10 APOBEC1 ETS2 MSLN SLC6A6 APOE
FABP6 MSN SLC7A5 ASCL2 FAM84A MTHFD1L SLCO4A1 AURKA FAP MXRA5
SLITRK6 BACE2 FCGR3B MYC SMOC2 C14orf94 FLJ37644 MYL9 SORD
C20orf199 FOXQ1 NEBL SOX4 C20orf42 FSTL1 NFE2L3 SOX9 CALD1 G0S2
NLF1 SQLE CCND1 GALNT6 NNMT SULF1 CD163 GJA1 NPDC1 SULF2 CD44 GPR56
NPM1 TACSTD2 CD55 GPSM2 NQO1 TAGLN CD93 GPX2 OLFML2B TBX3 CDC2 H19
PALM2- TDGF1 CDCA7 HNT AKAP2 TESC CDH11 HOXA9 PCCA TGIF1 CDH3 HOXB6
PCSK1 THY1 CKS2 HSPH1 PDZK1IP1 TMEM97 CLDN1 IFITM1 PFDN4 TMEPAI
COL10A1 ISLR PHLDA1 TPX2 COL11A1 ITGA6 PLCB4 TRIM29 COL12A1 KCNN4
PLOD2 TYROBP COL4A2 KIAA1199 PSAT1 UBD COL6A2 KIAA1913 PUS7 UBE2C
CSE1L KRT23 RAB31 UBE2S CTSE L1TD1 RDHE2 VIM CTSK LBH RFC3 WDR51B
CYP3A5 LGALS1 RNF43 WDR72 CYP3A5P2 LGR5 RP5-875H10.1 ZNRF3 DACH1
LOC387763 RPESP DKC1 RPL22L1 DPEP1 RRM2
[0134] Reference to "nucleic acid molecule" should be understood as
a reference to both deoxyribonucleic acid molecules and ribonucleic
acid molecules and fragments thereof. The present invention
therefore extends to both directly screening for mRNA levels in a
biological sample or screening for the complementary cDNA which has
been reverse-transcribed from an mRNA population of interest. It is
well within the skill of the person of skill in the art to design
methodology directed to screening for either DNA or RNA. As
detailed above, the method of the present invention also extends to
screening for the protein product translated from the subject
mRNA.
[0135] Preferably, the level of gene expression is measured by
reference to genes which encode a protein product and, more
particularly, said level of expression is measured at the protein
level. Accordingly, to the extent that the present invention is
directed to screening for markers which are detailed in the
preceding table, said screening is preferably directed to the
encoded protein.
[0136] As detailed hereinbefore, it should be understood that
although the present invention is exemplified with respect to the
detection of expressed nucleic acid molecules (e.g. mRNA), it also
encompasses methods of detection based on screening for the protein
product of the subject genes. The present invention should also be
understood to encompass methods of detection based on identifying
both proteins and/or nucleic acid molecules in one or more
biological samples. This may be of particular significance to the
extent that some of the neoplastic markers of interest may
correspond to genes or gene fragments which do not encode a protein
product. Accordingly, to the extent that this occurs it would not
be possible to test for a protein and the subject marker would have
to be assessed on the basis of transcription expression
profiles.
[0137] In terms of screening for the upregulation of expression of
a marker it would also be well known to the person of skill in the
art that changes which are detectable at the DNA level are
indicative of changes to gene expression activity and therefore
changes to expression product levels. Such changes include but are
not limited to, changes to DNA methylation. Accordingly, reference
herein to "screening the level of expression" and comparison of
these "levels of expression" to control "levels of expression"
should be understood as a reference to assessing DNA factors which
are related to transcription, such as gene/DNA methylation
patterns.
[0138] The term "protein" should be understood to encompass
peptides, polypeptides and proteins (including protein fragments).
The protein may be glycosylated or unglycosylated and/or may
contain a range of other molecules fused, linked, bound or
otherwise associated to the protein such as amino acids, lipids,
carbohydrates or other peptides, polypeptides or proteins.
Reference herein to a "protein" includes a protein comprising a
sequence of amino acids as well as a protein associated with other
molecules such as amino acids, lipids, carbohydrates or other
peptides, polypeptides or proteins.
[0139] The proteins encoded by the neoplastic markers of the
present invention may be in multimeric form meaning that two or
more molecules are associated together. Where the same protein
molecules are associated together, the complex is a homomultimer.
An example of a homomultimer is a homodimer. Where at least one
marker protein is associated with at least one non-marker protein,
then the complex is a heteromultimer such as a heterodimer.
[0140] Reference to a "fragment" should be understood as a
reference to a portion of the subject nucleic acid molecule or
protein. This is particularly relevant with respect to screening
for modulated RNA levels in stool samples since the subject RNA is
likely to have been degraded or otherwise fragmented due to the
environment of the gut. One may therefore actually be detecting
fragments of the subject RNA molecule, which fragments are
identified by virtue of the use of a suitably specific probe.
[0141] Reference to the "onset" of a neoplasm, such as adenoma or
adenocarcinoma, should be understood as a reference to one or more
cells of that individual exhibiting dysplasia. In this regard, the
adenoma or adenocarcinoma may be well developed in that a mass of
dysplastic cells has developed. Alternatively, the adenoma or
adenocarcinoma may be at a very early stage in that only relatively
few abnormal cell divisions have occurred at the time of diagnosis.
The present invention also extends to the assessment of an
individual's predisposition to the development of a neoplasm, such
as an adenoma or adenocarcinoma. Without limiting the present
invention in any way, changed levels of the neoplastic markers may
be indicative of that individual's predisposition to developing a
neoplasia, such as the future development of an adenoma or
adenocarcinoma or another adenoma or adenocarcinoma.
[0142] In yet another related aspect of the present invention,
markers have been identified which enable the characterisation of
neoplastic tissue of the large intestine in terms of whether it is
an adenoma or a cancer. This development now provides a simple yet
accurate means of characterising tissue using means other than the
traditional methods which are currently utilised.
[0143] According to this aspect of the present invention, there is
provided a method of characterising a neoplastic cell or cellular
population, which cell or cellular population is derived from the
large intestine of an individual, said method comprising measuring
the level of expression of one or more genes or transcripts
selected from:
TABLE-US-00023 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 200884_at 214234_s_at 226248_s_at
203240_at 214235_at 226302_at 203963_at 214433_s_at 227676_at
204508_s_at 215125_s_at 227719_at 204607_at 215867_x_at 227725_at
204811_s_at 217109_at 228232_s_at 204895_x_at 217110_s_at 229070_at
204897_at 218211_s_at 231832_at 205259_at 219543_at 232176_at
205765_at 219955_at 232481_s_at 205927_s_at 221841_s_at 235976_at
208063_s_at 221874_at 236894_at 208937_s_at 223969_s_at 237521_x_at
210107_at 223970_at 242601_at 213106_at; and/or (ii) CLCA1 CTSE
ATP8B1 FCGBP C6orf105 CACNA2D2 HMGCS2 CKB KLF4 RETNLB ATP8A1
CYP3A5P2 L1TD1 MUC4 CAPN9 SLITRK6 UGT1A1 NR3C2 VSIG2 SELENBP1 PBLD
LOC253012 PTGER4 CA12 ST6GALNAC1 MLPH WDR51B ID1 KIAA1324 FAM3D
CYP3A5
in said cell or cellular population wherein a higher level of
expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal cancer cell level is indicative
of an adenoma cell or a cell predisposed to the onset of an adenoma
state.
[0144] In another aspect there is provided a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00024 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 200600_at 204006_s_at 213428_s_at
200665_s_at 204051_s_at 213524_s_at 200832_s_at 204122_at
213869_x_at 200974_at 204320_at 213905_x_at 200986_at 204475_at
214247_s_at 201058_s_at 204620_s_at 215049_x_at 201069_at
205479_s_at 215076_s_at 201105_at 205547_s_at 215646_s_at 201141_at
205828_at 216442_x_at 201147_s_at 207173_x_at 217430_x_at
201150_s_at 207191_s_at 217762_s_at 201162_at 208747_s_at
217763_s_at 201163_s_at 208782_at 217764_s_at 201185_at 208788_at
218468_s_at 201261_x_at 208850_s_at 218469_at 201289_at 208851_s_at
218559_s_at 201426_s_at 209101_at 218638_s_at 201438_at 209156_s_at
219087_at 201616_s_at 209218_at 221011_s_at 201645_at 209395_at
221729_at 201667_at 209396_s_at 221730_at 201744_s_at 209596_at
221731_x_at 201792_at 209875_s_at 37892_at 201842_s_at 209955_s_at
223122_s_at 201852_x_at 210095_s_at 223235_s_at 201859_at
210495_x_at 224560_at 201893_x_at 210511_s_at 224694_at 202237_at
210764_s_at 224724_at 202238_s_at 210809_s_at 225664_at 202283_at
211161_s_at 225681_at 202291_s_at 211571_s_at 225710_at 202310_s_at
211719_x_at 225799_at 202311_s_at 211813_x_at 226237_at 202403_s_at
211896_s_at 226311_at 202404_s_at 211959_at 226694_at 202450_s_at
211964_at 226777_at 202620_s_at 211966_at 226930_at 202766_s_at
211980_at 227099_s_at 202859_x_at 211981_at 227140_at 202878_s_at
212077_at 227566_at 202917_s_at 212344_at 229218_at 202998_s_at
212353_at 229802_at 203083_at 212354_at 231579_s_at 203325_s_at
212464_s_at 231766_s_at 203382_s_at 212488_at 231879_at 203477_at
212489_at 232458_at 203570_at 212667_at 233555_s_at 203645_s_at
213125_at 234994_at 203878_s_at; and/or (ii) COL1A2 LGALS1 SRGN
CTHRC1 ELOVL5 LBH FN1 MGP CTGF POSTN MMP2 TNC SPP1 LOXL2 G0S2 MMP1
MYL9 SQLE SPARC DCN EFEMP1 LUM CALD1 APOE GREM1 FBN1 MSN IL8 MMP3
IGFBP3 IGFBP5 IGFBP7 SERPINF1 SFRP2 FSTL1 ISLR SULF1 COL4A2 HNT
ASPN VCAN COL5A1 COL6A3 SMOC2 OLFML2B COL8A1 HTRA1 KIAA1913 COL12A1
CYR61 PALM2-AKAP2 COL5A2 FAP SERPING1 CDH11 VIM TYROBP THBS2 TIMP2
ACTA2 COL15A1 SCD COL3A1 COL11A1 TIMP3 PLOD2 S100A8 AEBP1 MMP11
FNDC1 GJA1 CD163 SFRP4 NNMT FCGR3B INHBA COL1A1 PLAU COL6A2 SULF2
MAFB ANTXR1 COL6A1 LOC541471 GPNMB SPON2 LOC387763 BGN CTSK CHI3L1
TAGLN MXRA5 THY1 COL4A1 C1S LOXL1 RAB31 DKK3 CD93
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal adenoma cell level is
indicative of a cancer or a cell predisposed to the onset of a
cancerous state.
[0145] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0146] Reference to an "adenoma control level" or "cancer control
level" should be understood as a reference to the level of said
gene expression in a population of adenoma or cancer
gastrointestinal cells, respectively. As discussed hereinbefore in
relation to "normal levels", the subject level may be a discrete
level or a range of levels. Accordingly, the definition of "adenoma
control level" or "cancer control level" should be understood to
have a corresponding definition to "normal level", albeit in the
context of the expression of genes by a neoplastic population of
large intestine cells.
[0147] In terms of this aspect of the present invention, the
subject analysis is performed on a population of neoplastic cells.
These cells may be derived in any manner, such as sloughed of
neoplastic cells which have been collected via an enema wash or
from a gastrointestinal sample, such as a stool sample.
Alternatively, the subject cells may have been obtained via a
biopsy or other surgical technique.
[0148] Without limiting this aspect of the invention in any way,
several of the markers of this aspect of the present invention have
been determined to be expressed at particularly significant levels
above those of neoplastic cells. For example, increased expression
levels of 3- and 5-fold have been observed in respect of the
following markers, when assessed by the method exemplified herein,
which are indicative of gastrointestinal adenomas.
TABLE-US-00025 Gene or genes detected by Fold Increase Affymetrix
Probe No: Gene 5 210107_at CLCA1 3 203240_at FCGBP 204607_at HMGCS2
223969_s_at RETNLB 219955_at L1TD1 232481_s_at SLITRK6 228232_s_at
VSIG2 242601_at LOC253012 227725_at ST6GALNAC1
[0149] In another example, increased expression levels of between
3- and 9-fold have been observed in respect of the following
markers which are indicative of gastrointestinal cancers, when
assessed by the method herein exemplified:
TABLE-US-00026 Gene or genes detected by Fold Increase Affymetrix
Probe No: Gene 9 202404_s_at COL1A2 8 225681_at CTHRC1 7
212464_s_at FN1 210809_s_at POSTN 6 209875_s_at SPP1 5 227140_st
MMP1 204475_at 4 200665_s_at SPARC 201744_s_at LUM 218468_s_at
GREM1 202859_x_at IL8 211959_at IGFBP5 3 223122_s_at SFRP2
212353_at SULF1 219087_at ASPN 201438_at COL6A3 226237_at COL8A1
225664_at COL12A1 221730_at COL5A2 207173_x_at CDH11 203083_at
THBS2 203477_at COL15A1 37892_at COL11A1 202917_s_at S100A8
226930_at FNDC1 204051_s_at SFRP4 210511_s_at INHBA 209156_s_at
COL6A2 224694_at ANTXR1 201141_at GPNMB 213905_x_at BGN 205547_s_at
TAGLN
[0150] According to this embodiment, there is therefore provided a
method of characterising a neoplastic cell or cellular population,
which cell or cellular population is derived from the large
intestine of an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from: [0151] (i) the gene or genes detected by Affymetrix probeset
IDs: [0152] 210107_at; and/or [0153] (ii) CLCA1 in a biological
sample from said individual wherein a higher level of expression of
the genes or transcripts of group (i) and/or group (ii) relative to
a gastrointestinal cancer control level is indicative of an adenoma
cell or a cell predisposed to the onset of an adenoma state.
[0154] In another embodiment, there is provided a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00027 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 203240_at 219955_at 242601_at
204607_at 232481_s_at 227725_at 223969_s_at 228232_s_at; and/or
(ii) FCGBP L1TD1 LOC253012 HMGCS2 SLITRK6 ST6GALNAC1 RETNLB
VSIG2
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or group
(ii) relative to a gastrointestinal cancer control level is
indicative of an adenoma cell or a cell predisposed to the onset of
an adenoma state.
[0155] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0156] Still more preferably, said biological sample is a tissue
sample.
[0157] In another preferred embodiment the present invention is
directed to a method of characterising a cell or cellular
population, which cell or cellular population is derived from the
large intestine of an individual, said method comprising measuring
the level of expression of one or more genes or transcripts
selected from:
TABLE-US-00028 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 202404_s_at 210809_s_at 227140_at
225681_at 209875_s_at 204475_at 212464_s_at; and/or (ii) COL1A2 FN1
SPP1 CTHRC1 POSTN MMP1
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to a gastrointestinal adenoma control level is indicative
of a cancer or a cell predisposed to the onset of a cancerous
state.
[0158] In yet another preferred embodiment the present invention is
directed to a method of characterising a cell or cellular
population, which cell or cellular population is derived from the
large intestine of an individual, said method comprising measuring
the level of expression of one or more genes or transcripts
selected from:
TABLE-US-00029 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 200665_s_at 218468_s_at 211959_at
201744_s_at 202859_x_at; and/or (ii) SPARC GREM1 IGFBP5 LUM IL8
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to a gastrointestinal adenoma control level is indicative
of a cancer or a cell predisposed to the onset of a cancerous
state.
[0159] In still yet another preferred embodiment the present
invention is directed to a method of characterising a cell or
cellular population, which cell or cellular population is derived
from the large intestine of an individual, said method comprising
measuring the level of expression of one or more genes or
transcripts selected from:
TABLE-US-00030 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 223122_s_at 207173_x_at 210511_s_at
212353_at 203083_at 209156_s_at 219087_at 203477_at 224694_at
201438_at 37892_at 201141_at 226237_at 202917_s_at 213905_x_at
225664_at 226930_at 205547_s_at 221730_at 204051_s_at;_ and/or (ii)
SFRP2 CDH11 INHBA SULF1 THBS2 COL6A2 ASPN COL15A1 ANTXR1 COL6A3
COL11A1 GPNMB COL8A1 S100A8 BGN COL12A1 FNDC1 TAGLN COL5A2
SFRP4
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to a gastrointestinal adenoma control level is indicative
of a cancer or a cell predisposed to the onset of a cancerous
state.
[0160] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0161] Even more preferably, said biological sample is a tissue
sample.
[0162] In still another related aspect it has been determined that
a subset of the markers of this aspect of the present invention are
useful as qualitative markers of neoplastic tissue characterisation
in that these markers, if detectable above background levels in
neoplastic tissue are indicative of either adenoma or cancerous
tissue.
[0163] According to this aspect, the present invention provides a
method of characterising a neoplastic cell or cellular population,
which cell or cellular population is derived from the large
intestine of an individual, said method comprising measuring the
level of expression of one or more genes or transcripts selected
from:
TABLE-US-00031 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 235976_at 236894_at; and/or (ii)
SLITRK6 L1TD1
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to neoplastic tissue background levels is indicative of an
adenoma cell or a cell predisposed to the onset of an adenoma
state.
[0164] In another aspect the present invention provides a method of
characterising a neoplastic cell or cellular population, which cell
or cellular population is derived from the large intestine of an
individual, said method comprising measuring the level of
expression of one or more genes or transcripts selected from:
TABLE-US-00032 the gene, genes or transcripts detected by
Affymetrix probeset IDs: (i) 202311_s_at 209396_s_at 226237_at
204320_at 215646_s_at 227140_at 204475_at 37892_at 229802_at
209395_at; and/or (ii) COL1A1 VCAN CHI3L1 MMP1 COL8A1 COL11A1
in a biological sample from said individual wherein a higher level
of expression of the genes or transcripts of group (i) and/or (ii)
relative to neoplastic tissue background neoplastic cell levels is
indicative of a cancer or a cell predisposed to the onset of a
cancerous state.
[0165] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0166] Still more preferably, said biological sample is a tissue
sample.
[0167] In a most preferred embodiment, the methods of the present
invention are preferably directed to screening for proteins encoded
by the markers of the present invention.
[0168] Although the preferred method is to detect the expression
products of the neoplastic markers for the purpose of diagnosing
neoplasia development or predisposition thereto, the detection of
converse changes in the levels of said markers may be desired under
certain circumstances, for example, to monitor the effectiveness of
therapeutic or prophylactic treatment directed to modulating a
neoplastic condition, such as adenoma or adenocarcinoma
development. For example, where elevated levels of the subject
markers indicate that an individual has developed a condition
characterised by adenoma or adenocarcinoma development, for
example, screening for a decrease in the levels of these markers
subsequently to the onset of a therapeutic regime may be utilised
to indicate reversal or other form of improvement of the subject
individual's condition.
[0169] The method of the present invention is therefore useful as a
one-time test or as an on-going monitor of those individuals
thought to be at risk of neoplasia development or as a monitor of
the effectiveness of therapeutic or prophylactic treatment regimes
directed to inhibiting or otherwise slowing neoplasia development.
In these situations, mapping the modulation of neoplastic marker
expression levels in any one or more classes of biological samples
is a valuable indicator of the status of an individual or the
effectiveness of a therapeutic or prophylactic regime which is
currently in use. Accordingly, the method of the present invention
should be understood to extend to monitoring for increases or
decreases in marker expression levels in an individual relative to
their normal level (as hereinbefore defined), background control
levels, cancer levels, adenoma levels or relative to one or more
earlier marker expression levels determined from a biological
sample of said individual.
[0170] Means of testing for the subject expressed neoplasm markers
in a biological sample can be achieved by any suitable method,
which would be well known to the person of skill in the art, such
as but not limited to:
[0171] (i) In vivo detection. [0172] Molecular Imaging may be used
following administration of imaging probes or reagents capable of
disclosing altered expression of the markers in the intestinal
tissues. [0173] Molecular imaging (Moore et al., BBA, 1402:239-249,
1988; Weissleder et al., Nature Medicine 6:351-355, 2000) is the in
vivo imaging of molecular expression that correlates with the
macro-features currently visualized using "classical" diagnostic
imaging techniques such as X-Ray, computed tomography (CT), MRI,
Positron Emission Tomography (PET) or endoscopy.
[0174] (ii) Detection of up-regulation of RNA expression in the
cells by Fluorescent In Situ Hybridization (FISH), or in extracts
from the cells by technologies such as Quantitative Reverse
Transcriptase Polymerase Chain Reaction (QRTPCR) or Flow cytometric
qualification of competitive RT-PCR products (Wedemeyer et al.,
Clinical Chemistry 48:9 1398-1405, 2002).
[0175] (iii) Assessment of expression profiles of RNA, for example
by array technologies (Alon et al., Proc. Natl. Acad. Sci. USA: 96,
6745-6750, June 1999). [0176] A "microarray" is a linear or
multi-dimensional array of preferably discrete regions, each having
a defined area, formed on the surface of a solid support. The
density of the discrete regions on a microarray is determined by
the total numbers of target polynucleotides to be detected on the
surface of a single solid phase support. As used herein, a DNA
microarray is an array of oligonucleotide probes placed onto a chip
or other surfaces used to detect complementary oligonucleotides
from a complex nucleic acid mixture. Since the position of each
particular group of probes in the array is known, the identities of
the target polynucleotides can be determined based on their binding
to a particular position in the microarray. [0177] Recent
developments in DNA microarray technology make it possible to
conduct a large scale assay of a plurality of target nucleic acid
molecules on a single solid phase support. U.S. Pat. No. 5,837,832
(Chee et al.) and related patent applications describe immobilizing
an array of oligonucleotide probes for hybridization and detection
of specific nucleic acid sequences in a sample. Target
polynucleotides of interest isolated from a tissue of interest are
hybridized to the DNA chip and the specific sequences detected
based on the target polynucleotides' preference and degree of
hybridization at discrete probe locations. One important use of
arrays is in the analysis of differential gene expression, where
the profile of expression of genes in different cells or tissues,
often a tissue of interest and a control tissue, is compared and
any differences in gene expression among the respective tissues are
identified. Such information is useful for the identification of
the types of genes expressed in a particular tissue type and
diagnosis of conditions based on the expression profile. [0178] In
one example, RNA from the sample of interest is subjected to
reverse transcription to obtain labelled cDNA. See U.S. Pat. No.
6,410,229 (Lockhart et al.) The cDNA is then hybridized to
oligonucleotides or cDNAs of known sequence arrayed on a chip or
other surface in a known order. In another example, the RNA is
isolated from a biological sample and hybridised to a chip on which
are anchored cDNA probes. The location of the oligonucleotide to
which the labelled cDNA hybridizes provides sequence information on
the cDNA, while the amount of labelled hybridized RNA or cDNA
provides an estimate of the relative representation of the RNA or
cDNA of interest. See Schena, et al. Science 270:467-470 (1995).
For example, use of a cDNA microarray to analyze gene expression
patterns in human cancer is described by DeRisi, et al. (Nature
Genetics 14:457-460 (1996)). [0179] In a preferred embodiment,
nucleic acid probes corresponding to the subject nucleic acids are
made. The nucleic acid probes attached to the microarray are
designed to be substantially complementary to the nucleic acids of
the biological sample such that specific hybridization of the
target sequence and the probes of the present invention occurs.
This complementarity need not be perfect, in that there may be any
number of base pair mismatches that will interfere with
hybridization between the target sequence and the single stranded
nucleic acids of the present invention. It is expected that the
overall homology of the genes at the nucleotide level probably will
be about 40% or greater, probably about 60% or greater, and even
more probably about 80% or greater; and in addition that there will
be corresponding contiguous sequences of about 8-12 nucleotides or
longer. However, if the number of mutations is so great that no
hybridization can occur under even the least stringent of
hybridization conditions, the sequence is not a complementary
target sequence. Thus, by "substantially complementary" herein is
meant that the probes are sufficiently complementary to the target
sequences to hybridize under normal reaction conditions,
particularly high stringency conditions. [0180] A nucleic acid
probe is generally single stranded but can be partly single and
partly double stranded. The strandedness of the probe is dictated
by the structure, composition, and properties of the target
sequence. In general, the oligonucleotide probes range from about
6, 8, 10, 12, 15, 20, 30 to about 100 bases long, with from about
10 to about 80 bases being preferred, and from about 15 to about 40
bases being particularly preferred. That is, generally entire genes
are rarely used as probes. In some embodiments, much longer nucleic
acids can be used, up to hundreds of bases. The probes are
sufficiently specific to hybridize to a complementary template
sequence under conditions known by those of skill in the art. The
number of mismatches between the probe's sequences and their
complementary template (target) sequences to which they hybridize
during hybridization generally do not exceed 15%, usually do not
exceed 10% and preferably do not exceed 5%, as-determined by BLAST
(default settings). [0181] Oligonucleotide probes can include the
naturally-occurring heterocyclic bases normally found in nucleic
acids (uracil, cytosine, thymine, adenine and guanine), as well as
modified bases and base analogues. Any modified base or base
analogue compatible with hybridization of the probe to a target
sequence is useful in the practice of the invention. The sugar or
glycoside portion of the probe can comprise deoxyribose, ribose,
and/or modified forms of these sugars, such as, for example,
2'-O-alkyl ribose. In a preferred embodiment, the sugar moiety is
2'-deoxyribose; however, any sugar moiety that is compatible with
the ability of the probe to hybridize to a target sequence can be
used. [0182] In one embodiment, the nucleoside units of the probe
are linked by a phosphodiester backbone, as is well known in the
art. In additional embodiments, internucleotide linkages can
include any linkage known to one of skill in the art that is
compatible with specific hybridization of the probe including, but
not limited to phosphorothioate, methylphosphonate, sulfamate
(e.g., U.S. Pat. No. 5,470,967) and polyamide (i.e., peptide
nucleic acids). Peptide nucleic acids are described in Nielsen et
al. (1991) Science 254: 1497-1500, U.S. Pat. No. 5,714,331, and
Nielsen (1999) Curr. Opin. Biotechnol. 10:71-75. [0183] In certain
embodiments, the probe can be a chimeric molecule; i.e., can
comprise more than one type of base or sugar subunit, and/or the
linkages can be of more than one type within the same primer. The
probe can comprise a moiety to facilitate hybridization to its
target sequence, as are known in the art, for example,
intercalators and/or minor groove binders. Variations of the bases,
sugars, and internucleoside backbone, as well as the presence of
any pendant group on the probe, will be compatible with the ability
of the probe to bind, in a sequence-specific fashion, with its
target sequence. A large number of structural modifications, are
possible within these bounds. Advantageously, the probes according
to the present invention may have structural characteristics such
that they allow the signal amplification, such structural
characteristics being, for example, branched DNA probes as those
described by Urdea et al. (Nucleic Acids Symp. Ser., 24:197-200
(1991)) or in the European Patent No. EP-0225,807. Moreover,
synthetic methods for preparing the various heterocyclic bases,
sugars, nucleosides and nucleotides that form the probe, and
preparation of oligonucleotides of specific predetermined sequence,
are well-developed and known in the art. A preferred method for
oligonucleotide synthesis incorporates the teaching of U.S. Pat.
No. 5,419,966. [0184] Multiple probes may be designed for a
particular target nucleic acid to account for polymorphism and/or
secondary structure in the target nucleic acid, redundancy of data
and the like. In some embodiments, where more than one probe per
sequence is used, either overlapping probes or probes to different
sections of a single target gene are used. That is, two, three,
four or more probes, are used to build in a redundancy for a
particular target. The probes can be overlapping (i.e. have some
sequence in common), or are specific for distinct sequences of a
gene. When multiple target polynucleotides are to be detected
according to the present invention, each probe or probe group
corresponding to a particular target polynucleotide is situated in
a discrete area of the microarray. [0185] Probes may be in
solution, such as in wells or on the surface of a micro-array, or
attached to a solid support. Examples of solid support materials
that can be used include a plastic, a ceramic, a metal, a resin, a
gel and a membrane. Useful types of solid supports include plates,
beads, magnetic material, microbeads, hybridization chips,
membranes, crystals, ceramics and self-assembling monolayers. One
example comprises a two-dimensional or three-dimensional matrix,
such as a gel or hybridization chip with multiple probe binding
sites (Pevzner et al., J. Biomol. Struc. & Dyn. 9:399-410,
1991; Maskos and Southern, Nuc. Acids Res. 20:1679-84, 1992).
Hybridization chips can be used to construct very large probe
arrays that are subsequently hybridized with a target nucleic acid.
Analysis of the hybridization pattern of the chip can assist in the
identification of the target nucleotide sequence. Patterns can be
manually or computer analyzed, but it is clear that positional
sequencing by hybridization lends itself to computer analysis and
automation. In another example, one may use an Affymetrix chip on a
solid phase structural support in combination with a fluorescent
bead based approach. In yet another example, one may utilise a cDNA
microarray. In this regard, the oligonucleotides described by
Lockkart et al. (i.e. Affymetrix synthesis probes in situ on the
solid phase) are particularly preferred, that is, photolithography.
[0186] As will be appreciated by those in the art, nucleic acids
can be attached or immobilized to a solid support in a wide variety
of ways. By "immobilized" herein is meant the association or
binding between the nucleic acid probe and the solid support is
sufficient to be stable under the conditions of binding, washing,
analysis, and removal. The binding can be covalent or non-covalent.
By "non-covalent binding" and grammatical equivalents herein is
meant one or more of either electrostatic, hydrophilic, and
hydrophobic interactions. Included in non-covalent binding is the
covalent attachment of a molecule, such as streptavidin, to the
support and the non-covalent binding of the biotinylated probe to
the streptavidin. By "covalent binding" and grammatical equivalents
herein is meant that the two moieties, the solid support and the
probe, are attached by at least one bond, including sigma bonds, pi
bonds and coordination bonds. Covalent bonds can be formed directly
between the probe and the solid support or can be formed by a cross
linker or by inclusion of a specific reactive group on either the
solid support or the probe or both molecules. Immobilization may
also involve a combination of covalent and non-covalent
interactions. [0187] Nucleic acid probes may be attached to the
solid support by covalent binding such as by conjugation with a
coupling agent or by covalent or non-covalent binding such as
electrostatic interactions, hydrogen bonds or antibody-antigen
coupling, or by combinations thereof. Typical coupling agents
include biotin/avidin, biotin/streptavidin, Staphylococcus aureus
protein A/IgG antibody F.sub.c fragment, and streptavidin/protein A
chimeras (T. Sano and C. R. Cantor, Bio/Technology 9:1378-81
(1991)), or derivatives or combinations of these agents. Nucleic
acids may be attached to the solid support by a photocleavable
bond, an electrostatic bond, a disulfide bond, a peptide bond, a
diester bond or a combination of these sorts of bonds. The array
may also be attached to the solid support by a selectively
releasable bond such as 4,4'-dimethoxytrityl or its derivative.
Derivatives which have been found to be useful include 3 or 4
[bis-(4-methoxyphenyl)]-methyl-benzoic acid, N-succinimidyl-3 or 4
[bis-(4-methoxyphenyl)]-methyl-benzoic acid, N-succinimidyl-3 or 4
[bis-(4-methoxyphenyl)]-hydroxymethyl-benzoic acid,
N-succinimidyl-3 or 4 [bis-(4-methoxyphenyl)]-chloromethyl-benzoic
acid, and salts of these acids. [0188] In general, the probes are
attached to the microarray in a wide variety of ways, as will be
appreciated by those in the art. As described herein, the nucleic
acids can either be synthesized first, with subsequent attachment
to the microarray, or can be directly synthesized on the
microarray. [0189] The microarray comprises a suitable solid
substrate. By "substrate" or "solid support" or other grammatical
equivalents herein is meant any material that can be modified to
contain discrete individual sites appropriate for the attachment or
association of the nucleic acid probes and is amenable to at least
one detection method. The solid phase support of the present
invention can be of any solid materials and structures suitable for
supporting nucleotide hybridization and synthesis. Preferably, the
solid phase support comprises at least one substantially rigid
surface on which the primers can be immobilized and the reverse
transcriptase reaction performed. The substrates with which the
polynucleotide microarray elements are stably associated and may be
fabricated from a variety of materials, including plastics,
ceramics, metals, acrylamide, cellulose, nitrocellulose, glass,
polystyrene, polyethylene vinyl acetate, polypropylene,
polymethacrylate, polyethylene, polyethylene oxide, polysilicates,
polycarbonates, Teflon, fluorocarbons, nylon, silicon rubber,
polyanhydrides, polyglycolic acid, polylactic acid,
polyorthoesters, polypropylfumerate, collagen, glycosaminoglycans,
and polyamino acids. Substrates may be two-dimensional or
three-dimensional in form, such as gels, membranes, thin films,
glasses, plates, cylinders, beads, magnetic beads, optical fibers,
woven fibers, etc. A preferred form of array is a three-dimensional
array. A preferred three-dimensional array is a collection of
tagged beads. Each tagged bead has different primers attached to
it. Tags are detectable by signalling means such as color (Luminex,
Illumina) and electromagnetic field (Pharmaseq) and signals on
tagged beads can even be remotely detected (e.g., using optical
fibers). The size of the solid support can be any of the standard
microarray sizes, useful for DNA microarray technology, and the
size may be tailored to fit the particular machine being used to
conduct a reaction of the invention. In general, the substrates
allow optical detection and do not appreciably fluoresce. [0190] In
one embodiment, the surface of the microarray and the probe may be
derivatized with chemical functional groups for subsequent
attachment of the two. Thus, for example, the microarray is
derivatized with a chemical functional group including, but not
limited to, amino groups, carboxy groups, oxo groups and thiol
groups, with amino groups being particularly preferred. Using these
functional groups, the probes can be attached using functional
groups on the probes. For example, nucleic acids containing amino
groups can be attached to surfaces comprising amino groups, for
example using linkers as are known in the art; for example, homo-or
hetero-bifunctional linkers as are well known. In addition, in some
cases, additional linkers, such as alkyl groups (including
substituted and heteroalkyl groups) may be used.
[0191] In this embodiment, the oligonucleotides are synthesized as
is known in the art, and then attached to the surface of the solid
support. As will be appreciated by those skilled in the art, either
the 5' or 3' terminus may be attached to the solid support, or
attachment may be via an internal nucleoside. In an additional
embodiment, the immobilization to the solid support may be very
strong, yet non-covalent. For example, biotinylated
oligonucleotides can be made, which bind to surfaces covalently
coated with streptavidin, resulting in attachment. [0192] The
arrays may be produced according to any convenient methodology,
such as preforming the polynucleotide microarray elements and then
stably associating them with the surface. Alternatively, the
oligonucleotides may be synthesized on the surface, as is known in
the art. A number of different array configurations and methods for
their production are known to those of skill in the art and
disclosed in WO 95/25116 and WO 95/35505 (photolithographic
techniques), U.S. Pat. No. 5,445,934 (in situ synthesis by
photolithography), U.S. Pat. No. 5,384,261 (in situ synthesis by
mechanically directed flow paths); and U.S. Pat. No. 5,700,637
(synthesis by spotting, printing or coupling); the disclosure of
which are herein incorporated in their entirety by reference.
Another method for coupling DNA to beads uses specific ligands
attached to the end of the DNA to link to ligand-binding molecules
attached to a bead. Possible ligand-binding partner pairs include
biotin-avidin/streptavidin, or various antibody/antigen pairs such
as digoxygenin-antidigoxygenin antibody (Smith et al., Science
258:1122-1126 (1992)). Covalent chemical attachment of DNA to the
support can be accomplished by using standard coupling agents to
link the 5'-phosphate on the DNA to coated microspheres through a
phosphoamidate bond. Methods for immobilization of oligonucleotides
to solid-state substrates are well established. See Pease et al.,
Proc. Natl. Acad. Sci. USA 91(11):5022-5026 (1994). A preferred
method of attaching oligonucleotides to solid-state substrates is
described by Guo et al., Nucleic Acids Res. 22:5456-5465 (1994).
Immobilization can be accomplished either by in situ DNA synthesis
(Maskos and Southern, supra) or by covalent attachment of
chemically synthesized oligonucleotides (Guo et al., supra) in
combination with robotic arraying technologies. [0193] In addition
to the solid-phase technology represented by microarray arrays,
gene expression can also be quantified using liquid-phase assays.
One such system is kinetic polymerase chain reaction (PCR). Kinetic
PCR allows for the simultaneous amplification and quantification of
specific nucleic acid sequences. The specificity is derived from
synthetic oligonucleotide primers designed to preferentially adhere
to single-stranded nucleic acid sequences bracketing the target
site. This pair of oligonucleotide primers form specific,
non-covalently bound complexes on each strand of the target
sequence. These complexes facilitate in vitro transcription of
double-stranded DNA in opposite orientations. Temperature cycling
of the reaction mixture creates a continuous cycle of primer
binding, transcription, and re-melting of the nucleic acid to
individual strands. The result is an exponential increase of the
target dsDNA product. This product can be quantified in real time
either through the use of an intercalating dye or a sequence
specific probe. SYBR(r) Green 1, is an example of an intercalating
dye, that preferentially binds to dsDNA resulting in a concomitant
increase in the fluorescent signal. Sequence specific probes, such
as used with TaqMan technology, consist of a fluorochrome and a
quenching molecule covalently bound to opposite ends of an
oligonucleotide. The probe is designed to selectively bind the
target DNA sequence between the two primers. When the DNA strands
are synthesized during the PCR reaction, the fluorochrome is
cleaved from the probe by the exonuclease activity of the
polymerase resulting in signal dequenching. The probe signalling
method can be more specific than the intercalating dye method, but
in each case, signal strength is proportional to the dsDNA product
produced. Each type of quantification method can be used in
multi-well liquid phase arrays with each well representing primers
and/or probes specific to nucleic acid sequences of interest. When
used with messenger RNA preparations of tissues or cell lines, an
array of probe/primer reactions can simultaneously quantify the
expression of multiple gene products of interest. See Germer et
al., Genome Res. 10:258-266 (2000); Heid et al., Genome Res.
6:986-994 (1996).
[0194] (iv) Measurement of altered neoplastic marker protein levels
in cell extracts, for example by immunoassay. [0195] Testing for
proteinaceous neoplastic marker expression product in a biological
sample can be performed by any one of a number of suitable methods
which are well known to those skilled in the art. Examples of
suitable methods include, but are not limited to, antibody
screening of tissue sections, biopsy specimens or bodily fluid
samples. [0196] To the extent that antibody based methods of
diagnosis are used, the presence of the marker protein may be
determined in a number of ways such as by Western blotting, ELISA
or flow cytometry procedures. These, of course, include both
single-site and two-site or "sandwich" assays of the
non-competitive types, as well as in the traditional competitive
binding assays. These assays also include direct binding of a
labelled antibody to a target. [0197] Sandwich assays are among the
most useful and commonly used assays. A number of variations of the
sandwich assay technique exist, and all are intended to be
encompassed by the present invention. Briefly, in a typical forward
assay, an unlabelled antibody is immobilized on a solid substrate
and the sample to be tested brought into contact with the bound
molecule. After a suitable period of incubation, for a period of
time sufficient to allow formation of an antibody-antigen complex,
a second antibody specific to the antigen, labelled with a reporter
molecule capable of producing a detectable signal is then added and
incubated, allowing time sufficient for the formation of another
complex of antibody-antigen-labelled antibody. Any unreacted
material is washed away, and the presence of the antigen is
determined by observation of a signal produced by the reporter
molecule. The results may either be qualitative, by simple
observation of the visible signal, or may be quantitated by
comparing with a control sample. Variations on the forward assay
include a simultaneous assay, in which both sample and labelled
antibody are added simultaneously to the bound antibody. These
techniques are well known to those skilled in the art, including
any minor variations as will be readily apparent. [0198] In the
typical forward sandwich assay, a first antibody having specificity
for the marker or antigenic parts thereof, is either covalently or
passively bound to a solid surface. The solid surface is typically
glass or a polymer, the most commonly used polymers being
cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride
or polypropylene. The solid supports may be in the form of tubes,
beads, discs of microplates, or any other surface suitable for
conducting an immunoassay. The binding processes are well-known in
the art and generally consist of cross-linking, covalently binding
or physically adsorbing, the polymer-antibody complex is washed in
preparation for the test sample. An aliquot of the sample to be
tested is then added to the solid phase complex and incubated for a
period of time sufficient (e.g. 2-40 minutes) and under suitable
conditions (e.g. 25.degree. C.) to allow binding of any subunit
present in the antibody. Following the incubation period, the
antibody subunit solid phase is washed and dried and incubated with
a second antibody specific for a portion of the antigen. The second
antibody is linked to a reporter molecule which is used to indicate
the binding of the second antibody to the antigen. [0199] An
alternative method involves immobilizing the target molecules in
the biological sample and then exposing the immobilized target to
specific antibody which may or may not be labelled with a reporter
molecule. Depending on the amount of target and the strength of the
reporter molecule signal, a bound target may be detectable by
direct labelling with the antibody. Alternatively, a second
labelled antibody, specific to the first antibody is exposed to the
target-first antibody complex to form a target-first
antibody-second antibody tertiary complex. The complex is detected
by the signal emitted by the reporter molecule. [0200] By "reporter
molecule" as used in the present specification, is meant a molecule
which, by its chemical nature, provides an analytically
identifiable signal which allows the detection of antigen-bound
antibody. Detection may be either qualitative or quantitative. The
most commonly used reporter molecules in this type of assay are
either enzymes, fluorophores or radionuclide containing molecules
(i.e. radioisotopes) and chemiluminescent molecules. [0201] In the
case of an enzyme immunoassay, an enzyme is conjugated to the
second antibody, generally by means of glutaraldehyde or periodate.
As will be readily recognized, however, a wide variety of different
conjugation techniques exist, which are readily available to the
skilled artisan. Commonly used enzymes include horseradish
peroxidase, glucose oxidase, beta-galactosidase and alkaline
phosphatase, amongst others. The substrates to be used with the
specific enzymes are generally chosen for the production, upon
hydrolysis by the corresponding enzyme, of a detectable color
change. Examples of suitable enzymes include alkaline phosphatase
and peroxidase. It is also possible to employ fluorogenic
substrates, which yield a fluorescent product rather than the
chromogenic substrates noted above. In all cases, the
enzyme-labelled antibody is added to the first antibody hapten
complex, allowed to bind, and then the excess reagent is washed
away. A solution containing the appropriate substrate is then added
to the complex of antibody-antigen-antibody. The substrate will
react with the enzyme linked to the second antibody, giving a
qualitative visual signal, which may be further quantitated,
usually spectrophotometrically, to give an indication of the amount
of antigen which was present in the sample. "Reporter molecule"
also extends to use of cell agglutination or inhibition of
agglutination such as red blood cells on latex beads, and the like.
[0202] Alternately, fluorescent compounds, such as fluorecein and
rhodamine, may be chemically coupled to antibodies without altering
their binding capacity. When activated by illumination with light
of a particular wavelength, the fluorochrome-labelled antibody
adsorbs the light energy, inducing a state to excitability in the
molecule, followed by emission of the light at a characteristic
color visually detectable with a light microscope. As in the EIA,
the fluorescent labelled antibody is allowed to bind to the first
antibody-hapten complex. After washing off the unbound reagent, the
remaining tertiary complex is then exposed to the light of the
appropriate wavelength the fluorescence observed indicates the
presence of the hapten of interest. Immunofluorescence and EIA
techniques are both very well established in the art and are
particularly preferred for the present method. However, other
reporter molecules, such as radioisotope, chemiluminescent or
bioluminescent molecules, may also be employed.
[0203] (v) Without limiting the present invention to any one theory
or mode of action, during development gene expression is regulated
by processes that alter the availability of genes for expression in
different cell lineages without any alteration in gene sequence,
and these states can be inherited through a cell division--a
process called epigenetic inheritance. Epigenetic inheritance is
determined by a combination of DNA methylation (modification of
cytosine to give 5-methyl cytosine, 5meC) and by modifications of
the histone chromosomal proteins that package DNA. Thus methylation
of DNA at CpG sites and modifications such as deacetylation of
histone H3 on lysine 9, and methylation on lysine 9 or 27 are
associated with inactive chromatin, while the converse state of a
lack of DNA methylation, acetylation of lysine 9 of histone H3 is
associated with open chromatin and active gene expression. In
cancer, this epigenetic regulation of gene expression is frequently
found to be disrupted (Esteller & Herman, 2000; Jones &
Baylin, 2002). Genes such as tumour suppressor or metastasis
suppressor genes are often found to be silenced by DNA methylation,
while other genes may be hypomethylated and inappropriately
expressed. Thus, among genes that elevated or inappropriate
expression in cancer, this in some instances is characterised by a
loss of methylation of the promoter or regulatory region of the
gene. [0204] A variety of methods are available for detection of
aberrantly methylated DNA of a specific gene, even in the presence
of a large excess of normal DNA (Clark 2007). Thus, elevated
expression of certain genes may be detected through detection of
the presence of hypomethylated sequences in tissue, bodily fluid or
other patient samples. [0205] Epigenetic alterations and chromatin
changes in cancer are also evident in the altered association of
modified histones with specific genes(Esteller, 2007); for example
activated genes are often found associated with histone H3 that is
acetylated on lysine 9 and methylated on lysine 4. The use of
antibodies targeted to altered histones allows for the isolation of
DNA associated with particular chromatin states and has potential
use in cancer diagnosis.
[0206] (vi) Determining altered expression of protein neoplastic
markers on the cell surface, for example by
immunohistochemistry.
[0207] (vii) Determining altered protein expression based on any
suitable functional test, enzymatic test or immunological test in
addition to those detailed in points (iv) and (v) above.
[0208] A person of ordinary skill in the art could determine, as a
matter of routine procedure, the appropriateness of applying a
given method to a particular type of biological sample.
[0209] Without limiting the present invention in any way, and as
detailed above, gene expression levels can be measured by a variety
of methods known in the art. For example, gene transcription or
translation products can be measured. Gene transcription products,
i.e., RNA, can be measured, for example, by hybridization assays,
run-off assays, Northern blots, or other methods known in the
art.
[0210] Hybridization assays generally involve the use of
oligonucleotide probes that hybridize to the single-stranded RNA
transcription products. Thus, the oligonucleotide probes are
complementary to the transcribed RNA expression product. Typically,
a sequence-specific probe can be directed to hybridize to RNA or
cDNA. A "nucleic acid probe", as used herein, can be a DNA probe or
an RNA probe that hybridizes to a complementary sequence. One of
skill in the art would know how to design such a probe such that
sequence specific hybridization will occur. One of skill in the art
will further know how to quantify the amount of sequence specific
hybridization as a measure of the amount of gene expression for the
gene was transcribed to produce the specific RNA.
[0211] The hybridization sample is maintained under conditions that
are sufficient to allow specific hybridization of the nucleic acid
probe to a specific gene expression product. "Specific
hybridization", as used herein, indicates near exact hybridization
(e.g., with few if any mismatches). Specific hybridization can be
performed under high stringency conditions or moderate stringency
conditions. In one embodiment, the hybridization conditions for
specific hybridization are high stringency. For example, certain
high stringency conditions can be used to distinguish perfectly
complementary nucleic acids from those of less complementarity.
"High stringency conditions", "moderate stringency conditions" and
"low stringency conditions" for nucleic acid hybridizations are
explained on pages 2.10.1-2.10.16 and pages 6.3.1-6.3.6 in Current
Protocols in Molecular Biology (Ausubel, F. et al., "Current
Protocols in Molecular Biology", John Wiley & Sons, (1998), the
entire teachings of which are incorporated by reference herein).
The exact conditions that determine the stringency of hybridization
depend not only on ionic strength (e.g., 0.2.times.SSC,
0.1.times.SSC), temperature (e.g., room temperature, 42.degree. C.,
68.degree. C.) and the concentration of destabilizing agents such
as formamide or denaturing agents such as SDS, but also on factors
such as the length of the nucleic acid sequence, base composition,
percent mismatch between hybridizing sequences and the frequency of
occurrence of subsets of that sequence within other non-identical
sequences. Thus, equivalent conditions can be determined by varying
one or more of these parameters while maintaining a similar degree
of identity or similarity between the two nucleic acid molecules.
Typically, conditions are used such that sequences at least about
60%, at least about 70%, at least about 80%, at least about 90% or
at least about 95% or more identical to each other remain
hybridized to one another. By varying hybridization conditions from
a level of stringency at which no hybridization occurs to a level
at which hybridization is first observed, conditions that will
allow a given sequence to hybridize (e.g., selectively) with the
most complementary sequences in the sample can be determined.
[0212] Exemplary conditions that describe the determination of wash
conditions for moderate or low stringency conditions are described
in Kraus, M. and Aaronson, S., 1991. Methods Enzymol., 200:546-556;
and in, Ausubel et al., Current Protocols in Molecular Biology,
John Wiley & Sons, (1998). Washing is the step in which
conditions are usually set so as to determine a minimum level of
complementarity of the hybrids. Generally, starting from the lowest
temperature at which only homologous hybridization occurs, each
.degree. C. by which the final wash temperature is reduced (holding
SSC concentration constant) allows an increase by 1% in the maximum
mismatch percentage among the sequences that hybridize. Generally,
doubling the concentration of SSC results in an increase in T.sub.m
of about 17.degree. C. Using these guidelines, the wash temperature
can be determined empirically for high, moderate or low stringency,
depending on the level of mismatch sought. For example, a low
stringency wash can comprise washing in a solution containing
0.2.times.SSC/0.1% SDS for 10 minutes at room temperature; a
moderate stringency wash can comprise washing in a pre-warmed
solution (42.degree. C.) solution containing 0.2.times.SSC/0.1% SDS
for 15 minutes at 42.degree. C.; and a high stringency wash can
comprise washing in pre-warmed (68.degree. C.) solution containing
0.1.times.SSC/0.1% SDS for 15 minutes at 68.degree. C. Furthermore,
washes can be performed repeatedly or sequentially to obtain a
desired result as known in the art. Equivalent conditions can be
determined by varying one or more of the parameters given as an
example, as known in the art, while maintaining a similar degree of
complementarity between the target nucleic acid molecule and the
primer or probe used (e.g., the sequence to be hybridized).
[0213] A related aspect of the present invention provides a
molecular array, which array comprises a plurality of: [0214] (i)
nucleic acid molecules comprising a nucleotide sequence
corresponding to any one or more of the neoplastic marker genes
hereinbefore described or a sequence exhibiting at least 80%
identity thereto or a functional derivative, fragment, variant or
homologue of said nucleic acid molecule; or [0215] (ii) nucleic
acid molecules comprising a nucleotide sequence capable of
hybridising to any one or more of the sequences of (i) under medium
stringency conditions or a functional derivative, fragment, variant
or homologue of said nucleic acid molecule; or [0216] (iii) nucleic
acid probes or oligonucleotides comprising a nucleotide sequence
capable of hybridising to any one or more of the sequences of (i)
under medium stringency conditions or a functional derivative,
fragment, variant or homologue of said nucleic acid molecule; or
[0217] (iv) probes capable of binding to any one or more of the
proteins encoded by the nucleic acid molecules of (i) or a
derivative, fragment or, homologue thereof wherein the level of
expression of said marker genes of (i) or proteins of (iv) is
indicative of the neoplastic state of a cell or cellular
subpopulation derived from the large intestine.
[0218] Preferably, said percent identity is at least 85%, 90%, 91%,
92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%.
[0219] Low stringency includes and encompasses from at least about
1% v/v to at least about 15% v/v formamide and from at least about
1M to at least about 2M salt for hybridisation, and at least about
1M to at least about 2M salt for washing conditions. Alternative
stringency conditions may be applied where necessary, such as
medium stringency, which includes and encompasses from at least
about 16% v/v at least about 30% v/v formamide and from at least
about 0.5M to at least about 0.9M salt for hybridisation, and at
least about 0.5M to at least about 0.9M salt for washing
conditions, or high stringency, which includes and encompasses from
at least about 31% v/v to at least about 50% v/v formamide and from
at least about 0.01M to at least about 0.15M salt for
hybridisation, and at least about 0.01M to at least about 0.15M
salt for washing conditions. In general, washing is carried out at
T.sub.m=69.3 +0.41 (G+C) % [19]=-12.degree. C. However, the T.sub.m
of a duplex DNA decreases by 1.degree. C. with every increase of 1%
in the number of mismatched based pairs (Bonner et al (1973) J.
Mol. Biol. 81:123).
[0220] Preferably, the subject probes are designed to bind to the
nucleic acid or protein to which they are directed with a level of
specificity which minimises the incidence of non-specific
reactivity. However, it would be appreciated that it may not be
possible to eliminate all potential cross-reactivity or
non-specific reactivity, this being an inherent limitation of any
probe based system.
[0221] In terms of the probes which are used to detect the subject
proteins, they may take any suitable form including antibodies and
aptamers.
[0222] A library or array of nucleic acid or protein probes
provides rich and highly valuable information. Further, two or more
arrays or profiles (information obtained from use of an array) of
such sequences are useful tools for comparing a test set of results
with a reference, such as another sample or stored calibrator. In
using an array, individual probes typically are immobilized at
separate locations and allowed to react for binding reactions.
Primers associated with assembled sets of markers are useful for
either preparing libraries of sequences or directly detecting
markers from other biological samples.
[0223] A library (or array, when referring to physically separated
nucleic acids corresponding to at least some sequences in a
library) of gene markers exhibits highly desirable properties.
These properties are associated with specific conditions, and may
be characterized as regulatory profiles. A profile, as termed here
refers to a set of members that provides diagnostic information of
the tissue from which the markers were originally derived. A
profile in many instances comprises a series of spots on an array
made from deposited sequences.
[0224] A characteristic patient profile is generally prepared by
use of an array. An array profile may be compared with one or more
other array profiles or other reference profiles. The comparative
results can provide rich information pertaining to disease states,
developmental state, receptiveness to therapy and other information
about the patient.
[0225] Another aspect of the present invention provides a
diagnostic kit for assaying biological samples comprising an agent
for detecting one or more neoplastic markers and reagents useful
for facilitating the detection by said agent. Further means may
also be included, for example, to receive a biological sample. The
agent may be any suitable detecting molecule.
[0226] The present invention is further described by the following
non-limiting examples:
EXAMPLE 1
[0227] Methods and Materials
[0228] Affymetrix GeneChip Data
[0229] Gene expression profiling data and accompanying clinical
data was purchased from GeneLogic Inc (Gaithersburg, Md. USA). For
each tissue analyzed, oligonucleotide microarray data for 44,928
probesets (Affymetrix HGU133A & HGU133B, combined),
experimental and clinical descriptors, and digitally archived
microscopy images of histological preparations were received. A
quality control analysis was performed to remove arrays not meeting
essential quality control measures as defined by the
manufacturer.
[0230] Transcript expression levels were calculated by both
Microarray Suite (MAS) 5.0 (Affymetrix) and the Robust Multichip
Average (RMA) normalization techniques (Affymetrix. GeneChip
expression data analysis fundamentals. Affymetrix, Santa Clara,
Calif. USA, 2001; Hubbell et al. Bioinformatics, 18:1585-1592,
2002; Irizarry et al. Nucleic Acid Research, 31, 2003)MAS
normalized data was used for performing standard quality control
routines and the final data set was normalized with RMA for all
subsequent analyses.
[0231] Univariate Differential Expression
[0232] Differentially expressed gene transcripts were identified
using a moderated t-test implemented in the limma library
downloaded from the Bioconductor repository for R. (G. K. Smyth.
Statistical Applications in Genetics and Molecular Biology,
3(1):Article 3, 2004; G K Smyth. Bioinformatics and Computational
Biology Solutions using R and Bioconductor. Springer, N.Y., 2005).
Significance estimates (p-values) were corrected to adjust for
multiple hypothesis testing using the Bonferonni correction.
[0233] Tissue Specific Expression Patterns
[0234] To construct a filter for hypothetically `turned on` gene
expression the mean expression level for all 44,928 probesets
across the full range of 454 tissues was first estimated. To
estimate an expression on/off threshold, the 44,928 mean values
were ranked and the expression value equivalent to the 30th
percentile across the dataset calculated. This arbitrary threshold
was chosen because it was theorized that the majority of
transcripts (and presumably more than 30%) in a given specimen
should be transcriptionally silenced. Thus this threshold
represents a conservative upper bound for what is estimated as
non-specific, or background, signal.
[0235] Gene Symbol Annotations
[0236] To map Affymetrix probeset names to official gene symbols
the annotation metadata available from Bioconductor was used.
hgu133plus2 library version 1.16.0, which was assembled using
Entrez Gene data downloaded on 15 Mar. 2007, was used.
[0237] Estimates of Performance Characteristics
[0238] Diagnostic utility for each table of markers shown herein
was estimated including: sensitivity, specificity, positive
predictive value, negative predictive value, likelihood ratio
positive, likelihood ratio negative. These estimates were
calculated in the same data used to discover the markers and will
therefore potentially overestimate the performance characteristics
in future tissue samples. To improve the generalisabilty of the
estimates a modified jackknife resampling technique was used to
calculate a less biased value for each characteristic.
[0239] Results
[0240] A range of univariate statistical tests were applied on
Affymetrix oligonucleotide microarray data to reveal human genes
that could be used to discriminate colorectal neoplastic tissues
from non-neoplastic tissues. There were further identified a number
of gene transcripts that appear to be useful for differentiating
colorectal adenomas from colorectal carcinoma. Also identified were
a subset of these transcripts that may have particular diagnostic
utility because due to the protein products being either secreted
or displayed on the cell surface of epithelial cells. Finally,
there were identified a further subset of transcripts expressed
specifically in neoplastic tissues and at low- or near-background
levels in non-neoplastic tissues.
[0241] Genes Differentially Expressed in Neoplastic Tissues
[0242] From a total GeneChip set of 44,928 probesets it was
determined that over 11,000 probesets were differentially expressed
by moderated t-test using the limma package in BioConductor (G. K.
Smyth, 2004 supra) employing conservative (Bonferroni) multiple
test correction. When this list was further filtered to include
only those probesets demonstrating a 2-fold or greater mean
expression change between the neoplastic and non-neoplastic
tissues, 206 probesets were found to be expressed higher in
neoplasias relative to normals.
[0243] These 205 probesets were annotated using the most recent
metadata and annotation packages available for the chips. The 205
overexpressed probesets were mapped to 174 gene symbols.
TABLE-US-00033 .DELTA.-expression ProbeSet ID Gene Symbol Maps UP
205 157
[0244] Hypothetical Markers Specific for Colorectal Neoplasia
[0245] While differential gene expression patterns are useful for
diagnostic purposes, this project also seeks to identify diagnostic
proteins shed into the lumen of the gut by neoplastic colorectal
epithelia. To discover candidate proteins the list of
differentially expressed transcripts were filtered with a selection
criteria aimed at identifying markers specifically expressed in
colorectal neoplasia tissues. This filter criteria is based on a
theoretical assumption that most genes on the GeneChip will be
turned `off` and that any microarray signals for such `off`
transcripts will reflect technical assay background and
non-specific oligonucleotide binding. Accordingly, to select genes
specifically expressed in neoplastic tumours (i.e. `on`) the
non-neoplastic signals were compared with a hypothetical background
signal threshold from across all genes on the chip. By design, all
transcripts in the candidate pool from which the `on` transcripts
are chosen are at least two fold overexpressed in the diseased
tissues. Combined, it is hypothesized that these criteria yield the
subset of differentially expressed genes that are specifically
expressed in neoplasia. The expression profile for a representative
`on` transcript is shown in FIG. 1.
[0246] Genes Differentially Expressed Between Adenomas and Cancer
Tissues
[0247] There were 33 transcripts observed that were differentially
expressed at least two-fold higher in adenoma tissues relative to
cancer tissues. In particular, there were identified several
transcripts that exhibit an expression pattern specific for
adenomas, including SLITRK6 and L1TD1, shown in FIG. 2.
[0248] Further, there were also identified cancer specific
transcripts. The expression profile of one such transcript, COL11A1
is shown in FIG. 3.
EXAMPLE 2
Probesets Elevated in Neoplasia
[0249] Differential expression analysis was applied to Affymetrix
gene chip data measuring RNA concentration in 454 colorectal
tissues including 161 adenocarcinoma specimens, 29 adenoma
specimens, 42 colitis specimens and 222 non-diseased tissues. Using
conservative corrections for multiple hypothesis testing, it was
determined that over 25% of the 44,928 probesets measured in each
tissue experiment were differentially expressed between the 190
neoplasia specimens and 264 non-neoplasia controls. To identify
robust biomarkers for colorectal neoplasia the list of putative
probeset biomarkers were further filtered to include only those
probesets shown to be expressed at least 2-fold higher in
neoplastic vs. non-neoplastic tissues.
[0250] 205 probesets hybridising to approximately 157 putative
genes were observed to be expressed at a statistically significant
higher level in neoplastic tissues relative to non-neoplastic
controls.
[0251] Validation/Hypothesis Testing
[0252] To validate these discovery results the hybridisation of 199
candidate probesets were measured against RNA extracts from 68
clinical specimens comprising 19 adenomas, 19 adenocarcinomas, and
30 non-diseased controls using a custom-designed `Adenoma Gene
Chip`. Six (6) probesets were not tested as they were not included
on the custom design. It was confirmed that 186/199 (88%) of the
target probesets or probesets which also hybridise to the target
locus were likewise differentially expressed (P<0.05) in these
independently-derived tissues. The results of testing these
probesets in 68 independently collected clinical specimens is shown
in Table 1.
[0253] We further tested the 142 of the 157 unique gene loci to
which the 205 probesets are understood to hybridise. We note the
remaining 15 gene symbols were not represented in the validation
data. We observed that 133 of 142 gene symbols were represented in
the validation data by at least one differentially expressed
probeset and many symbols included multiple probesets against
regions across the putative locus. A complete list of probesets
that bind to target loci is shown in Table 2.
[0254] Conclusion
[0255] The candidate probesets shown in Tables 1 and 2 are
differentially expressed in neoplastic colorectal tissues compared
to non-neoplastic controls.
EXAMPLE 3
Probesets Demonstrating a Neoplasia-Specific Profile
[0256] During analysis of the data, a novel expression profile was
observed between neoplastic and non-neoplastic phenotypes. It was
hypothesized that a subset of quantitatively differentially
expressed probesets are furthermore qualitatively differentially
expressed. Such probesets show evidence of a neoplasia-specific
gene expression profile, i.e. these probesets appear to be
expressed above background levels in neoplastic tissues only. This
observation and the resulting hypothesis are based on two
principles: [0257] 1. That the majority of human transcripts that
are present on a genome-wide GeneChip (e.g. U133) will not likely
be expressed in the colorectal mucosa; and [0258] 2. That
microarray binding intensity for such `off` probesets to labelled
cRNA will reflect technical assay background, i.e. non-specific
oligonucleotide binding.
[0259] To generate a list of neoplasia specific probesets the
non-neoplastic intensity of differentially expressed probesets was
compared with a hypothetical background signal threshold from
across all probesets on the chip. Bydesign, all probesets in the
candidate pool from which the `on` transcripts are chosen are at
least two fold over-expressed in the diseased tissues. Combined,
these criteria yield the subset of differentially expressed
transcript species that are specifically expressed in
neoplasia.
[0260] Validation/Hypothesis Testing
[0261] The custom gene chip design precludes testing the
hypothetically neoplasia-specific probesets using the same
principles as used for discovery. In particular, the custom gene
chip (by design) does not contain a large pool of probesets
anticipated to hybridise to hypothetically `off`/'non-transcribed'
gene transcripts. This is because the custom gene chip design is
biased toward differentially expressed transcripts in colorectal
neoplastic tissues.
[0262] The usual differential expression testing (limma) was
therefore to these candidate probesets for neoplasia-specific
transcripts. Of the 33 probesets on the custom gene chip, 32
probesets (or probesets which bind to the same locus) were
differentially expressed between the 38 neoplastic tissues (adenoma
& cancer) and non-neoplastic controls. The results of these
validation experiments is shown in Table 3.
[0263] All probesets which are known to hybridise to the gene loci
to which the 33 probesets claimed herein were tested. Of the 32
putative gene loci targeted by the probesets, 29 were present in
the validation data. Twenty-eight (28) of these 29 gene symbols
demonstrated at least one hybridising probeset which was
differentially expressed in the neoplastic tissues. Results for
these experiments, including all probesets that bind to each target
locus in a differentially expressed manner are shown in Table
4.
EXAMPLE 4
Probesets Useful for Characterizing Neoplastic Tissues
[0264] Differential expression analysis was applied to Affymetrix
gene chip data measuring RNA concentration in neoplastic tissues
including 161 adenocarcinoma specimens and 29 adenoma specimens. It
was observed that 43 probesets hybridizing to approximately 33
putative gene symbols were expressed higher (P<0.05) in adenoma
tissues relative to cancer tissues. Conversely, 145 probesets (104
gene symbols) were identified to be expressed higher in cancer
relative to adenomas.
[0265] Validation/Hypothesis Testing 188 (43+145) of these
probesets were then measured in a set of independent clinical
specimens including 19 adenoma tissues and 19 cancer tissues. It
was confirmed that 158 (30+128) of the target probesets (or
probesets against the same gene locus) were likewise differentially
expressed (P<0.05) in these independently-derived tissues.
Probesets elevated in adenoma and cancers relative to each other
are shown in Table 5 and Table 6 respectively.
[0266] It was further observed that 137 (33+104) gene loci are
diagnostically useful for discriminating colorectal adenomas and
cancers relative to each phenotype. The validation data included
probesets designed to hybridise to 128 of these candidate gene
symbols. It was observed that 21 of the 31 genes elevated in
adenomas relative to cancers were likewise differentially expressed
by at least one probeset. Of the 97 gene symbols elevated in cancer
relative to adenoma it was confirmed that 89 gene symbols
demonstrated at least one probeset in the validation data to be
likewise differentially expressed. The validation testing of the
adenoma and cancer elevated gene loci is shown in Table 7 and Table
8, respectively.
[0267] Conclusion
[0268] It was concluded that the candidate probesets shown in FIXME
are differentially expressed between adenomatous and adenocarcinoma
tissues and thus useful for distinguishing these tissues. Gene
transcripts that hybridise to these probesets are thus
diagnostically informative in a clinical setting to classify such
neoplastic tissues.
EXAMPLE 5
Materials and Methods for Examples 2 To 3
[0269] Gene expression profiling data measured in 454 colorectal
tissue specimens including neoplastic, normal and non-neoplastic
disease controls was purchased from GeneLogic Inc (Gaithersburg,
Md. USA). For each tissue specimen an Affymetrix (Santa Clara,
Calif. USA) oligonucleotide microarray data totalling 44,928
probesets (HGU133A & HGU133B, combined), experimental and
clinical descriptors, and digitally archived microscopy images of
histological preparations was received. Prior to applying discovery
methods to these data extensive quality control methods were
carried out, including statistical exploration, review of clinical
records for consistency and histopathology audit of a random sample
of arrays. Microarrays that did not meet acceptable quality
criteria were removed from the analysis.
[0270] Hypothesis Testing
[0271] Candidate transcription biomarkers were tested using a
custom oligonucleotide microarray of 25-mer oligonucleotide
probesets designed to hybridise to candidate RNA transcripts
identified during discovery. Differential expression hypotheses
were tested using RNA extracts derived from independently collected
clinical samples comprising 30 normal colorectal tissues, 19
colorectal adenoma tissues, and 19 colorectal adenocarcinoma
tissues. Each RNA extract was confirmed to meet strict quality
control criteria.
[0272] Colorectal Tissue Specimens
[0273] All tissues used for hypothesis testing were obtained from a
tertiary referral hospital tissue bank in metropolitan Adelaide,
Australia (Repatriation General Hospital and Flinders Medical
Centre). Access to the tissue bank for this research was approved
by the Research and Ethics Committee of the Repatriation General
Hospital and the Ethics Committee of Flinders Medical Centre.
Informed patient consent was received for each tissue studied.
[0274] Following surgical resection, specimens were placed in a
sterile receptacle and collected from theatre. The time from
operative resection to collection from theatre was variable but not
more than 30 minutes. Samples, approximately 125 mm3
(5.times.5.times.5 mm) in size, were taken from the macroscopically
normal tissue as far from pathology as possible, defined both by
colonic region as well as by distance either proximal or distal to
the pathology. Tissues were placed in cryovials, then immediately
immersed in liquid nitrogen and stored at -150C until
processing.
[0275] RNA extraction
[0276] RNA extractions were performed using Trizol(R)reagent
(Invitrogen, Carlsbad, Calif., USA) as per manufacturer's
instructions. Each sample was homogenised in 300 .mu.L of Trizol
reagent using a modified Dremel drill and sterilised disposable
pestles. An additional 200 .mu.L of Trizol reagent was added to the
homogenate and samples were incubated at RT for 10 minutes. 100
.mu.L of chloroform was then added, samples were shaken vortexed
for 15 seconds, and incubated at RT for 3 further minutes. The
aqueous phase containing target RNA was obtained by centrifugation
at 12,000 rpm for 15 min, 40 C. RNA was then precipitated by
incubating samples at RT for 10 min with 250 .mu.L of isopropanol.
Purified RNA precipitate was collected by centrifugation at 12,000
rpm for 10 minutes, 40 C. and supernatants were discarded. Pellets
were then washed with 1 mL 75% ethanol, followed by vortexing and
centrifugation at 7,500g for 8 min, 40 C. Finally, pellets were
air-dried for 5 min and resuspended in 80 .mu.L of RNase free
water. To improve subsequent solubility samples were incubated at
55.degree. C. for 10 min. RNA was quantified by measuring the
optical density at A260/280 nm. RNA quality was assessed by
electrophoresis on a 1.2% agarose formaldehyde gel.
[0277] Gene Chip Processing
[0278] To test hypotheses related to biomarker candidates for
colorectal neoplasia RNA extracts were assayed using a custom
GeneChip designed in collaboration with Affymetrix (Santa Clara,
Calif. USA). These custom GeneChips were processed using the
standard Affymetrix protocol developed for the HU Gene ST 1.0 array
described in (Affy:WTAssay).
[0279] Statistical software and Data Processing
[0280] The R statistics environment R and BioConductor libraries
(BioConductor, www.bioconductor.org) (BIOC) were used for most
analyses. To map probeset IDs to gene symbol on the Custom
GeneChip, hgu133plus2 library version 2.2.0, which was assembled
using Entrez Gene data downloaded on Apr 18 12:30:55 2008 (BIOC)
was used.
[0281] Hypothesis Testing of Differentially Expressed
Biomarkers
[0282] To assess differential expression between tissue classes,
the Student's t test for equal means between two samples or the
robust variant provided by the limma library (Smyth)(limma) was
used. The impact of false discovery due to multiple hypothesis
testing was mitigated by applying a Bonferroni adjustment to P
values in the discovery process (MHT:Bonf). For hypotheses testing
the slightly less conservative multiple hypothesis testing
correction of Benjamini & Hochberg, which aims to control the
false discovery rate of solutions(MHT:BH) was applied.
[0283] Discovery of Tissue-Specific Gene Expression Patterns
[0284] Discovery methods using gene expression data often yield
numerous candidates, many of which are not suitable for commercial
products because they involve subtle gene expression differences
that would be difficult to detect in laboratory practice. Pepe et
al. note that the `ideal` biomarker is detectable in tumor tissue
but not detectable (at all) in non-tumour tissue
(Pepe:biomarker:development.) To bias toward candidates that meet
this criterion, an analysis method was developed that aims to
enrich the candidates for biomarkers whose qualitative absence or
presence measurement is diagnostic for the phenotype of interest.
This method attempts to select candidates that show a prototypical
`turned-on` or `turned-off` pattern relative to an estimate of the
background/noise expression across the chip. Such RNA transcripts
are more likely to correlate with downstream translated proteins
with diagnostic potential or to predict upstream genomic changes
(e.g. methylation status) that can be used diagnostically. This
focus on qualitative rather than quantitative outcomes may simplify
the product development process for such biomarkers.
[0285] The method is based on the assumption that the pool of
extracted RNA species in any given tissue (e.g. colorectal mucosae)
will specifically bind to a relatively small subset of the full set
of probesets on a GeneChip designed to measure the whole genome. On
this assumption, it is estimated that most probesets on a full
human gene chip will not exhibit specific, high-intensity
signals.
[0286] This observation is utilised to approximate the background
or `non-specific binding` across the chip by choosing a theoretical
level equal to the value of e.g. lowest 30% quantile of the ranked
mean values. This quantile can be arbitrarily set to some level
below which a reasonable assumption is made that the signals do not
represent above-background RNA binding. Finally, this background
estimate is used as a threshold to estimate the `OFF` probesets in
an experiment for, say, the non-neoplastic tissue specimens.
[0287] Conversely, probesets which are 1) expressed above this
theoretical threshold level and 2) at differentially higher levels
in the tumour specimens may be a tumour specific candidate
biomarker. In this case the concept of `fold-change` thresholds can
also be conveniently applied to further emphasize the concept of
absolute expression increases in a putatively `ON` probeset.
[0288] Given the assumption of low background binding for a
sizeable fraction of the measured probesets, this method was only
used in the large GeneLogic data and discovery. To construct a
filter for hypothetically `turned on` biomarkers in the GeneLogic
discovery data, the mean expression level for all 44,928 probesets
was first estimated across the full range of 454 tissues. The
44,928 mean values were then ranked and the expression value
equivalent to the 25th percentile across the dataset calculated.
This arbitrary threshold was chosen because it was theorized that
the majority of transcripts (and presumably more than 25%) in a
given specimen should exhibit low concentration which effectively
transcriptional silence. Thus this threshold represents a
conservative upper bound for what is estimated as non-specific, or
background, expression.
EXAMPLE 6
Determine Gene Identity of a Nucleic Acid Sequence of Interest
which is Define by an Affymetrix Probeset
[0289] BLAST the sequence of interest using online available Basic
Local Alignment Search Tools [BLAST]. e.g. NCBI/BLAST [0290]
(http://blast.ncbi.nlm.nih.gov/Blast.cgi) [0291] (a) Select "Human"
in BLAST ASSEMBLED GENOMES on the web page
http://blast.ncbi.nlm.nih.gov/Blast.cgi [0292] (b) Leave the
default settings, i.e.: [0293] Database: Genome (all assemblies)
[0294] Program: megaBLAST: compare highly related nucleotide
sequences [0295] Optional parameters: Expect: 0.01, Filter:
default, Descriptions: 100, Alignments: 100 [0296] (c) Copy/Paste
Sequence into the "BLAST" window [0297] (d) Click "Begin Search"
[0298] (e) Click "View Report"
[0299] Assessment of the Open BLAST Search Results
[0300] Multiple significant sequence alignments may be identified
when "blasting" the sequence.
[0301] Identify Gene Nomenclature of the Identified Sequence Match
[0302] (a) Click the link to one of the identified hits [0303] (b)
The new page will schematically depict the position of the hit on
one chromosome. It will be apparent which gene is hit. [0304] (c)
Retrieve the "hit" sequence clicking on the link [0305] (d) Do a
search for the gene in the provided "search" window. This provides
the gene nucleotide coordinates for the gene.
[0306] Determine Promiscuity of Sequence [0307] (a) Open the
NCBI/BLAST tool, (http://blast.ncbi.nlm.nih.gov/Blast.cgi) [0308]
(b) Click on "nucleotide Blast" under "basic BLAST" [0309] (c)
Copy/paste the sequence of interest into the "Query Sequence"
window [0310] (d) Click "Blast".
[0311] Assessment of the nBLAST Search Results of the Sequence
[0312] (a) The nBLAST exercise with the Sequence may result in
multiple Blast hits of which some accession entry numbers are
listed in "Description". [0313] (b) These hits should be
reviewed.
[0314] Determine Location of the Sequence in the Gene
[0315] The Ensembl database is an online database, which produces
and maintains automatic annotation selected eukaryotic genomes
(www.ensembl.orq/index.html)
[0316] Identify Location of the Sequence in the Gene [0317] (a) Set
"Search" to Homo Sapiens, Type "the gene name" in the provided
Search Field Ensemble.org/index.html) [0318] (b) Click "Go" [0319]
(c) Click the "vega protein_coding Gene: OTTHUMG000000144184" link
to get an annotation report [0320] (d) Click on "Gene DAS Report"
to retrieve information regarding Alternative splice site database:
Type "the gene name" in search field [0321] Click on "the gene
entry" [0322] Scroll down to "evidence" [0323] Review alternative
splice sites [0324] Click "Confirmed intron/exons" to get a list of
coordinates for the exons & introns.
[0325] Alternative Splicing and/or Transcription
[0326] The AceView Database provides curated and non-redundant
sequence representation of all public mRNA sequences. The database
is available through NCBI:
http;//www.ncbi.nlm.nih.gov/IEB/Research/Acembly/
[0327] Further Investigation of the Gene mRNA Transcripts [0328]
(a) Type "the gene name" into the provided "search" field [0329]
(b) Click "Go" [0330] (c) The following information is available
from the resulting entry in AceView: [0331] The number of cDNA
clones from which the gene is constructed (ie originated-from
experimental work involving isolation of mRNA) [0332] The mRNAs
predicted to be produced by the gene [0333] The existence of
non-overlapping alternative exons and validated alternative
polyadenylation sites [0334] The existence of truncations [0335]
The possibility of regulated alternate expression [0336] Introns
recorded as participating in alternatively splicing of the gene
[0337] (d) Classic splice site motives
[0338] Application of Method to LOC643911/hCG_1815491
[0339] Materials and Methods
[0340] Extraction of RNA
[0341] RNA extractions were performed using Trizol(R) reagent
(Invitrogen, Carlsbad, Calif., USA) as per manufacturer's
instructions. Each sample was homogenised in 300 .mu.L of Trizol
reagent using a modified dremel drill and sterilised disposable
pestles. Additional 200 .mu.L of Trizol reagent was added to the
homogenate and samples were incubated at RT for 10 minutes. 100
.mu.L of chloroform was then added, samples were shaken vortexed
for 15 seconds, and incubated at RT for 3 further minutes. The
aqueous phase containing target RNA was obtained by centrifugation
at 12,000 rpm for 15 min, 40.degree. C. RNA was then precipitated
by incubating samples at RT for 10 min with 250 .mu.L of
isopropanol. Purified RNA precipitate was collected by
centrifugation at 12,000 rpm for 10 minutes, 40. C and supernatants
were discarded. Pellets were then washed with 1 mL 75% ethanol,
followed by vortexing and centrifugation at 7,500 g for 8 min,
40.degree. C. Finally, pellets were air-dried for 5 min and
resuspended in 80 .mu.L of RNase free water. To improve subsequent
solubility samples were incubated at 55.degree. C. for 10 min. RNA
was quantified by measuring the optical density at A260/280 nm. RNA
quality was assessed by electrophoresis on a 1.2% agarose
formaldehyde gel.
[0342] Gene Chip Processing
[0343] RNA samples to analyze on Human Exon 1.0 ST GeneChips were
processed using the Affymetrix WT target labeling and control kit
(part# 900652) following the protocol described in (Affymetrix 2007
P/N 701880 Rev.4). Briefly: First cycle cDNA was synthesized from
100 ng ribosomal reduced RNA using random hexamer primers tagged
with T7 promoter sequence and SuperScript II (Invitrogen, Carlsbad
Calif.), this was followed by DNA Polymerase I synthesis of the
second strand cDNA. Anti-sense cRNA was then synthesized using T7
polymerase. Second cycle sense cDNA was then synthesised using
SuperScript II, dNTP+dUTP, and random hexamers to produce sense
strand cDNA incorporating uracil. This single stranded uracil
containing cDNA was then fragmented using a combination of uracil
DNA glycosylase (UDG) and apurinic/apyrimidinic endonuclease1 (APE
1). Finally the DNA was biotin labelled using terminal
deoxynucleotidyl transferase (TdT) and the Affymetrix proprietary
DNA Labeling reagent. Hybridization to the arrays was carried out
at 45.degree. C. for 16-18hours.
[0344] Washing and staining of the hybridized GeneChips was carried
out using the Affymetrix Fluidics Station 450 and scanned with the
Affymetrix Scanner 3000 following recommended protocols.
[0345] SYBR Green Based Quantitative Real Time-PCR
[0346] Quantitative real time polymerase chain reaction was
performed on RNA isolated from clinical samples for the
amplification and detection of the various hCG_1815491
transcripts.
[0347] Firstly cDNA was synthesized from 2ug of total RNA using the
Applied Biosystems High Capacity Reverse transcription Kit (P/N
4368814). After synthesis the reaction was diluted 1:2 with water
to obtain a final volume of 40 ul and 1 ul of this diluted cDNA
used in subsequent PCR reactions.
[0348] PCR was performed in a 25 ul volume using 12.5 ul Promega
2.times. PCR master mix (P/N M7502), 1.5 ul 5 uM forward primer,
1.5 ul 5 uM reverse primer, 7.875 ul water, 0.625 ul of a 1:3000
dilution of 10,000.times. stock of SYBR green 1 pure dye
(Invitrogen P/N S7567), and 1 ul of cDNA.
[0349] Cycling conditions for amplification were 95.degree. for
2minutes.times.1 cycle, 95.degree. for 15 seconds and 60.degree.
for 1 minute.times.40 cycles. The amplification reactions were
performed in a Corbett Research Rotor-Gene RG3000 or a Roche
LightCycler480 real-time PCR machine. When the Roche LightCycler480
real-time PCR machine was used for amplification the reaction
volume was reduced to 10 ul and performed in a 384 well plate but
the relative ratios between all the components remained the same.
Final results were calculated using the .DELTA..DELTA.Ct method
with the expression levels of the various hCG_1815491 transcripts
being calculated relative to the expression level of the endogenous
house keeping gene HPRT.
[0350] End-Point PCR
[0351] End point PCR was performed on RNA isolated from clinical
samples for the various hCG_1815491 transcripts. Conditions were
identical to those described for the SYBR green assay above but
with the SYBR green dye being replaced with water. The
amplification reactions were performed in a MJ Research PTC-200
thermal cycler. 2.5 .mu.l of the amplified products were analysed
on 2% agarose E-gel (Invitrogen) along with a 100-base pair DNA
Ladder Marker.
[0352] Results
[0353] The nucleotide structure and expression levels of
transcripts related to hCG_1815491 was analysed based on the
identification of diagnostic utility of Affymetrix probesets
238021_s_at and 238022_at from the gene chip analysis.
[0354] The gene hCG_1815491 is currently represented in NCBI as a
single RefSeq sequence, XM_93911. The RefSeq sequence of
hCG_1815491 is based on 89 GenBank accessions from 83 cDNA clones.
Prior to March 2006, these clones were predicted to represent two
overlapping genes, LOC388279 and LOC650242 (the latter also known
as LOC643911). In March 2006, the human genome database was
filtered against clone rearrangements, co-aligned with the genome
and clustered in a minimal non-redundant way. As a result,
LOC388272 and LOC650242 were merged into one gene named hCG_1815491
(earlier references to hCG_1815491 are: LOC388279, LOC643911,
LOC650242, XM_944116, AF275804, XM_373688). It has been determined
that the Ref Sequence, which is defined by the genomic coordinates
8579310 to 8562303 on human chromosome 16 as defined by the NCBI
contig reference NT_010498.15|Hs16_10655, NCBI 36 March 2006 genome
encompasses hCG_1815491. The 10 predicted RNA variants derived from
this gene have been aligned with the genomic nucleotide sequence
residing in the map region 8579310 to 8562303. This alignment
analysis revealed the existence of at least 6 exons of which
several are alternatively spliced. The identified exons are in
contrast to the just 4 exons specified in the NCBI hCG_1815491
RefSeq XM_93911. Two additional putative exons were also identified
in the Ref Sequence by examination of included probesets on
Affymetrix Genechip HuGene Exon 1.0 that target nucleotide
sequences embedded in the Ref Sequence. The identified and expanded
exon-intron structure of hCG_1815491 have been used to design
specific oligonucleotide primers, which allowed measurement of the
expression of RNA variants generated from the Ref Sequence by using
PCR-based methodology (FIG. 4)
EXAMPLE 7
[0355] Immunohistochemistry is a useful method for evaluating
changes in local expression of up or down-regulated markers in
human tissue.
[0356] Materials and Methods:
[0357] Four micrometre sections were incubated in a universal
decloaking buffer for 75 minutes at 80 .mu.L to expose masked
epitopes. Protein expression was determined using an antibody
targeting the C-terminal domain of Mesothelin (MSLN) on colonic
biopsies from 30 patients (10 normals, 10 cancers, 10 adenomas).
Antibodies were applied for one hour at room temperature. After
washing, sections were incubated with polymeric horse-radish
peroxidase. Antibody localization was visualized using 3'3'
diaminobenzidine.
[0358] Result:
[0359] There was a marked upregulation of MSLN in the adenoma and
cancer tissues compared to the normal controls. The normal tissues
showed mild staining for MSLN in the cytoplasm of the colonic
epithelium but the cancer and particularly the adenomas tissues
shows significant upregulation of MSLN in their multilayered
epithelium. This upregulation was observed in all 10 adenomas
tissue and in 9 out of the 10 cancer tissues. These patterns of
staining are illustrated in FIGS. 4, 5 and 6.
[0360] Conclusion:
[0361] Elevated expression of MSLN has been detected in colon
neoplasia, confirming the upregulation observed in the mRNA
expression data and verifying the diagnostic utility of both the
MSLN mRNA and protein for detection of colorectal neoplasia.
EXAMPLE 8
Evidence of MMP3 Protein Expression in Stools of Patients with
Colorectal Neoplasia
[0362] Affymetrix probeset designated 205828_at was identified to
be expressed higher in 190 neoplastic tissue specimens relative to
264 non-neoplastic specimens. The probeset 205828_at hybridizes to
RNA transcribed from the gene encoding Matrix Metalloproteinase 3
(MMP3) NM_002422. The differential expression profile of probeset
205828_at was further demonstrated by profiling RNA collected from
68 independent clinical specimens comprising 19 adenomas, 19
adenocarcinomas and 30 non-disease controls, FIG. 7.
[0363] Materials and Methods
[0364] A commercially available bead-suspension immunoassay
targeting the protein MMP3 was purchased from R&D Systems (MMP
Kit reagents LMP000 and LMP513) to measure MMP3 concentration in
stools of human patients diagnosed with colorectal neoplasia.
Proteins were extracted from stool specimens using a phosphate
buffered saline wash from 6 non-disease controls, 10 adenoma and 11
adenocarcinoma subjects. The resulting protein extracts were
analyzed using the Luminex bead-based suspension MMP3 assay as
recommended by manufacturer.
[0365] Results
[0366] An elevated endogenous expression of MMP3 was observed in
stool specimens from patients diagnosed with colon adenomas or
adenocarcinomas relative to non-neoplastic controls (FIG. 8).
[0367] Conclusion
[0368] Measurement of MMP3 protein in bodily fluids such as stool
samples is useful for diagnosing colorectal neoplasia.
[0369] Tables
[0370] Probeset designations include both HG-133plus2 probeset IDs
and Human Gene 1.0 ST array probe ids. The latter can be
conveniently mapped to Transcript Cluster ID using the Human Gene
1.0ST probe tab file provided by Affymetrix
(http://www.affymetrix.com/Auth/analysis/downloads/na22/wtgene/HuGene-1_0-
-st-v1.probe.tab.zip). Using publicly available software such as
NetAffx (provided by Affymetrix), the Transcript Cluster ID may be
further mapped to gene symbol, chromosomal location, etc.
[0371] Table 1.
[0372] Probesets demonstrated to be expressed higher in neoplastic
tissues relative to non-neoplastic controls. TargetPS: Affymetrix
HG-U133plus2 probeset id; Symbol: putative gene symbol
corresponding to target probeset id--multiple symbol names indicate
the possibility of probeset hybridisation to multiple gene targets;
Signif. FDR: Adjusted p-value for mean difference testing between
RNA extracted from neoplasia and non-neoplastic tissues. Adjustment
is made using Benjamini & Hochberg correction for multiple
hypothesis testing (Benjamini and Hochberg, 1995); D.value50:
Diagnostic effectiveness parameter estimate corresponding to the
area of a receiver operator characteristic ROC. This parameter
provides a convenient estimate of diagnostic utility and is
described in (Saunders, 2006); FC: fold change between mean
expression level of neoplasia vs. non-neoplasia; Sens-Spec:
Estimate of diagnostic performance corresponding to the ROC curve
point demonstrating equal sensitivity and specificity; CI (95): 95%
confidence interval of sensitivity and specificity estimates.
[0373] Table 2.
[0374] Evidence of multiple probesets which correspond to gene
symbols claimed herein exhibiting RNA concentration differences
between neoplasia and non-neoplastic controls. Symbol: gene symbol;
ValidPS_UP: Affymetrix probeset IDs demonstrating statistically
significant overexpression in neoplastic RNA extracts relative to
non-neoplastic controls. Signif. FDR: Adjusted p-value for mean
difference testing between RNA extracted from neoplasia and
non-neoplastic tissues. Adjustment is made using Benjamini &
Hochberg correction for multiple hypothesis testing (Benjamini and
Hochberg, 1995); D.value50: Diagnostic effectiveness parameter
estimate corresponding to the area of a receiver operator
characteristic ROC. This parameter provides a convenient estimate
of diagnostic utility and is described in (Saunders, 2006); FC:
fold change between mean expression level of neoplasia vs.
non-neoplasia; Sens-Spec: Estimate of diagnostic performance
corresponding to the ROC curve point demonstrating equal
sensitivity and specificity; CI (95): 95% confidence interval of
sensitivity and specificity estimates.
Example 2
[0375] Table 3.
[0376] Probesets which demonstrate a qualitatively (in addition to
quantitative) elevated profile in neoplastic tissues relative to
non-neoplastic controls. TargetPS: Affymetrix HG-U133plus2 probeset
id; Symbol: putative gene symbol corresponding to target probeset
id--multiple symbol names indicate the possibility of probeset
hybridisation to multiple gene targets; Signif. FDR: Adjusted
p-value for mean difference testing between RNA extracted from
neoplasia and non-neoplastic tissues. Adjustment is made using
Benjamini & Hochberg correction for multiple hypothesis testing
(Benjamini and Hochberg, 1995); D.value50: Diagnostic effectiveness
parameter estimate corresponding to the area of a receiver operator
characteristic ROC. This parameter provides a convenient estimate
of diagnostic utility and is described in (Saunders, 2006); FC:
fold change between mean expression level of neoplasia vs.
non-neoplasia; Sens-Spec: Estimate of diagnostic performance
corresponding to the ROC curve point demonstrating equal
sensitivity and specificity; CI (95): 95% confidence interval of
sensitivity and specificity estimates.
[0377] Table 4.
[0378] Evidence of multiple probesets which correspond to gene
symbols claimed herein exhibiting qualitative changes in RNA
concentration in neoplastic tissues. Symbol: gene symbol;
ValidPS_UP: Affymetrix probeset IDs demonstrating statistically
significant overexpression in neoplastic RNA extracts relative to
non-neoplastic controls. Signif. FDR: Adjusted p-value for mean
difference testing between RNA extracted from neoplasia and
non-neoplastic tissues. Adjustment is made using Benjamini &
Hochberg correction for multiple hypothesis testing (Benjamini and
Hochberg, 1995); D.value50: Diagnostic effectiveness parameter
estimate corresponding to the area of a receiver operator
characteristic ROC. This parameter provides a convenient estimate
of diagnostic utility and is described in (Saunders, 2006); FC:
fold change between mean expression level of neoplasia vs.
non-neoplasia; Sens-Spec: Estimate of diagnostic performance
corresponding to the ROC curve point demonstrating equal
sensitivity and specificity; CI (95): 95% confidence interval of
sensitivity and specificity estimates.
[0379] Table 5
[0380] Probesets demonstrated to be expressed higher in adenoma
tissues relative to cancer tissues. TargetPS: Affymetrix
HG-U133plus2 probeset id; Symbol: putative gene symbol
corresponding to target probeset id--multiple symbol names indicate
the possibility of probeset hybridisation to multiple gene targets;
Signif. FDR: Adjusted p-value for mean difference testing between
RNA extracted from neoplasia and non-neoplastic tissues. Adjustment
is made using Benjamini & Hochberg correction for multiple
hypothesis testing (Benjamini and Hochberg, 1995); D.value50:
Diagnostic effectiveness parameter estimate corresponding to the
area of a receiver operator characteristic ROC. This parameter
provides a convenient estimate of diagnostic utility and is
described in (Saunders, 2006); FC: fold change between mean
expression level of adenomas vs. cancers; Sens-Spec: Estimate of
diagnostic performance corresponding to the ROC curve point
demonstrating equal sensitivity and specificity; CI (95): 95%
confidence interval of sensitivity and specificity estimates.
[0381] Table 6
[0382] Probesets demonstrated to be expressed higher in cancer
tissues relative to adenoma tissues. TargetPS: Affymetrix
HG-U133plus2 probeset id; Symbol: putative gene symbol
corresponding to target probeset id--multiple symbol names indicate
the possibility of probeset hybridisation to multiple gene targets;
Signif. FDR: Adjusted p-value for mean difference testing between
RNA extracted from neoplasia and non-neoplastic tissues. Adjustment
is made using Benjamini & Hochberg correction for multiple
hypothesis testing (Benjamini and Hochberg, 1995); D.value50:
Diagnostic effectiveness parameter estimate corresponding to the
area of a receiver operator characteristic ROC. This parameter
provides a convenient estimate of diagnostic utility and is
described in (Saunders, 2006); FC: fold change between mean
expression level of cancer tissues vs. adenoma tissues; Sens-Spec:
Estimate of diagnostic performance corresponding to the ROC curve
point demonstrating equal sensitivity and specificity; CI (95): 95%
confidence interval of sensitivity and specificity estimates.
[0383] Table 7
[0384] Evidence of multiple probesets which correspond to gene
symbols claimed herein exhibiting RNA concentration differences
between adenoma and cancer tissues. Symbol: gene symbol;
ValidPS_UP: Affymetrix probeset IDs demonstrating statistically
significant overexpression in neoplastic RNA extracts relative to
non-neoplastic controls. Signif. FDR: Adjusted p-value for mean
difference testing between RNA extracted from neoplasia and
non-neoplastic tissues. Adjustment is made using Benjamini &
Hochberg correction for multiple hypothesis testing (Benjamini and
Hochberg, 1995); D.value50: Diagnostic effectiveness parameter
estimate corresponding to the area of a receiver operator
characteristic ROC. This parameter provides a convenient estimate
of diagnostic utility and is described in (Saunders, 2006); FC:
fold change between mean expression level of adenoma tissues vs.
cancer tissues; Sens-Spec: Estimate of diagnostic performance
corresponding to the ROC curve point demonstrating equal
sensitivity and specificity; CI (95): 95% confidence interval of
sensitivity and specificity estimates.
[0385] Table 8
[0386] Evidence of multiple probesets which correspond to gene
symbols claimed herein exhibiting RNA concentration differences
between cancer and adenoma tissues. Symbol: gene symbol;
ValidPS_UP: Affymetrix probeset IDs demonstrating statistically
significant overexpression in neoplastic RNA extracts relative to
non-neoplastic controls. Signif. FDR: Adjusted p-value for mean
difference testing between RNA extracted from neoplasia and
non-neoplastic tissues. Adjustment is made using Benjamini &
Hochberg correction for multiple hypothesis testing (Benjamini and
Hochberg, 1995); D.value50: Diagnostic effectiveness parameter
estimate corresponding to the area of a receiver operator
characteristic ROC. This parameter provides a convenient estimate
of diagnostic utility and is described in (Saunders, 2006); FC:
fold change between mean expression level of cancer tissues vs.
adenoma tissues; Sens-Spec: Estimate of diagnostic performance
corresponding to the ROC curve point demonstrating equal
sensitivity and specificity; CI (95): 95% confidence interval of
sensitivity and specificity estimates.
[0387] Those skilled in the art will appreciate that the invention
described herein is susceptible to variations and modifications
other than those specifically described. It is to be understood
that the invention includes all such variations and modifications.
The invention also includes all of the steps, features,
compositions and compounds referred to or indicated in this
specification, individually or collectively, and any and all
combinations of any two or more of said steps or features.
TABLE-US-00034 TABLE 1 Signif. D.val Sens- TargetPS Symbol FDR 5 FC
Spec CI (95) 203256_at CDH3 3.75E-31 4.2476 37.54 98.3 95.5-99.5
200660_at S100A11:LOC730558: 2.68E-27 3.8969 3.83 97.4 93.9-99.1
LOC730278:LOC729659 201341_at ENC1 1.44E-26 3.667 3.93 96.7
92.6-98.7 212063_at MAPK10:CD44 3.35E-26 3.7161 7.06 96.8 92.9-98.8
217523_at MAPK10:CD44 3.35E-26 3.7151 7.06 96.8 92.9-98.8 201563_at
SORD 3.44E-25 3.4659 4.36 95.8 91.3-98.3 202431_s_at LOC731404:
5.19E-25 3.6014 4.11 96.4 92.2-98.6 LOC729194:MYC 221577_x_at GDF15
5.51E-25 3.5554 5.84 96.2 91.8-98.5 204702_s_at LOC650331:NFE2L3:
1.51E-24 3.52 4.57 96.1 91.6-98.4 LOC642996 203961_at NEBL 5.41E-24
3.5292 5.52 96.1 91.7-98.4 203962_s_at NEBL 5.41E-24 3.5295 5.52
96.1 91.7-98.4 201338_x_at GTF3A 1.74E-22 3.2283 2.92 94.7
89.6-97.6 215091_s_at GTF3A 1.74E-22 3.2283 2.92 94.7 89.5-97.6
207850_at CXCL2:CXCL3 5.76E-22 3.2874 7.85 95 90-97.8 222549_at
CLDN1 6.10E-22 3.2561 13.09 94.8 89.7-97.7 204259_at MMP7 7.61E-22
3.2624 69.29 94.9 89.8-97.7 228754_at SLC6A6:LOC728721 1.15E-21
3.2282 5.02 94.7 89.5-97.6 209774_x_at CXCL2:CXCL3 1.88E-21 3.2884
7.85 95 90-97.8 218872_at TESC 3.26E-21 3.2134 16.84 94.6 89.5-97.6
212942_s_at KIAA1199 8.12E-21 3.0489 25.16 93.6 88-97 209369_at
ANXA3 1.15E-20 3.0417 3.34 93.6 87.9-97 204404_at SLC12A2 1.40E-20
3.0281 3.42 93.5 87.9-96.9 225835_at SLC12A2 1.40E-20 3.0261 3.42
93.5 87.8-96.9 219911_s_at SLCO4A1 1.46E-20 3.0968 4.84 93.9
88.4-97.2 203510_at MET 1.50E-20 3.0806 3.35 93.8 88.3-97.1
202936_s_at SOX9 1.63E-20 3.0982 3.85 93.9 88.4-97.2 201416_at SOX4
2.30E-20 3.0179 2.89 93.4 87.8-96.9 201417_at SOX4 2.30E-20 3.0146
2.89 93.4 87.7-96.9 208712_at CCND1 7.06E-20 2.9082 2.85 92.7
86.7-96.4 204351_at S100P 4.56E-19 2.9463 4.37 93 87.1-96.6
227475_at FOXQ1 4.85E-19 2.9494 10.97 93 87.1-96.6 205983_at DPEP1
5.27E-19 2.8878 23.9 92.6 86.6-96.3 204470_at CXCL2:CXCL1 5.53E-19
2.9257 10.4 92.8 86.8-96.5 212531_at LCN2 5.68E-19 2.9407 14.6 92.9
87-96.5 217867_x_at BACE2 5.87E-19 2.9042 3.8 92.7 86.7-96.4
228915_at DACH1 1.05E-18 2.9218 5.81 92.8 86.9-96.5 218704_at RNF43
2.12E-18 2.9218 3.24 92.8 86.9-96.5 202504_at TRIM29 2.36E-18
2.8231 11.01 92.1 85.9-96 241031_at NLF1 3.12E-18 2.7999 8.12 91.9
85.6-95.9 201195_s_at SLC7A5:LAT1-3TM 5.11E-18 2.7562 6.31 91.6
85.2-95.7 201656_at ITGA6 7.38E-18 2.6842 2.62 91 84.5-95.3
229215_at ASCL2 7.76E-18 2.7573 7.73 91.6 85.3-95.7 217996_at
PHLDA1 1.34E-17 2.7007 5.27 91.2 84.6-95.4 205476_at CCL20 2.03E-17
2.6222 10.14 90.5 83.8-94.9 226360_at ZNRF3 2.03E-17 2.7245 4.91
91.3 84.9-95.6 219956_at GALNT6:ELA1 2.90E-17 2.682 5.27 91
84.4-95.3 201506_at TGFBI 4.14E-17 2.6863 4.31 91 84.5-95.3
212070_at GPR56 7.45E-17 2.5866 2.6 90.2 83.5-94.7 212281_s_at
LOC731966: 1.88E-16 2.583 2.77 90.2 83.4-94.7 LOC729599: TMEM97
202831_at GPX2 4.00E-16 2.397 3.56 88.5 81.2-93.5 225541_at
LOC442108: 4.37E-16 2.5983 4.19 90.3 83.5-94.8 RPL22L1 218984_at
PUS7:LOC730279 5.26E-16 2.6006 3.06 90.3 83.6-94.8 219630_at
PDZK1IP1 5.38E-16 2.506 4.22 89.5 82.5-94.2 202935_s_at FLJ37644
1.04E-15 2.4727 3.64 89.2 82.1-94 204401_at KCNN4 1.85E-15 2.4677
3.07 89.1 82-94 222696_at AXIN2 1.90E-15 2.4301 4.44 88.8 81.6-93.7
221923_s_at NPM1 2.22E-15 2.6018 2.18 90.3 83.5-94.8 201666_at
TIMP1 2.44E-15 2.4295 3.01 88.8 81.6-93.7 210511_s_at INHBA
2.80E-15 2.5137 3.76 89.6 82.6-94.3 223062_s_at LOC651255:PSAT1:
3.32E-15 2.4895 5.52 89.3 82.3-94.1 LOC389173: LOC729779:C8orf62
225520_at MTHFD1L 4.46E-15 2.4846 4.04 89.3 82.3-94.1 206224_at
CST1 7.04E-15 2.4174 13.01 88.7 81.5-93.6 201014_s_at PAICS
1.19E-14 2.3935 2.49 88.4 81.3-93.5 209309_at AZGP1:LOC401393
1.31E-14 2.3949 6.19 88.4 81.2-93.5 218796_at C20orf42 1.38E-14
2.4561 2.78 89 82-93.9 60474_at C20orf42 1.38E-14 2.4547 2.78 89
81.9-93.9 219787_s_at ECT2 1.42E-14 2.4283 2.82 88.8 81.6-93.7
231832_at WDR51B:GALNT4 1.79E-14 2.4259 2.12 88.7 81.6-93.7
218507_at HIG2 2.50E-14 2.3654 4.25 88.2 80.9-93.3 202286_s_at
TACSTD2 3.13E-14 2.3701 15.71 88.2 80.9-93.3 205513_at TCN1
4.81E-14 2.3019 15.22 87.5 80.1-92.8 224428_s_at CDCA7:LOC442172
6.41E-14 2.2662 4.27 87.1 79.6-92.5 203124_s_at SLC11A2 7.07E-14
2.3616 2.18 88.1 80.8-93.3 224915_x_at TALDO1:C20orf199 8.45E-14
2.2732 2.87 87.2 79.7-92.6 226227_x_at TALDO1:C20orf199 8.45E-14
2.2707 2.87 87.2 79.7-92.6 226835_s_at TALDO1:C20orf199 8.45E-14
2.2746 2.87 87.2 79.7-92.6 200832_s_at SCD:LOC651109: 1.23E-13
2.2759 4.28 87.2 79.8-92.6 LOC645313 204170_s_at CKS2 2.13E-13
2.2413 4.15 86.9 79.3-92.3 219682_s_at TBX3 3.27E-13 2.2498 4.94 87
79.4-92.4 203313_s_at TGIF 3.35E-13 2.175 2.12 86.2 78.4-91.8
201601_x_at IFITM1 4.78E-13 2.0659 3.87 84.9 77-90.8 214022_s_at
IFITM1 4.78E-13 2.065 3.87 84.9 77-90.8 201328_at ETS2 5.23E-13
2.2182 2.36 86.6 79-92.2 201112_s_at CSE1L 7.98E-13 2.2336 2.28
86.8 79.2-92.2 210766_s_at CSE1L 7.98E-13 2.232 2.28 86.8 79.2-92.2
205361_s_at TMEM23:PFDN4: 1.69E-12 2.2328 2.24 86.8 79.2-92.3 HDAC9
218086_at NPDC1 2.66E-12 2.169 2.53 86.1 78.4-91.8 206286_s_at
TDGF1:TDGF3 3.07E-12 2.1205 6.33 85.5 77.7-91.4 204855_at SERPINB5
4.80E-12 2.1265 10.36 85.6 77.8-91.4 203878_s_at MMP11 6.30E-12
2.0959 4.55 85.3 77.4-91.1 202833_s_at SERPINA1 7.12E-12 2.0804
3.43 85.1 77.1-91 211429_s_at SERPINA1 7.12E-12 2.0818 3.43 85.1
77.2-91 228303_at No Symbol 9.19E-12 2.1527 1.61 85.9 78.2-91.6
225767_at No Symbol 9.19E-12 2.1514 1.614 85.9 78.1-91.6 226311_at
No Symbol 9.19E-12 2.1527 1.61 85.9 78.1-91.6 226777_at No Symbol
9.19E-12 2.152 1.61 85.9 78.1-91.6 227140_at No Symbol 9.19E-12
2.152 1.61 85.9 78.1-91.6 229802_at No Symbol 9.19E-12 2.1519 1.61
85.9 78.2-91.6 232151_at No Symbol 9.19E-12 2.1534 1.61 85.9
78.1-91.6 213880_at LGR5 1.10E-11 2.0619 7.89 84.9 76.9-90.8
225295_at SLC39A10 2.32E-11 2.1227 1.93 85.6 77.7-91.3 205470_s_at
KLK11 3.11E-11 2.0097 6.04 84.3 76.2-90.3 205174_s_at QPCT 3.46E-11
2.0435 3.03 84.7 76.6-90.7 222449_at TMEPAI 3.73E-11 2.0605 2.2
84.9 77-90.8 222450_at TMEPAI 3.73E-11 2.0616 2.2 84.9 76.9-90.9
238021_s_at LOC643911 3.73E-11 1.647 1.33 79.5 70.8-86.5 227174_at
WDR72 5.22E-11 1.9844 14.11 83.9 75.8-90.1 202779_s_at
UBE2S:LOC731049, 5.62E-11 1.9821 2.4 83.9 75.8-90 UBE2S:LOC731049
219727_at DUOX2 9.34E-11 1.9355 9.27 83.3 75.1-89.6 210445_at FABP6
1.28E-10 1.9366 3.01 83.4 75.1-89.6 205828_at MMP3 1.44E-10 1.8964
15.63 82.8 74.6-89.2 218963_s_at KRT23 3.58E-10 1.8856 6.81 82.7
74.5-89.1 223447_at REG4 5.97E-10 1.8052 7.75 81.7 73.2-88.3
238984_at REG4 5.97E-10 1.8036 7.75 81.6 73.3-88.3 204475_at MMP1
1.22E-09 1.8132 10.59 81.8 73.4-88.3 228653_at RP5-875H10.1
1.33E-09 1.8788 1.99 82.6 74.3-89.1 204580_at MMP12 1.99E-09 1.7881
6.24 81.4 73-88.1 203895_at PLCB4 2.29E-09 1.8389 2.37 82.1
73.7-88.6 203896_s_at PLCB4 2.29E-09 1.8414 2.37 82.1 73.8-88.6
235210_s_at RPESP 2.38E-09 1.8005 9.07 81.6 73.2-88.2 201468_s_at
NQO1 2.68E-09 1.6978 2.62 80.2 71.6-87.1 210519_s_at NQO1 2.68E-09
1.6973 2.62 80.2 71.6-87 222608_s_at ANLN 4.94E-09 1.7543 2.63 81
72.5-87.7 212344_at SULF1 9.70E-09 1.7754 1.74 81.3 72.9-88
212353_at SULF1 9.70E-09 1.7777 1.74 81.3 72.9-88 212354_at SULF1
9.70E-09 1.7751 1.74 81.3 72.8-87.9 201925_s_at CD55 1.45E-08
1.7612 2.22 81.1 72.6-87.8 201926_s_at CD55 1.45E-08 1.7603 2.22
81.1 72.5-87.8 202954_at PAK3:UBE2C 1.74E-08 1.6455 2.82 79.5
70.9-86.4 209792_s_at KLK10 2.64E-08 1.6142 4.52 79 70.2-86.1
205890_s_at UBD:GABBR1, UBD 4.07E-08 1.6362 6.59 79.3 70.6-86.3
209773_s_at RRM2 4.25E-08 1.6077 2.25 78.9 70.2-86 234331_s_at
FAM84A:LOC653602 5.97E-08 1.6031 1.73 78.9 70.1-86 206976_s_at
HSPH1 6.17E-08 1.6476 1.85 79.5 70.8-86.5 202718_at IGFBP2 8.07E-08
1.6348 1.93 79.3 70.6-86.3 225664_at TMEM30A:COL12A1 9.48E-08
1.6379 3.16 79.4 70.7-86.3 231766_s_at TMEM30A:COL12A1 9.48E-08
1.6394 3.16 79.4 70.7-86.3 201261_x_at BGN 1.01E-07 1.5939 2.69
78.7 69.9-85.9 213905_x_at BGN 1.01E-07 1.596 2.69 78.8 69.9-85.8
204127_at RFC3 1.25E-07 1.5497 2.25 78.1 69.2-85.3 207457_s_at
C6orf21:LY6G6D, 1.34E-07 1.5549 6.64 78.2 69.3-85.4 C6orf21:LY6G6D,
C6orf21:LY6G6D 210052_s_at TPX2 1.56E-07 1.6655 2.03 79.8 71.1-86.7
202859_x_at LOC652128:IGHG1: 1.99E-07 1.6331 3.1 79.3 70.6-86.3
IGHM:IGHV4-31: LOC647189:IGHV1-69: IGHA1:IL8:EXOC7:SIX6:
IGHD:IGH@:IGHG3: C12orf32:ZCWPW2: IFI6:IGHG4:IGHA2: IGHG2:RAC1
211506_s_at LOC652128:IGHG1: 1.99E-07 1.6324 3.1 79.3 70.6-86.4
IGHM:IGHV4-31: LOC647189:IGHV1-69: IGHA1:IL8:EXOC7: SIX6:IGHD:IGH@:
IGHG3:C12orf32: ZCWPW2:IFI6: IGHG4:IGHA2: IGHG2:RAC1 205479_s_at
PLAU 2.25E-07 1.5392 3.5 77.9 69.1-85.1 238017_at RDHE2 2.71E-07
1.5511 2.52 78.1 69.3-85.3 204320_at COL11A1 2.93E-07 1.5718 2.6
78.4 69.6-85.6 37892_at COL11A1 2.93E-07 1.57 2.6 78.4 69.5-85.6
203213_at CDC2 3.58E-07 1.5342 2.72 77.8 69-85.1 210559_s_at CDC2
3.58E-07 1.5348 2.72 77.9 69-85.1 232252_at DUSP27 4.68E-07 1.5123
4.81 77.5 68.7-84.8 225799_at MGC4677, 7.40E-07 1.4933 2.04 77.2
68.3-84.6 MGC4677: LOC541471 206239_s_at SPINK1 1.70E-06 1.4816
2.74 77.1 68.1-84.5 225806_at C14orf94 2.40E-06 1.6542 1.19 79.6
70.9-86.5 204885_s_at MSLN 3.78E-06 1.4263 1.93 76.2 67.2-83.7
202998_s_at ENTPD4:LOXL2 4.81E-06 1.3717 2.19 75.4 66.3-83
207158_at APOBEC1 9.49E-06 1.3811 1.63 75.5 66.4-83.1 218211_s_at
MLPH 1.16E-05 1.4176 1.47 76.1 67.1-83.6 205366_s_at HOXB6 1.33E-05
1.3346 1.87 74.8 65.7-82.5 225681_at CTHRC1 1.83E-05 1.2913 2.57
74.1 64.9-81.8 205815_at REG3A 2.22E-05 1.2228 12.09 73 63.8-80.9
214974_x_at CXCL5 2.79E-05 1.281 4.48 73.9 64.8-81.7 207173_x_at
CDH11 3.44E-05 1.2644 2.25 73.6 64.4-81.5 209955_s_at IFIH1:FAP
6.66E-05 1.2544 2.33 73.5 64.3-81.3 205886_at REG1B 8.08E-05 1.1731
13.15 72.1 62.8-80.1 205713_s_at COMP 0.0001 1.1543 1.69 71.8
62.6-79.9 208079_s_at AURKA:STK6P 0.0001 1.1173 1.81 71.2 61.8-79.3
209218_at SQLE 0.0001 1.1362 2.69 71.5 62.2-79.6 212190_at SERPINE2
0.0002 1.1279 1.9 71.4 62.1-79.5 219955_at L1TD1 0.0002 1.1579 2.36
71.9 62.6-79.9 236894_at L1TD1 0.0002 1.1598 2.36 71.9 62.6-79.9
209875_s_at SPP1 0.0004 1.0666 3.32 70.3 60.9-78.5 205910_s_at CEL
0.0006 1.0877 1.46 70.7 61.2-78.8 209752_at REG1A 0.0006 1.0018
10.93 69.2 59.8-77.5 213975_s_at LILRA1:LILRB1 0.0013 1.0772 1.55
70.5 61.1-78.7 202310_s_at COL1A1 0.0018 1.007 2.5 69.3 59.9-77.5
202311_s_at COL1A1 0.0018 1.0058 2.5 69.2 59.8-77.5 217430_x_at
COL1A1 0.0018 1.006 2.5 69.3 59.9-77.5 221729_at COL5A2 0.0026
1.054 1.36 70.1 60.7-78.4 221730_at COL5A2 0.0026 1.0559 1.36 70.1
60.8-78.4 205825_at PCSK1 0.0029 1.107 1.48 71 61.6-79.2 203860_at
PCCA 0.0038 0.9396 1.42 68.1 58.6-76.5 224646_x_at RPS12:H19 0.0051
1.0213 1.47 69.5 60.1-77.8 205941_s_at COL10A1 0.0143 0.8495 2.05
66.4 57-75.1 226237_at COL8A1 0.0254 0.8307 1.43 66.1 56.6-74.8
223970_at RETNLB 0.0304 0.8148 1.47 65.8 56.3-74.4 205765_at
CYP3A5:CYP3A7 0.0545 0.8252 1.58 66 56.4-74.6 232176_at SLITRK6
0.0576 0.8693 1.31 66.8 57.3-75.4 232481_s_at SLITRK6 0.0576 0.8701
1.31 66.8 57.4-75.3 235976_at SLITRK6 0.0576 0.868 1.31 66.8
57.4-75.3 200665_s_at SPARC 0.0684 0.6727 1.45 63.2 53.6-72
205927_s_at CTSE 0.0694 0.7488 1.83 64.6 55.1-73.3 214651_s_at
HOXA9 0.0759 0.7491 1.41 64.6 55-73.3 204051_s_at SFRP4 0.0829
0.6983 1.29 63.7 54.1-72.4 202404_s_at COL1A2: 0.1891 0.6492 1.9
62.7 53.1-71.6 LOC728628 204620_s_at CSPG2 0.9788 0.1834 1.05 53.7
44-63 221731_x_at CSPG2 0.9788 0.183 1.05 53.6 44.1-63 203083_at
THBS2 0.9844 0.2784 1.26 55.5 46-64.8 214235_at CYP3A5:CYP3A43:
0.9932 0.3165 1.16 56.3 46.7-65.6 CYP3A5P2
TABLE-US-00035 TABLE 2 Gene Signif. Sens- CI Symbol ValidPS_UP
Symbol FDR D.val5 FC Spec (95) CDH3
802708-HuGene_st:280037-HuGene_st:1019645- CDH3 3.75E-31 4.2474
37.54 98.3 95.5-99.5 HuGene_st:119416-HuGene_st:642035-
HuGene_st:665706-HuGene_st:249831-
HuGene_st:604066-HuGene_st:260528-
HuGene_st:166615-HuGene_st:411984-
HuGene_st:520679-HuGene_st:1071177-
HuGene_st:988525-HuGene_st:317603-
HuGene_st:301020-HuGene_st:693824-
HuGene_st:468436-HuGene_st:203256_at:
265728-HuGene_st:806796-HuGene_st:893171- HuGene_st ENC1
216704-HuGene_st:529141-HuGene_st:968541- ENC1 1.44E-26 3.6666 3.93
96.7 92.6-98.7 HuGene_st:1015647-HuGene_st:524348-
HuGene_st:291883-HuGene_st:154485-
HuGene_st:174870-HuGene_st:967480-
HuGene_st:729586-HuGene_st:826381-
HuGene_st:40464-HuGene_st:340065-
HuGene_st:1066975-HuGene_st:1090631-
HuGene_st:201340_s_at:86039-HuGene_st:686829-
HuGene_st:733896-HuGene_st:201341_at:698873-
HuGene_st:730768-HuGene_st:403595-HuGene_st CD44
366106-HuGene_st:314808-HuGene_st:59730- MAPK10:CD44 3.35E-26
3.7114 7.06 96.8 92.9-98.8 HuGene_st:599371-HuGene_st:391296-
HuGene_st:1031797-HuGene_st:314340-
HuGene_st:10723-HuGene_st:950067-
HuGene_st:282016-HuGene_st:480680-
HuGene_st:69560-HuGene_st:388781-
HuGene_st:243049-HuGene_st:374652-
HuGene_st:194553-HuGene_st:1075454- HuGene_st:204489_s_at:619139-
HuGene_st:210916_s_at:542762-
HuGene_st:1557905_s_at:212014_x_at:229221_at:
204490_s_at:234418_x_at:209835_x_at:212063_at:
216062_at:777408-HuGene_st:234411_x_at:217523_at: 216056_at:
1565868_at:83114-HuGene_st SORD
510024-HuGene_st:895709-HuGene_st:1079720- SORD 3.44E-25 3.4665
4.36 95.8 91.3-98.3 HuGene_st:566899-HuGene_st:339498-
HuGene_st:91263-HuGene_st:256497-
HuGene_st:720484-HuGene_st:187420-
HuGene_st:580807-HuGene_st:267000-
HuGene_st:321981-HuGene_st:1019581-
HuGene_st:1020801-HuGene_st:520376-
HuGene_st:670131-HuGene_st:201562_s_at:
455746-HuGene_st:67454-HuGene_st:201563_at:
309303-HuGene_st:1001165-HuGene_st:411387-
HuGene_st:49636-HuGene_st MYC
292645-HuGene_st:257928-HuGene_st:284020- LOC731404: 5.19E-25
3.5977 4.11 96.4 92.2-98.6 HuGene_st:517374-HuGene_st:869576-
LOC729194: HuGene_st:1099727-HuGene_st:33994- MYC
HuGene_st:781657-HuGene_st:509634-
HuGene_st:273419-HuGene_st:1068468-
HuGene_st:1095763-HuGene_st:149150-
HuGene_st:841622-HuGene_st:730300-
HuGene_st:964312-HuGene_st:963427-
HuGene_st:202431_s_at:522112-HuGene_st:
244089_at:239931_at:649622-HuGene_st GDF15
716715-HuGene_st:81268-HuGene_st:221576_at: GDF15 5.51E-25 3.5534
5.84 96.2 91.9-98.5 1032661-HuGene_st:430762-HuGene_st:392223-
HuGene_st:325978-HuGene_st:273598-
HuGene_st:229868_s_at:835644-HuGene_st:271704-
HuGene_st:1097896-HuGene_st:692830-
HuGene_st:1033023-HuGene_st:85522-
HuGene_st:954824-HuGene_st:221577_x_at:
634293-HuGene_st:594344-HuGene_st:
231517-HuGene_st:307405-HuGene_st:31827-
HuGene_st:496173-HuGene_st:636515- HuGene_st:30047-HuGene_st NFE2L3
95873-HuGene_st:1058969-HuGene_st:86088- LOC650331: 1.51E-24 3.523
4.57 96.1 91.7-98.4 HuGene_st:1093456-HuGene_st:347351- NFE2L3:
HuGene_st:878719-HuGene_st:880179- LOC642996
HuGene_st:240089_at:822197-HuGene_st:873612-
HuGene_st:517821-HuGene_st:489354-
HuGene_st:20603-HuGene_st:204702_s_at NEBL
923272-HuGene_st:580150-HuGene_st:925039- NEBL 5.41E-24 3.5322 5.52
96.1 91.7-98.4 HuGene_st:451073-HuGene_st:23015-
HuGene_st:714203-HuGene_st:479241-
HuGene_st:1092604-HuGene_st:458919- HuGene_st:207279_s_at:932542-
HuGene_st:203962_s_at:889861- HuGene_st:106510-HuGene_st:997698-
HuGene_st:116329-HuGene_st:1000081- HuGene_st:216882_s_at:374229-
HuGene_st:107562-HuGene_st:203961_at:
103041-HuGene_st:553617-HuGene_st:244077_at:
92634-HuGene_st:233280_at:217585_at GTF3A
955636-HuGene_st:336043-HuGene_st:876286- GTF3A 1.74E-22 3.2254
2.92 94.7 89.5-97.6 HuGene_st:147251-HuGene_st:27776-HuGene_st:
88229-HuGene_st:508903-HuGene_st:98817-
HuGene_st:158745-HuGene_st:386048-
HuGene_st:611132-HuGene_st:23049-
HuGene_st:247205-HuGene_st:995043-
HuGene_st:655976-HuGene_st:140189-
HuGene_st:1043983-HuGene_st:903143-
HuGene_st:577269-HuGene_st:659477-
HuGene_st:215091_s_at:201338_x_at:942640- HuGene_st CLDN1
557209-HuGene_st:769363-HuGene_st:96611- CLDN1 6.10E-22 3.2528
13.09 94.8 89.7-97.7 HuGene_st:517610-HuGene_st:737746-
HuGene_st:847409-HuGene_st:100345-
HuGene_st:391208-HuGene_st:98926-
HuGene_st:130886-HuGene_st:134239-
HuGene_st:647196-HuGene_st:1054117- HuGene_st:218182_s_at:511075-
HuGene_st:510210-HuGene_st:781587-
HuGene_st:1081991-HuGene_st:155669-
HuGene_st:1020398-HuGene_st:620570-
HuGene_st:222549_at:502206-HuGene_st:
943250-HuGene_st:916987-HuGene_st MMP7
267137-HuGene_st:1068392-HuGene_st:794865- MMP7 7.61E-22 3.2633
69.29 94.9 89.8-97.7 HuGene_st:876922-HuGene_st:669567-
HuGene_st:1039935-HuGene_st:514120-
HuGene_st:1092830-HuGene_st:745768-
HuGene_st:272260-HuGene_st:30733-
HuGene_st:401681-HuGene_st:854024-
HuGene_st:221616-HuGene_st:805045-
HuGene_st:783838-HuGene_st:204259_at:
934756-HuGene_st:446688-HuGene_st:10259-
HuGene_st:267021-HuGene_st:889042-HuGene_st SLC6A6
128406-HuGene_st:85866-HuGene_st:835577- SLC6A6: 1.15E-21 3.2313
5.02 94.7 89.6-97.6 HuGene_st:475923-HuGene_st:249964- LOC728721
HuGene_st:362002-HuGene_st:126399- HuGene_st:205921_s_at:319890-
HuGene_st:748425-HuGene_st:447287-
HuGene_st:1091412-HuGene_st:62392-
HuGene_st:44403-HuGene_st:825742-
HuGene_st:510986-HuGene_st:205920_at:661693-
HuGene_st:843791-HuGene_st:228754_at:705910-
HuGene_st:1561538_at:972205-HuGene_st:65222-
HuGene_st:747017-HuGene_st:239474_at:955688- HuGene_st:211030_s_at
CXCL1 11327-HuGene_st:626337-HuGene_st:322604- CXCL2: 1.88E-21
3.2911 7.85 95 90-97.8 HuGene_st:256806-HuGene_st:261067-HuGene_st:
CXCL3 448247-HuGene_st:666569-HuGene_st:222646-
HuGene_st:262117-HuGene_st:798675-
HuGene_st:391369-HuGene_st:865299-
HuGene_st:877897-HuGene_st:575433- HuGene_st:43120-HuGene_st:42070-
HuGene_st:33632-HuGene_st:965957-
HuGene_st:556939-HuGene_st:26460-HuGene_st:
796450-HuGene_st:230101_at:541868-
HuGene_st:1064107-HuGene_st:490134-
HuGene_st:230192-HuGene_st:645829-
HuGene_st:455502-HuGene_st:249140-
HuGene_st:906606-HuGene_st:1098767-
HuGene_st:721989-HuGene_st:500578-
HuGene_st:33301-HuGene_st:204470_at:
622384-HuGene_st:209774_x_at:432036-
HuGene_st:30559-HuGene_st:187557-
HuGene_st:1101027-HuGene_st:1038334-
HuGene_st:260925-HuGene_st:515662-
HuGene_st:258081-HuGene_st:1569203_at:280828-
HuGene_st:1000069-HuGene_st:509822-
HuGene_st:890213-HuGene_st:739461-
HuGene_st:342746-HuGene_st:98929-
HuGene_st:818131-HuGene_st:1091592-
HuGene_st:420504-HuGene_st:41644-
HuGene_st:655278-HuGene_st:188562- HuGene_st:458602-HuGene_st CXCL2
11327-HuGene_st:626337-HuGene_st:322604- CXCL2: 1.95E-21 3.2941
7.85 95 90-97.8 HuGene_st:256806-HuGene_st:261067- CXCL3
HuGene_st:448247-HuGene_st:666569-
HuGene_st:222646-HuGene_st:262117-
HuGene_st:798675-HuGene_st:391369-
HuGene_st:865299-HuGene_st:877897-
HuGene_st:575433-HuGene_st:43120- HuGene_st:42070-HuGene_st:33632-
HuGene_st:965957-HuGene_st:556939-
HuGene_st:26460-HuGene_st:796450-
HuGene_st:230101_at:541868-HuGene_st:
490134-HuGene_st:1064107-HuGene_st:
230192-HuGene_st:645829-HuGene_st:
455502-HuGene_st:249140-HuGene_st:
906606-HuGene_st:1098767-HuGene_st:
721989-HuGene_st:500578-HuGene_st:33301-
HuGene_st:207850_at:622384-HuGene_st:
204470_at:209774_x_at:432036-HuGene_st:
30559-HuGene_st:187557-HuGene_st:1101027-
HuGene_st:1038334-HuGene_st:260925-
HuGene_st:515662-HuGene_st:258081-
HuGene_st:1569203_at:280828-HuGene_st:
1000069-HuGene_st:509822-HuGene_st:890213-
HuGene_st:739461-HuGene_st:342746-HuGene_st:
98929-HuGene_st:818131-HuGene_st:1091592-
HuGene_st:420504-HuGene_st:41644-HuGene_st:
655278-HuGene_st:188562-HuGene_st:458602- HuGene_st CXCL3
11327-HuGene_st:626337-HuGene_st:322604- CXCL2: 1.95E-21 3.2892
7.85 95 90.1-97.8 HuGene_st:256806-HuGene_st:261067-HuGene_st:
CXCL3 448247-HuGene_st:666569-HuGene_st:222646-
HuGene_st:262117-HuGene_st:798675-HuGene_st:
391369-HuGene_st:865299-HuGene_st:877897-
HuGene_st:575433-HuGene_st:43120-HuGene_st:
42070-HuGene_st:33632-HuGene_st:965957-
HuGene_st:556939-HuGene_st:26460-HuGene_st:
796450-HuGene_st:230101_at:541868-
HuGene_st:490134-HuGene_st:1064107-
HuGene_st:230192-HuGene_st:645829-HuGene_st:
455502-HuGene_st:249140-HuGene_st:906606-
HuGene_st:1098767-HuGene_st:721989-
HuGene_st:500578-HuGene_st:33301-HuGene_st:
207850_at:622384-HuGene_st:209774_x_at:
432036-HuGene_st:30559-HuGene_st:187557-
HuGene_st:1101027-HuGene_st:1038334-
HuGene_st:260925-HuGene_st:515662-HuGene_st:
258081-HuGene_st:1569203_at:280828-
HuGene_st:1000069-HuGene_st:509822-HuGene_st:
890213-HuGene_st:739461-HuGene_st:342746-
HuGene_st:98929-HuGene_st:818131-HuGene_st:
1091592-HuGene_st:420504-HuGene_st:41644-
HuGene_st:655278-HuGene_st:188562-HuGene_st: 458602-HuGene_st TESC
921201-HuGene_st:608171-HuGene_st:146516- TESC 3.26E-21 3.2128
16.84 94.6 89.4-97.6 HuGene_st:484639-HuGene_st:107953-HuGene_st:
765929-HuGene_st:948263-HuGene_st:78061-
HuGene_st:808895-HuGene_st:69258-
HuGene_st:1017219-HuGene_st:244981-
HuGene_st:116590-HuGene_st:263121-HuGene_st:
260709-HuGene_st:218872_at:240553_at:
243302-HuGene_st:936401-HuGene_st:8542- HuGene_st KIAA1199
1008852-HuGene_st:897250-HuGene_st:264350- KIAA1199 8.12E-21 3.0498
25.16 93.6 88-97 HuGene_st:309186-HuGene_st:442314-
HuGene_st:14957-HuGene_st:16406- HuGene_st:742741-HuGene_st:115371-
HuGene_st:864695-HuGene_st:83178-HuGene_st:
107689-HuGene_st:444553-HuGene_st:972252-
HuGene_st:822568-HuGene_st:55289-
HuGene_st:744719-HuGene_st:999558-
HuGene_st:93042-HuGene_st:287365-
HuGene_st:215140_at:239747_s_at:1554685_a_at:
239746_at:719670-HuGene_st:212942_s_at: 15281-HuGene_st ANXA3
839382-HuGene_st:366797-HuGene_st:1053078- ANXA3 1.15E-20 3.0459
3.34 93.6 88-97 HuGene_st:469415-HuGene_st:506093-HuGene_st:
78819-HuGene_st:149613-HuGene_st:48457-
HuGene_st:316401-HuGene_st:35420-
HuGene_st:165320-HuGene_st:987987-
HuGene_st:437259-HuGene_st:34408-HuGene_st:
689653-HuGene_st:212737-HuGene_st:1018751-
HuGene_st:358834-HuGene_st:1097138-
HuGene_st:931805-HuGene_st:796166-
HuGene_st:209369_at:358455-HuGene_st SLCO4A1
181673-HuGene_st:556210-HuGene_st:125087- SLCO4A1 1.46E-20 3.0952
4.84 93.9 88.4-97.2 HuGene_st:555973-HuGene_st:690409-
HuGene_st:885495-HuGene_st:52728- HuGene_st:272770-HuGene_st:21709-
HuGene_st:661785-HuGene_st:229239_x_at:1554332_a_at:
233439-HuGene_st:471571-HuGene_st:219911_s_at:
556433-HuGene_st:248366-HuGene_st:543178-
HuGene_st:1026187-HuGene_st:981152-
HuGene_st:236109-HuGene_st:381101-
HuGene_st:141523-HuGene_st:739914-HuGene_st MET
388394-HuGene_st:648631-HuGene_st:15602- MET 1.50E-20 3.0827 3.35
93.8 88.3-97.1 HuGene_st:176281-HuGene_st:748069-HuGene_st:
1008518-HuGene_st:1087950-HuGene_st:988485-
HuGene_st:796914-HuGene_st:331502-
HuGene_st:103511-HuGene_st:61232-
HuGene_st:278022-HuGene_st:112349-HuGene_st:
926399-HuGene_st:510918-HuGene_st:213816_s_at:
211599_x_at:367353-HuGene_st:311383-
HuGene_st:791322-HuGene_st:1076627- HuGene_st:213807_x_at:697685-
HuGene_st:203510_at:825027-HuGene_st SOX9
772629-HuGene_st:546810-HuGene_st:787388- SOX9 1.63E-20 3.0954 3.85
93.9 88.4-97.2 HuGene_st:629934-HuGene_st:1026354-
HuGene_st:863993-HuGene_st:573850-
HuGene_st:583284-HuGene_st:944246-
HuGene_st:56367-HuGene_st:851353-
HuGene_st:191947-HuGene_st:202936_s_at:610027-
HuGene_st:564548-HuGene_st:361189-
HuGene_st:978036-HuGene_st:10753-
HuGene_st:762890-HuGene_st:399511-
HuGene_st:669806-HuGene_st:893973- HuGene_st SOX4
455510-HuGene_st:631864-HuGene_st:41874- SOX4 2.30E-20 3.0197 2.89
93.4 87.7-96.9 HuGene_st:1567906_at:213665_at:1001159-
HuGene_st:1082118-HuGene_st:11876-HuGene_st:
195182-HuGene_st:6275-HuGene_st:1032572-
HuGene_st:413494-HuGene_st:251834-
HuGene_st:201416_at:213668_s_at:622600-
HuGene_st:201418_s_at:389422- HuGene_st:731726-HuGene_st:119384-
HuGene_st:201417_at:438341-HuGene_st: 893969-HuGene_st:591113-
HuGene_st:725118-HuGene_st CCND1
210671-HuGene_st:693250-HuGene_st:850876- CCND1 7.06E-20 2.9073
2.85 92.7 86.8-96.4 HuGene_st:140311-HuGene_st:1002162-
HuGene_st:1018086-HuGene_st:407388-
HuGene_st:984437-HuGene_st:141586-
HuGene_st:647830-HuGene_st:790359-HuGene_st:
210601-HuGene_st:794719-HuGene_st:
208711_s_at:179331-HuGene_st:208712_at:592143-
HuGene_st:583936-HuGene_st:960743-
HuGene_st:632867-HuGene_st:125910- HuGene_st FOXQ1
763699-HuGene_st:567459-HuGene_st:447803- FOXQ1 4.85E-19 2.9444
10.97 93 87.1-96.6 HuGene_st:319823-HuGene_st:304771-HuGene_st:
1086901-HuGene_st:444851-HuGene_st:742304-
HuGene_st:301921-HuGene_st:227475_at:541230-
HuGene_st:894028-HuGene_st:89134-
HuGene_st:1082772-HuGene_st:850136-
HuGene_st:293941-HuGene_st:55647- HuGene_st DPEP1
195459-HuGene_st:60499-HuGene_st:783842- DPEP1 5.27E-19 2.8897 23.9
92.6 86.5-96.3 HuGene_st:457180-HuGene_st:450442-
HuGene_st:414432-HuGene_st:312589-
HuGene_st:598841-HuGene_st:13146-
HuGene_st:677461-HuGene_st:66845-HuGene_st:
26927-HuGene_st:405654-HuGene_st:931982-
HuGene_st:205983_at:529997-HuGene_st:496293-
HuGene_st:301001-HuGene_st:312462-
HuGene_st:495102-HuGene_st:270434- HuGene_st:1074719-HuGene_st:
734183-HuGene_st LCN2 769185-HuGene_st:478322-HuGene_st:1089212-
LCN2 5.68E-19 2.9407 14.6 92.9 87-96.6 HuGene_st:427722-
HuGene_st:341012-HuGene_st:277123-
HuGene_st:866455-HuGene_st:545638-
HuGene_st:974940-HuGene_st:942257-
HuGene_st:446106-HuGene_st:666350-
HuGene_st:755674-HuGene_st:1040520-HuGene_st:
212531_at:374635-HuGene_st:924701-
HuGene_st:899307-HuGene_st:911350- HuGene_st:586877-HuGene_st BACE2
790683-HuGene_st:54885-HuGene_st:545060- BACE2 5.87E-19 2.9056 3.8
92.7 86.7-96.4 HuGene_st:863425-HuGene_st:159264-HuGene_st:
718321-HuGene_st:211932-HuGene_st:705852-
HuGene_st:1090860-HuGene_st:1004109-
HuGene_st:281923-HuGene_st:449589-
HuGene_st:1049187-HuGene_st:217867_x_at:
222446_s_at:733284-HuGene_st:378351-
HuGene_st:525711-HuGene_st:834444-HuGene_st:
889532-HuGene_st:172501-HuGene_st:659292-
HuGene_st:748638-HuGene_st DACH1
686187-HuGene_st:985190-HuGene_st:1011822- DACH1 1.05E-18 2.9243
5.81 92.8 86.8-96.5 HuGene_st:1092705-HuGene_st:693255-
HuGene_st:722787-HuGene_st:465556-
HuGene_st:113230-HuGene_st:49101-
HuGene_st:290879-HuGene_st:646013- HuGene_st:3984-HuGene_st:378631-
HuGene_st:1002554-HuGene_st:620749-
HuGene_st:802309-HuGene_st:82679-
HuGene_st:205471_s_at:303920-HuGene_st:
338273-HuGene_st:20454-HuGene_st:1567100_at:
205472_s_at:228915_at:1562342_at:169641-
HuGene_st:984254-HuGene_st:1567101_at RNF43
680908-HuGene_st:971480-HuGene_st:933045- RNF43 2.12E-18 2.9237
3.24 92.8 86.9-96.5 HuGene_st:512035-HuGene_st:246870-
HuGene_st:542187-HuGene_st:235920-
HuGene_st:398750-HuGene_st:377708-
HuGene_st:509050-HuGene_st:292965-
HuGene_st:228826_at:228828_at:581833-
HuGene_st:205211-HuGene_st:292037-
HuGene_st:297431-HuGene_st:875834-
HuGene_st:101494-HuGene_st:631606-
HuGene_st:110817-HuGene_st:442527-
HuGene_st:218704_at:284952-HuGene_st:239588_s_at:
7711-HuGene_st:244226_s_at:232238-HuGene_st:
239589_at:678261-HuGene_st:978591-HuGene_st:
692794-HuGene_st:401794-HuGene_st:29943-
HuGene_st:997900-HuGene_st:1085055-HuGene_st:612499-
HuGene_st:202326-HuGene_st:520369-HuGene_st:728337-
HuGene_st:469125-HuGene_st:529498-HuGene_st:166542-
HuGene_st:963597-HuGene_st:82123- HuGene_st:851970-HuGene_st TRIM29
84230-HuGene_st:776118-HuGene_st:317358- TRIM29 2.36E-18 2.8229
11.01 92.1 85.9-96
HuGene_st:848242-HuGene_st:304181-HuGene_st:245405-
HuGene_st:150773-HuGene_st:398649-HuGene_st:
202504_at:653465-HuGene_st:693258-HuGene_st:
211002_s_at:393591-HuGene_st:584774-
HuGene_st:816340-HuGene_st:426369-
HuGene_st:1085014-HuGene_st:1023102-
HuGene_st:105055-HuGene_st:237257-
HuGene_st:1076218-HuGene_st:905217-HuGene_st NLF1
269939-HuGene_st:314919-HuGene_st:552234- NLF1 3.12E-18 2.7997 8.12
91.9 85.7-95.9 HuGene_st:622058-HuGene_st:68900-HuGene_st:
376228-HuGene_st:194806-HuGene_st:923707-
HuGene_st:745661-HuGene_st:996995-
HuGene_st:534469-HuGene_st:560627-
HuGene_st:711203-HuGene_st:241031_at:93378-
HuGene_st:611899-HuGene_st:57671-
HuGene_st:443570-HuGene_st:231416-HuGene_st SLC7A5
496060-HuGene_st:951443-HuGene_st:212037- SLC7A5: 5.11E-18 2.7527
6.31 91.6 85.2-95.7 HuGene_st:766877-HuGene_st:54540- LAT1-3TM
HuGene_st:467618-HuGene_st:663825-
HuGene_st:705196-HuGene_st:426149-
HuGene_st:852968-HuGene_st:215712-
HuGene_st:854122-HuGene_st:885601-
HuGene_st:517431-HuGene_st:127432-
HuGene_st:330269-HuGene_st:545636-
HuGene_st:636901-HuGene_st:814676-
HuGene_st:201195_s_at:450412-HuGene_st: 389490-HuGene_st ASCL2
342676-HuGene_st:857204-HuGene_st:748900- ASCL2 7.76E-18 2.7559
7.73 91.6 85.3-95.7 HuGene_st:853536-HuGene_st:945534-
HuGene_st:295182-HuGene_st:1038742-
HuGene_st:1100969-HuGene_st:940755-
HuGene_st:229215_at:209473-HuGene_st:710287-
HuGene_st:920942-HuGene_st:236012-
HuGene_st:474427-HuGene_st:207607_at:272814-
HuGene_st:584635-HuGene_st:793415-HuGene_st:
724997-HuGene_st:746596-HuGene_st:792089-
HuGene_st:623773-HuGene_st:1085101-HuGene_st PHLDA1
810737-HuGene_st:617999-HuGene_st:84013- PHLDA1 1.34E-17 2.7011
5.27 91.2 84.7-95.4 HuGene_st:972772-HuGene_st:843746-
HuGene_st:217999_s_at:218000_s_at:865439-
HuGene_st:949246-HuGene_st:660326-
HuGene_st:759020-HuGene_st:140047-
HuGene_st:217997_at:942344-HuGene_st:
1056055-HuGene_st:793477-HuGene_st:
800341-HuGene_st:363808-HuGene_st:217998_at:
225842_at:234244-HuGene_st:893315-
HuGene_st:217996_at:940094-HuGene_st:
588322-HuGene_st:706809-HuGene_st CCL20
454699-HuGene_st:213798-HuGene_st:391284- CCL20 2.03E-17 2.6209
10.14 90.5 83.8-94.9 HuGene_st:628958-HuGene_st:733349-
HuGene_st:609947-HuGene_st:437757-
HuGene_st:803267-HuGene_st:400137-
HuGene_st:542758-HuGene_st:650731-
HuGene_st:781726-HuGene_st:617384-
HuGene_st:537758-HuGene_st:176182-
HuGene_st:297268-HuGene_st:205476_at:183884-
HuGene_st:486887-HuGene_st:827625-
HuGene_st:314818-HuGene_st:65947-HuGene_st ZNRF3
395397-HuGene_st:749062-HuGene_st:491467- ZNRF3 2.03E-17 2.7278
4.91 91.4 84.9-95.5 HuGene_st:978668-HuGene_st:364904-
HuGene_st:157166-HuGene_st:176366-
HuGene_st:296148-HuGene_st:428183-
HuGene_st:867313-HuGene_st:732465-
HuGene_st:426052-HuGene_st:244820_at:
31672-HuGene_st:226360_at:149994-
HuGene_st:620378-HuGene_st:243014_at:
401539-HuGene_st:713294-HuGene_st:814560-
HuGene_st:205482-HuGene_st:276580-HuGene_st: 231419-HuGene_st
TMEM97 458988-HuGene_st:845548-HuGene_st:184387- LOC731966:
1.88E-16 2.5821 2.77 90.2 83.4-94.7
HuGene_st:583199-HuGene_st:1045327- LOC729599:
HuGene_st:568790-HuGene_st:52799- TMEM97
HuGene_st:1018996-HuGene_st:212279_at:
980043-HuGene_st:942215-HuGene_st:184687-
HuGene_st:979249-HuGene_st:212282_at:825431-
HuGene_st:1008874-HuGene_st:280056-
HuGene_st:212281_s_at:256071-HuGene_st:596777-
HuGene_st:10453-HuGene_st GPX2
526503-HuGene_st:607351-HuGene_st:824087- GPX2 4.00E-16 2.3996 3.56
88.5 81.2-93.5 HuGene_st:249710-HuGene_st:1052500-
HuGene_st:727999-HuGene_st:129991-
HuGene_st:548286-HuGene_st:912827-
HuGene_st:228033-HuGene_st:138844-
HuGene_st:93652-HuGene_st:953341-
HuGene_st:365006-HuGene_st:402697-
HuGene_st:434203-HuGene_st:552705-
HuGene_st:651410-HuGene_st:106023-
HuGene_st:408006-HuGene_st:281352-
HuGene_st:202831_at:721501-HuGene_st:239595_at RPL22L1
772808-HuGene_st:181084-HuGene_st:494932- LOC442108: 4.37E-16
2.6007 4.19 90.3 83.6-94.9
HuGene_st:1058299-HuGene_st:463691- RPL22L1
HuGene_st:43581-HuGene_st:383669-
HuGene_st:852429-HuGene_st:507824-
HuGene_st:759518-HuGene_st:225541_at:302606-
HuGene_st:635124-HuGene_st:399732-
HuGene_st:97487-HuGene_st:449121-
HuGene_st:533177-HuGene_st:373445-
HuGene_st:986445-HuGene_st:656340-
HuGene_st:494985-HuGene_st:249336-
HuGene_st:673318-HuGene_st:815820-
HuGene_st:226052-HuGene_st:282085-
HuGene_st:990639-HuGene_st:20450-
HuGene_st:133162-HuGene_st:403826-
HuGene_st:856534-HuGene_st:437128-
HuGene_st:563837-HuGene_st:1032326-
HuGene_st:57026-HuGene_st:792488-
HuGene_st:165053-HuGene_st:244269-
HuGene_st:618543-HuGene_st:292279-
HuGene_st:848648-HuGene_st:23825-
HuGene_st:210450-HuGene_st:278025-HuGene_st PUS7
188478-HuGene_st:676751-HuGene_st:364450- PUS7: 5.26E-16 2.6017
3.06 90.3 83.6-94.8 HuGene_st:323572-HuGene_st:1073917- LOC730279
HuGene_st:520873-HuGene_st:104521-
HuGene_st:38904-HuGene_st:243458-
HuGene_st:233716-HuGene_st:521418-
HuGene_st:189829-HuGene_st:622175-
HuGene_st:352376-HuGene_st:404327-
HuGene_st:795156-HuGene_st:965807-
HuGene_st:360606-HuGene_st:447010-
HuGene_st:853552-HuGene_st:218984_at: 233563-HuGene_st PDZK1IP1
327351-HuGene_st:692667-HuGene_st:61336- PDZK1IP1 5.38E-16 2.5049
4.22 89.5 82.5-94.2 HuGene_st:120414-HuGene_st:874822-
HuGene_st:922904-HuGene_st:783689-
HuGene_st:301666-HuGene_st:976408-
HuGene_st:1003400-HuGene_st:653237-
HuGene_st:76927-HuGene_st:1050028-
HuGene_st:984155-HuGene_st:834996-
HuGene_st:1553589_a_at:219630_at:211897-
HuGene_st:289125-HuGene_st:27948-
HuGene_st:678521-HuGene_st:768406- HuGene_st:834666-HuGene_st
FLJ37644 202935_s_at:230419_at FLJ37644 1.04E-15 2.4695 3.64 89.2
82.1-94 KCNN4 144049-HuGene_st:871303-HuGene_st:187064- KCNN4
1.85E-15 2.4698 3.07 89.2 82.1-94
HuGene_st:1009798-HuGene_st:306542-
HuGene_st:945226-HuGene_st:489209-
HuGene_st:846968-HuGene_st:468559-
HuGene_st:546781-HuGene_st:993022-
HuGene_st:510713-HuGene_st:39255-
HuGene_st:176231-HuGene_st:204401_at:140466-
HuGene_st:534792-HuGene_st:511374-
HuGene_st:319720-HuGene_st:745030-HuGene_st AXIN2
466765-HuGene_st:940175-HuGene_st:409416- AXIN2 1.90E-15 2.4309
4.44 88.8 81.7-93.7 HuGene_st:855558-HuGene_st:201699-
HuGene_st:717222-HuGene_st:650014-
HuGene_st:376280-HuGene_st:1046349-
HuGene_st:218016-HuGene_st:224498_x_at:
222695_s_at:43779-HuGene_st:309785-HuGene_st:
679194-HuGene_st:606406-HuGene_st:48333-
HuGene_st:758349-HuGene_st:224176_s_at:982781-
HuGene_st:222696_at:904523-HuGene_st:732685-
HuGene_st:774988-HuGene_st:189491- HuGene_st:317267-HuGene_st NPM1
771033-HuGene_st:995636-HuGene_st:360439- NPM1 2.22E-15 2.6004 2.18
90.3 83.6-94.8 HuGene_st:808147-HuGene_st:1046029-
HuGene_st:740084-HuGene_st:221691_x_at: 200063_s_at TIMP1
676809-HuGene_st:14950-HuGene_st:152072- TIMP1 2.44E-15 2.4307 3.01
88.8 81.6-93.7 HuGene_st:1042197-HuGene_st:480229-
HuGene_st:344184-HuGene_st:1032497-
HuGene_st:101433-HuGene_st:1010207-
HuGene_st:338299-HuGene_st:192845-HuGene_st:
153535-HuGene_st:1063549-HuGene_st:685630-
HuGene_st:761585-HuGene_st:357407-
HuGene_st:362978-HuGene_st:686046-
HuGene_st:201666_at:296784-HuGene_st:
242170-HuGene_st:677163-HuGene_st INHBA
402595-HuGene_st:289422-HuGene_st:151327- INHBA 2.80E-15 2.5141
3.76 89.6 82.7-94.3 HuGene_st:363337-HuGene_st:344276-
HuGene_st:874496-HuGene_st:395552-
HuGene_st:36929-HuGene_st:1088123-
HuGene_st:328796-HuGene_st:838338-
HuGene_st:623455-HuGene_st:1088331-
HuGene_st:1030680-HuGene_st:865665-
HuGene_st:21051l_s_at:746887-HuGene_st:909672-
HuGene_st:204926_at:548889-HuGene_st PSAT1
139416-HuGene_st:795030-HuGene_st:160439- LOC651255: 3.32E-15
2.4893 5.52 89.3 82.3-94.2 HuGene_st:322148-HuGene_st:85375- PSAT1:
HuGene_st:223335-HuGene_st:2658- LOC389173:
HuGene_st:399855-HuGene_st:220892_s_at: LOC729779:
941491-HuGene_st:1017348-HuGene_st:856207- C8orf62
HuGene_st:194347-HuGene_st:553133-
HuGene_st:223062_s_at:987517-HuGene_st:336174- HuGene_st MTHFD1L
478940-HuGene_st:729886-HuGene_st:826803- MTHFD1L 4.46E-15 2.4849
4.04 89.3 82.3-94.1 HuGene_st:504735-HuGene_st:632092-
HuGene_st:926226-HuGene_st:417984-
HuGene_st:752367-HuGene_st:919180-
HuGene_st:574022-HuGene_st:1096822-
HuGene_st:516882-HuGene_st:683402-
HuGene_st:843250-HuGene_st:548091-
HuGene_st:209210-HuGene_st:238923-
HuGene_st:852630-HuGene_st:231094_s_at:
97046-HuGene_st:225520_at:225518_x_at:
240552_at:106397-HuGene_st:363602-HuGene_st CST1
95123-HuGene_st:125297-HuGene_st:235257- CST1 7.04E-15 2.4183 13.01
88.7 81.6-93.7 HuGene_st:102028-HuGene_st:291462-
HuGene_st:206224_at:906914-HuGene_st:
936009-HuGene_st:1055285-HuGene_st PAICS
426927-HuGene_st:871276-HuGene_st:297278- PAICS 1.19E-14 2.3937
2.49 88.4 81.2-93.5 HuGene_st:832875-HuGene_st:287760-HuGene_st:
667051-HuGene_st:1057511-HuGene_st:1064821-
HuGene_st:25834-HuGene_st:467534-
HuGene_st:1057741-HuGene_st:760475-
HuGene_st:2629-HuGene_st:151478-HuGene_st:667637-
HuGene_st:302338-HuGene_st:201014_s_at:264119-
HuGene_st:685936-HuGene_st:201013_s_at:171734-
HuGene_st:333427-HuGene_st AZGP1
363333-HuGene_st:620891-HuGene_st:619378- AZGP1: 1.31E-14 2.3989
6.19 88.5 81.3-93.5 HuGene_st:741747-HuGene_st:28018- LOC401393
HuGene_st:594026-HuGene_st:222884-
HuGene_st:1006522-HuGene_st:974237-
HuGene_st:473891-HuGene_st:784628-
HuGene_st:488818-HuGene_st:209309_at:
217014_s_at:63620-HuGene_st:366096-
HuGene_st:950952-HuGene_st:601798-
HuGene_st:399823-HuGene_st:734365- HuGene_st:1054227-HuGene_st
C20orf42 405380-HuGene_st:276728-HuGene_st: C20orf42 1.38E-14
2.4573 2.78 89 82-93.9 60228-HuGene_st:754922-HuGene_st:444538-
HuGene_st:733591-HuGene_st:159372-
HuGene_st:763243-HuGene_st:978177-
HuGene_st:752032-HuGene_st:673425-
HuGene_st:591638-HuGene_st:229545_at:
60474_at:335096-HuGene_st:1029169-
HuGene_st:326834-HuGene_st:1028510-
HuGene_st:218796_at:15777-HuGene_st:582076-
HuGene_st:455924-HuGene_st:835558- HuGene_st:232479_at:889482-
HuGene_st:915156-HuGene_st ECT2
770888-HuGene_st:82454-HuGene_st:171418- ECT2 1.42E-14 2.4271 2.82
88.8 81.6-93.7 HuGene_st:52318-HuGene_st:530079-
HuGene_st:288145-HuGene_st:234992_x_at:
64803-HuGene_st:705846-HuGene_st:158755-
HuGene_st:554622-HuGene_st:237241_at:629949-
HuGene_st:222681-HuGene_st:241642-
HuGene_st:143403-HuGene_st:770445-
HuGene_st:218688-HuGene_st:700408-HuGene_st:
165018-HuGene_st:917458-HuGene_st:219787_s_at:
609829-HuGene_st:110350-HuGene_st WDR51B
659635-HuGene_st:465621-HuGene_st:886760- WDR51B: 1.79E-14 2.4266
2.12 88.7 81.6-93.7 HuGene_st:222145-HuGene_st:67663- GALNT4
HuGene_st:359031-HuGene_st:36172-
HuGene_st:290669-HuGene_st:148935-
HuGene_st:41107-HuGene_st:229778- HuGene_st:965397-HuGene_st:51869-
HuGene_st:583938-HuGene_st:640969-
HuGene_st:744231-HuGene_st:371123-
HuGene_st:1059241-HuGene_st:39345-
HuGene_st:684483-HuGene_st:231832_at: 226283_at:313270-HuGene_st
HIG2 246364-HuGene_st:881374-HuGene_st:841420- HIG2 2.50E-14 2.366
4.25 88.2 80.9-93.3 HuGene_st:674772-HuGene_st:761463-
HuGene_st:977422-HuGene_st:470541-
HuGene_st:82081-HuGene_st:266176-
HuGene_st:127241-HuGene_st:833078-
HuGene_st:218507_at:766773-HuGene_st:153456-
HuGene_st:1554452_a_at:727443- HuGene_st:342125-HuGene_st:921181-
HuGene_st:507618-HuGene_st:128889-
HuGene_st:786248-HuGene_st:801240- HuGene_st:286419-HuGene_st
TACSTD2 1004611-HuGene_st:755233-HuGene_st:815649- TACSTD2 3.13E-14
2.3686 15.71 88.2 80.9-93.3 HuGene_st:567105-HuGene_st:8281-
HuGene_st:1041491-HuGene_st:339450- HuGene_st:227128_s_at:653539-
HuGene_st:1079680-HuGene_st:958592-
HuGene_st:202286_s_at:620831-HuGene_st: 53075-HuGene_st:1009541-
HuGene_st:861600-HuGene_st:181597-HuGene_st:
130895-HuGene_st:849592-HuGene_st TCN1
293164-HuGene_st:505517-HuGene_st:1070815- TCN1 4.81E-14 2.3035
15.22 87.5 80-92.8 HuGene_st:178742-HuGene_st:286092-
HuGene_st:479663-HuGene_st:464294-
HuGene_st:243324-HuGene_st:181726-
HuGene_st:321817-HuGene_st:593508-
HuGene_st:779892-HuGene_st:1077339-
HuGene_st:951254-HuGene_st:91481-
HuGene_st:801919-HuGene_st:329572-
HuGene_st:415460-HuGene_st:611568-
HuGene_st:888427-HuGene_st:352827- HuGene_st:205513_at CDCA7
776822-HuGene_st:460577-HuGene_st:73904- CDCA7: 6.41E-14 2.2638
4.27 87.1 79.6-92.5 HuGene_st:164226-HuGene_st:268581- LOC442172
HuGene_st:1038532-HuGene_st:418719-
HuGene_st:491386-HuGene_st:701450-
HuGene_st:1021593-HuGene_st:207989-
HuGene_st:516224-HuGene_st:872337-
HuGene_st:299408-HuGene_st:46784-
HuGene_st:187234-HuGene_st:745531-
HuGene_st:754921-HuGene_st:142653-
HuGene_st:230060_at:310790-HuGene_st: 224428_s_at:929597-HuGene_st
SLC11A2 107248-HuGene_st:501575-HuGene_st:23656- SLC11A2 7.07E-14
2.362 2.18 88.1 80.7-93.2 HuGene_st:221382-HuGene_st:774882-
HuGene_st:752508-HuGene_st:132318-
HuGene_st:1009819-HuGene_st:60401-
HuGene_st:914535-HuGene_st:1037630-
HuGene_st:519284-HuGene_st:19391-
HuGene_st:873314-HuGene_st:437100- HuGene_st:203125_x_at:1028733-
HuGene_st:203123_s_at:1029520-
HuGene_st:1078393-HuGene_st:203124_s_at:
237106_at:357798-HuGene_st:210047_at SCD
446192-HuGene_st:562893-HuGene_st:713000- SCD: 1.23E-13 2.2789 4.28
87.3 79.8-92.6 HuGene_st:1054693-HuGene_st:698268- LOC651109:
HuGene_st:1088784-HuGene_st:87215- LOC645313
HuGene_st:64902-HuGene_st:211708_s_at:1019041-
HuGene_st:749928-HuGene_st:211162_x_at:891971-
HuGene_st:433956-HuGene_st:200831_s_at:130491-
HuGene_st:200832_s_at:214388-HuGene_st CKS2
139489-HuGene_st:193566-HuGene_st:404458- CKS2 2.13E-13 2.2406 4.15
86.9 79.2-92.3 HuGene_st:318195-HuGene_st:744649-
HuGene_st:710242-HuGene_st:221677-
HuGene_st:452466-HuGene_st:274401-
HuGene_st:1091509-HuGene_st:617848-
HuGene_st:871385-HuGene_st:869931- HuGene_st:204170_s_at
TBX3 976999-HuGene_st:995051-HuGene_st:1093752- TBX3 3.27E-13 2.249
4.94 87 79.5-92.4 HuGene_st:228344_s_at:91464-HuGene_st:185883-
HuGene_st:152524-HuGene_st:229565_x_at:761496-
HuGene_st:396474-HuGene_st:34571-HuGene_st:
862915-HuGene_st:50568-HuGene_st:229576_s_at:
1041335-HuGene_st:897089-HuGene_st:193698-
HuGene_st:222917_s_at:58151-HuGene_st:18446-
HuGene_st:821350-HuGene_st:470069-
HuGene_st:219682_s_at:243234_at:385428-
HuGene_st:872020-HuGene_st:219399-
HuGene_st:225544_at:652999-HuGene_st CSE1L
757480-HuGene_st:23664-HuGene_st:913239- CSE1L 7.98E-13 2.2314 2.28
86.8 79.2-92.3 HuGene_st:766409-HuGene_st:353842-
HuGene_st:248622-HuGene_st:173835-
HuGene_st:570272-HuGene_st:545123-
HuGene_st:843659-HuGene_st:313522-
HuGene_st:517527-HuGene_st:795866-
HuGene_st:485221-HuGene_st:1003371-
HuGene_st:110422-HuGene_st:564736- HuGene_st:201112_s_at:706263-
HuGene_st:210766_s_at:224382-HuGene_st:
201111_at:985134-HuGene_st:720754-HuGene_st PFDN4
28403-HuGene_st:31309-HuGene_st:925296- TMEM23: 1.69E-12 2.2333
2.24 86.8 79.1-92.3 HuGene_st:587633-HuGene_st:918571- PFDN4:
HuGene_st:547690-HuGene_st:702390- HDAC9
HuGene_st:291601-HuGene_st:218399-
HuGene_st:990433-HuGene_st:1455-HuGene_st:
975016-HuGene_st:990960-HuGene_st:
205361_s_at:39033-HuGene_st:763499-
HuGene_st:663125-HuGene_st:20745-
HuGene_st:254305-HuGene_st:205360_at NPDC1
907995-HuGene_st:26898-HuGene_st:921321- NPDC1 2.66E-12 2.1699 2.53
86.1 78.3-91.7 HuGene_st:845513-HuGene_st:273361-
HuGene_st:1018950-HuGene_st:398079-
HuGene_st:268093-HuGene_st:299764-
HuGene_st:963808-HuGene_st:81566-
HuGene_st:785389-HuGene_st:951435-
HuGene_st:218086_at:1014678-HuGene_st:
304194-HuGene_st:206447-HuGene_st:914011-
HuGene_st:276494-HuGene_st:1069732-
HuGene_st:405336-HuGene_st:962827-
HuGene_st:117974-HuGene_st:554799-
HuGene_st:711186-HuGene_st:884580-
HuGene_st:351662-HuGene_st:691470-
HuGene_st:92212-HuGene_st:354271-
HuGene_st:539456-HuGene_st:125362-
HuGene_st:166269-HuGene_st:15150-
HuGene_st:586601-HuGene_st:100718-HuGene_st:
364482-HuGene_st:323014-HuGene_st:928836-
HuGene_st:229380-HuGene_st:317669-
HuGene_st:310638-HuGene_st:561684-
HuGene_st:151109-HuGene_st:432072-
HuGene_st:425009-HuGene_st:883763- HuGene_st TDGF1
509506-HuGene_st:636337-HuGene_st:1020236- TDGF1: 3.07E-12 2.1179
6.33 85.5 77.7-91.3 HuGene_st:764617-HuGene_st:287790- TDGF3
HuGene_st:206286_s_at:1012920-HuGene_st:633937-
HuGene_st:2464-HuGene_st:85190-HuGene_st IL8
1044664-HuGene_st:714746-HuGene_st:442029- AHNAK: 3.28E-12 2.3281
1.73 87.8 80.3-93 HuGene_st:119200-HuGene_st:550444- IGHG1
HuGene_st:493978-HuGene_st:713906-
HuGene_st:943156-HuGene_st:504843-
HuGene_st:501902-HuGene_st:497219-
HuGene_st:23149-HuGene_st:387164-
HuGene_st:562654-HuGene_st:1047492-
HuGene_st:538558-HuGene_st:239300-
HuGene_st:211430_s_at:390695-HuGene_st:1081759-
HuGene_st:144630-HuGene_st:661013-HuGene_st:393191-
HuGene_st:55017-HuGene_st:1005159-HuGene_st:359116-
HuGene_st:373132-HuGene_st:689050-HuGene_st:611041-
HuGene_st:715689-HuGene_st:289354-HuGene_st:820633-
HuGene_st:555788-HuGene_st:988945-HuGene_st:307991-
HuGene_st:211506_s_at:924368-HuGene_st:47911-
HuGene_st:929972-HuGene_st:561100-
HuGene_st:68522-HuGene_st:217039_x_at:
231668_x_at:1080400-HuGene_st:141662-
HuGene_st:765200-HuGene_st:648539- HuGene_st:274868-
HuGene_st:233969_at SERPINB5
237063-HuGene_st:329959-HuGene_st:806576- SERPINB5 4.80E-12 2.1258
10.36 85.6 77.8-91.4 HuGene_st:690681-HuGene_st:536963-
HuGene_st:923557-HuGene_st:183189-
HuGene_st:25703-HuGene_st:959811-
HuGene_st:1087872-HuGene_st:774653-
HuGene_st:1019802-HuGene_st:909910-
HuGene_st:533096-HuGene_st:213088-
HuGene_st:387940-HuGene_st:769890-
HuGene_st:133132-HuGene_st:204855_at:806980-
HuGene_st:749473-HuGene_st:470592-
HuGene_st:254090-HuGene_st:1555551_at MMP11
324921-HuGene_st:203877_at:718792- MMP11 6.30E-12 2.0946 4.55 85.3
77.4-91.1 HuGene_st:935371-HuGene_st:514533-
HuGene_st:213602_s_at:671549-HuGene_st:858774-
HuGene_st:986917-HuGene_st:127919-HuGene_st:
943793-HuGene_st:670295-HuGene_st:1036101-
HuGene_st:922731-HuGene_st:203878_s_at:844472-
HuGene_st:519881-HuGene_st:203876_s_at:715236-
HuGene_st:963997-HuGene_st:155442-HuGene_st SERPINA1
1045251-HuGene_st:994130-HuGene_st:83597- SERPINA1 7.12E-12 2.0812
3.43 85.1 77.1-91 HuGene_st:515713-HuGene_st:853812-
HuGene_st:1018939-HuGene_st:52824-
HuGene_st:624314-HuGene_st:75136-
HuGene_st:667302-HuGene_st:975350-
HuGene_st:616531-HuGene_st:211429_s_at:521503-
HuGene_st:1068115-HuGene_st:560886-HuGene_st:
202833_s_at:135752-HuGene_st:646987-
HuGene_st:230318_at:141207-HuGene_st:520102-
HuGene_st:228566-HuGene_st:723345-HuGene_st LGR5
784585-HuGene_st:777519-HuGene_st:937559- LGR5 1.10E-11 2.0623 7.89
84.9 76.9-90.8 HuGene_st:297045-HuGene_st:796093-
HuGene_st:783411-HuGene_st:876648-
HuGene_st:842003-HuGene_st:102017-
HuGene_st:562251-HuGene_st:295997-
HuGene_st:747520-HuGene_st:811121-
HuGene_st:677407-HuGene_st:522834-
HuGene_st:475414-HuGene_st:802999-
HuGene_st:1066925-HuGene_st:216864-
HuGene_st:890928-HuGene_st:179502-
HuGene_st:79633-HuGene_st:210393_at: 241266_at:213880_at KLK11
549986-HuGene_st:890775-HuGene_st:236557- KLK11 3.11E-11 2.0091
6.04 84.2 76.1-90.4 HuGene_st:450049-HuGene_st:1004334-
HuGene_st:1069590-HuGene_st:300088-
HuGene_st:787829-HuGene_st:220172-
HuGene_st:668386-HuGene_st:205470_s_at:232801-
HuGene_st:569957-HuGene_st:273555-
HuGene_st:471415-HuGene_st:171521- HuGene_st:1060009-HuGene_st QPCT
261837-HuGene_st:108729-HuGene_st:942514- QPCT 3.46E-11 2.0418 3.03
84.6 76.6-90.6 HuGene_st:184578-HuGene_st:454020-
HuGene_st:202482-HuGene_st:1012784-
HuGene_st:854999-HuGene_st:62841-
HuGene_st:271540-HuGene_st:524919- HuGene_st:78507-HuGene_st:89785-
HuGene_st:728309-HuGene_st:625205-
HuGene_st:170279-HuGene_st:561083-
HuGene_st:322236-HuGene_st:205174_s_at: 303448-HuGene_st TMEPAI
69901-HuGene_st:272000-HuGene_st:290146- TMEPAI 3.73E-11 2.0603 2.2
84.9 76.9-90.8 HuGene_st:949819-HuGene_st:38546-
HuGene_st:576310-HuGene_st:1043092-
HuGene_st:1032094-HuGene_st:54841-
HuGene_st:520417-HuGene_st:482971-
HuGene_st:390671-HuGene_st:222449_at:
217875_s_at:616128-HuGene_st:626087-
HuGene_st:452007-HuGene_st:222450_at:793710-
HuGene_st:935955-HuGene_st:190534-
HuGene_st:147633-HuGene_st:505849- HuGene_st:108118-HuGene_st WDR72
829740-HuGene_st:1063796-HuGene_st:725768- WDR72 5.22E-11 1.9862
14.11 84 75.8-90.1 HuGene_st:227174_at:36564-HuGene_st:
236741_at:604794-HuGene_st:1040675-HuGene_st:
527199-HuGene_st:1052168-HuGene_st:1563874_at:
177868-HuGene_st:667158-HuGene_st:542462-
HuGene_st:136243-HuGene_st:551835-HuGene_st UBE2S
50114-HuGene_st:827969-HuGene_st:618483- UBE2S: 5.62E-11 1.9793 2.4
83.9 75.8-90.1 HuGene_st:403161-HuGene_st:202779_s_at:588403-
LOC731049, HuGene_st:235992-HuGene_st:261249- UBE2S:
HuGene_st:692372-HuGene_st:86733- LOC731049
HuGene_st:892371-HuGene_st:415931-
HuGene_st:285497-HuGene_st:1092919-
HuGene_st:692891-HuGene_st:651401-
HuGene_st:1097987-HuGene_st:753061-
HuGene_st:989526-HuGene_st:209702-
HuGene_st:883359-HuGene_st:356270-
HuGene_st:946490-HuGene_st:975035- HuGene_st:9564-HuGene_st DUOX2
1099413-HuGene_st:659224-HuGene_st:156555- DUOX2 9.34E-11 1.9359
9.27 83.3 75.1-89.6 HuGene_st:324189-HuGene_st:213344-
HuGene_st:978958-HuGene_st:301512-
HuGene_st:541945-HuGene_st:793215-
HuGene_st:791778-HuGene_st:737640-
HuGene_st:246083-HuGene_st:798367-
HuGene_st:826588-HuGene_st:442908-
HuGene_st:870549-HuGene_st:1015396-
HuGene_st:79359-HuGene_st:587684-
HuGene_st:633860-HuGene_st:659015-
HuGene_st:219727_at:307924-HuGene_st FABP6
306586-HuGene_st:486210-HuGene_st:205174- FABP6 1.28E-10 1.9367
3.01 83.4 75.2-89.6 HuGene_st:918118-HuGene_st:123214-
HuGene_st:776487-HuGene_st:292087-
HuGene_st:399564-HuGene_st:791516-
HuGene_st:221287-HuGene_st:288462-
HuGene_st:210445_at:86381-HuGene_st:191002-
HuGene_st:62247-HuGene_st:248143-
HuGene_st:618873-HuGene_st:117294-HuGene_st MMP3
542596-HuGene_st:149350-HuGene_st:35444- MMP3 1.44E-10 1.8957 15.63
82.8 74.5-89.2 HuGene_st:200029-HuGene_st:438906-
HuGene_st:357556-HuGene_st:206224-
HuGene_st:483424-HuGene_st:701539-
HuGene_st:945713-HuGene_st:766524-
HuGene_st:664043-HuGene_st:560206-
HuGene_st:191436-HuGene_st:526573-
HuGene_st:822598-HuGene_st:634624- HuGene_st:7912-HuGene_st:392207-
HuGene_st:205828_at:134417-HuGene_st: 569533-HuGene_st KRT23
962342-HuGene_st:65048-HuGene_st:941972- KRT23 3.58E-10 1.887 6.81
82.7 74.4-89.1 HuGene_st:290153-HuGene_st:120900-
HuGene_st:151180-HuGene_st:980580-
HuGene_st:587527-HuGene_st:33349-
HuGene_st:439472-HuGene_st:882546-
HuGene_st:693456-HuGene_st:611219-
HuGene_st:917080-HuGene_st:890494-
HuGene_st:274715-HuGene_st:218963_s_at:
501017-HuGene_st:82313-HuGene_st:590458- HuGene_st MMP1
61706-HuGene_st:300572-HuGene_st:1020786- MMP1 1.22E-09 1.8163
10.59 81.8 73.5-88.4 HuGene_st:437171-HuGene_st:671620-
HuGene_st:689073-HuGene_st:622653-
HuGene_st:958445-HuGene_st:445730-
HuGene_st:914223-HuGene_st:693724-
HuGene_st:673683-HuGene_st:524115-
HuGene_st:422476-HuGene_st:361198-
HuGene_st:710307-HuGene_st:468477-
HuGene_st:840324-HuGene_st:1070117-
HuGene_st:473664-HuGene_st:732367-
HuGene_st:204475_at:353235-HuGene_st RP5-
538290-HuGene_st:177752-HuGene_st:428459- RP5- 1.33E-09 1.8807 1.99
82.6 74.4-89.1 875H10.1 HuGene_st:376412-HuGene_st:769774- 875H10.1
HuGene_st:862879-HuGene_st:242626_at:811503-
HuGene_st:488462-HuGene_st:964336-
HuGene_st:498480-HuGene_st:1047616-HuGene_st:
187658-HuGene_st:201892-HuGene_st:372716-
HuGene_st:1038921-HuGene_st:930484-
HuGene_st:1569433_at:990429-HuGene_st:1077002-
HuGene_st:193834-HuGene_st:228653_at:208211- HuGene_st MMP12
372865-HuGene_st:108955-HuGene_st:80569- MMP12 1.99E-09 1.7858 6.24
81.4 73-88
HuGene_st:354173-HuGene_st:1078790-
HuGene_st:969948-HuGene_st:868781-
HuGene_st:574015-HuGene_st:615370-
HuGene_st:628463-HuGene_st:515838-
HuGene_st:130587-HuGene_st:165281-
HuGene_st:49605-HuGene_st:821221-
HuGene_st:131503-HuGene_st:337285-
HuGene_st:759246-HuGene_st:1040687- HuGene_st:204580_at PLCB4
10322-HuGene_st:957911-HuGene_st:35530- PLCB4 2.29E-09 1.8407 2.37
82.1 73.8-88.6 HuGene_st:107476-HuGene_st:770342-
HuGene_st:701058-HuGene_st:76455-
HuGene_st:662074-HuGene_st:330909-
HuGene_st:98190-HuGene_st:895165-
HuGene_st:120897-HuGene_st:215874-
HuGene_st:575063-HuGene_st:618779-
HuGene_st:370708-HuGene_st:874698-
HuGene_st:203896_s_at:203895_at:768644-
HuGene_st:958443-HuGene_st:976920-
HuGene_st:531382-HuGene_st:240728_at: 1024936-HuGene_st RPESP
216316-HuGene_st:211185-HuGene_st:396353- RPESP 2.38E-09 1.8014
9.07 81.6 73.1-88.2 HuGene_st:723267-HuGene_st:853543-
HuGene_st:472245-HuGene_st:177506-
HuGene_st:271443-HuGene_st:437371-
HuGene_st:429127-HuGene_st:1010482-
HuGene_st:629529-HuGene_st:814381-
HuGene_st:619363-HuGene_st:235209_at: 235210_s_at:296762-HuGene_st
ANLN 522941-HuGene_st:550252-HuGene_st:477118- ANLN 4.94E-09 1.7558
2.63 81 72.5-87.7 HuGene_st:858635-HuGene_st:34728-
HuGene_st:165560-HuGene_st:226318-
HuGene_st:207100-HuGene_st:842538-
HuGene_st:343961-HuGene_st:899690-
HuGene_st:705871-HuGene_st:42619-
HuGene_st:984996-HuGene_st:733290-
HuGene_st:1008901-HuGene_st:752472-
HuGene_st:619756-HuGene_st:674545-
HuGene_st:558324-HuGene_st:261208-
HuGene_st:222608_s_at:1552619_a_at SULF1
807443-HuGene_st:671986-HuGene_st:381424- SULF1 9.70E-09 1.7762
1.74 81.3 72.8-87.9 HuGenez_st:187508-HuGene_st:532406-
HuGene_st:740854-HuGene_st:730003-
HuGene_st:754502-HuGene_st:20084-
HuGene_st:517026-HuGene_st:1045684-
HuGene_st:512275-HuGene_st:166879- HuGene_st:72604-HuGene_st:34752-
HuGene_st:933799-HuGene_st:212353_at:
212354_at:1063384-HuGene_st:492122- HuGene_st:212344_at:482916-
HuGene_st:530745-HuGene_st CD55
422754-HuGene_st:440808-HuGene_st:531637- CD55 1.45E-08 1.7603 2.22
81.1 72.6-87.8 HuGene_st:22645-HuGene_st:891581-
HuGene_st:980059-HuGene_st:907061-
HuGene_st:536297-HuGene_st:31908-
HuGene_st:1051267-HuGene_st:154663-
HuGene_st:688144-HuGene_st:216097-
HuGene_st:988881-HuGene_st:932482-
HuGene_st:813995-HuGene_st:449911-
HuGene_st:1555950_a_at:201926_s_at:
201925_s_at:241616_at:243395_at:630657-
HuGene_st:288375-HuGene_st:750208-
HuGene_st:241615_x_at:721979-HuGene_st UBE2C
352222-HuGene_st:202954_at:1098731- PAK3: 1.74E-08 1.6437 2.82 79.4
70.8-86.5 HuGene_st:627921-HuGene_st:49079- UBE2C
HuGene_st:989700-HuGene_st:941779- HuGene_st:9599-HuGene_st:736605-
HuGene_st:814147-HuGene_st:379525-
HuGene_st:514999-HuGene_st:634987-
HuGene_st:1070235-HuGene_st:697185-
HuGene_st:1032891-HuGene_st:827728-
HuGene_st:109552-HuGene_st:956095- HuGene_st:489433-HuGene_st KLK10
303816-HuGene_st:935808-HuGene_st:586276- KLK10 2.64E-08 1.6155
4.52 79 70.3-86.1 HuGene_st:1045718-HuGene_st:209792_s_at:279985-
HuGene_st:679337-HuGene_st:542814-
HuGene_st:238963-HuGene_st:910249-
HuGene_st:1009566-HuGene_st:989821-
HuGene_st:167404-HuGene_st:140675-
HuGene_st:702375-HuGene_st:497565-
HuGene_st:868046-HuGene_st:428218- HuGene_st:196226-HuGene_st UBD
918426-HuGene_st:402478-HuGene_st:152370- UBD: 4.07E-08 1.6371 6.59
79.3 70.5-86.3 HuGene_st:1031056-HuGene_st:266533- GABBR1,
HuGene_st:338984-HuGene_st:248325- UBD
HuGene_st:675615-HuGene_st:917763-
HuGene_st:74769-HuGene_st:435761- HuGene_st:94745-HuGene_st:614172-
HuGene_st:871149-HuGene_st:374784- HuGene_st:205890_s_at:757108-
HuGene_st RRM2 158317-HuGene_st:573546-HuGene_st:788577- RRM2
4.25E-08 1.608 2.25 78.9 70.2-86
HuGene_st:209773_s_at:126031-HuGene_st:1064973-
HuGene_st:456984-HuGene_st:503676-
HuGene_st:236699-HuGene_st:240795-
HuGene_st:523072-HuGene_st:201890_at FAM84A
351279-HuGene_st:452541-HuGene_st: FAM84A: 5.97E-08 1.6052 1.73
78.9 70-86 228319_at:973835-HuGene_st:412010- LOC653602
HuGene_st:1032585-HuGene_st:254221-
HuGene_st:948951-HuGene_st:252448-
HuGene_st:968035-HuGene_st:367165-
HuGene_st:1079872-HuGene_st:641006-
HuGene_st:104989-HuGene_st:401120-
HuGene_st:87362-HuGene_st:910211-
HuGene_st:234335_s_at:228459_at:714477-
HuGene_st:725313-HuGene_st:225667_s_at: 234331_s_at HSPH1
74086-HuGene_st:246081-HuGene_st:887199- HSPH1 6.17E-08 1.647 1.85
79.5 70.8-86.5 HuGene_st:430002-HuGene_st:268776-
HuGene_st:760404-HuGene_st:454747-
HuGene_st:984599-HuGene_st:205087-
HuGene_st:215482-HuGene_st:208744_x_at:
398393-HuGene_st:315510-HuGene_st:
957456-HuGene_st:468891-HuGene_st:669816-
HuGene_st:1086868-HuGene_st:774542-
HuGene_st:160544-HuGene_st:1033297-
HuGene_st:977601-HuGene_st:206976_s_at: 363341-HuGene_st IGFBP2
50377-HuGene_st:401927-HuGene_st:845904- IGFBP2 8.07E-08 1.6359
1.93 79.3 70.6-86.3 HuGene_st:601554-HuGene_st:398340-
HuGene_st:314502-HuGene_st:218007-
HuGene_st:686058-HuGene_st:788427-
HuGene_st:964835-HuGene_st:376015-
HuGene_st:1093382-HuGene_st:202718_at:
303829-HuGene_st:1089028-HuGene_st:
439677-HuGene_st:715676-HuGene_st:
801130-HuGene_st:696938-HuGene_st:224352-
HuGene_st:983285-HuGene_st COL12A1
405565-HuGene_st:874183-HuGene_st:1057284- TMEM30A: 9.48E-08 1.6377
3.16 79.4 70.7-86.3 HuGene_st:234951_s_at:180263-HuGene_st:905983-
COL12A1 HuGene_st:140178-HuGene_st:620694-
HuGene_st:913204-HuGene_st:1063560-
HuGene_st:289954-HuGene_st:567963-
HuGene_st:319853-HuGene_st:1009559-
HuGene_st:415220-HuGene_st:419264-
HuGene_st:31736-HuGene_st:303383- HuGene_st:231766_s_at:595404-
HuGene_st:435472-HuGene_st:447689-
HuGene_st:759154-HuGene_st:794749- HuGene_st:225664_at:231879_at
BGN 279145-HuGene_st:429977-HuGene_st:45294- BGN 1.01E-07 1.594
2.69 78.7 70-85.8 HuGene_st:722197-HuGene_st:171694-
HuGene_st:643594-HuGene_st:201262_s_at: 1090822-HuGene_st:497499-
HuGene_st:1051954-HuGene_st:381650-
HuGene_st:978124-HuGene_st:422042-
HuGene_st:1096605-HuGene_st:861988-
HuGene_st:973749-HuGene_st:164623- HuGene_st:213905_x_at:838396-
HuGene_st:11448-HuGene_st:201261_x_at:
987820-HuGene_st:111675-HuGene_st: 298959-HuGene_st RFC3
848747-HuGene_st:3592-HuGene_st:785802- RFC3 1.25E-07 1.551 2.25
78.1 69.2-85.3 HuGene_st:404399-HuGene_st:837611-
HuGene_st:815998-HuGene_st:697366-
HuGene_st:133672-HuGene_st:180712-
HuGene_st:435344-HuGene_st:756480-
HuGene_st:567461-HuGene_st:204128_s_at:898295-
HuGene_st:952352-HuGene_st:976745-
HuGene_st:665489-HuGene_st:11314- HuGene_st:204127_at LY6G6D
80885-HuGene_st:260184-HuGene_st:222480- C6orf21: 1.34E-07 1.5536
6.64 78.1 69.3-85.4 HuGene_st:123649-HuGene_st:290348- LY6G6D,
HuGene_st:207457_s_at:263557- C6orf21:
HuGene_st:49853-HuGene_st:556933- LY6G6D,
HuGene_st:153804-HuGene_st:89374- C6orf21:
HuGene_st:738758-HuGene_st:883797- LY6G6D
HuGene_st:649378-HuGene_st:787525-
HuGene_st:974035-HuGene_st:722632-
HuGene_st:736016-HuGene_st:254189-
HuGene_st:152334-HuGene_st:318378- HuGene_st:35133-HuGene_st TPX2
210052_s_at:626194-HuGene_st:116965- TPX2 1.56E-07 1.6664 2.03 79.8
71.1-86.7 HuGene_st:631447-HuGene_st:218832-
HuGene_st:835196-HuGene_st:865389-
HuGene_st:784001-HuGene_st:653583-
HuGene_st:150197-HuGene_st:583927-
HuGene_st:501611-HuGene_st:1101424-
HuGene_st:715774-HuGene_st:1097812-
HuGene_st:290350-HuGene_st:325542-
HuGene_st:635970-HuGene_st:157916-
HuGene_st:918534-HuGene_st:787891-HuGene_st PLAU
131855-HuGene_st:471777-HuGene_st:246040- PLAU 2.25E-07 1.5372 3.5
77.9 69.1-85.2 HuGene_st:31176-HuGene_st:323438-HuGene_st:
211668_s_at:1027344-HuGene_st:1076162-
HuGene_st:186016-HuGene_st:156254-
HuGene_st:692506-HuGene_st:783863-
HuGene_st:52541-HuGene_st:738306- HuGene_st:611756-HuGene_st:7925-
HuGene_st:1085903-HuGene_st:585614-
HuGene_st:205479_s_at:410729-HuGene_st:390198-
HuGene_st:1043179-HuGene_st:708663- HuGene_st:589365-HuGene_st
RDHE2 533383-HuGene_st:530222-HuGene_st:515817- RDHE2 2.71E-07
1.5509 2.52 78.1 69.2-85.3 HuGene_st:163536-HuGene_st:229834-
HuGene_st:178723-HuGene_st:795130-
HuGene_st:850113-HuGene_st:964061-
HuGene_st:314806-HuGene_st:905527-
HuGene_st:740748-HuGene_st:581500-
HuGene_st:238017_at:133825-HuGene_st:
320855-HuGene_st:855530-HuGene_st:945673-
HuGene_st:436054-HuGene_st:665205-HuGene_st COL11A1
254341-HuGene_st:485975-HuGene_st:869898- COL111A1 2.93E-07 1.5722
2.6 78.4 69.6-85.5 HuGene_st:755872-HuGene_st:2674-
HuGene_st:230890-HuGene_st:6042-
HuGene_st:1100922-HuGene_st:800510-
HuGene_st:64257-HuGene_st:301971-
HuGene_st:360139-HuGene_st:549979-
HuGene_st:603002-HuGene_st:756718-
HuGene_st:1043994-HuGene_st:198973-
HuGene_st:550144-HuGene_st:986684-
HuGene_st:743059-HuGene_st:708360-
HuGene_st:575064-HuGene_st:633985-
HuGene_st:392228-HuGene_st:204320_at:
121425-HuGene_st:468885-HuGene_st:20543- HuGene_st:170503-HuGene_st
CDC2 1086386-HuGene_st:472750-HuGene_st:503957- CDC2 3.58E-07
1.5339 2.72 77.8 69-85.1
HuGene_st:486448-HuGene_st:210559_s_at:601189-
HuGene_st:231534_at:251684-HuGene_st:1039286-
HuGene_st:373877-HuGene_st:490933-
HuGene_st:913358-HuGene_st:714839- HuGene_st:203214_x_at:428760-
HuGene_st:203213_at:217937- HuGene_st:922512-HuGene_st:422389-
HuGene_st:44156-HuGene_st:15376- HuGene_st:576658-HuGene_st:302174-
HuGene_st:127098-HuGene_st DUSP27
612025-HuGene_st:737703-HuGene_st:124098- DUSP27 4.68E-07 1.5106
4.81 77.5 68.6-84.8 HuGene_st:102948-HuGene_st:35826-
HuGene_st:226732-HuGene_st:513585-
HuGene_st:135885-HuGene_st:737040-
HuGene_st:446627-HuGene_st:724445- HuGene_st:289189-HuGene_st:5396-
HuGene_st:520095-HuGene_st:172210-
HuGene_st:277848-HuGene_st:312172-
HuGene_st:903613-HuGene_st:232252_at:303717-
HuGene_st:846174-HuGene_st LOC541471
276744-HuGene_st:644672-HuGene_st:812194- MGC4677, 7.40E-07 1.4932
2.04 77.2 68.3-84.6 HuGene_st:279980-HuGene_st:225799_at:624891-
MGC4677: HuGene_st:149287-HuGene_st:277416- LOC541471
HuGene_st:709116-HuGene_st:236489-
HuGene_st:873188-HuGene_st:129947-HuGene_st:
569637-HuGene_st:916693- HuGene_st:469295-HuGene_st SPINK1
366191-HuGene_st:47871-HuGene_st:365962- SPINK1 1.70E-06 1.4805
2.74 77 68.1-84.4 HuGene_st:427748-HuGene_st:190115-
HuGene_st:393701-HuGene_st:206239_s_at:67198-
HuGene_st:507942-HuGene_st:547524-
HuGene_st:755318-HuGene_st:814516-
HuGene_st:511654-HuGene_st:159182-
HuGene_st:250165-HuGene_st:381410-
HuGene_st:85856-HuGene_st:199974- HuGene_st:97379-HuGene_st:620717-
HuGene_st:1058758-HuGene_st:267993- HuGene_st:371764-HuGene_st
C14orf94 225806_at:243446_at:88782-HuGene_st:537586- C14orf94
2.40E-06 1.653 1.19 79.6 70.8-86.5
HuGene_st:973643-HuGene_st:646464-
HuGene_st:729584-HuGene_st:973338-
HuGene_st:95576-HuGene_st:301260-
HuGene_st:559586-HuGene_st:942952-
HuGene_st:82798-HuGene_st:218383_at: 165751-
HuGene_st:965936-HuGene_st:31043-
HuGene_st:650638-HuGene_st:984201-
HuGene_st:925802-HuGene_st:306659- HuGene_st:345230-HuGene_st MSLN
63302-HuGene_st:821643-HuGene_st:99135- MSLN 3.78E-06 1.4279 1.93
76.2 67.2-83.8 HuGene_st:192667-HuGene_st:765000-
HuGene_st:44188-HuGene_st:59621- HuGene_st:465236-HuGene_st:559922-
HuGene_st:82252-HuGene_st:1039687-
HuGene_st:1053735-HuGene_st:204885_s_at: 870302-HuGene_st:246473-
HuGene_st:58043-HuGene_st:122629-
HuGene_st:826602-HuGene_st:689741-
HuGene_st:931732-HuGene_st:227498-HuGene_st LOXL2
818138-HuGene_st:46172-HuGene_st:346541- ENTPD4:LOXL2 4.81E-06
1.373 2.19 75.4 66.3-82.9 HuGene_st:281266-HuGene_st:202998_s_at:
1074111-HuGene_st:228808_s_at:271051-
HuGene_st:827532-HuGene_st:228823-
HuGene_st:950166-HuGene_st:254550-
HuGene_st:260752-HuGene_st:937941-
HuGene_st:328673-HuGene_st:966956- HuGene_st:84360-HuGene_st:34062-
HuGene_st:291104-HuGene_st:898787- HuGene_st:202997_s_at:626390-
HuGene_st:929733-HuGene_st APOBEC1
735977-HuGene_st:188849-HuGene_st:423265- APOBEC1 9.49E-06 1.3847
1.63 75.6 66.5-83.1 HuGene_st:882201-HuGene_st:237979-
HuGene_st:708999-HuGene_st:293863-
HuGene_st:372914-HuGene_st:237042-
HuGene_st:207158_at:1080489-HuGene_st:
815110-HuGene_st:417875-HuGene_st:745636-
HuGene_st:34403-HuGene_st:650730-
HuGene_st:164111-HuGene_st:360993- HuGene_st MLPH
549562-HuGene_st:92890-HuGene_st:305885- MLPH 1.16E-05 1.4174 1.47
76.1 67.1-83.6 HuGene_st:709610-HuGene_st:337433-
HuGene_st:128794-HuGene_st:824637-
HuGene_st:131043-HuGene_st:702794-
HuGene_st:533212-HuGene_st:398611-
HuGene_st:423382-HuGene_st:865544-
HuGene_st:546078-HuGene_st:505182-
HuGene_st:400420-HuGene_st:316126-
HuGene_st:586617-HuGene_st:506198- HuGene_st:218211_s_at:229150_at:
976628-HuGene_st HOXB6 339062-HuGene_st:885612-HuGene_st:1075575-
HOXB6 1.33E-05 1.3346 1.87 74.8 65.6-82.4
HuGene_st:746940-HuGene_st:103632-
HuGene_st:883931-HuGene_st:552163-
HuGene_st:249935-HuGene_st:726433-
HuGene_st:31257-HuGene_st:242080-
HuGene_st:630137-HuGene_st:959882-
HuGene_st:546294-HuGene_st:241578-
HuGene_st:142774-HuGene_st:881260-
HuGene_st:290100-HuGene_st:447667- HuGene_st:205366_s_at:299629-
HuGene_st:831836-HuGene_st CTHRC1
235232-HuGene_st:86783-HuGene_st:426340- CTHRC1 1.83E-05 1.2895
2.57 74 64.9-81.8 HuGene_st:385407-HuGene_st:647908-
HuGene_st:756615-HuGene_st:978256-
HuGene_st:651961-HuGene_st:193568-
HuGene_st:310105-HuGene_st:393578- HuGene_st REG3A
290546-HuGene_st:265033-HuGene_st:385905- REG3A 2.22E-05 1.2218
12.09 72.9 63.7-80.8 HuGene_st:459677-HuGene_st:230871-
HuGene_st:214805-HuGene_st:1060074-
HuGene_st:816902-HuGene_st:1092213-
HuGene_st:942177-HuGene_st:191737-HuGene_st:
729928-HuGene_st:205815_at:256155- HuGene_st:677349-HuGene_st CXCL5
264137-HuGene_st:272626-HuGene_st:745715- CXCL5 2.79E-05 1.2805
4.48 73.9 64.8-81.7 HuGene_st:968572-HuGene_st:1054472-
HuGene_st:394185-HuGene_st:181128-
HuGene_st:456756-HuGene_st:415578- HuGene_st:215101_s_at:214974_x
at:935926- HuGene_st:781518-HuGene_st:235326-HuGene_st:
941963-HuGene_st:242589-HuGene_st:798477-
HuGene_st:257906-HuGene_st:350119- HuGene_st:222708-HuGene_st CDH11
167614-HuGene_st:234040-HuGene_st:609892- CDH11 3.44E-05 1.2652
2.25 73.7 64.4-81.5 HuGene_st:583244-HuGene_st:863670-
HuGene_st:599824-HuGene_st:142981-
HuGene_st:96018-HuGene_st:217538- HuGene_st:634855-HuGene_st:60296-
HuGene_st:546348-HuGene_st:206371-
HuGene_st:960949-HuGene_st:353648-
HuGene_st:184349-HuGene_st:356919-
HuGene_st:611963-HuGene_st:626011- HuGene_st:543798-HuGene_st:
207173_x_at:207172 s at FAP
993707-HuGene_st:132558-HuGene_st:581008- IFIH1: 6.66E-05 1.2541
2.33 73.5 64.2-81.3 HuGene_st:209955_s_at:600137- FAP
HuGene_st:284881-HuGene_st:40379- HuGene_st_ REG1B
796972-HuGene_st:1089426-HuGene_st:762519- REG1B 8.08E-05 1.1728
13.15 72.1 62.8-80.1 HuGene_st:270006-HuGene_st:553619-
HuGene_st:279169-HuGene_st:342759-
HuGene_st:337497-HuGene_st:898145-
HuGene_st:603979-HuGene_st:134214-
HuGene_st:469380-HuGene_st:332107-
HuGene_st:608771-HuGene_st:965588-
HuGene_st:205886_at:1010838-HuGene_st:714363-
HuGene_st:29068-HuGene_st:215693-HuGene_st COMP
401785-HuGene_st:710767-HuGene_st:996888- COMP 0.0001 1.1565 1.69
71.8 62.6-79.9 HuGene_st:348725-HuGene_st:492440-
HuGene_st:307171-HuGene_st:121009- HuGene_st:205713_s_at AURKA
147919-HuGene_st:826493-HuGene_st:453415- AURKA: 0.0001 1.1173 1.81
71.2 61.8-79.3 HuGene_st:126529-HuGene_st:799451- STK6P
HuGene_st:673418-HuGene_st:571370-
HuGene_st:470643-HuGene_st:926370-
HuGene_st:93908-HuGene_st:426906-
HuGene_st:636365-HuGene_st:326617-
HuGene_st:208080_at:582788-HuGene_st:647783-
HuGene_st:458308-HuGene_st:204092_s_at:121857-
HuGene_st:1059753-HuGene_st:70315- HuGene_st SQLE
181699-HuGene_st:213577_at:285928- SQLE 0.0001 1.1354 2.69 71.5
62.1-79.6 HuGene_st:367103-HuGene_st:827097-
HuGene_st:213562_s_at:819545-HuGene_st:354972-
HuGene_st:779168-HuGene_st:1010566-
HuGene_st:47822-HuGene_st:861626- HuGene_st:895693-HuGene_st:94812-
HuGene_st:967759-HuGene_st:625566-
HuGene_st:890030-HuGene_st:566347-
HuGene_st:296617-HuGene_st:894379-
HuGene_st:1023221-HuGene_st:198540- HuGene_st:117280-HuGene_st
L1TD1 859419-HuGene_st:968483-HuGene_st:1010927- L1TD1 0.0002
1.1589 2.36 71.9 62.6-79.9
HuGene_st:236894_at:715579-HuGene_st:540230-
HuGene_st:414266-HuGene_st:572495-
HuGene_st:327643-HuGene_st:1058922-
HuGene_st:18534-HuGene_st:1063550-
HuGene_st:1030986-HuGene_st:842123-
HuGene_st:709222-HuGene_st:887612-
HuGene_st:219955_at:496121-HuGene_st:
942986-HuGene_st:799837-HuGene_st SERPINE2
443903-HuGene_st:959444-HuGene_st:48734- SERPINE2 0.0002 1.1283 1.9
71.4 62.1-79.4 HuGene_st:664848-HuGene_st:1052179-
HuGene_st:227487_s_at:902213-HuGene_st:621638-
HuGene_st:230208-HuGene_st:14188-HuGene_st:
854259-HuGene_st:929830-HuGene_st:670835-
HuGene_st:48860-HuGene_st:31861-HuGene_st:
722385-HuGene_st:1057158-HuGene_st:466703-
HuGene_st:10961-HuGene_st:824130-
HuGene_st:347407-HuGene_st:205406-HuGene_st CEL 1553970_s_at:
898561-HuGene_st:857424- CEL 0.0006 1.0863 1.46 70.6 61.3-78.8
HuGene_st:456577-HuGene_st:1035054-
HuGene_st:539061-HuGene_st:788693-
HuGene_st:314198-HuGene_st:786044-
HuGene_st:205910_s_at:958725-HuGene_st:473620-
HuGene_st:74757-HuGene_st:169727-
HuGene_st:711091-HuGene_st:461956-
HuGene_st:897116-HuGene_st:911062- HuGene_st:796522-HuGene_st
LILRB1 213975_s_at LILRA1: 0.0013 1.0781 1.55 70.5 61.1-78.7 LILRB1
COL1A1 487433-HuGene_st:719132- COL1A1 0.0018 1.0063 2.5 69.3
59.9-77.6 HuGene_st:1556499_s_at:202311_s_at: 202310_s_at:1003153-
HuGene_st:1029566-HuGene_st COL5A2 292241-HuGene_st COL5A2 0.0026
1.0556 1.36 70.1 60.8-78.3 PCSK1
981596-HuGene_st:31911-HuGene_st:701212- PCSK1 0.0029 1.1077 1.48
71 61.7-79.1 HuGene_st:673651-HuGene_st:166044-
HuGene_st:989024-HuGene_st:1039153-
HuGene_st:688811-HuGene_st:1068709-
HuGene_st:1083910-HuGene_st:527047-
HuGene_st:994213-HuGene_st:190818-
HuGene_st:785459-HuGene_st:127562-
HuGene_st:1012339-HuGene_st:343010-
HuGene_st:109185-HuGene_st:115345-
HuGene_st:470044-HuGene_st:856975- HuGene_st:454100-HuGene_st PCCA
54827-HuGene_st:1042448-HuGene_st:175778- PCCA 0.0038 0.939 1.42
68.1 58.6-76.5 HuGene_st:203860_at H19
634871-HuGene_st:51379-HuGene_st:803516- RPS12: 0.0051 1.0228 1.47
69.5 60.2-77.8 HuGene_st:336451-HuGene_st:254511- H19
HuGene_st:632993-HuGene_st COL10A1 288876-HuGene_st:815716- COL10A1
0.0143 0.8493 2.05 66.4 56.9-74.9
HuGene_st:615071-HuGene_st:865385- HuGene_st:1067078-HuGene_st
CYP3A5 NA CYP3A5: 0.0562 0.8249 1.58 66 56.5-74.6 CYP3A7 CYP3A5P2
NA CYP3A5: 0.0562 0.8246 1.58 66 56.5-74.6 CYP3A7 SLITRK6 NA
SLITRK6 0.0576 0.8687 1.31 66.8 57.3-75.3 SPARC NA SPARC 0.0684
0.6714 1.45 63.1 53.6-72 CTSE NA CTSE 0.0694 0.7465 1.83 64.6
55-73.3 HOXA9 NA HOXA9 0.0759 0.7505 1.41 64.6 55.1-73.3 SFRP4 NA
SFRP4 0.0829 0.6983 1.29 63.7 54-72.4 COL1A2 NA COL1A2: 0.1891
0.6508 1.9 62.8 53.1-71.6 LOC728628 THBS2 NA THBS2 0.9844 0.2782
1.26 55.5 45.9-64.8
TABLE-US-00036 TABLE 3 Signif. Sens- TargetPS Symbol FDR D.val5 FC
Spec CI (95) 217523_at MAPK10:CD44 3.35E-26 3.7166 7.06 96.8
92.9-98.8 204702_s_at LOC650331:NFE2L3:LOC642996 1.51E-24 3.521
4.57 96.1 91.7-98.4 207850_at CXCL2:CXCL3 5.76E-22 3.2893 7.85 95
90-97.8 204259_at MMP7 7.61E-22 3.2634 69.29 94.9 89.8-97.7
228915_at DACH1 1.05E-18 2.9232 5.81 92.8 86.9-96.5 241031_at NLF1
3.12E-18 2.8001 8.12 91.9 85.7-95.9 223062_s_at
LOC651255:PSAT1:LOC389173:LOC729779: 3.32E-15 2.4882 5.52 89.3
82.3-94.2 C8orf62 206224_at CST1 7.04E-15 2.4165 13.01 88.7
81.5-93.6 209309_at AZGP1:LOC401393 1.31E-14 2.3986 6.19 88.5
81.3-93.5 219787_s_at ECT2 1.42E-14 2.4245 2.82 88.7 81.6-93.7
202286_s_at TACSTD2 3.13E-14 2.3676 15.71 88.2 80.9-93.3 227140_at
No Symbol 9.19E-12 2.1522 1.61 85.9 78.2-91.6 229802_at No Symbol
9.19E-12 2.1536 1.61 85.9 78.2-91.6 213880_at LGR5 1.10E-11 2.0621
7.89 84.9 76.9-90.8 205174_s_at QPCT 3.46E-11 2.0422 3.03 84.6
76.7-90.6 238021_s_at LOC643911 3.73E-11 1.6459 1.33 79.5 70.8-86.5
227174_at WDR72 5.22E-11 1.9854 14.11 84 75.8-90.1 238984_at REG4
5.97E-10 1.8033 7.75 81.6 73.2-88.3 204475_at MMP1 1.22E-09 1.8138
10.59 81.8 73.4-88.4 222608_s_at ANLN 4.94E-09 1.7541 2.63 81
72.4-87.7 211506_s_at LOC652128:IGHG1:IGHM:IGHV4- 1.99E-07 1.6343
3.1 79.3 70.6-86.3 31:LOC647189:IGHV1-
69:IGHA1:IL8:EXOC7:SIX6:IGHD: IGH@:IGHG3:C12orf32:ZCWPW2:
IFI6:IGHG4:IGHA2:IGHG2:RAC1 204320_at COL11A1 2.93E-07 1.5718 2.6
78.4 69.6-85.6 37892_at COL11A1 2.93E-07 1.5707 2.6 78.4 69.6-85.6
232252_at DUSP27 4.68E-07 1.5112 4.81 77.5 68.6-84.8 225806_at
C14orf94 2.40E-06 1.6519 1.19 79.6 70.9-86.6 204885_s_at MSLN
3.78E-06 1.4266 1.93 76.2 67.2-83.7 214974_x_at CXCL5 2.79E-05
1.2818 4.48 73.9 64.7-81.6 236894_at L1TD1 0.0002 1.1596 2.36 71.9
62.6-79.9 205910_s_at CEL 0.0006 1.0869 1.46 70.7 61.3-78.8
202311_s_at COL1A1 0.0018 1.0054 2.5 69.2 59.9-77.6 205825_at PCSK1
0.0029 1.1086 1.48 71 61.7-79.1 226237_at COL8A1 0.0254 0.8303 1.43
66.1 56.6-74.7 235976_at SLITRK6 0.0576 0.8689 1.31 66.8
57.2-75.3
TABLE-US-00037 TABLE 4 Gene Signif. Sens- CI Symbol ValidPS_UP
Symbol FDR D.val5 FC Spec (95) CD44
366106-HuGene_st:314808-HuGene_st:59730- MAPK10:CD44 3.35E-26
3.7136 7.06 96.8 92.9-98.8 HuGene_st:599371-HuGene_st:391296-
HuGene_st:1031797-HuGene_st:314340-
HuGene_st:10723-HuGene_st:950067-
HuGene_st:282016-HuGene_st:480680-
HuGene_st:69560-HuGene_st:388781-
HuGene_st:243049-HuGene_st:374652-
HuGene_st:194553-HuGene_st:1075454- HuGene_st:204489_s_at:619139-
HuGene_st:210916_s_at:542762-
HuGene_st:1557905_s_at:212014_x_at:229221_at:
204490_s_at:234418_x_at:209835_x_at:212063_at: 216062_at:777408-
HuGene_st:234411_x_at:217523_at:216056_at:
1565868_at:83114-HuGene_st NFE2L3
95873-HuGene_st:1058969-HuGene_st:86088- LOC650331:NFE2L3: 1.51E-24
3.5213 4.57 96.1 91.6-98.4 HuGene_st:1093456-HuGene_st:347351-
LOC642996 HuGene_st:878719-HuGene_st:880179-
HuGene_st:240089_at:822197- HuGene_st:873612-HuGene_st:517821-
HuGene_st:489354-HuGene_st:20603- HuGene_st:204702_s_at MMP7
267137-HuGene_st:1068392- MMP7 7.61E-22 3.2652 69.29 94.9 89.8-97.8
HuGene_st:794865-HuGene_st:876922-
HuGene_st:669567-HuGene_st:1039935-
HuGene_st:514120-HuGene_st:1092830-
HuGene_st:745768-HuGene_st:272260-
HuGene_st:30733-HuGene_st:401681-
HuGene_st:854024-HuGene_st:221616-
HuGene_st:805045-HuGene_st:783838- HuGene_st:204259_at:934756-
HuGene_st:446688-HuGene_st:10259-
HuGene_st:267021-HuGene_st:889042- HuGene_st CXCL3
11327-HuGene_st:626337-HuGene_st:322604- CXCL2:CXCL3 1.95E-21
3.2907 7.85 95 .sup. 90-97.8 HuGene_st:256806-HuGene_st:261067-
HuGene_st:448247-HuGene_st:666569-
HuGene_st:222646-HuGene_st:262117-
HuGene_st:798675-HuGene_st:391369-
HuGene_st:865299-HuGene_st:877897-
HuGene_st:575433-HuGene_st:43120- HuGene_st:42070-HuGene_st:33632-
HuGene_st:965957-HuGene_st:556939-
HuGene_st:26460-HuGene_st:796450- HuGene_st:230101_at:541868-
HuGene_st:490134-HuGene_st:1064107-
HuGene_st:230192-HuGene_st:645829-
HuGene_st:455502-HuGene_st:249140-
HuGene_st:906606-HuGene_st:1098767-
HuGene_st:721989-HuGene_st:500578- HuGene_st:33301-
HuGene_st:207850_at:622384- HuGene_st:209774_x_at:432036-
HuGene_st:30559-HuGene_st:187557-
HuGene_st:1101027-HuGene_st:1038334-
HuGene_st:260925-HuGene_st:515662- HuGene_st:258081-
HuGene_st:1569203_at:280828- HuGene_st:1000069-HuGene_st:509822-
HuGene_st:890213-HuGene_st:739461-
HuGene_st:342746-HuGene_st:98929-
HuGene_st:818131-HuGene_st:1091592-
HuGene_st:420504-HuGene_st:41644-
HuGene_st:655278-HuGene_st:188562- HuGene_st:458602-HuGene_st DACH1
686187-HuGene_st:985190- DACH1 1.05E-18 2.9206 5.81 92.8 86.9-96.5
HuGene_st:1011822-HuGene_st:1092705-
HuGene_st:693255-HuGene_st:722787-
HuGene_st:465556-HuGene_st:113230-
HuGene_st:49101-HuGene_st:290879- HuGene_st:646013-HuGene_st:3984-
HuGene_st:378631-HuGene_st:1002554-
HuGene_st:620749-HuGene_st:802309- HuGene_st:82679-
HuGene_st:205471_s_at:303920- HuGene_st:338273-HuGene_st:20454-
HuGene_st:1567100_at:205472_s_at: 228915_at:562342_at:169641-
HuGene_st:984254-HuGene_st:1567101_at NLF1 269939-HuGene_st:314919-
NLF1 3.12E-18 2.8001 8.12 91.9 85.7-95.9
HuGene_st:552234-HuGene_st:622058-
HuGene_st:68900-HuGene_st:376228-
HuGene_st:194806-HuGene_st:923707-
HuGene_st:745661-HuGene_st:996995-
HuGene_st:534469-HuGene_st:560627- HuGene_st:711203-
HuGene_st:241031_at:93378- HuGene_st:611899-HuGene_st:57671-
HuGene_st:443570-HuGene_st:231416- HuGene_st PSAT1
139416-HuGene_st:795030- LOC651255:PSAT1: 3.32E-15 2.4883 5.52 89.3
82.3-94.1 HuGene_st:160439-HuGene_st:322148- LOC389173:LOC729779:
HuGene_st:85375-HuGene_st:223335- C8orf62
HuGene_st:2658-HuGene_st:399855- HuGene_st:220892_s_at:941491-
HuGene_st:1017348-HuGene_st:856207-
HuGene_st:194347-HuGene_st:553133- HuGene_st:223062_s_at:987517-
HuGene_st:336174-HuGene_st CST1
95123-HuGene_st:125297-HuGene_st:235257- CST1 7.04E-15 2.4165 13.01
88.7 81.5-93.7 HuGene_st:102028-HuGene_st:291462-
HuGene_st:206224_at:906914- HuGene_st:936009-HuGene_st:1055285-
HuGene_st AZGP1 363333-HuGene_st:620891- AZGP1:LOC401393 1.31E-14
2.3984 6.19 88.5 81.3-93.5 HuGene_st:619378-HuGene_st:741747-
HuGene_st:28018-HuGene_st:594026-
HuGene_st:222884-HuGene_st:1006522-
HuGene_st:974237-HuGene_st:473891-
HuGene_st:784628-HuGene_st:488818-
HuGene_st:209309_at:217014_s_at:63620-
HuGene_st:366096-HuGene_st:950952-
HuGene_st:601798-HuGene_st:399823-
HuGene_st:734365-HuGene_st:1054227- HuGene_st ECT2
770888-HuGene_st:82454-HuGene_st:171418- ECT2 1.42E-14 2.4269 2.82
88.8 81.6-93.7 HuGene_st:52318-HuGene_st:530079- HuGene_st:288145-
HuGene_st:234992_x_at:64803- HuGene_st:705846-HuGene_st:158755-
HuGene_st:554622- HuGene_st:237241_at:629949-
HuGene_st:222681-HuGene_st:241642-
HuGene_st:143403-HuGene_st:770445-
HuGene_st:218688-HuGene_st:700408-
HuGene_st:165018-HuGene_st:917458- HuGene_st:219787_s_at:609829-
HuGene_st:110350-HuGene_st TACSTD2 1004611-HuGene_st:755233-
TACSTD2 3.13E-14 2.3693 15.71 88.2 80.9-93.3
HuGene_st:815649-HuGene_st:567105-
HuGene_st:8281-HuGene_st:1041491- HuGene_st:339450-
HuGene_st:227128_s_at:653539- HuGene_st:1079680-HuGene_st:958592-
HuGene_st:202286_s_at:620831- HuGene_st:53075-HuGene_st:1009541-
HuGene_st:861600-HuGene_st:181597-
HuGene_st:130895-HuGene_st:849592- HuGene_st IL8
1044664-HuGene_st:714746- AHNAK:IGHG1 3.28E-12 2.3273 1.73 87.8
80.3-93.sup. HuGene_st:442029-HuGene_st:119200-
HuGene_st:550444-HuGene_st:493978-
HuGene_st:713906-HuGene_st:943156-
HuGene_st:504843-HuGene_st:501902-
HuGene_st:497219-HuGene_st:23149-
HuGene_st:387164-HuGene_st:562654-
HuGene_st:1047492-HuGene_st:538558- HuGene_st:239300-
HuGene_st:211430_s_at:390695- HuGene_st:1081759-HuGene_st:144630-
HuGene_st:661013-HuGene_st:393191-
HuGene_st:55017-HuGene_st:1005159-
HuGene_st:359116-HuGene_st:373132-
HuGene_st:689050-HuGene_st:611041-
HuGene_st:715689-HuGene_st:289354-
HuGene_st:820633-HuGene_st:555788-
HuGene_st:988945-HuGene_st:307991- HuGene_st:211506_s_at:924368-
HuGene_st:47911-HuGene_st:929972- HuGene_st:561100-HuGene_st:68522-
HuGene_st:217039_x_at:231668_x_at:1080400-
HuGene_st:141662-HuGene_st:765200-
HuGene_st:648539-HuGene_st:274868- HuGene_st:233969_at LGR5
784585-HuGene_st:777519- LGR5 1.10E-11 2.0645 7.89 84.9 76.9-90.8
HuGene_st:937559-HuGene_st:297045-
HuGene_st:796093-HuGene_st:783411-
HuGene_st:876648-HuGene_st:842003-
HuGene_st:102017-HuGene_st:562251-
HuGene_st:295997-HuGene_st:747520-
HuGene_st:811121-HuGene_st:677407-
HuGene_st:522834-HuGene_st:475414-
HuGene_st:802999-HuGene_st:1066925-
HuGene_st:216864-HuGene_st:890928-
HuGene_st:179502-HuGene_st:79633-
HuGene_st:210393_at:241266_at:213880_at QPCT
261837-HuGene_st:108729- QPCT 3.46E-11 2.0415 3.03 84.6 76.7-90.6
HuGene_st:942514-HuGene_st:184578-
HuGene_st:454020-HuGene_st:202482-
HuGene_st:1012784-HuGene_st:854999-
HuGene_st:62841-HuGene_st:271540- HuGene_st:524919-HuGene_st:78507-
HuGene_st:89785-HuGene_st:728309-
HuGene_st:625205-HuGene_st:170279-
HuGene_st:561083-HuGene_st:322236-
HuGene_st:205174_s_at:303448-HuGene_st WDR72
829740-HuGene_st:1063796- WDR72 5.22E-11 1.9856 14.11 84
75.9-90.sup. HuGene_st:725768- HuGene_st:227174_at:36564-
HuGene_st:236741_at:604794- HuGene_st:1040675-HuGene_st:527199-
HuGene_st:1052168- HuGene_st:1563874_at:177868-
HuGene_st:667158-HuGene_st:542462-
HuGene_st:136243-HuGene_st:551835- HuGene_st REG4
186424-HuGene_st:382639- REG4 5.97E-10 1.8057 7.75 81.7 73.3-88.3
HuGene_st:931162-HuGene_st:400261-
HuGene_st:638045-HuGene_st:852602-
HuGene_st:628254-HuGene_st:849775- HuGene_st:274371-
HuGene_st:1554436_a_at:1092015- HuGene_st:223447_at:29614-
HuGene_st:661518-HuGene_st:580789-
HuGene_st:929866-HuGene_st:160171-
HuGene_st:954850-HuGene_st:758344- HuGene_st:254891-
HuGene_st:238984_at:421464- HuGene_st:758547-HuGene_st:364821-
HuGene_st:701510-HuGene_st MMP1 61706-HuGene_st:300572- MMP1
1.22E-09 1.8141 10.59 81.8 73.4-88.4
HuGene_st:1020786-HuGene_st:437171-
HuGene_st:671620-HuGene_st:689073 -
HuGene_st:622653-HuGene_st:958445-
HuGene_st:445730-HuGene_st:914223-
HuGene_st:693724-HuGene_st:673683-
HuGene_st:524115-HuGene_st:422476-
HuGene_st:361198-HuGene_st:710307-
HuGene_st:468477-HuGene_st:840324-
HuGene_st:1070117-HuGene_st:473664- HuGene_st:732367-
HuGene_st:204475_at:353235-HuGene_st ANLN 522941-HuGene_st:550252-
ANLN 4.94E-09 1.7566 2.63 81 72.5-87.7
HuGene_st:477118-HuGene_st:858635-
HuGene_st:34728-HuGene_st:165560-
HuGene_st:226318-HuGene_st:207100-
HuGene_st:842538-HuGene_st:343961-
HuGene_st:899690-HuGene_st:705871-
HuGene_st:42619-HuGene_st:984996-
HuGene_st:733290-HuGene_st:1008901-
HuGene_st:752472-HuGene_st:619756-
HuGene_st:674545-HuGene_st:558324- HuGene_st:261208-
HuGene_st:222608_s_at:1552619_a_at
COL11A1 254341-HuGene_st:485975- COL11A1 2.93E-07 1.5724 2.6 78.4
69.6-85.6 HuGene_st:869898-HuGene_st:755872-
HuGene_st:2674-HuGene_st:230890- HuGene_st:6042-HuGene_st:1100922-
HuGene_st:800510-HuGene_st:64257-
HuGene_st:301971-HuGene_st:360139-
HuGene_st:549979-HuGene_st:603002-
HuGene_st:756718-HuGene_st:1043994-
HuGene_st:198973-HuGene_st:550144-
HuGene_st:986684-HuGene_st:743059-
HuGene_st:708360-HuGene_st:575064-
HuGene_st:633985-HuGene_st:392228- HuGene_st:204320_at:121425-
HuGene_st:468885-HuGene_st:20543- HuGene_st:170503-HuGene_st DUSP27
612025-HuGene_st:737703- DUSP27 4.68E-07 1.5098 4.81 77.5 68.6-84.8
HuGene_st:124098-HuGene_st:102948-
HuGene_st:35826-HuGene_st:226732-
HuGene_st:513585-HuGene_st:135885-
HuGene_st:737040-HuGene_st:446627-
HuGene_st:724445-HuGene_st:289189- HuGene_st:5396-HuGene_st:520095-
HuGene_st:172210-HuGene_st:277848-
HuGene_st:312172-HuGene_st:903613- HuGene_st:232252_at:303717-
HuGene_st:846174-HuGene_st C14orf94 225806_at:243446_at:88782-
C14orf94 2.40E-06 1.6524 1.19 79.6 70.9-86.5
HuGene_st:537586-HuGene_st:973643-
HuGene_st:646464-HuGene_st:729584-
HuGene_st:973338-HuGene_st:95576-
HuGene_st:301260-HuGene_st:559586-
HuGene_st:942952-HuGene_st:82798- HuGene_st:218383_at:165751-
HuGene_st:965936-HuGene_st:31043-
HuGene_st:650638-HuGene_st:984201-
HuGene_st:925802-HuGene_st:306659- HuGene_st:345230-HuGene_st MSLN
63302-HuGene_st:821643-HuGene_st:99135- MSLN 3.78E-06 1.427 1.93
76.2 67.2-83.7 HuGene_st:192667-HuGene_st:765000-
HuGene_st:44188-HuGene_st:59621- HuGene_st:465236-HuGene_st:559922-
HuGene_st:82252-HuGene_st:1039687- HuGene_st:1053735-
HuGene_st:2048 85_s_at:870302- HuGene_st:246473-HuGene_st:58043-
HuGene_st:122629-HuGene_st:826602-
HuGene_st:689741-HuGene_st:931732- HuGene_st:227498-HuGene_st CXCL5
264137-HuGene_st:272626- CXCL5 2.79E-05 1.2814 4.48 73.9 64.7-81.7
HuGene_st:745715-HuGene_st:968572-
HuGene_st:1054472-HuGene_st:394185-
HuGene_st:181128-HuGene_st:456756- HuGene_st:415578-
HuGene_st:215101_s_at:214974_x_at:935926-
HuGene_st:781518-HuGene_st:235326-
HuGene_st:941963-HuGene_st:242589-
HuGene_st:798477-HuGene_st:257906-
HuGene_st:350119-HuGene_st:222708- HuGene_st L1TD1
859419-HuGene_st:968483- L1TD1 2.00E-04 1.1595 2.36 71.9 62.6-79.9
HuGene_st:1010927- HuGene_st:236894_at:715579-
HuGene_st:540230-HuGene_st:414266-
HuGene_st:572495-HuGene_st:327643-
HuGene_st:1058922-HuGene_st:18534-
HuGene_st:1063550-HuGene_st:1030986-
HuGene_st:842123-HuGene_st:709222- HuGene_st:887612-
HuGene_st:219955_at:496121- HuGene_st:942986-HuGene_st:799837-
HuGene_st CEL 1553970_s_at:898561-HuGene_st:857424- CEL 6.00E-04
1.0872 1.46 70.7 61.3-78.8 HuGene_st:456577-HuGene_st:1035054-
HuGene_st:539061-HuGene_st:788693-
HuGene_st:314198-HuGene_st:786044- HuGene_st:205910_s_at:958725-
HuGene_st:473620-HuGene_st:74757-
HuGene_st:169727-HuGene_st:711091-
HuGene_st:461956-HuGene_st:897116-
HuGene_st:911062-HuGene_st:796522- HuGene_st COL1A1
487433-HuGene_st:719132- COL1A1 1.80E-03 1.0053 2.5 69.2 59.9-77.6
HuGene_st:1556499_s_at:202311_s_at: 202310_s_at:1003153-
HuGene_st:1029566-HuGene_st PCSK1
981596-HuGene_st:31911-HuGene_st:701212- PCSK1 2.90E-03 1.1082 1.48
71 61.6-79.1 HuGene_st:673651-HuGene_st:166044-
HuGene_st:989024-HuGene_st:1039153-
HuGene_st:688811-HuGene_st:1068709-
HuGene_st:1083910-HuGene_st:527047-
HuGene_st:994213-HuGene_st:190818-
HuGene_st:785459-HuGene_st:127562-
HuGene_st:1012339-HuGene_st:343010-
HuGene_st:109185-HuGene_st:115345- HuGene_st:470044-HuGene_st:85
6975- HuGene_st:454100-HuGene_st COL8A1 713455-HuGene_st COL8A1
2.54E-02 0.8325 1.43 66.1 56.6-74.7
TABLE-US-00038 TABLE 5 Signif. Sens- CI TargetPS Symbol FDR D.val5
FC Spec (95) 213106_at ATP8A1 6.60E-08 2.2884 3.11 87.4 76.9-94.1
210107_at CLCA1 3.19E-07 2.1573 9.98 86 75.2-93.1 204811_s_at
CACNA2D2 3.61E-05 1.659 4.41 79.7 67.7-88.5 223969_s_at RETNLB
4.3968E-05 1.6581 11.64 79.6 67.7-88.5 223970_at RETNLB 4.3968E-05
1.6576 11.64 79.6 67.8-88.5 228232_s_at VSIG2 0.0001 1.5718 2.4
78.4 66.3-87.6 242601_at LOC253012 0.0001 1.5777 5.28 78.5
66.5-87.6 227719_at No Symbol 0.0002 1.642 1.98 79.4 67.4-88.3
237521_x_at No Symbol 0.0002 1.6433 1.98 79.4 67.5-88.3 203240_at
FCGBP 3.00E-04 1.5005 3.07 77.3 65.2-86.7 204897_at PTGER4 6.00E-04
1.4732 1.55 76.9 64.7-86.4 227676_at FAM3D 0.001 1.2706 2.15 73.7
61.3-83.8 205765_at CYP3A5 1.20E-03 1.5279 1.8 77.8 65.6-87.1
232176_at SLITRK6 0.0016 1.3618 5.96 75.2 62.8-85.sup. 232481_s_at
SLITRK6 0.0016 1.3607 5.96 75.2 62.9-85.sup. 235976_at SLITRK6
0.0016 1.3648 5.96 75.3 62.9-84.9 221874_at KIAA1324 3.80E-03 1.325
2.1 74.6 62.2-84.5 226248_s_at KIAA1324 0.0038 1.3246 2.1 74.6
62.2-84.6 204607_at HMGCS2 5.20E-03 1.2354 3.59 73.2 60.7-83.3
203963_at CA12 6.50E-03 1.1828 1.86 72.3 59.7-82.6 204508_s_at CA12
6.50E-03 1.1861 1.86 72.3 59.8-82.6 215867_x_at CA12 6.50E-03
1.1858 1.86 72.3 59.7-82.6 227725_at ST6GALNAC1 0.0068 1.1419 1.76
71.6 59-82 200884_at CKB 7.30E-03 1.1481 2.25 71.7 59.1-82.1
219955_at L1TD1 7.70E-03 1.2502 3.27 73.4 60.9-83.5 236894_at L1TD1
0.0077 1.2465 3.27 73.3 60.9-83.5 205259_at NR3C2 1.29E-02 1.1933
1.63 72.5 60.1-82.8 218211_s_at MLPH 1.38E-02 1.2269 1.59 73
60.5-83.2 214234_s_at CYP3A5P2 1.94E-02 1.098 1.7 70.8 58.1-81.3
214235_at CYP3A5P2 1.94E-02 1.0976 1.7 70.8 58.2-81.3 204895_x_at
MUC4:TAF5L:LOC650855:LOC645744 4.53E-02 1.1998 1.31 72.6 60.1-82.8
217109_at MUC4:TAF5L:LOC650855:LOC645744 4.53E-02 1.2028 1.31 72.6
60.2-82.8 217110_s_at MUC4:TAF5L:LOC650855:LOC645744 4.53E-02 1.198
1.31 72.5 .sup. 60-82.8 221841_s_at KLF4 7.31E-02 1.0009 1.58 69.2
56.5-79.9 215125_s_at UGT1A9 7.37E-02 1.0664 1.28 70.3 57.6-80.9
208063_s_at CAPN9 7.40E-02 0.998 1.84 69.1 56.4-79.9 214433_s_at
SELENBP1 9.02E-02 0.9783 2 68.8 .sup. 56-79.6 226302_at ATP8B1
0.093 1.039 1.4 69.8 57.2-80.5 231832_at WDR51B 0.1284 1.0008 1.28
69.2 56.5-79.9 219543_at PBLD 1.66E-01 0.8734 1.89 66.9 54.2-77.9
208937_s_at ID1 2.34E-01 0.7639 1.66 64.9 52.1-76.2 205927_s_at
CTSE 2.81E-01 0.7393 3.23 64.4 51.6-75.8 229070_at C6orf105 0.7794
0.7027 1.37 63.7 50.9-75.2
TABLE-US-00039 TABLE 6 Signif. Sens- CI TargetPS Symbol FDR D.val5
FC Spec (95) 200665_s_at SPARC 3.05E-09 2.3771 3.24 88.3 .sup.
78-94.6 212667_at SPARC 3.0479E-09 2.3752 3.24 88.3 78.1-94.6
211964_at COL4A2 5.5315E-09 2.4316 2.87 88.8 78.8-95.sup. 211966_at
COL4A2 5.5315E-09 2.4321 2.87 88.8 78.8-95.sup. 211980_at COL4A1
1.243E-08 2.3031 3.03 87.5 77.2-94.2 211981_at COL4A1 1.243E-08
2.3045 3.03 87.5 77.2-94.2 218638_s_at SPON2 1.9471E-08 2.3321 3.38
87.8 77.5-94.3 221729_at COL5A2 5.7658E-08 2.2145 3.31 86.6 .sup.
76-93.5 221730_at COL5A2 5.7658E-08 2.2138 3.31 86.6 75.9-93.6
208782_at FSTL1 7.8434E-08 2.228 2.64 86.7 76.1-93.7 201261_x_at
BGN 9.6881E-08 2.2253 2.99 86.7 .sup. 76-93.6 213905_x_at BGN
9.6881E-08 2.2232 2.99 86.7 76.1-93.6 209955_s_at IFIH1:FAP
1.358E-07 2.2261 4.88 86.7 76.2-93.6 226237_at COL8A1 3.6053E-07
2.1456 3.09 85.8 75-93 202310_s_at COL1A1 5.44E-07 2.012 3.29 84.3
73-92 202311_s_at COL1A1 5.44E-07 2.0131 3.29 84.3 73.1-92.sup.
217430_x_at COL1A1 5.4426E-07 2.015 3.29 84.3 73.2-92.sup.
201438_at COL6A3 5.7026E-07 2.0286 2.73 84.5 73.5-92.1 202403_s_at
COL1A2:LOC728628 8.85E-07 2.0609 2.62 84.9 73.9-92.4 202404_s_at
COL1A2:LOC728628 8.85E-07 2.0621 2.62 84.9 73.7-92.4 229218_at
COL1A2:LOC728628 8.8466E-07 2.0618 2.62 84.9 73.9-92.4 208850_s_at
THY1 1.0326E-06 1.9159 3.34 83.1 71.8-91.1 208851_s_at THY1
1.0326E-06 1.915 3.34 83.1 71.7-91.1 213869_x_at THY1 1.0326E-06
1.9132 3.34 83.1 71.7-91.1 203477_at COL15A1 1.0611E-06 2.0121 3.37
84.3 73.2-91.9 201616_s_at CALD1 1.11E-06 2.1136 1.7 85.5 74.6-92.8
212077_at CALD1 1.1059E-06 2.1131 1.7 85.5 74.5-92.8 201162_at
IGFBP7 1.1574E-06 2.0016 1.91 84.2 72.9-91.8 201163_s_at IGFBP7
1.16E-06 1.999 1.91 84.1 .sup. 73-91.9 210511_s_at INHBA 1.1943E-06
2.0027 3.38 84.2 .sup. 73-91.9 225664_at TMEM30A:COL12A1 1.2492E-06
2.0313 4.16 84.5 73.4-92.1 231766_s_at TMEM30A:COL12A1 1.2492E-06
2.0303 4.16 84.5 73.4-92.1 231879_at TMEM30A:COL12A1 1.2492E-06
2.0325 4.16 84.5 73.5-92.1 203325_s_at COL5A1 1.6076E-06 1.934 2.75
83.3 72.1-91.3 212488_at COL5A1 1.6076E-06 1.9342 2.75 83.3
72.1-91.3 212489_at COL5A1 1.6076E-06 1.9339 2.75 83.3 .sup.
72-91.2 203083_at THBS2 2.3382E-06 1.9081 6.5 83 71.6-91.sup.
202291_s _at MGP:C12orf46 2.50E-06 1.999 2.62 84.1 .sup. 73-91.9
201645_at TNC 3.74E-06 1.9608 2.14 83.7 72.5-91.5 201852_x_at
COL3A1 9.29E-06 1.8472 2.32 82.2 70.7-90.5 211161_s_at COL3A1
9.2906E-06 1.8501 2.32 82.3 70.7-90.5 215076_s_at COL3A1 9.2906E-06
1.8495 2.32 82.2 70.7-90.5 232458_at COL3A1 9.2906E-06 1.8473 2.32
82.2 70.7-90.5 212344_at SULF1 1.4436E-05 1.7528 2.84 81 69.3-89.5
212353_at SULF1 1.4436E-05 1.7555 2.84 81 69.2-89.5 212354_at SULF1
1.4436E-05 1.7521 2.84 80.9 69.3-89.5 201185_at HTRA1 1.7178E-05
1.7346 2.29 80.7 68.9-89.3 202998_s_at ENTPD4:LOXL2 1.99E-05 1.7754
2.45 81.3 69.6-89.7 224724_at SULF2 2.0766E-05 1.6837 2.25 80
68.2-88.7 233555_s_at SULF2 2.0766E-05 1.6795 2.25 79.9 .sup.
68-88.7 201069_at MMP2 2.5409E-05 1.7345 3.02 80.7 .sup. 69-89.3
201147_s_at TIMP3 2.62E-05 1.7776 2.56 81.3 69.6-89.7 201150_s_at
TIMP3 2.62E-05 1.7774 2.56 81.3 69.6-89.7 209156_s_at COL6A2
2.9551E-05 1.7373 1.67 80.7 .sup. 69-89.4 227099_s_at LOC387763
0.00003052 1.8968 1.43 82.9 71.4-90.9 214247_s_at DKK3 3.1838E-05
1.7434 1.86 80.8 69.1-89.5 202450_s_at CTSK 3.98E-05 1.7153 2.16
80.4 68.7-89.1 225799_at MGC4677, MGC4677:LOC541471 4.1139E-05
1.8003 1.45 81.6 70-90 209395_at CHI3L1:MYBPH 5.1515E-05 1.6358
3.06 79.3 67.4-88.2 209396_s_at CHI3L1:MYBPH 5.1515E-05 1.6352 3.06
79.3 67.4-88.2 202878_ s_at CD93 5.19E-05 1.667 2.36 79.8 67.9-88.6
204320_at COL11A1 5.3391E-05 1.7594 2.55 81 69.3-89.6 37892_at
COL11A1 5.3391E-05 1.7556 2.55 81 69.3-89.6 221011_s_at LBH
6.3299E-05 1.6771 1.9 79.9 68.1-88.7 213125_at OLFML2B 6.6557E-05
1.7057 1.97 80.3 68.5-89.sup. 204475_at MMP1 7.0616E-05 1.6759 3.91
79.9 .sup. 68-88.8 226694_at AKAP2:PALM2:PALM2-AKAP2 7.4206E-05
1.7231 1.58 80.6 68.8-89.2 202766_s_at FBN1 0.0001 1.5984 1.48 78.8
66.7-87.9 205828_at MMP3 0.0001 1.6223 6.68 79.1 67.3-88.1
207191_s_at ISLR 0.0001 1.6448 1.87 79.5 67.5-88.4 213428_s_at
COL6A1 0.0001 1.7301 1.58 80.6 68.8-89.3 226930_at FNDC1 0.0001
1.521 3.14 77.7 65.6-87.sup. 201792_at AEBP1 0.0002 1.4772 2.11 77
64.8-86.5 203878_s_at MMP11 0.0002 1.6971 1.28 80.2 68.4-88.9
211959_at IGFBP5 0.0002 1.5662 3.96 78.3 66.3-87.5 225710_at No
Symbol 0.0002 1.6426 1.98 79.4 67.5-88.4 226311_at No Symbol 0.0002
1.6436 1.98 79.4 67.5-88.3 226777_at No Symbol 0.0002 1.645 1.98
79.5 67.5-88.4 227140_at No Symbol 0.0002 1.6427 1.98 79.4
67.6-88.3 229802_at No Symbol 0.0002 1.6421 1.98 79.4 67.5-88.3
205479_s_at PLAU 0.0003 1.484 2.11 77.1 64.9-86.5 210495_x_at FN1
0.0003 1.494 2.87 77.2 65.1-86.6 211719_x_at FN1 0.0003 1.4894 2.87
77.2 65.1-86.7 212464_s_at FN1 0.0003 1.493 2.87 77.2 .sup. 65-86.7
216442_x_at FN1 0.0003 1.4935 2.87 77.2 .sup. 65-86.6 217762_s_at
RAB31 0.0003 1.4864 2.08 77.1 .sup. 65-86.6 217763_s_at RAB31
0.0003 1.4848 2.08 77.1 64.9-86.6 217764_s_at RAB31 0.0003 1.4882
2.08 77.2 .sup. 65-86.5 225681_at CTHRC1 0.0003 1.4588 3.41 76.7
64.5-86.3 201105_at LGALS1 0.0004 1.4844 1.61 77.1 64.9-86.6
208788_at ELOVL5 0.0004 1.5418 1.86 78 65.8-87.2 224694_at ANTXR1
0.0005 1.52 2 77.6 65.5-86.9 200974_at ACTA2 0.0006 1.4251 1.75
76.2 .sup. 64-85.8 210095_s_at IGFBP3 0.0006 1.5538 1.38 78.1 .sup.
66-87.4 201426_s_at VIM 8.00E-04 1.4819 1.48 77.1 64.9-86.4
219087_at ASPN 0.0009 1.4046 2.75 75.9 63.6-85.5 227566_at HNT
0.001 1.4215 2.26 76.1 .sup. 64-85.7 201667_at GJA1 1.30E-03 1.4084
1.63 75.9 63.7-85.6 200600_at MSN 1.40E-03 1.4942 1.36 77.2 .sup.
65-86.7 204051_s_at SFRP4 0.0015 1.4056 2.2 75.9 63.6-85.6
209101_at CTGF 0.0015 1.3331 1.78 74.7 62.4-84.6 204620_s_at CSPG2
0.0016 1.21 1.38 72.7 60.3-83.sup. 211571_s_at CSPG2 0.0016 1.2123
1.38 72.8 60.1-82.9 215646_s_at CSPG2 0.0016 1.2095 1.38 72.7
60.3-83.sup. 221731_x_at CSPG2 0.0016 1.2115 1.38 72.8 60.3-83.sup.
204006_s_at FCGR3B 0.0026 1.2308 2.14 73.1 60.6-83.2 203570_at
LOXL1 0.0027 1.4048 1.33 75.9 63.7-85.6 201744_s_at LUM 2.90E-03
1.3418 2.18 74.9 62.5-84.7 202283_at SERPINF1 3.10E-03 1.2121 1.76
72.8 60.2-83.sup. 209596_at MXRA5 0.0034 1.2974 1.62 74.2 61.7-84.1
210809_s_at POSTN 0.005 1.3011 2.58 74.2 61.8-84.2 205547_s_at
TAGLN 0.0051 1.1829 2.19 72.3 59.7-82.6 202237_at NNMT 5.40E-03
1.223 1.44 73 60.4-83.1 202238_s_at NNMT 5.40E-03 1.2259 1.44 73
60.5-83.1 218468_s_at GREM1 0.007 1.3017 1.31 74.2 61.8-84.2
218469_at GREM1 0.007 1.3027 1.31 74.3 61.9-84.2 208747_s_at C1S
0.0088 1.3575 1.77 75.1 62.9-85.sup. 224560_at TIMP2 0.0097 1.1629
1.72 72 59.4-82.3 231579_s_at TIMP2 0.0097 1.1641 1.72 72 59.5-82.4
209875_s_at SPP1 0.0109 1.0673 3.91 70.3 57.6-80.9 202859_x_at IL8
0.0112 1.3238 4.54 74.6 62.2-84.5 200832_s_at
SCD:LOC651109:LOC645313 1.27E-02 1.0749 2.33 70.5 57.9-81.1
201058_s_at MYL9 0.0131 1.1765 1.37 72.2 59.6-82.5 203645_s_at
CD163 0.0146 1.1655 2.19 72 59.4-82.3 215049_x_at CD163 0.0146
1.1664 2.19 72 59.4-82.3 202917_s_at S100A8 1.48E-02 1.0979 3.17
70.8 58.3-81.4 201289_at CYR61 0.015 1.0919 1.69 70.7 58.1-81.2
210764_s_at CYR61 0.015 1.0938 1.69 70.8 58.2-81.2 218559_s_at MAFB
0.0182 1.162 1.48 71.9 59.3-82.3 203382_s_at APOE 0.0285 1.1124
1.43 71.1 58.5-81.6 201893_x_at DCN 3.64E-02 1.0821 1.29 70.6 .sup.
58-81.1 211813_x_at DCN 0.0364 1.083 1.29 70.6 57.8-81.1
211896_s_at DCN 0.0364 1.0814 1.29 70.6 .sup. 58-81.1 213524_s_at
G0S2 0.0383 0.994 1.53 69 56.3-79.8 207173_x_at CDH11 0.0384 1.0121
1.98 69.4 56.6-80.1 209218_at SQLE 0.041 1.0162 2.15 69.4 56.6-80.1
201141_at GPNMB 0.0623 1.0165 1.52 69.4 56.7-80.1 201859_at PRG1
0.0634 0.798 1.34 65.5 52.6-76.7 234994_at KIAA1913 0.1061 0.9579
1.2 68.4 55.7-79.3 223122_s_at SFRP2 0.1336 0.968 1.24 68.6
55.9-79.4 223235_s_at SMOC2 0.2175 0.6547 2.06 62.8 .sup. 50-74.4
200986_at SERPING1 0.2636 0.7831 1.26 65.2 52.4-76.4 201842_s_at
EFEMP1 4.91E-01 0.6821 1.27 63.3 50.5-74.8 204122_at TYROBP 0.4923
0.7066 1.23 63.8 51.1-75.3 202620_s_at PLOD2 5.15E-01 0.7784 1.51
65.1 52.3-76.4
TABLE-US-00040 TABLE 7 Gene Signif. Sens- CI Symbol ValidPS_UP
Symbol FDR D.val5 FC Spec (95) ATP8A1 231484_at:792569- ATP8A1
6.60E-08 2.2854 3.11 87.3 76.9-94.sup. HuGene_st:210192_at:393806-
HuGene_st:743026-HuGene_st:200684- HuGene_st:1570592_a_at:645563-
HuGene_st:245580-HuGene_st:175799-
HuGene_st:20566-HuGene_st:636204-
HuGene_st:376757-HuGene_st:273140-
HuGene_st:873028-HuGene_st:864954-
HuGene_st:349056-HuGene_st:538894-
HuGene_st:167620-HuGene_st:807498- HuGene_st CLCA1
210107_at:426361-HuGene_st:389155- CLCA1 3.19E-07 2.1536 9.98 85.9
75.1-93.1 HuGene_st:622359-HuGene_st:523802-
HuGene_st:196470-HuGene_st:1078884-
HuGene_st:515258-HuGene_st:638133-
HuGene_st:764167-HuGene_st:921948-
HuGene_st:372283-HuGene_st:252084-
HuGene_st:98798-HuGene_st:1059095-
HuGene_st:441678-HuGene_st:490107-
HuGene_st:284008-HuGene_st:258568-
HuGene_st:602588-HuGene_st:472452- HuGene_st:640066-HuGene_st
CACNA2D2 805306-HuGene_st:1022165- CACNA2D2 3.61E-05 1.6587 4.41
79.7 67.8-88.5 HuGene_st:356782-HuGene_st:70395-
HuGene_st:525161-HuGene_st:729314-
HuGene_st:866616-HuGene_st:13978-
HuGene_st:715678-HuGene_st:299289-
HuGene_st:592015-HuGene_st:756393-
HuGene_st:607464-HuGene_st:862691- HuGene_st:229636_at:885048-
HuGene_st:680228-HuGene_st:393608-
HuGene_st:886897-HuGene_st:413699- HuGene_st RETNLB
173654-HuGene_st:223970_at:1094109- RETNLB 4.40E-05 1.6599 11.64
79.7 67.8-88.5 HuGene_st:708431-HuGene_st:231770-
HuGene_st:1065075-HuGene_st:318917-
HuGene_st:719419-HuGene_st:380366-
HuGene_st:221119-HuGene_st:774168- HuGene_st:223969_s_at:523432-
HuGene_st:45260-HuGene_st:963420-
HuGene_st:329703-HuGene_st:223761-
HuGene_st:1036667-HuGene_st:143113-
HuGene_st:414008-HuGene_st:232543- HuGene_st VSIG2
391438-HuGene_st:228232_s_at:265221- VSIG2 0.0001 1.5745 2.4 78.4
66.3-87.6 HuGene_st:343187-HuGene_st:223925-
HuGene_st:652010-HuGene_st:1069591-
HuGene_st:265186-HuGene_st:1095607-
HuGene_st:788466-HuGene_st:675062-
HuGene_st:826720-HuGene_st:1093892-
HuGene_st:985113-HuGene_st:637781- HuGene_st:997596-HuGene_st
LOC253012 1014415-HuGene_st:912640- LOC253012 0.0001 1.5764 5.28
78.5 66.5-87.7 HuGene_st:463072-HuGene_st:749900-
HuGene_st:381523-HuGene_st:896826-
HuGene_st:804632-HuGene_st:304834-
HuGene_st:39629-HuGene_st:568837-
HuGene_st:1070854-HuGene_st:162938-
HuGene_st:1026726-HuGene_st:441915- HuGene_st:242601_at:51876-
HuGene_st:199784-HuGene_st:363568-
HuGene_st:50979-HuGene_st:736612- HuGene_st FCGBP
203240_at:88809-HuGene_st:1085208- FCGBP 0.0003 1.4997 3.07 77.3
65.2-86.7 HuGene_st:338164-HuGene_st:71797-
HuGene_st:1079875-HuGene_st:63672-
HuGene_st:997435-HuGene_st:226428-
HuGene_st:948120-HuGene_st:22847- HuGene_st:36995-HuGene_st:508230-
HuGene_st:16108-HuGene_st:311904- HuGene_st:426005-HuGene_st:27264-
HuGene_st:516715-HuGene_st:841000-
HuGene_st:708701-HuGene_st:781083-
HuGene_st:634071-HuGene_st:948682- HuGene_st PTGER4
204896_s_at:109314-HuGene_st:986807- PTGER4 0.0006 1.4713 1.55 76.9
64.7-86.4 HuGene_st:446764-HuGene_st:548266-
HuGene_st:919403-HuGene_st:965220- HuGene_st:192344-HuGene_st:1943-
HuGene_st:252442-HuGene_st:392964- HuGene_st:23686-
HuGene_st:204897_at:812085-HuGene_st FAM3D 361373-HuGene_st:963526-
FAM3D 0.001 1.2699 2.15 73.7 61.3-83.8 HuGene_st:227676_at:741172-
HuGene_st:608385-HuGene_st:1074915-
HuGene_st:182670-HuGene_st:24363-
HuGene_st:269456-HuGene_st:833883-
HuGene_st:280625-HuGene_st:187246-
HuGene_st:964986-HuGene_st:66738- HuGene_st:80884-HuGene_st CYP3A5
205765_at:67735- CYP3A5 0.0012 1.5288 1.8 77.8 65.7-87.sup.
HuGene_st:214234_s_at:941416- HuGene_st:238807-HuGene_st:611620-
HuGene_st CYP3A5P2 205765_at:67735- CYP3A5 0.0012 1.5297 1.8 77.8
65.6-87.sup. HuGene_st:214234_s_at:941416-
HuGene_st:238807-HuGene_st:611620- HuGene_st SLITRK6
936650-HuGene_st:921047- SLITRK6 0.0016 1.36 5.96 75.2 62.8-85.sup.
HuGene_st:371185-HuGene_st:510939-
HuGene_st:356154-HuGene_st:205559-
HuGene_st:386297-HuGene_st:483895-
HuGene_st:227644-HuGene_st:458058- HuGene_st:232481_s_at:907326-
HuGene_st:255645-HuGene_st:830582-
HuGene_st:615220-HuGene_st:369624-
HuGene_st:78770-HuGene_st:573187-
HuGene_st:1025122-HuGene_st:584646- HuGene_st KIAA1324
243349_at:226248_s_at:1052694- KIAA1324 0.0038 1.3258 2.1 74.6
62.2-84.5 HuGene_st:893707-HuGene_st:597814-
HuGene_st:585604-HuGene_st:240530- HuGene_st HMGCS2
616916-HuGene_st:283650- HMGCS2 0.0052 1.234 3.59 73.1 60.6-83.3
HuGene_st:204607_at:43162- HuGene_st:371076-HuGene_st:407398-
HuGene_st:900260-HuGene_st:619083-
HuGene_st:729816-HuGene_st:171889-
HuGene_st:253113-HuGene_st:448587-
HuGene_st:593619-HuGene_st:624250-
HuGene_st:865416-HuGene_st:888308-
HuGene_st:397691-HuGene_st:789982- HuGene_st:658722-HuGene_st CA12
215867_x_at:210735_s_at:204508_s_at: CA12 0.0065 1.1823 1.86 72.3
59.7-82.6 203963_at:638145- HuGene_st:1013062-HuGene_st:280470-
HuGene_st:214164_x_at:875965- HuGene_st:749017-HuGene_st:1049334-
HuGene_st:439438-HuGene_st:65565-
HuGene_st:1017708-HuGene_st:226479-
HuGene_st:125567-HuGene_st:698714-
HuGene_st:963408-HuGene_st:189118- HuGene_st:1049350-HuGene_st
ST6GALNAC1 524915-HuGene_st:694442- ST6GALNAC1 0.0068 1.1407 1.76
71.6 58.9-82.sup. HuGene_st:372293-HuGene_st:247017-
HuGene_st:186959-HuGene_st:149798-
HuGene_st:611157-HuGene_st:887450- HuGene_st:227725_at:608767-
HuGene_st:891399-HuGene_st:95718-
HuGene_st:780611-HuGene_st:1006431-
HuGene_st:266448-HuGene_st:768462-
HuGene_st:616368-HuGene_st:66760-
HuGene_st:1067993-HuGene_st:69927- HuGene_st:104705-HuGene_st CKB
200884_at:435665-HuGene_st:888623- CKB 0.0073 1.1468 2.25 71.7
59.2-82.1 HuGene_st:480007-HuGene_st:396007-
HuGene_st:963331-HuGene_st:40899- HuGene_st:373774-HuGene_st:25470-
HuGene_st:16603-HuGene_st:766369-
HuGene_st:405417-HuGene_st:718720-
HuGene_st:1041238-HuGene_st:23457-
HuGene_st:24890-HuGene_st:769422-
HuGene_st:896708-HuGene_st:581051-
HuGene_st:549987-HuGene_st:384128- HuGene_st L1TD1
219955_at:842123-HuGene_st:1095330- L1TD1 0.0077 1.2497 3.27 73.4
60.9-83.5 HuGene_st:1058922-HuGene_st:572495-
HuGene_st:414266-HuGene_st:887612-
HuGene_st:799837-HuGene_st:177635-
HuGene_st:715579-HuGene_st:709222-
HuGene_st:968483-HuGene_st:1030986-
HuGene_st:327643-HuGene_st:540230- HuGene_st NR3C2
100953-HuGene_st:239673_at:981978- NR3C2 0.0129 1.1951 1.63 72.5
59.9-82.7 HuGene_st MLPH 218211_s_at MLPH 0.0138 1.2275 1.59 73
60.5-83.2 UGT1A1 208596_s_at:221305_s_at:204532_x_at: UGT1A3 0.0376
1.0578 1.68 70.2 57.5-80.8 232654_s_at MUC4 NA
MUC4:TAF5L:LOC650855: 0.0453 1.1986 1.31 72.6 60.1-82.8 LOC645744
KLF4 NA KLF4 0.0731 1.0018 1.58 69.2 56.5-79.9 CAPN9 NA CAPN9 0.074
0.9979 1.84 69.1 56.4-79.9 SELENBP1 NA SELENBP1 0.0902 0.9777 2
68.8 56.1-79.6 ATP8B1 NA ATP8B1 0.093 1.0347 1.4 69.8 57.2-80.4
WDR51B NA WDR51B 0.1284 1.0004 1.28 69.2 56.5-80.sup. PBLD NA PBLD
0.1655 0.8731 1.89 66.9 54.1-78.sup. ID1 NA ID1 0.2342 0.7662 1.66
64.9 52.2-76.2 CTSE NA CTSE 0.2809 0.7409 3.23 64.4 51.7-75.8
C6orf105 NA C6orf105 0.7794 0.7003 1.37 63.7 50.8-75.1
TABLE-US-00041 TABLE 8 Gene Signif. Sens- CI Symbol ValidPS_UP
Symbol FDR D.val5 FC Spec (95) SPARC 677215-HuGene_st:456544- SPARC
3.0479E-09 2.3799 3.24 88.3 78.1-94.6
HuGene_st:1041514-HuGene_st:868223-
HuGene_st:1053181-HuGene_st:196416-
HuGene_st:1078055-HuGene_st:213861-
HuGene_st:452422-HuGene_st:1078242-
HuGene_st:497056-HuGene_st:1285- HuGene_st:793848-HuGene_st:455765-
HuGene_st:72235-HuGene_st:568912-
HuGene_st:887159-HuGene_st:255885-
HuGene_st:225477-HuGene_st:162094- HuGene_st:1026630-
HuGene_st:200665_s_at COL4A2 540082-HuGene_st:295949- COL4A2
5.5315E-09 2.4297 2.87 88.8 78.6-95.sup.
HuGene_st:1009411-HuGene_st:245530-
HuGene_st:834880-HuGene_st:801333-
HuGene_st:500428-HuGene_st:990355-
HuGene_st:469754-HuGene_st:980150-
HuGene_st:184258-HuGene_st:580118-
HuGene_st:281233-HuGene_st:732269-
HuGene_st:1075712-HuGene_st:643598- HuGene_st:772366-
HuGene_st:211966_at:512520- HuGene_st:973004-HuGene_st:839631-
HuGene_st:211964_at:316644- HuGene_st:1015712-HuGene_st COL4A1
831741-HuGene_st:634068- COL4A1 1.243E-08 2.3004 3.03 87.5 .sup.
77-94.2 HuGene_st:816476-HuGene_st:1030276-
HuGene_st:144637-HuGene_st:24196-
HuGene_st:272762-HuGene_st:604042-
HuGene_st:392785-HuGene_st:782962-
HuGene_st:381555-HuGene_st:576333-
HuGene_st:310901-HuGene_st:237606-
HuGene_st:719873-HuGene_st:914012-
HuGene_st:30564-HuGene_st:828024- HuGene_st:687375-
HuGene_st:211981_at:211980_at:812556-
HuGene_st:681655-HuGene_st:233652_at SPON2 173417-HuGene_st:845288-
SPON2 1.9471E-08 2.3295 3.38 87.8 77.4-94.3
HuGene_st:170898-HuGene_st:6411-
HuGene_st:981126-HuGene_st:1098117-
HuGene_st:1049111-HuGene_st:1018834-
HuGene_st:300655-HuGene_st:45524-
HuGene_st:256565-HuGene_st:533681-
HuGene_st:346131-HuGene_st:251693-
HuGene_st:937110-HuGene_st:347749-
HuGene_st:645379-HuGene_st:107844- HuGene_st:396405-
HuGene_st:218638_s_at:1569496_s_at COL5A2 631247-HuGene_st:59739-
COL5A2 5.7658E-08 2.2164 3.31 86.6 .sup. 76-93.5
HuGene_st:260654-HuGene_st:125943-
HuGene_st:292068-HuGene_st:788391-
HuGene_st:408375-HuGene_st:561511-
HuGene_st:838505-HuGene_st:915389-
HuGene_st:684636-HuGene_st:817279-
HuGene_st:514415-HuGene_st:583557-
HuGene_st:1009654-HuGene_st:416341-
HuGene_st:260479-HuGene_st:292241-
HuGene_st:1034540-HuGene_st:101178- HuGene_st:221730_at:221729_at
FSTL1 1020674-HuGene_st:291086- FSTL1 7.8434E-08 2.2277 2.64 86.7
76.1-93.6 HuGene_st:964097-HuGene_st:874354-
HuGene_st:745908-HuGene_st:129330-
HuGene_st:1039443-HuGene_st:855602-
HuGene_st:494940-HuGene_st:666633-
HuGene_st:10001-HuGene_st:654906-
HuGene_st:322189-HuGene_st:891629-
HuGene_st:225280-HuGene_st:67871- HuGene_st:965246-HuGene_st BGN
722197-HuGene_st:1090822- BGN 9.6881E-08 2.2246 2.99 86.7 76.1-93.6
HuGene_st:45294-HuGene_st:381650-
HuGene_st:987820-HuGene_st:978124-
HuGene_st:171694-HuGene_st:643594-
HuGene_st:429977-HuGene_st:1096605-
HuGene_st:861988-HuGene_st:164623- HuGene_st:201262_s_at:497499-
HuGene_st:422042-HuGene_st:1051954-
HuGene_st:262594-HuGene_st:279145-
HuGene_st:838396-HuGene_st:298959-
HuGene_st:11448-HuGene_st:111675-
HuGene_st:213905_x_at:201261_x_at: 973749-HuGene_st FAP
58645-HuGene_st:581008- IFIH1:FAP 1.358E-07 2.2253 4.88 86.7
76.1-93.6 HuGene_st:284881-HuGene_st:1022038-
HuGene_st:916010-HuGene_st:947725-
HuGene_st:477772-HuGene_st:22772- HuGene_st:636840-HuGene_st:40379-
HuGene_st:993707-HuGene_st:322964-
HuGene_st:759386-HuGene_st:132558-
HuGene_st:600137-HuGene_st:915847-
HuGene_st:246189-HuGene_st:445095-
HuGene_st:389696-HuGene_st:438119-
HuGene_st:748913-HuGene_st:209955_s_at COL8A1
333339-HuGene_st:214587_at:586420- COL8A1 3.6053E-07 2.1439 3.09
85.8 74.9-93.sup. HuGene_st:103513-HuGene_st:651142-
HuGene_st:617293-HuGene_st:107398-
HuGene_st:79621-HuGene_st:806363- HuGene_st:327074-HuGene_st:41199-
HuGene_st COL1A1 767019-HuGene_st:654019- COL1A1 5.4426E-07 2.0142
3.29 84.3 73.1-92.sup. HuGene_st:52480-HuGene_st:975188-
HuGene_st:731985-HuGene_st:849620-
HuGene_st:652845-HuGene_st:1077639-
HuGene_st:149590-HuGene_st:788754-
HuGene_st:1033327-HuGene_st:258815-
HuGene_st:719132-HuGene_st:971026-
HuGene_st:1061961-HuGene_st:435403-
HuGene_st:498576-HuGene_st:1003153-
HuGene_st:1029566-HuGene_st:487433-
HuGene_st:165153-HuGene_st:125258-
HuGene_st:217430_x_at:202310_s_at:1556 499_s_at:202311_s_at COL6A3
312177-HuGene_st:24239- COL6A3 5.7026E-07 2.0313 2.73 84.5
73.5-92.1 HuGene_st:337032-HuGene_st:31627-
HuGene_st:72819-HuGene_st:85665- HuGene_st:51265-HuGene_st:315258-
HuGene_st:423421-HuGene_st:976272-
HuGene_st:627131-HuGene_st:547019-
HuGene_st:482866-HuGene_st:871788-
HuGene_st:273133-HuGene_st:945341-
HuGene_st:223275-HuGene_st:768482-
HuGene_st:618342-HuGene_st:993598-
HuGene_st:716493-HuGene_st:153821- HuGene_st:201438_at COL1A2
918394-HuGene_st:75788- COL1A2:LOC728628 8.8466E-07 2.0613 2.62
84.9 73.9-92.3 HuGene_st:240155-HuGene_st:1079758-
HuGene_st:174439-HuGene_st:133455-
HuGene_st:720682-HuGene_st:723785-
HuGene_st:1076123-HuGene_st:252002-
HuGene_st:733200-HuGene_st:890123-
HuGene_st:1070579-HuGene_st:52384-
HuGene_st:928914-HuGene_st:257376-
HuGene_st:355867-HuGene_st:472073-
HuGene_st:349798-HuGene_st:153814- HuGene_st:825347-
HuGene_st:202404_s_at:202403_s_at THY1 149448-HuGene_st:804495-
THY1 1.0326E-06 1.9155 3.34 83.1 71.7-91.1
HuGene_st:287669-HuGene_st:329513-
HuGene_st:432229-HuGene_st:834028-
HuGene_st:462769-HuGene_st:408326-
HuGene_st:603473-HuGene_st:497809-
HuGene_st:301090-HuGene_st:606465- HuGene_st:208850_s_at:278686-
HuGene_st:804789-HuGene_st:236645-
HuGene_st:257047-HuGene_st:554409- HuGene_st:108391-
HuGene_st:208851_s_at:213869_x_at:9087
85-HuGene_st:516398-HuGene_st COL15A1 330621-HuGene_st:910395-
COL15A1 1.0611E-06 2.0128 3.37 84.3 73.2-92.sup.
HuGene_st:811192-HuGene_st:294092-
HuGene_st:958891-HuGene_st:407270-
HuGene_st:423090-HuGene_st:1079597-
HuGene_st:95084-HuGene_st:775288-
HuGene_st:813875-HuGene_st:1001637-
HuGene_st:49304-HuGene_st:970691- HuGene_st:346838-HuGene_st:91483-
HuGene_st:528528-HuGene_st:453998- HuGene_st:254490-
HuGene_st:203477_at:201064-HuGene_st CALD1 816439-HuGene_st:318906-
CALD1 1.1059E-06 2.1159 1.7 85.5 74.6-92.8
HuGene_st:558226-HuGene_st:755661-
HuGene_st:519079-HuGene_st:1094139-
HuGene_st:975649-HuGene_st:407536-
HuGene_st:908350-HuGene_st:576686-
HuGene_st:688034-HuGene_st:792918-
HuGene_st:596642-HuGene_st:797317-
HuGene_st:1023569-HuGene_st:450656-
HuGene_st:231881_at:165931-HuGene_st IGFBP7
363517-HuGene_st:787689- IGFBP7 1.1574E-06 1.9989 1.91 84.1
72.9-91.8 HuGene_st:86333-HuGene_st:882867-
HuGene_st:620969-HuGene_st:167271-
HuGene_st:192752-HuGene_st:521467-
HuGene_st:699448-HuGene_st:882712-
HuGene_st:211325-HuGene_st:329940-
HuGene_st:980809-HuGene_st:22805-
HuGene_st:288233-HuGene_st:230028-
HuGene_st:551901-HuGene_st:921418- HuGene_st:232544_at:969620-
HuGene_st:985682-HuGene_st INHBA 1088123-HuGene_st:151327- INHBA
1.1943E-06 2.0051 3.38 84.2 .sup. 73-91.9
HuGene_st:363337-HuGene_st:874496-
HuGene_st:402595-HuGene_st:289422-
HuGene_st:838338-HuGene_st:746887-
HuGene_st:623455-HuGene_st:395552-
HuGene_st:865665-HuGene_st:328796-
HuGene_st:1088331-HuGene_st:751719-
HuGene_st:36929-HuGene_st:548889- HuGene_st:909672-
HuGene_st:210511_s_at:344276- HuGene_st:204926_at:112496-HuGene_st
COL12A1 905983-HuGene_st:794749- TMEM30A:COL12A1 1.2492E-06 2.03
4.16 84.5 73.4-92.1 HuGene_st:1063560-HuGene_st:567963-
HuGene_st:140178-HuGene_st:289954-
HuGene_st:620694-HuGene_st:31736-
HuGene_st:1009559-HuGene_st:435472-
HuGene_st:415220-HuGene_st:447689-
HuGene_st:405565-HuGene_st:180263-
HuGene_st:595404-HuGene_st:759154-
HuGene_st:419264-HuGene_st:319853-
HuGene_st:225664_at:231879_at:874183- HuGene_st:913204-
HuGene_st:231766_s_at:234951_s_at: 1057284-HuGene_st COL5A1
64984-HuGene_st:815841- COL5A1 1.6076E-06 1.9335 2.75 83.3 .sup.
72-91.3 HuGene_st:299983-HuGene_st:751853-
HuGene_st:33784-HuGene_st:366345- HuGene_st:63200-HuGene_st:293998-
HuGene_st:544275-HuGene_st:940629-
HuGene_st:383962-HuGene_st:995286-
HuGene_st:640471-HuGene_st:77586- HuGene_st:212489_at:633141-
HuGene_st:203325_s_at:777727- HuGene_st:400357-
HuGene_st:212488_at:291267- HuGene_st:285959-HuGene_st:886716-
HuGene_st THBS2 789762-HuGene_st:451028- THBS2 2.3382E-06 1.9035
6.5 82.9 71.6-91.sup. HuGene_st:807449-HuGene_st:895973-
HuGene_st:360384-HuGene_st:885374-
HuGene_st:178235-HuGene_st:241784-
HuGene_st:774957-HuGene_st:565405-
HuGene_st:684979-HuGene_st:890746-
HuGene_st:588267-HuGene_st:1033680-
HuGene_st:387904-HuGene_st:1096131-
HuGene_st:739113-HuGene_st:614690-
HuGene_st:270369-HuGene_st:892858- HuGene_st TNC
441837-HuGene_st:278723- TNC 3.7414E-06 1.9636 2.14 83.7
72.4-91.6
HuGene_st:1030770-HuGene_st:767997-
HuGene_st:514659-HuGene_st:873244-
HuGene_st:837401-HuGene_st:621609-
HuGene_st:888816-HuGene_st:660419-
HuGene_st:889974-HuGene_st:780538-
HuGene_st:157747-HuGene_st:908522-
HuGene_st:263796-HuGene_st:280913- HuGene_st:201645_at:1016643-
HuGene_st:243540_at:537682- HuGene_st:859608-HuGene_st:1079032-
HuGene_st:458991-HuGene_st:241272_at MGP 148839-HuGene_st
MGP:C12orf46 5.8225E-06 1.9994 2.62 84.1 .sup. 73-91.9 COL3A1
410491-HuGene_st:718613- COL3A1 9.2906E-06 1.8484 2.32 82.2
70.8-90.5 HuGene_st:1083201-HuGene_st:364429-
HuGene_st:857967-HuGene_st:714343-
HuGene_st:977793-HuGene_st:295757-
HuGene_st:22453-HuGene_st:804687-
HuGene_st:682411-HuGene_st:490951-
HuGene_st:622631-HuGene_st:782663-
HuGene_st:425013-HuGene_st:214723-
HuGene_st:86407-HuGene_st:651938-
HuGene_st:403765-HuGene_st:376736-
HuGene_st:376290-HuGene_st:248520- HuGene_st SULF1
740854-HuGene_st:517026- SULF1 0.000014436 1.7533 2.84 81 69.2-89.6
HuGene_st:933799-HuGene_st:72604-
HuGene_st:1045684-HuGene_st:492122-
HuGene_st:20084-HuGene_st:512275-
HuGene_st:754502-HuGene_st:730003-
HuGene_st:532406-HuGene_st:187508-
HuGene_st:671986-HuGene_st:34752-
HuGene_st:381424-HuGene_st:166879-
HuGene_st:530745-HuGene_st:1018600-
HuGene_st:212344_at:212354_at:482916- HuGene_st:212353_at HTRA1
660603-HuGene_st:252436- HTRA1 0.000017178 1.7312 2.29 80.7
68.9-89.3 HuGene_st:299850-HuGene_st:317595-
HuGene_st:977390-HuGene_st:311841-
HuGene_st:946172-HuGene_st:761215-
HuGene_st:577479-HuGene_st:332527-
HuGene_st:1082067-HuGene_st:981054-
HuGene_st:5171-HuGene_st:1019008-
HuGene_st:757466-HuGene_st:723015- HuGene_st LOXL2
937941-HuGene_st:827532- ENTPD4:LOXL2 0.000019895 1.7774 2.45 81.3
69.6-89.7 HuGene_st:346541-HuGene_st:271051-
HuGene_st:228808_s_at:254550- HuGene_st:260752-HuGene_st:46172-
HuGene_st:950166-HuGene_st:281266-
HuGene_st:818138-HuGene_st:626390-
HuGene_st:291104-HuGene_st:84360-
HuGene_st:228823-HuGene_st:966956- HuGene_st:202997_s_at:898787-
HuGene_st:202999_s_at:1074111- HuGene_st:1064065-
HuGene_st:202998_s_at:328673- HuGene_st:1562263_at:34062-HuGene_st
SULF2 367910-HuGene_st:661661- SULF2 0.000020766 1.6803 2.25 80
68.1-88.8 HuGene_st:43751-HuGene_st:395846-
HuGene_st:771921-HuGene_st:550105-
HuGene_st:195771-HuGene_st:435480-
HuGene_st:229718-HuGene_st:826084-
HuGene_st:262732-HuGene_st:848382-
HuGene_st:861858-HuGene_st:907457-
HuGene_st:801956-HuGene_st:54769-
HuGene_st:214147-HuGene_st:1034817- HuGene_st:929065-
HuGene_st:233555_s_at:430325-HuGene_st MMP2 650123-HuGene_st:78720-
MMP2 0.000025409 1.7328 3.02 80.7 68.8-89.3
HuGene_st:168982-HuGene_st:598990-
HuGene_st:346729-HuGene_st:356008-
HuGene_st:821467-HuGene_st:905494-
HuGene_st:568028-HuGene_st:711286-
HuGene_st:666575-HuGene_st:208210-
HuGene_st:20913-HuGene_st:382005-
HuGene_st:186287-HuGene_st:355238- HuGene_st:60728-
HuGene_st:1566677_at:1027926- HuGene_st:38019-HuGene_st:39088-
HuGene_st TIMP3 686923-HuGene_st:767021- TIMP3 0.000026195 1.7785
2.56 81.3 69.6-89.8 HuGene_st:231888_at:201148_s_at:326731-
HuGene_st:72249-HuGene_st:369765-
HuGene_st:711121-HuGene_st:844721-
HuGene_st:856619-HuGene_st:241221-
HuGene_st:515184-HuGene_st:948668- HuGene_st:410881-HuGene_st
COL6A2 404866-HuGene_st:420794- COL6A2 0.000029551 1.7418 1.67 80.8
.sup. 69-89.4 HuGene_st:536399-HuGene_st:813295-
HuGene_st:160736-HuGene_st:501950-
HuGene_st:148827-HuGene_st:501480-
HuGene_st:375216-HuGene_st:143566-
HuGene_st:1086501-HuGene_st:475436-
HuGene_st:794188-HuGene_st:704415- HuGene_st:213290_at LOC387763
724781-HuGene_st:816467-HuGene_st LOC387763 0.00003052 1.8978 1.43
82.9 71.4-90.9 DKK3 573143-HuGene_st:509897- DKK3 0.000031838
1.7435 1.86 80.8 69.1-89.5 HuGene_st:829432-HuGene_st:425906-
HuGene_st:1076690-HuGene_st:480668-
HuGene_st:302214-HuGene_st:673860-
HuGene_st:584666-HuGene_st:966441-
HuGene_st:138862-HuGene_st:19243-
HuGene_st:600102-HuGene_st:778172- HuGene_st:387542-
HuGene_st:202196_s_at:230508_at:86457- HuGene_st CTSK
592586-HuGene_st:682010- CTSK 0.000039778 1.7156 2.16 80.4
68.8-89.1 HuGene_st:30909-HuGene_st:235976-
HuGene_st:913861-HuGene_st:25198- HuGene_st:96515-HuGene_st:221416-
HuGene_st:341005-HuGene_st:371949-
HuGene_st:796154-HuGene_st:555578-
HuGene_st:416489-HuGene_st:123013-
HuGene_st:50644-HuGene_st:636682- HuGene_st:63600-HuGene_st:356075-
HuGene_st:321593-HuGene_st LOC541471 19600-HuGene_st:149287-
MGC4677, 0.000041139 1.804 1.45 81.6 69.9-90.sup.
HuGene_st:916693-HuGene_st:569637- MGC4677:LOC541471
HuGene_st:868769-HuGene_st:469295-
HuGene_st:277416-HuGene_st:71551- HuGene_st:1558836_at:129947-
HuGene_st:644672-HuGene_st:276744-
HuGene_st:873188-HuGene_st:830227-
HuGene_st:101170-HuGene_st:624891-
HuGene_st:85671-HuGene_st:236489-
HuGene_st:709116-HuGene_st:279980- HuGene_st:812194-HuGene_st
CHI3L1 561691-HuGene_st:116044- CHI3L1:MYBPH 0.000051515 1.6351
3.06 79.3 67.4-88.3 HuGene_st:261087-HuGene_st:57128-
HuGene_st:970931-HuGene_st:518568-
HuGene_st:362438-HuGene_st:388847- HuGene_st:738096-
HuGene_st:209396_s_at:171378- HuGene_st:968794-HuGene_st:477315-
HuGene_st:852388-HuGene_st:90371- HuGene_st:209395_at:657732-
HuGene_st:1050574-HuGene_st:1074100-
HuGene_st:219902-HuGene_st:744799- HuGene_st CD93
392816-HuGene_st:131787- CD93 0.000051891 1.6662 2.36 79.8
67.8-88.6 HuGene_st:900048-HuGene_st:1024597-
HuGene_st:449159-HuGene_st:937408-
HuGene_st:835153-HuGene_st:231835-
HuGene_st:1084191-HuGene_st:970338-
HuGene_st:835439-HuGene_st:345929-
HuGene_st:310915-HuGene_st:381822-
HuGene_st:627382-HuGene_st:731932- HuGene_st COL11A1
372742-HuGene_st:523307- COL11A1 0.000053391 1.7583 2.55 81
69.3-89.5 HuGene_st:360139-HuGene_st:64257-
HuGene_st:633985-HuGene_st:986684- HuGene_st:2674-HuGene_st:575064-
HuGene_st:1023506-HuGene_st:198973-
HuGene_st:20543-HuGene_st:254341- HuGene_st:81512-HuGene_st:549979-
HuGene_st:347332-HuGene_st LBH 764120-HuGene_st:189486- LBH
0.000063299 1.6753 1.9 79.9 67.9-88.7
HuGene_st:766856-HuGene_st:1083711-
HuGene_st:541408-HuGene_st:375190-
HuGene_st:938798-HuGene_st:133862-
HuGene_st:956722-HuGene_st:97472- HuGene_st:19277-HuGene_st OLFML2B
1085957-HuGene_st:354052- OLFML2B 0.000066557 1.705 1.97 80.3
68.5-89.sup. HuGene_st:682043-HuGene_st:249054-
HuGene_st:867838-HuGene_st:430882-
HuGene_st:704400-HuGene_st:1065400-
HuGene_st:588559-HuGene_st:827842-
HuGene_st:272527-HuGene_st:134966-
HuGene_st:523921-HuGene_st:895516-
HuGene_st:1022747-HuGene_st:529564-
HuGene_st:539568-HuGene_st:427677- HuGene_st:122501-HuGene_st MMP1
524115-HuGene_st:689073- MMP1 0.000070616 1.6771 3.91 79.9
68.1-88.7 HuGene_st:300572-HuGene_st:914223-
HuGene_st:958445-HuGene_st:61706-
HuGene_st:437171-HuGene_st:422476-
HuGene_st:361198-HuGene_st:693724-
HuGene_st:671620-HuGene_st:673683-
HuGene_st:1020786-HuGene_st:732367-
HuGene_st:710307-HuGene_st:445730-
HuGene_st:622653-HuGene_st:468477-
HuGene_st:1070117-HuGene_st:840324- HuGene_st:473664-HuGene_st
PALM2- 945487-HuGene_st:454513- AKAP2:PALM2:PALM2- 0.000074206
1.724 1.58 80.6 68.9-89.2 AKAP2 HuGene_st:799637-HuGene_st:91787-
AKAP2 HuGene_st:448601-HuGene_st:839008-
HuGene_st:1044350-HuGene_st:327679-
HuGene_st:665040-HuGene_st:79769-
HuGene_st:216125-HuGene_st:205232-
HuGene_st:818531-HuGene_st:169199-
HuGene_st:537891-HuGene_st:667958- HuGene_st:202760_s_at FBN1
288955-HuGene_st:112593- FBN1 0.0001 1.5949 1.48 78.7 66.7-87.8
HuGene_st:427611-HuGene_st:921008-
HuGene_st:82155-HuGene_st:828273-
HuGene_st:999573-HuGene_st:192029-
HuGene_st:162818-HuGene_st:794561-
HuGene_st:316216-HuGene_st:971683-
HuGene_st:394963-HuGene_st:600623-
HuGene_st:169932-HuGene_st:941525- HuGene_st:202765_s_at:1094040-
HuGene_st:192231-HuGene_st:235318_at MMP3 7912-HuGene_st:438906-
MMP3 0.0001 1.6224 6.68 79.1 67.2-88.1
HuGene_st:483424-HuGene_st:634624-
HuGene_st:191436-HuGene_st:542596-
HuGene_st:664043-HuGene_st:766524-
HuGene_st:134417-HuGene_st:945713-
HuGene_st:149350-HuGene_st:357556-
HuGene_st:206224-HuGene_st:560206-
HuGene_st:822598-HuGene_st:200029-
HuGene_st:701539-HuGene_st:526573- HuGene_st:35444-HuGene_st ISLR
1034362-HuGene_st:755902- ISLR 0.0001 1.6424 1.87 79.4 67.4-88.4
HuGene_st:864958-HuGene_st:599962- HuGene_st:207191_s_at:256349-
HuGene_st:223953-HuGene_st:172743- HuGene_st:46312-HuGene_st:11475-
HuGene_st:500169-HuGene_st COL6A1 138884-HuGene_st:100156- COL6A1
0.0001 1.7314 1.58 80.7 68.9-89.3
HuGene_st:694215-HuGene_st:133534-
HuGene_st:354247-HuGene_st:737256- HuGene_st:214200_s_at:212939_at:
216904_at:884210-HuGene_st:57954-
HuGene_st:138366-HuGene_st:175316-
HuGene_st:459478-HuGene_st:190064-
HuGene_st:914102-HuGene_st:392220- HuGene_st:212937_s_at:125972-
HuGene_st:214513-HuGene_st:528191- HuGene_st:858575-
HuGene_st:212938_at:212091_s_at:212940_at: 871472-HuGene_st FNDC1
194684-HuGene_st:358155- FNDC1 0.0001 1.5241 3.14 77.7 65.6-87.sup.
HuGene_st:959100-HuGene_st:187071-
HuGene_st:449250-HuGene_st:879569-
HuGene_st:588958-HuGene_st:162623-
HuGene_st:711103-HuGene_st:30750- HuGene_st:34787-HuGene_st:260399-
HuGene_st:418036-HuGene_st
AEBP1 479622-HuGene_st:192126- AEBP1 0.0002 1.4786 2.11 77
64.8-86.4 HuGene_st:209682-HuGene_st:285969-
HuGene_st:1041745-HuGene_st:668627-
HuGene_st:913865-HuGene_st:944753-
HuGene_st:446850-HuGene_st:118310-
HuGene_st:342980-HuGene_st:845095-
HuGene_st:185307-HuGene_st:901268- HuGene_st:494284-
HuGene_st:201792_at:51739- HuGene_st:262459-HuGene_st MMP11
203878_s_at:213602_s_at:203877_at:32492 MMP11 0.0002 1.6993 1.28
80.2 68.3-89.sup. 1-HuGene_st:718792-HuGene_st:514533-
HuGene_st:720030-HuGene_st:935371-
HuGene_st:844472-HuGene_st:548687-
HuGene_st:519881-HuGene_st:858774- HuGene_st:943793
-HuGene_st:671549- HuGene_st:127919-HuGene_st:670295-
HuGene_st:235908_at:203876_s_at:986917-
HuGene_st:155442-HuGene_st:1036101- HuGene_st IGFBP5
532497-HuGene_st:823295- IGFBP5 0.0002 1.5676 3.96 78.3 66.4-87.5
HuGene_st:323206-HuGene_st:941332-
HuGene_st:723182-HuGene_st:301318-
HuGene_st:1007784-HuGene_st:503864-
HuGene_st:492730-HuGene_st:370183 -
HuGene_st:867094-HuGene_st:965814- HuGene_st:778210-
HuGene_st:203425_s_at:692986- HuGene_st:1006982-HuGene_st:807775-
HuGene_st:1035577-HuGene_st:158302- HuGene_st:73598-
HuGene_st:1555997_s_at:231985- HuGene_st:203424_s_at:211958_at:
203426_s_at:334486- HuGene_st:383523-HuGene_st PLAU
611756-HuGene_st:246040- PLAU 0.0003 1.4846 2.11 77.1 64.8-86.5
HuGene_st:783863-HuGene_st:1027344-
HuGene_st:186016-HuGene_st:31176- HuGene_st:692506-HuGene_st:52541-
HuGene_st:205479_s_at:471777- HuGene_st:156254-HuGene_st:1085903-
HuGene_st:211668_s_at:131855- HuGene_st:585614-HuGene_st:1076162-
HuGene_st:323438-HuGene_st:410729- HuGene_st CTHRC1
647908-HuGene_st:235232- CTHRC1 0.0003 1.4612 3.41 76.7 64.5-86.2
HuGene_st:86783-HuGene_st:756615-
HuGene_st:779928-HuGene_st:385407-
HuGene_st:978256-HuGene_st:607929- HuGene_st:426340-HuGene_st FN1
1002635-HuGene_st:585884- FN1 0.0003 1.4907 2.87 77.2 .sup. 65-86.6
HuGene_st:338536-HuGene_st:586400-
HuGene_st:445068-HuGene_st:395670-
HuGene_st:19848-HuGene_st:443264-
HuGene_st:662053-HuGene_st:144815-
HuGene_st:103145-HuGene_st:372804-
HuGene_st:652840-HuGene_st:935697-
HuGene_st:484350-HuGene_st:422572-
HuGene_st:814551-HuGene_st:235724- HuGene_st:214701_s_at:692191-
HuGene_st:132330- HuGene_st:210495_x_at:639087-
HuGene_st:216442_x_at:211719_x_at: 214702_at:212464_s_at:1558199_at
RAB31 784521-HuGene_st:805481- RAB31 0.0003 1.4857 2.08 77.1 .sup.
65-86.6 HuGene_st:936297-HuGene_st:576193-
HuGene_st:321915-HuGene_st:282618-
HuGene_st:930765-HuGene_st:397177-
HuGene_st:861778-HuGene_st:411822- HuGene_st:240571_at:816751-
HuGene_st:1028297-HuGene_st:291722-
HuGene_st:722575-HuGene_st:904649-
HuGene_st:991710-HuGene_st:1032281-
HuGene_st:217764_s_at:252384-HuGene_st LGALS1
540889-HuGene_st:882911- LGALS1 0.0004 1.4863 1.61 77.1 64.8-86.5
HuGene_st:289133-HuGene_st:775286-
HuGene_st:179375-HuGene_st:877452- HuGene_st:697650-HuGene_st:1720-
HuGene_st:107624-HuGene_st:810235-
HuGene_st:190535-HuGene_st:529287-
HuGene_st:725969-HuGene_st:976579-
HuGene_st:1075722-HuGene_st:453861- HuGene_st:216405_at:624673-
HuGene_st:724499-HuGene_st ELOVL5 559433-HuGene_st:422981- ELOVL5
0.0004 1.542 1.86 78 65.8-87.2 HuGene_st:211457-HuGene_st:551828-
HuGene_st:412588-HuGene_st:912245-
HuGene_st:287185-HuGene_st:103066-
HuGene_st:399004-HuGene_st:528360-
HuGene_st:938564-HuGene_st:1000247-
HuGene_st:620190-HuGene_st:336885- HuGene_st:165821-
HuGene_st:214153_at:731356- HuGene_st:601072-HuGene_st:755480-
HuGene_st:8873- HuGene_st:1567222_x_at:208788_at:1093316- HuGene_st
ANTXR1 203217-HuGene_st:501276- ANTXR1 0.0005 1.5167 2 77.6
65.4-86.9 HuGene_st:799524-HuGene_st:85875-
HuGene_st:12099-HuGene_st:230429-
HuGene_st:368173-HuGene_st:369297- HuGene_st:227660_at:86683-
HuGene_st:682518-HuGene_st:129277-
HuGene_st:827509-HuGene_st:901442-
HuGene_st:408237-HuGene_st:414321- HuGene_st:330209-
HuGene_st:234430_at:241549_at:755570- HuGene_st:220093_at ACTA2
479447_HuGene_st:183075- ACTA2 6.00E-04 1.4242 1.75 76.2 63.8-85.8
HuGene_st:1070983-HuGene_st:548186-
HuGene_st:529704-HuGene_st:530590-
HuGene_st:630797-HuGene_st:404109-
HuGene_st:237159-HuGene_st:90357-
HuGene_st:293590-HuGene_st:1078299-
HuGene_st:120087-HuGene_st:855050-
HuGene_st:757648-HuGene_st:980364-
HuGene_st:785232-HuGene_st:313690- HuGene_st:670805-HuGene_st
IGFBP3 242422-HuGene_st:1046998- IGFBP3 0.0006 1.552 1.38 78.1
.sup. 66-87.3 HuGene_st:585931-HuGene_st:145671-
HuGene_st:71362-HuGene_st:719466-
HuGene_st:412306-HuGene_st:922332-
HuGene_st:491408-HuGene_st:929740-
HuGene_st:276131-HuGene_st:201952- HuGene_st VIM
1093618-HuGene_st:398387- VIM 0.0008 1.4804 1.48 77 64.9-86.5
HuGene_st:837477-HuGene_st:1079757-
HuGene_st:339807-HuGene_st:302722-
HuGene_st:139661-HuGene_st:436158-
HuGene_st:564251-HuGene_st:234475-
HuGene_st:770617-HuGene_st:155888-
HuGene_st:319318-HuGene_st:527110-
HuGene_st:994975-HuGene_st:192324- HuGene_st ASPN
720939-HuGene_st:96944- ASPN 0.0009 1.4011 2.75 75.8 63.5-85.6
HuGene_st:224396_s_at:640448- HuGene_st:1055545-HuGene_st:447994-
HuGene_st:835521-HuGene_st:567513- HuGene_st:546047-
HuGene_st:219087_at:673 620-HuGene_st HNT 291569-HuGene_st:1099035-
HNT 0.001 1.425 2.26 76.2 63.8-85.8 HuGene_st:237480-
HuGene_st:222020_s_at:959054- HuGene_st:941200-HuGene_st:715332-
HuGene_st:761810-HuGene_st:673027- HuGene_st:653559-
HuGene_st:241934_at:403764- HuGene_st:719722-HuGene_st:227566_at
GJA1 210697-HuGene_st:348617- GJA1 0.0013 1.4083 1.63 75.9
63.7-85.6 HuGene_st:100706-HuGene_st:202715-
HuGene_st:817684-HuGene_st:851453-
HuGene_st:317083-HuGene_st:852817-
HuGene_st:150947-HuGene_st:491742-
HuGene_st:612542-HuGene_st:352375- HuGene_st:684816-HuGene_st MSN
77554-HuGene_st:103225- MSN 1.40E-03 1.4927 1.36 77.2 65.1-86.7
HuGene_st:1038630-HuGene_st:555838-
HuGene_st:250445-HuGene_st:770842- HuGene_st:240960_at:905037-
HuGene_st:693942-HuGene_st:788076-
HuGene_st:102934-HuGene_st:686613- HuGene_st SFRP4
965138-HuGene_st:512201- SFRP4 0.0015 1.407 2.2 75.9 63.5-85.5
HuGene_st:321583-HuGene_st:784119-
HuGene_st:4568-HuGene_st:1073348-
HuGene_st:606783-HuGene_st:203475-
HuGene_st:779727-HuGene_st:236875- HuGene_st:674172-
HuGene_st:204051_s_at:1084814- HuGene_st CTGF
418229-HuGene_st:547481- CTGF 0.0015 1.334 1.78 74.8 62.4-84.6
HuGene_st:661089-HuGene_st:338622-
HuGene_st:353624-HuGene_st:466254-
HuGene_st:691815-HuGene_st:156933-
HuGene_st:1031177-HuGene_st:265466-
HuGene_st:1079612-HuGene_st:1073900- HuGene_st:1080114-HuGene_st
FCGR3B p75320-HuGene_st:483078- FCGR3B 0.0026 1.232 2.14 73.1
60.5-83.3 HuGene_st:897088-HuGene_st:891504-
HuGene_st:288407-HuGene_st:367930-
HuGene_st:512343-HuGene_st:524627- HuGene_st:290249-
HuGene_st:204007_at:993144- HuGene_st:1084295-HuGene_st:606544-
HuGene_st:160442-HuGene_st:974942-
HuGene_st:582410-HuGene_st:117174- HuGene_st LOXL1
244262-HuGene_st:240421- LOXL1 0.0027 1.4045 1.33 75.9 63.7-85.5
HuGene_st:999775-HuGene_st LUM 253522-HuGene_st:646969- LUM 0.0029
1.3426 2.18 74.9 62.5-84.7 HuGene_st:566007-HuGene_st:629878-
HuGene_st:346266-HuGene_st:749731-
HuGene_st:848594-HuGene_st:781980-
HuGene_st:838285-HuGene_st:594339-
HuGene_st:1095278-HuGene_st:450762-
HuGene_st:205322-HuGene_st:130751-
HuGene_st:183047-HuGene_st:15672- HuGene_st SERPINF1
837342-HuGene_st SERPINF1 0.0031 1.2108 1.76 72.8 60.2-83.sup.
MXRA5 319799-HuGene_st:432137- MXRA5 0.0034 1.2959 1.62 74.1
61.6-84.1 HuGene_st:408065-HuGene_st:291182-
HuGene_st:549236-HuGene_st:217706-
HuGene_st:260019-HuGene_st:1079370-
HuGene_st:216837-HuGene_st:607674-
HuGene_st:829671-HuGene_st:348569-
HuGene_st:357055-HuGene_st:394366-
HuGene_st:192313-HuGene_st:124763- HuGene_st POSTN
954838-HuGene_st:153510- POSTN 0.005 1.301 2.58 74.2 61.7-84.3
HuGene_st:538299-HuGene_st:649547-
HuGene_st:779754-HuGene_st:106590-
HuGene_st:636479-HuGene_st:874100-
HuGene_st:13993-HuGene_st:417058-
HuGene_st:724846-HuGene_st:588010- HuGene_st:608772-
HuGene_st:210809_s_at:743877- HuGene_st:713459-HuGene_st:713707-
HuGene_st:753556-HuGene_st:776445- HuGene_st:388659-HuGene_st TAGLN
613243-HuGene_st:823959- TAGLN 0.0051 1.1811 2.19 72.3 59.6-82.6
HuGene_st:898711-HuGene_st:505391-
HuGene_st:26929-HuGene_st:458482- HuGene_st:66114-HuGene_st:304704-
HuGene_st:543865- HuGene_st:226523_at:270642-
HuGene_st:179049-HuGene_st:279405-
HuGene_st:902958-HuGene_st:931316- HuGene_st NNMT
231559_at:588888-HuGene_st:160284- NNMT 0.0054 1.2225 1.44 72.9
60.5-83.2 HuGene_st:591616-HuGene_st:968910-
HuGene_st:789017-HuGene_st:218836- HuGene_st:775762-
HuGene_st:202238_s_at:95357- HuGene_st:1098599-HuGene_st:793701-
HuGene_st IL8 471213-HuGene_st:373132-HuGene_st LOC731467:C6orf142:
0.0062 1.6808 1.33 80 68.1-88.7 CCDC42:IFI6:TRBV21-1:
H2AFZ:RNF20:TRBV5-4: TRBC1:TRBV3-1:TRBV19: TRBV7-2:IL23A GREM1
651822-HuGene_st:546941- GREM1 0.007 1.3044 1.31 74.3 61.8-84.2
HuGene_st:639839-HuGene_st:326978-
HuGene_st:593695-HuGene_st:127360-
HuGene_st:407017-HuGene_st:1081939-
HuGene_st:345681-HuGene_st:292333-
HuGene_st:864620-HuGene_st:2445-
HuGene_st:556201-HuGene_st:569365-
HuGene_st:411208-HuGene_st:330742- HuGene_st CIS
947234-HuGene_st:962144- C1S 0.0088 1.3551 1.77 75.1 62.8-84.9
HuGene_st:567397-HuGene_st:490300-
HuGene_st:459367-HuGene_st:1059233-
HuGene_st:915378-HuGene_st:682561-
HuGene_st:881984-HuGene_st:332123-
HuGene_st:37033-HuGene_st:433793-
HuGene_st:564959-HuGene_st:240802-
HuGene_st:245571-HuGene_st:156493-
HuGene_st:186313-HuGene_st:866948-
HuGene_st:661278-HuGene_st:665064-
HuGene_st:615340-HuGene_st:981405-
HuGene_st:127169-HuGene_st:224321-
HuGene_st:426716-HuGene_st:905688-
HuGene_st:1009344-HuGene_st:184395- HuGene_st TIMP2
310783-HuGene_st:526357- TIMP2 0.0097 1.1623 1.72 71.9 59.4-82.3
HuGene_st:965142-HuGene_st:463158-
HuGene_st:563754-HuGene_st:914626-
HuGene_st:106688-HuGene_st:1087828-
HuGene_st:740790-HuGene_st:799495- HuGene_st SPP1
87046-HuGene_st:904296- SPP1 0.0109 1.0677 3.91 70.3 57.6-80.9
HuGene_st:809583-HuGene_st:44881- HuGene_st:1568574_x_at:459132-
HuGene_st:963342-HuGene_st:909306-
HuGene_st:1070547-HuGene_st:31302-
HuGene_st:975259-HuGene_st:743585-
HuGene_st:530424-HuGene_st:709614-
HuGene_st:1022539-HuGene_st:575437-
HuGene_st:809262-HuGene_st:259921- HuGene_st SCD
214388-HuGene_st:1054693- SCD:LOC651109: 1.27E-02 1.073 2.33 70.4
57.7-81.sup. HuGene_st:433956-HuGene_st:1088784- LOC645313
HuGene_st:1019041-HuGene_st:698268-
HuGene_st:64902-HuGene_st:749928-
HuGene_st:713000-HuGene_st:562893- HuGene_st MYL9
206106-HuGene_st:608837- MYL9 0.0131 1.1754 1.37 72.2 59.6-82.4
HuGene_st:706186-HuGene_st:874422-
HuGene_st:543240-HuGene_st:676360-
HuGene_st:117460-HuGene_st:404703- HuGene_st:979054-
HuGene_st:244149_at:467647- HuGene_st:925187-HuGene_st:173220-
HuGene_st:923797-HuGene_st CD163 967100-HuGene_st:180883- CD163
0.0146 1.1667 2.19 72 59.4-82.3 HuGene_st:900552-HuGene_st:662901-
HuGene_st:217692-HuGene_st:74082-
HuGene_st:620892-HuGene_st:899841- HuGene_st:97726-HuGene_st S100A8
508168-HuGene_st:306748- S100A8 0.0148 1.1001 3.17 70.9 58.3-81.3
HuGene_st:473960-HuGene_st:98947-
HuGene_st:777038-HuGene_st:233365-
HuGene_st:671798-HuGene_st:214328- HuGene_st:214370_at:368299-
HuGene_st:16960-HuGene_st:627642- HuGene_st:669207-HuGene_st:75346-
HuGene_st:521635-HuGene_st:215650- HuGene_st:618819-HuGene_st CYR61
709380-HuGene_st:788428- CYR61 0.015 1.093 1.69 70.8 58.2-81.3
HuGene_st:385534-HuGene_st:924057-
HuGene_st:951763-HuGene_st:48239-
HuGene_st:462225-HuGene_st:789527-
HuGene_st:673588-HuGene_st:306375- HuGene_st MAFB 883249-HuGene_st
MAFB 0.0182 1.1589 1.48 71.9 59.3-82.3 APOE
555956-HuGene_st:99757-HuGene_st APOE 0.0285 1.1117 1.43 71.1
58.6-81.5 DCN 570449-HuGene_st:1067446-HuGene_st DCN 0.0364 1.0819
1.29 70.6 .sup. 58-81.1 G0S2 888942-HuGene_st:346957- G0S2 0.0383
0.9923 1.53 69 56.3-79.9 HuGene_st:62728-HuGene_st:334340-
HuGene_st:897401-HuGene_st CDH11 60296-HuGene_st:609892- CDH11
0.0384 1.01 1.98 69.3 56.7-80.sup.
HuGene_st:167614-HuGene_st:184349-
HuGene_st:546348-HuGene_st:960949-
HuGene_st:583244-HuGene_st:599824-
HuGene_st:626011-HuGene_st:96018-
HuGene_st:217538-HuGene_st:180379- HuGene_st SQLE
861626-HuGene_st:198540- SQLE 0.041 1.0133 2.15 69.4 56.7-80.1
HuGene_st:1010566-HuGene_st:895693-
HuGene_st:967759-HuGene_st:894379- HuGene_st:827097-HuGene_st GPNMB
NA GPNMB 0.0623 1.0155 1.52 69.4 56.8-80.1 KIAA1913 NA KIAA1913
0.1061 0.9593 1.2 68.4 55.7-79.3 SFRP2 NA SFRP2 0.1336 0.9696 1.24
68.6 .sup. 56-79.4 SMOC2 NA SMOC2 0.2175 0.6581 2.06 62.9 .sup.
50-74.4 SERPING1 NA SERPING1 2.64E-01 0.7805 1.26 65.2 52.5-76.5
EFEMP1 NA EFEMP1 0.4911 0.6831 1.27 63.4 50.5-74.9 TYROBP NA TYROBP
0.4923 0.7065 1.23 63.8 51.1-75.2 PLOD2 NA PLOD2 0.5151 0.7775 1.51
65.1 52.3-76.3
TABLE-US-00042 TABLE 9 SEQ ID Probe NO: Set ID Target Sequence 1
200660
caaggctgggccgggaagggcgtgggttgaggagaggctccagacccgcacgccgcgcgcaca-
gagctctcagc _at
gccgctcccagccacagcctcccgcgcctcgctcagctccaacatggcaaaaatctccagccctacaga-
gactgagc
ggtgcatcgagtccctgattgctgtcttccagaagtatgctggaaaggatggttataactacactctctcca-
agacagagtt
cctaagcttcatgaatacagaactagctgccttcacaaagaaccagaaggaccctggtgtccttgaccgcat-
gatgaaga
aactggacaccaacagtgatggtcagctagatttctcagaatttcttaatctgattggtggcctagctatgg-
cttgccatgac tccttcctcaaggctgtcccttcccagaagcggacctgaggaccc 2 200665
gttggttcaaacttttgggagcacggactgtcagttctctgggaagtggtcagcgcatcctgc-
agggcttctcctcctctgt _s_at
cttttggagaaccagggctcttctcaggggctctagggactgccaggctgtttcagccaggaaggcc-
aaaatcaagagt
gagatgtagaaagttgtaaaatagaaaaagtggagttggtgaatcggttgttctttcctcacatttggatga-
ttgtcataagg
tttttagcatgttcctccttttcttcaccctcccctttgttcttctattaatcaagagaaacttcaaagtta-
atgggatggtcggat
ctcacaggctgagaactcgttcacctccaagcatttcatgaaaaagctgcttcttattaatcatacaaactc-
tcaccatgatg tg 3 200832
aaaagcgaggtggccatgttatgctggtggttgccagggcctccaaccactgtgccactgact-
tgctgtgtgaccctggg _s_at
caagtcacttaactataaggtgcctcagttttccttctgttaaaatggggataataatactgaccta-
cctcaaagggcagtttt
gaggcatgactaatgctttttagaaagcattttgggatccttcagcacaggaattctcaagacctgagtatt-
ttttataatagg
aatgtccaccatgaacttgatacgtccgtgtgtcccagatgctgtcattagtctatatggttctccaagaaa-
ctgaatgaatc
cattggagaagcggtggataactagccagacaaaatttgagaatacataaacaacgcattgccacggaaaca-
tacaga
ggatgccttttctgtgattgggtgggattttttccctttttatgtgggatatagtagttacttgtgacaaga-
ataattttggaataa tttctattaatatcaactctgaagctaattgtactaatctgagat 4
200903
gcagcgggaacagagtaccctcttcaagccccggtcatgatggaggtcccagccacagggaac-
catgagctcagtgg _s_at
tcttggaacagctcactaagtcagtccttccttagcctggaagccagtagtggagtcacaaagccca-
tgtgttttgccatct
aggccttcacctggtctgtggacttatacctgtgtgcttggtttacaggtccagtggttcttcagcccatga-
cagatgagaa
ggggctatattgaagggcaaagaggaactgttgtttgaattttcctgagagcctggcttagtgctgggcctt-
ctcttaaacc tcattacaatgaggttagtacttttagtccctgt 5 201014
agtgttgatgggctctacttctgatcttggtcactgtgaaaaaatcaagaaggcctgtggaaa-
ttttggcattccatgtgaac _s_at
ttcgagtaacatctgcgcataaaggaccagatgaaactctgaggattaaagctgagtatgaagggga-
tggcattcctact
gtatttgtggcagtggcaggcagaagtaatggtttgggaccagtgatgtctgggaacactgcatatccagtt-
atcagc 6 201112
agatctgtgcggttggcataaccaacttactaacagaatgtcccccaatgatggacactgagt-
ataccaaactgtggactc _s_at
cattattacagtctttgattggtctttttgagttacccgaagatgataccattcctgatgaggaaca-
ttttattgacatagaagat
acaccaggatatcagactgccttctcacagttggcatttgctgggaaaaaagagcatgatcctgtaggtcaa-
atggtgaat
aaccccaaaattcacctggcacagtcacttcacatgttgtctaccgcctgtccaggaagggttc 7
201195
tcagaaggtaggggccgtgtcccgcggtgctgactgaggcctgcttccccctccccctcctgc-
tgtgctggaattccaca _s_at
gggaccagggccaccgcaggggactgtctcagaagacttgatttttccgtccctttttctccacact-
ccactgacaaacgt
ccccagcggtttccacttgtgggcttcaggtgttttcaagcacaacccaccacaacaagcaagtgcattttc-
agtcgttgtg
cttttttgttttgtgctaacgtcttactaatttaaagatgctgtcggcaccatgtttatttatttccagtgg-
tcatgctcagccttgc
tgctctgcgtggcgcaggtgccatgcctgctccctgtctgtgtcccagccacgcagggccatccactgtgac-
gtcggcc
gaccaggctggacaccctctgccgagtaatgacgtgtgtggctgggaccttctttattctgtgttaatggct-
aacctgttac actgggctgggttgggtagggtgttctggc 8 201261
tctctctttctgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtcttgtgcttcctca-
gacctttctcgcttctgagcttggt _x_at
ggcctgttccctccatctctccgaacctggcttcgcctgtccctttcactccacaccctctggcctt-
ctgccttgagctggga
ctgctttctgtctgtccggcctgcacccagcccctgcccacaaaaccccagggacagcggtctccccagcct-
gccctgc
tcaggccttgcccccaaacctgtactgtcccggaggaggttgggaggtggaggcccagcatcccgcgcagat-
gacac
catcaaccgccagagtcccagacaccggttttcctagaagcccctcacccccactggcccactggtggctag-
gtctccc
cttatccttctggtccagcgcaaggaggggctgcttctgaggtcggtggctgtctttccattaaagaaacac-
c 9 201292
tacagatactctactacactcagcctcttatgtgccaagtttttctttaagcaatgagaaatt-
gctcatgttcttcatcttctcaa _at
atcatcagaggccgaagaaaaacactttggctgtgtctataacttgacacagtcaatagaatgaagaaa-
attagagtagtt
atgtgattatttcagctcttgacctgtcccctctggctgcctctgagtctgaatctcccaaagagagaaacc-
aatttctaaga
ggactggattgcagaagactcggggacaacatttgatccaagatcttaaatgttatattgataaccatgctc-
agcaatgag
ctattagattcattttgggaaatctccataatttcaatttgtaaactttgttaagacctgtctacattgtta-
tatg 10 201328
agcatcggagccattcattcggagaaaacgttttgatcaaaatggagacttttgtagtcgttt-
caaaagagcacctgagtca _at
tgtgtattcccggcnnnctttataaatgacccggtcaagttggtttcaaagtncgacaggcttgtctgt-
ttactagctgcgtg
gccttggacgggtggctgacatctgtaaagaatcctcctgtgatgaaactgaggaatcgggtggccgggcaa-
gctggg
aagagcaaagccagnagctgcgctgcctcaatacccacaaaagaccattcccagtatacataagcacaggat-
gtttttct
caagagggatgtatttatcacttggacatctgtttataatataaacagacatgtgactgggaacatcttgct-
gccaaaagaat
cctaggcagtggctcattgtatgtgaggttgaaccacgtgaaattgccaatattaggctggcttttatctac-
aaagaaggag
tttcatggggttcagcctaacagttatggaaactacagtccttataaaccattggcatg 11
201338
gatgtatgtcgctgtccaagagaaggctgtggaagaacctatacaactgtgtttaatctccaa-
agccatatcctctccttcc _x_at
atgaggaaagccgcccttttgtgtgtgaacatgctggctgtggcaaaacatttgcaatgaaacaaag-
tctcactaggcatg
ctgttgtacatgatcctgacaagaagaaaatgaagctcaaagtcaaaaaatctcgtgaaaaacgggagtttg-
gcctctcat
ctcagtggatatatcctcccaaaaggaaacaagggcaaggcttatctttgtgtcaaaacggagagtcaccca-
actgtgtg
gaagacaagatgctctcgacagttgcagtacttacccttggctaagaactgcactgctttgtttaaaggact-
gcagaccaa ggagtcgagctttctctca 12 201341
ggtctgttcttgaatcctctattaattactgtgtgtgagccagagggagctgtggtaagggtt-
gggcccccagcctgtagg _at
gaactttctggactcccactctttgaatcgatataggcatttggtctcactacttgaccattctcaccc-
tgtgaaacgtcccac
actttgaagcaaatacaattcacagcacagtacacacaaaaaccaggccttaagacagagaaggttcttctt-
attttgtggg
ctggttgctgtagaaacatataacaaagggcagccctccacttctggtataattgtgtagccccttttcttt-
gggcttgacac ctgtcttgaataagagtgattagagctgcataatgtccctctctt 13 201416
gaggtcagatttggagcttctcattgcacgcggagattattattgcatcgggttccaagccaa-
tgggaagcccggggga _at
ggggtttggcatgaggaagcgttggttacagcagctgattggctgcagccaagactgtgaaaggataaa-
gaggcgcga
ggcggaattggggtctgctctaagctgcagcaagagaaactgtgtgtgaggggaagaggcctgtttcgctgt-
cgggtct
ctagttcttgcacgctctttaagagtctgcactggaggaactcctgccattaccagctcccttcttgcagaa-
gggaggggg
aaacatacatttattcatgccagtctgttgcatgcaggctttnnggcttcctaccttgcaacaaaataattg-
caccaactcctt
agtgccgattccgcccacagagagtcctggagccacagtcttttttgctttgcattgtaggagagggactaa-
gtgctagag actatgtcgctttcctgagctaccgagagcgctcgtgaactggaatcaact 14
201417
gtaaaccacatcttttttgcactttttttataagcaaaaacgtgccgtttaaaccactggatc-
tatctaaatgccgatttgagttc _at
gcgacactatgtactgcgtttttcattcttgtatttgactatttaatcctttctacttgtcgctaaata-
taattgttttagtcttatggc
atgatgatagcatatgtgttcaggtttatagctgttgtgtttaaaaattgaaaaaagtggaaaacatctttg-
tacatttaagtct
gtattataataagcaaaaagattgtgtgtatgtatgtttaatataacatgacaggcactaggacgtctgcct-
ttttaaggcagt
tccgttaagggtttttgtttttaaacttttttttgccatccatcctgtgcaatatgccgtgta 15
201468
gatgacttaccatgggatggggtccagtcccatgaccttggggtacaattgtaaacctagagt-
tttatcaactttggtgaac _s_at
agttttggcataatagtcaatttctacactggaagtcatctcattccactgttggtattatataatt-
caaggagaatatgataaa
acactgccctcttgtggtgcattgaaagaagagatgagaaatgatgaaaaggttgcctgaaaaatgggagac-
agcctctt
acttgccaagaaaatgaagggattggaccgagctggaaaacctcctttaccagatgctgactggcactggtg-
gtttttgct
ctcgacatatccacaatagctgacggctgggtgtttcagtttgcaaaatattttgttgccttcatcttcact-
gcaattttgtgta 16 201479
ttcagacccagtaactgtccgcagctgtctgctagtggttgtcttaacatcgtagtcctagtt-
tgcattttttaaatcccctctgt _at
ttaaaaggtttgtaaaacaaaaacaaaaaactaagtctgctcagtgaaatgctgtagaaccctaaataa-
gtggtagaaga
gtgtcactgaattttgtctctgaattcagtataactgagttttgtccatgctggtgtctgggttataggcct-
gatgggcctggta
gttttccatcttgttctggcctagaggtcagtcctttgcacttcctcaaagcttgtgtacagtgctcaccta-
aatccatctgact
acttgttcctgtgccctcttgttttaggcctcgtttacttttaaaaaatgaaattgttcattgctgggagaa-
gaatgttgtaattttt
acttattaaagtcaacttgttaagttttttatgtattcctgttgggttttcttgttg 17 201506
acaggaggaatgcaccacggcagctctccgccaatttctctcagatttccacagagactgttt-
gaatgttttcaaaaccaa _at
gtatcacactttaatgtacatgggccgcaccataatgagatgtgagccttgtgcatgtgggggaggagg-
gagagagatg
tactttttaaatcatgaccccctaaacatggctgttaacccactgcatgcagaaacttggatgtcactgcct-
gacattcactt
ccagagaggacctatcccaaatgtggaattgactgcctatgccaagtccctggaaaaggagcttcagtattg-
tggggctc
ataaaacatgaatcaagcaatccagcctcatgggaagtcctggcacagtttttgtaaagcccttgcacagct-
ggagaaat
ggcatcattataagctatgagttgaaatgttctgtcaaatgtgtctcacatctacacgtggcttggaggctt-
ttatggggccct
gtccaggtagaaaagaaatggtatgtagagcttagatttccctattgtgacagagcc 18 201563
aggaaactgctacttgtggacctcaccagagaccaggagggtttggttagctcacaggacttc-
ccccaccccagaagat _at
tagcatcccatactagactcatactcaactcaactaggctcatactcaattgatggttattagacaatt-
ccatttctttctggtta
ttataaacagaaaatctttcctcttctcattaccagtaaaggctcttggtatctttctgttggaatgatttc-
tatgaacttgtcttat
tttaatggtgggttttttttctggtaagatttagacctaaatcgcatcatgccaacttgtgactttgagact-
attcatcaagaatg
aggatatagtagccatgacatagcttgagctatagcctttaattccttactttggctatgggtggagggtga-
gtttgaagag gttctgattttcttgtaacctggga 19 201577
gattccgccttgttggtctgaaattcatgcaagcttccgaagatcttctcaaggaacactacg-
ttgacctgaaggaccgtcc _at
attctttgccggcctggtgaaatacatgcactcagggccggtagttgccatggtctgggaggggctgaa-
tgtggtgaaga
cgggccgagtcatgctcggggagaccaaccctgcagactccaagcctgggaccatccgtggagacttctgca-
tacaa
gttggcaggaacattatacatggcagtgattctgtggagagtgcagagaaggagatcggcttgtggtttcac-
cctgagga
actggtagattacacgagctgtgctcagaactggatctatgaatgacaggagggcagaccacattgcttttc-
acatccattt
cccctccttcccatgggcagaggaccaggctgtaggaaatctagttatttacaggaacttcatcataatttg-
gagggaagc tcttggagctgtgagttctccctgtacagtgttaccatc 20 201601
agaaaaccacacttctcataccttcactcaacacttccttccccaaagccagaagatgcacaa-
ggaggaacatgaggtg _x_at
gctgtgctgggggcaccccccagcaccatccttccaaggtccaccgtgattaacatccacagcgaga-
cctccgtgccc
gaccatgtcgtctggtccctgttcaacaccctcttcttgaactggtgctgtctgggcttcatagcattcgcc-
tactccgtaaa
gtctagggacaggaagatggttggcgacgtgaccggggcccaggcctatgcctccaccgccaagtgcctgaa-
catct
gggccctgattctgggcatcctcatgaccattggattcatcctgttactggtattcggctctgtaacagtct-
accatattatgtt
acagataatacaggaaaaacggggttactagtagccgcccatagcctgcaacctttgcactccactgtgcaa-
tgctggc c 21 201656
gtagtgccactgttgttttggggggggctttttttctttttccggaaaatccttaaaccttaa-
gatactaaggacgttgttttggt _at
tgtacttggaattcttagtcacaaaatatattttgtttacaaaaatttctgtaaaacaggttataacag-
tgtttaaagtctcagttt
cttgcttggggaacttgtgtccctaatgtgttagattgctagattgctaaggagctgatacttgacagtttt-
ttagacctgtgtt
actaaaaaaaagatgaatgtcggaaaagggtgttgggagggtggtcaacaaagaaacaaagatgttatggtg-
tttagac
ttatggttgttaaaaatgtcatctcaagtcaagtcactggtctgtttgcatttgatacatttttgtactaac-
tagcattgtaaaatt
atttcatgattagaaattacctgtggatatttgtataaaagtgtgaaataaattttttataaaagtgttcat-
tgtttcgtaacacag catt 22 201666
tcagggccaagttcgtggggacaccagaagtcaaccagaccaccttataccagcgttatgaga-
tcaagatgaccaagat _at
gtataaagggttccaagccttaggggatgccgctgacatccggttcgtctacacccccgccatggagag-
tgtctgcgga
tacttccacaggtcccacaaccgcagcgaggagtttctcattgctggaaaactgcaggatggactcttgcac-
atcactac
ctgcagtttcgtggctccctggaacagcctgagcttagctcagcgccggggcttcaccaagacctacactgt-
tggctgtg
aggaatgcacagtgtttccctgtttatccatcccctgcaaactgcagagtggcactcattgcttgtggacgg-
acc 23 201925
gtgatttttttccacaagtttctgtaatgttatttccacttataaaggaaataaaaaatgaaa-
aacattatttggatatcaaaagc _s_at
aaataaaaacccaattcagtctcttctaagcaaaattgctaaagagagatgaaccacattataaagt-
aatctttggctgtaa
ggcattttcatctttccttcgggaggcaaaatattttaaaggtaaaacatgctggtgaaccaggggtgttga-
tggtgataag
ggaggaatatagaatgaaagactgaatcttcctttgttgcacaaatagagtttggaaaaagcctgtgaaagg-
tgtcttcttt
gacttaatgtctttaaaagtatccagagatactacaatattaacataagaaaagattatatattatttctga-
atcgagatgtcca tagtcaaatttgtaa 24 201926
gagagcactctatttattgtactgtgaataatgatgaaggagagtggagtggcccaccacctg-
aatgcagaggaaaatct _s_at
ctaacttccaaggtcccaccaacagttcagaaacctaccacagtaaatgttccaactacagaagtct-
caccaacttctcag
aaaaccaccacaaaaaccaccacaccaaatgctcaagcaacacggagtacacctgtttccaggacaaccaag-
cattttc
atgaaacaaccccaaataaaggaagtggaaccacttcaggtactacccgtcttctatctgggcacacgtgtt-
tcacgttga
caggtttgcttgggacgctagtaaccatgggcttgctgacttagccaaagaagagttaagaagaaaatacac-
acaagtat acagactgttcctagtttcttagactta 25 202286
gtatgacaacccgggatcgtttgcaagtaactgaatccattgcgacattgtgaaggcttaaat-
gagtttagatgggaaata _s_at
gcgttgttatcgccttgggtttaaattatttgatgagttccacttgtatcatggcctacccgaggag-
aagaggagtttgttaac
tgggcctatgtagtagcctcatttaccatcgtttgtattactgaccacatatgcttgtcactgggaaagaag-
cctgtttcagct
gcctgaacgcagtttggatgtctttgaggacagacattgcccggaaactcagtctatttattcttcagcttg-
ccc 26 202310
tggcctacatggaccagcagactggcaacctcaagaaggccctgctcctccagggctccaacg-
agatcgagatccgc _s_at
gccgagggcaacagccgcttcacctacagcgtcactgtcgatggctgcacgagtcacaccggagcct-
ggggcaaga
cagtgattgaatacaaaaccaccaagacctcccgcctgcccatcatcgatgtggcccccttggacgttggtg-
ccccaga
ccaggaattcggcttcgacgttggccctgtctgcttcctgtaaactccctccatcccaacctggctccctcc-
cacccaacc
aactttccccccaacccggaaacagacaagcaacccaaactgaaccccctcaaaagccaaaaaatgggagac-
aatttc
acatggactttggaaaatatttttttcctttgcattcatctctcaaacttagtttttatctttgaccaaccg-
aacatgacca 27 202311
gctccccatttttataccaaaggtgctacatctatgtgatgggtggggtggggagggaatcac-
tggtgctatagaaattga _s_at
gatgcccccccaggccagcaaatgttcctttttgttcaaagtctatttttattccttgatatttttt-
ntttntttttttttttttttgtgga
tggggacttgtgaatttttctaaaggtgctatttaacatgggaggagagcgtgtgcggctccagcccagccc-
gctgctca
ctttccaccctctctccacctgcctctggcttctcaggcctctgctctccgacctctctcctctgaaaccct-
cctccacagct
gcagcccatcctcccggctccctcctagtctgtcctgcgtcctctgtccccgggtttcagagacaacttccc-
aaagcacaa agcagtttttncccctaggggtgggaggaagcaaaagactctgtacctattttgt
28 202403
aacctgaaaacatcccagccaagaactggtataggagctccaaggacaagaaacacgtctggc-
taggagaaactatca _s_at
atgctggcagccagtttgaatataatgtagaaggagtgacttccaaggaaatggctacccaacttgc-
cttcatgcgcctgc
tggccaactatgcctctcagaacatcacctaccactgcaagaacagcattgcatacatggatgaggagactg-
gcaacct
gaaaaaggctgtcattctacagggctctaatgatgttgaacttgttgctgagggcaacagcaggttcactta-
cactgttctt
gtagatggctgctctaaaaagacaaatgaatggggaaagacaatcattgaatacaaaacaaataagccatca-
cgcctgc
ccttccttgatattgcacctttggacatcggtggtgctgaccaggaattctttgtggacattggcccagtct-
gtt 29 202404
actttcccatgagtgtgatccacattgttaggtgctgacctagacagagatgaactgaggtcc-
ttgttttgttttgttcataata _s_at
caaaggtgctaattaatagtatttcagatacttgaagaatgttgatggtgctagaagaatttgagaa-
gaaatactcctgtatt
gagttgtatcgtgtggtgtattttttaaaaaatttgatttagcattcatattttccatcttattcccaatta-
aaagtatgcagattatt
tgcccaaagttgtcctcttcttcagattcagcatttgttctttgccagtctcattttcatcttcttccatgg-
ttccacagaagctttg tttcttgggca 30 202431
gcaacaaccgaaaatgcaccagccccaggtcctcggacaccgaggagaatgtcaagaggcgaa-
cacacaacgtctt _s_at
ggagcgccagaggaggaacgagctaaaacggagcttttttgccctgcgtgaccagatcccggagttg-
gaaaacaatg
aaaaggcccccaaggtagttatccttaaaaaagccacagcatacatcctgtccgtccaagcagaggagcaaa-
agctcat
ttctgaagaggacttgttgcggaaacgacgagaacagttgaaacacaaacttgaacagctacggaactcttg-
tgcgtaa
ggaaaagtaaggaaaacgattccttctaacagaaatgtcctgagcaatcacctatgaacttgtttcaaatgc-
atgatcaaat gcaacctcacaaccttggctgagtc 31 202504
ggaaacctctcagtgtcttgacatcaccctacccaggcggtgggtctccaccacagccacttt-
gagtctgtggtccctgg _at
agggtggcttctcctgactggcaggatgaccttagccaagatattcctctgttccctctgctgagataa-
agaattcccttaa
catgatataatccacccatgcaaatagctactggcccagctaccatttaccatttgcctacagaatttcatt-
cagtctacactt
tggcattctctctggcgatggagtgtggctgggctgaccgcaaaaggtgccttacacactgcccccaccctc-
agccgttg ccccatcagaggctgcctcctccttctgattaccccccatgttgcatatcaggg 32
202718
atccccaactgtgacaagcatggcctgtacaacctcaaacagtgcaagatgtctctgaacggg-
cagcgtggggagtgct _at
ggtgtgtgaaccccaacaccgggaagctgatccagggagcccccaccatccggggggaccccgagtgtc-
atctcttct
acaatgagcagcaggaggcttgcggggtgcacacccagcggatgcagtagaccgcagccagccggtgcctgg-
cgc ccctgccccccgcccctctccaaacaccggcagaaaacggagagtgcttgggtggtg 33
202779
ccgaacgtgggcgccaatggcgagatctgcgtcaacgtgctcaagagggactggacggctgag-
ctgggcatccgac _s_at
acgtactgctgaccatcaagtgcctgctgatccaccctaaccccgagtctgcactcaacgaggaggc-
gggccgcctgc
tcttggagaactacgaggagtatgcggctcgggcccgtctgctcacagagatccacgg 34
202831
ctacccttatgatgacccattttccctcatgaccgatcccaagctcatcatttggagccctgt-
gcgccgctcagatgtggcc _at
tggaactttgagaagttcctcatagggccggagggagagcccttccgacgctacagccgcaccttccca-
accatcaaca
ttgagcctgacatcaagcgcctccttaaagttgccatatagatgtgaactgctcaacacacagatctcctac-
tccatccagt
cctgaggagccttaggatgcagcatgccttcaggagacactgctggacctcagcattcccttgatatcagtc-
cccttcact
gcagagccttgcctttcccctctgcctgtttccttttcctctcccaaccctctggttggtgattcaacttgg-
gctccaagacttg
ggtaagctctgggccttcacagaatgatggcaccacctaaaccctcatgggtgg 35 202833
gaagcgtttaggcatgtttaacatccagcactgtaagaagctgtccagctgggtactgctaat-
gaaatacctgggcaatgc _s_at
caccgccatcttcttcctacctgatgaggggaaactacagcacctggaaaatgaactcacccacgat-
atcatcaccaagt
tcctggaaaatgaagacagaaggtctgccagcttacatttacccaaactgtccattactggaa 36
202859
gtacccagttaaattttcatttcagataaacaacaaataattttttagtataagtacattatt-
gtttatctgaaagttttaattgaac _x_at
taacaatcctagtttgatactcccagtcttgtcattgccagctgtgttggtagtgctgtgttgaatt-
acggaataatgagttag
aactattaaaacagccaaaactccacagtcaatattagtaatttcttgctggagaaacttgtttattatgta-
caaatagattctt
ataatattatttaaatgactgcatttttaaatacaaggctttattttttttaactttaagatgtttttatgt-
gctctccaaattttttttact gtttctgattgtat 37 202935
gagaggaccaaccagaattccctttggacatttgtgtttttttgtttttttttttttgttttg-
ttttttcttcttcttcttcttccttaaaga _s_at
catttaagctaaaggcaactcgtacccaaatttccaagacacaaacatgacctatccaagcgcatta-
cccacttgtggcca
atcagtggccaggccaaccttggctaaatggagcagcgaaatcaacgagaaactggactttttaaaccctct-
tcagagc
aagcgtggaggatgatggagaatcgtgtgatcagtgtgctaaatctctctgcctgtttggactttgtaatta-
tttttttagcagt
aattaaagaaaaaagtcctctgtgaggaatattctctattttaaatatttttagtatgtactgtgtatgatt-
cattaccattttgag
gggatttatacatattttagataaaattaaatgctcttatttttccaacagctaaactactcttagttgaac-
agtgtgccctagct tttcttgcaaccagagta 38 202936
gtagtgtatcactgagtcatttgcagtgttttctgccacagacctttgggctgccttatattg-
tgtgtgtgtgtgggtgtgtgtg _s_at
tgttttgacacaaaaacaatgcaagcatgtgtcatccatatttctctacatcttctcttggagtgag-
ggaggctacctggagg
ggatcagcccactgacagaccttaatcttaattactgctgtggctagagagtttgaggattgctttttaaaa-
aagacagcaa
acttttttttttatttaaaaaaagatatattaacagttttagaagtcagtagaataaaatcttaaagcactc-
ataatatggcatcct
tcaatttctgtataaaagcagatctttttaaaaaagatacttctgtaacttaagaaacctggcatttaaatc-
atattttgtctttag
gtaaaagctttggtttgtgttcgtgttttgtttgtttcacttgtttccctcccagccccaaaccttttgact-
ctccgtgaaacttac cttt 39 202954
gccttccctgaatcagacaaccttttcaaatgggtagggaccatccatggagcagctggaaca-
gtatatgaagacctgag _at
gtataagctctcgctagagttccccagtggctacccttacaatgcgcccacagtgaagttcctcacgcc-
ctgctatcaccc
caacgtggacacccagggtaacatatgcctggacatcctgaaggaaaagtggtctgccctgtatgatgtcag-
gaccatt
ctgctctccatccagagccttctaggagaacccaacattgatagtcccttgaacacacatgctgccgagctc-
tggaaaaa
ccccacagcttttaagaagtacctgcaagaaacctactcaaagcaggtcaccagccaggagccctgacccag-
gctgcc
cagcctgtccttgtgtcgtctttttaatttttccttagatggtctgtcctttttgtgattt 40
202998
gccagtcttgaccgggatgaggcccacagacaggttgtcatcagcttgtcccattcaagccac-
cgagctcaccacagac _s_at
acagtggagccgcgctcttctccagtgacacgtggacaaatgcgggctcatcagcccccccagagag-
ggtcaggccg
aaccccatttctcctcctcttaggtcattttcagcaaacttgaatatctagacctctcttccaatgaaaccc-
tccagtctattata
gtcacatagataatggtgccacgtgttttctgatttggtgagctcagacttggtgcttccctctccacaacc-
cccaccccttg
tttttcaagatactattattatattttcacagacttttgaagcacaaatttattggcatttaatattggaca-
tctgggcccttggaa
gtacaaatctaaggaaaaaccaacccactgtgtaagtgactcatcttcctgttgttccaattctgtgggttt-
ttgattcaacgg
tgctataaccagggtcctgggtgacagggcgctcactgagcaccatgtgtcatcacagaca 41
203083
caggaaatagtcactcatcccactccacataaggggtttagtaagagaagtctgtctgtctga-
tgatggatagggggcaa _at
atctttttcccctttctgttaatagtcatcacatttctatgccaaacaggaacgatccataactttagt-
cttaatgtacacattgca
ttttgataaaattaattttgttgtttcctttgaggttgatcgttgtgttgttttgctgcactttttactttt-
ttgcgtgtggagctgtattc
ccgagacaacgaagcgttgggatacttcattaaatgtagcgactgtcaacagcgtgcaggttttctgtttct-
gtgttgtggg
gtcaaccgtacaatggtgtgggaatgacgatgatgtgaatatttagaatgtaccatattttttgtaaattat-
ttatgtttttctaaa
caaatttatcgtataggagatgaaacgtcatgtgttttgccaaagactgtaaatatttatttatgtgttcac-
atggtcaaaatttc accactgaaaccctgcacttagctagaacct 42 203124
atggtaacatgtatctttgccctgggtctgggtgggtccagtcagtctcagatttacaagcat-
ttaggagcctaggtaaaag _s_at
ctgctagtattcttttaaaagttatatttatgacttgcaatgatagaaaactccttccaattaaatg-
gcattttataatattatgtgt
gtacttcacagtgttaaaaataccctcatacgttattgcatttgatatcacagaaagtgcattttaaccagt-
actctgggtgc
aataaataatatgtagaaatttaagtcctccaattccagcatatccagtgagttttgacagtgtgtttatgt-
ggaatgtttaagg
atatacaattgtactttatataaattggttcttgttcttcttaaatgtgacatgaaataattgtgctgctac-
attatactggaaatta
acaggggaaaagggaagagctcttggctcccttgaggttctgctagtggtgttaggagtggttacaactgag-
cttttagta accatttaaccg 43 203213
tgctaagttcaagtttcgtaatgctttgaagtatttttatgctctgaatgtttaaatgttctc-
atcagtttcttgccatgttgttaact _at
atacaacctggctaaagatgaatatttttctactggtattttaatttttgacctaaatgtttaagcatt-
cggaatgagaaaactat
acagatttgagaaatgatgctaaatttataggagttttcagtaacttaaaaagctaacatgagagcatgcca-
aaatttgctaa
gtcttacaaagatcaagggctgtccgcaacagggaagaacagttttgaaaatttatgaactatcttattttt-
aggtaggttttg
aaagctttttgtctaagtgaattcttatgccaggtcagagtaataactgaaggagntgcttatcttggcttt-
cgagtctgagtt taaaactacacattttgacatagtgtttattagcagccatc 44 203256
gtggccgtagcaacttggcggagacaggctatgagtctgacgttagagtggttgcttccttag-
ccatcaggatggagga _at
atgtgggcagtttgacttcagcactgaaaacctctccacctgggccagggttgcctcagaggccaagtt-
tccagaagcct
cttacctgccgtaaaatgctcaaccctgtgtcctgggcctgggcctgctgtgactgacctacagtggacttt-
ctctctggaa
tggaaccttcttaggcctcctggtgcaacttaatttttttttttaatgctatcttcaaaacgttagagaaag-
ttcttcaaaagtgc
agcccagagctgctgggcccactggccgtcctgcatttctggtttccagaccccaatgcctcccattcggat-
ggatctctg
cgtttttatactgagtgtgcctaggttgccccttattttttattttccctgttgcgttgctatagatg
45 203313
agagtggtcttttcaacactcctccccctactccaccggacctcaaccaggacttcagtggat-
ttcagcttctagtggatgtt _s_at
gcactcaaacgggctgcagagatggagcttcaggcaaaacttacagcttaacccattttcaagcaaa-
acagttctcagaa
atgtcatgattgccggggtgaaggcaagagatgaattgcattattttatatattttttattaatatttgcac-
atgggattgctaaa
acagcttcctgttactgagatgtcttcaatggaatacagtcattccaagaactataaacttaaagctactgt-
agaaacaaag
ggttttcttttttaaatgtttcttggtagattattcataatgtgagatggttcccaatatcatgtgattttt-
ttttttcctccccttccctt
tttttgttattttttcagactgtgcaatacttagagaacctatagcatcttctcattcccatgtggaacagg-
atgcccacatactg tctaatta 46 203510
gaagccaagggttaacccagcaagctacaaagagggtgtgtcacactgaaactcaatagttga-
gtttggctgttgttgca _at
ggaaaatgattataactaaaagctctctgatagtgcagagacttaccagaagacacaaggaattgtact-
gaagagctatta
caatccaaatattgccgtttcataaatgtaataagtaatactaattcacagagtattgtaaatggtggatga-
caaaagaaaat
ctgctctgtggaaagaaagaactgtctctaccagggtcaagagcatgaacgcatcaatagaaagaactcggg-
gaaaca
tcccatcaacaggactacacacttgtatatacattcttgagaacactgcaatgtgaaaatcacgtttgctat-
ttataaacttgt
ccttagattaatgtgtctggacagattgtgggagtaagtgattcttctaagaattagatacttgtcactgcc-
tatacctgcagc tgaactgaatggtacttcgtatg 47 203860
gaagcaggtggaaacatgagcattcagtttcttggtacagtgtacaaggtgaatatcttaacc-
agacttgccgcagaattg _at
aacaaatttatgctggaaaaagtgactgaggacacaagcagtgttctgcgttccccgatgcccggagtg-
gtggtggccg
tctctgtcaagcctggagacgcggtagcagaaggtcaagaaatttgtgtgattgaagccatgaaaatgcaga-
atagtatg
acagctgggaaaactggcacggtgaaatctgtgcactgtcaagctggagacacagttggagaaggggatctg-
ctcgtg
gagctggaatgaaggatttataacctttcagtcatcacccaatttaattagccatttgcatgatgctttcac-
acacaattgattc
aagcattatacaggaacacccctgtgcagctacgtttacgtcgtcatttattccacagagtcaagaccaata-
ttctgccaaa
aaatcaccaatggaaattttcatgatataaatacttgtactatagatgtacttctgctgtg 48
203878
tgccagcgactgtctcagactgggcagggaggctttggcatgacttaagaggaagggcagtct-
tgggacccgctatgc _s_at
aggtcctggcaaacctggctgccctgtctcatccctgtccctcagggtagcaccatggcaggactgg-
gggaactggagt
gtccttgctgtatccctgttgtgaggttccttccaggggctggcactgaagcaagggtgctggggccccatg-
gccttcag
ccctggctgagcaactgggctgtagggcagggccacttcctgaggtcaggtcttggtaggtgcctgcatctg-
tctgcctt
ctggctgacaatcctggaaatctgttctccagaatccaggccaaaaagttcacagtcaaatggggaggggta-
ttcttcatg
caggagaccccaggccctggaggctgcaacatacctcaatcctgtcccaggccggatcctcctgaagcccct-
ttcgcag
cactgctatcctccaaagccattgtaaatgtgtgtacagtgtgtataaaccttcttcttctt 49
203895
gactaatccatacacagttaacctaatgccaaataaatactggttaaataaatgtatggcaca-
gaatataatttgactatcaa _at
gacttttagcataatgaaaaaccctctctctatatatatatgtgtatatgaattatgtgggcattcttg-
atacttcaagttctagttt
gaaaaaaatacataactaatttaattttacacaaaaatatttatgcagattttcagaatttcatatcaggaa-
atgacccttttatgt
ctgttaaatatcaaaacaatttgctacagtgttaatctgcatggtctttaagcctgctgtagttgagttgca-
gacagtgcatga
aaaagtattccgctgggaattgagccatgccaccaaagccaagaggagcgcatggaaacccggtagtctaga-
actaat
cagattactgattttagggcacagcaccagatgaattgttgtatatgcttgtaaaaattgattctgtgtgtt-
cctctgaacaaa gcgg 50 203896
gtccagcttgaacatctagaattcctagagaaacagaatgagcaggcgaaggagatgcagcag-
atggtgaaattggaa _s_at
gccgagatggaccgcagaccagcaacagtagtatgaaactccaaaatgcaaactgaagcagcaaacc-
cacaaagcat
caaaagactcactcacaaaacactgaacacaaactccatggatgaaagctgtttattttgtttcctttatgt-
gtaaacaagat
gatatctgaaaccagagagacttggaatgtctgactgacttctatttaacagcttgagtattgcatttcctt-
ggccaaacaaa
aatagctacaaatccacaaaaatttactattccagtaaggcagagtccaaccattgataatacaacttaaac-
atgtttgctat
aaaataccatcacaagtaaatgagcttggtgtgaacaactcttcctttgtgatgccttagg 51
203961
ggactagagcaacatcgtgctgcccaaaggactaacctatgcaaactagttcacattttagtg-
gatgtcgcagttaatgtgt _at
aataagacattatttcccctgcataatgtacaacagcattgaaatgacacattaagcctagcatcacat-
tgtatagtacagtc
actcacaaacccttcaaggctaccctaatcattaacattaatatttgtttaaaagcaaatcaccgatttatc-
tattgaaactact
taaatgacggcaaaccaggaatgacagatggctgtgtcagcaatggctttaatgtgttccctgcaagtggtc-
tcctatgan
tagaactgcgttctcaaatgcactctcttcagggtcttaatattctgtgttttctctctgtatttgtaaaac-
attataacacattaat ttcctatctctacacatttgg 52 203962
gtcaaggcattgtatgttgcttctgtggttattattctgtgatgcttagactacttgaaccca-
taaacttggaagaatctttgag _s_at
caaattttctcagttgtctgtatgacttcagtatattcctgggaatgccataggattttttgtgctt-
gatacatggtatccagtttg
catagtatcacttctttgtaatccagttgctgttaagaatgatgtactttaaaggaaaagagaaaactgcat-
cacagtcccatt
ctccagtgtccatgcaatgaattgctgagcatttaggaagcagcaccaagtctattacaggcatggtgtgaa-
acttgatgtt
tgacctgtgatcaaaattgaaccattgtacagtttggcttctgtttgcttcaaaatatgtagaattgtggtt-
gatgattaatttgc
gagactaactttgagagtgtaacagttttgaagaaaacattgaatgttttacaaatgaaggggcttcacgga-
atgttacaa 53 204051
aaccagccagtcccaagaagaacattaaaactaggagtgcccagaagagaacaaacccgaaaa-
gagtgtgagctaac _s_at
tagtttccaaagcggagacttccgacttccttacaggatgaggctgggcattgcctgggacagccta-
tgtaaggccatgt
gccccttgccctaacaactcactgcagtgctcttcatagacacatcttgcagcatttttcttaaggctatgc-
ttcagtttttcttt gtaagccatcacaagccatagtggtaggtttgccctttggtacagaag 54
204127
ttgtgttttgtcattagctctgccctttttaattaaatattttggttcatggaccaaagggtt-
tacttgacaaatttgtgtgacaga _at
ctccgaacaattcctttactacgaagtataatttataaaataaaatatacccattttaagggtacagtt-
tgatttttgaccagtga
aactatgatcccaatcaaggtatagatgccgtcaccccaaaaagttccctccatatccctttgcagtcagtt-
catccctacc
ctggcccagatgatcactgatcttgtcattatagatgagttttgccagttcaagaatttaatggaatcagat-
attgtaagcatt
cttgtgtaatacttcattctctctcattattgagattcatccatattgttgaatgtttcactagttaatgtt-
tattgttcaatatttttgta tatacttttaaagcctattcacttgctgatggatctt 55
204170
cgctctcgtttcattttctgcagcgcgccacgaggatggcccacaagcagatctactactcgg-
acaagtacttcgacgaa _s_at
cactacgagtaccggcatgttatgttacccagagaactttccaaacaagtacctaaaactcatctga-
tgtctgaagaggag
tggaggagacttggtgtccaacagagtctaggctgggttcattacatgattcatgagccagaaccacatatt-
cttctctttag
acgacctcttccaaaagatcaacaaaaatgaagtttatctggggatcgtcaaatctttttcaaatttaatgt-
atatgtgtatata
aggtagtattcagtgaatacttgagaaatgtacaaatattctttccatacctgtgcatgagctgtattcttc-
acagcaacaga
gctcagttaaatgcaactgcaagtaggttactgtaagatgtttaagataaaagttcttccagtcagtttttc-
tcttaagtgcct 56 204259
ctcatggggactcctacccatttgatgggccaggaaacacgctggctcatgcctttgcgcctg-
ggacaggtctcggagg _at
agatgctcacttcgatgaggatgaacgctggacggatggtagcagtctagggattaacttcctgtatgc-
tgcaactcatga
acttggccattctttgggtatgggacattcctctgatcctaatgcagtgatgtatccaacctatggaaatgg-
agatccccaa
aattttaaactttcccaggatgatattaaaggcattcagaaactatatggaaagagaagtaattcaagaaag-
aaatagaaa
cttcaggcagaacatccattcattcattcattggattgtatatcattgttgcacaatcagaattgataagca-
ctgttcctccact
ccatttagcaattatgtcacccttttttattgcagttggtttttgaatgtctttcactccttttattggtta-
aactcctttatggtgtga ctgtgtcttattccatctatgagctttgtcagtgcgcgtagatgt 57
204320
gaaaatgtaccttggtgccaccaacccattttgtgccacatgcaagttttgaataaggatgta-
tggaaaacaacgctgcat _at
atacaggtaccatttaggaaataccgatgcctttgtgggggcagaatcacagacaaaagctttgaaaat-
cataaagatata
agttggtgtggctaagatggaaacagggctgattcttgattcccaattctcaactctccttttcctatttga-
atttctttggtgct
gtagaaaacaaaaaaagaaaaatatatattcataaaaaatatggtgctcattctcatccatccaggatgtac-
taaaacagtg
tgtttaataaattgtaattattttgtgtacagttctatactgttatctgtgtccatttccaaaacttgcacg-
tgtccctgaattccgc
tgactctaatttatgaggatgccgaactctgatggcaataatatatgtattatgaaaatgaagttatgattt-
ccgatgacccta agtcc 58 204351
gggtctgaatctagcaccatgacggaactagagacagccatgggcatgatcatagacgtcttt-
tcccgatattcgggcag _at
cgagggcagcacgcagaccctgaccaagggggagctcaaggtgctgatggagaaggagctaccaggctt-
cctgcag
agtggaaaagacaaggatgccgtggataaattgctcaaggacctggacgccaatggagatgcccaggtggac-
ttcagt
gagttcatcgtgttcgtggctgcaatcacgtctgcctgtcacaagtactttgagaaggcaggactcaaatga-
tgccctgga
gatgtcacagattcctgcagagccatggtcccaggcttcccaaaagtgtttgttggcaattattcccctagg-
ctgagcctg ctcatgtacc 59 204401
gtagctggacccacgaggaggaaccaggctactttccccagtactgaggtggtggacatcgtc-
tctgccactcctgacc _at
cagccctgaacaaagcacctcaagtgcaaggaccaaagggggccctggcttggagtgggttggcttgct-
gatggctgc
tggaggggacgctggctaaagtgggtaggccttggcccacctgaggccccaggtgggaacatggtcaccccc-
actct
gcataccctcatcaaaaacactctcactatgctgctatggacgacctccagctctcagttacaagtgcaggc-
gactggag
gcaggactcctgggtccctgggaaagagggtactaggggcccggatccaggattctgggaggcttcagttac-
cgctgg
ccgagctgaagaactgggtatgaggctggggcggggctggaggtggcgccccctggtgggacaacaaagagg-
aca ccatttttccagagctgc 60 204404
agaccaagacataccggcagatcaggttaaatgagttattaaaggaacattcaagcacagcta-
atattattgtcatgagtct _at
cccagttgcacgaaaaggtgctgtgtctagtgctctctacatggcatggttagaagctctatctaagga-
cctaccaccaat
cctcctagttcgtgggaatcatcagagtgtccttaccactattcataaatgttctatacagtggacagccct-
ccagaatggt
acttcagtgcctagtgtagtaacctgaaatcttcaatgacacattaacatcacaatggcgaatggtgacttt-
tctttcacgatt
tcattaatttgaaagcacacaggaaagcttgctccattgataacgtgtatggagacttcggttttagtcaat-
tccatatc 61 204470
tatgattaactctacctgcacactgtcctattatattcattctttttgaaatgtcaaccccaa-
gttagttcaatctggattcatattt _at
aatttgaaggtagaatgttttcaaatgttctccagtcattatgttaatatttctgaggagcctgcaaca-
tgccagccactgtga
tagaggctggcggatccaagcaaatggccaatgagatcattgtgaaggcaggggaatgtatgtgcacatctg-
ttttgtaa
ctgtttagatgaatgtcagttgttatttattgaaatgatttcacagtgtgtggtcaacatttctcatgttga-
aactttaagaactaa
aatgttctaaatatcccttggacattttatgtctttcttgtaaggcatactgccttgtttaatggtagtttt-
acagtgtttctggctta gaaca 62 204475
gaagaactgtctattttctcagtcatttttaacctctagagtcactgatacacagaatataat-
cttatttatacctcagtttgcata _at
tttttttactatttagaatgtagccctttagtactgatataatttagttccacaaatggtgggtacaaa-
aagtcaagtttgtggctt
atggattcatataggccagagttgcaaagatcttttccagagtatgcaactctgacgttgatcccagagagc-
agcttcagt
gacaaacatatcctttcaagacagaaagagacaggagacatgagtctttgccggaggaaaagcagctcaaga-
acacat gtgcagtcactggtgtcaccctggataggcaagggataactcttctaacaca 63
204580
agatgatggaccctggttatcccaaactgattaccaagaacttccaaggaatcgggcctaaaa-
ttgatgcagtcttctattc _at
taaaaacaaatactactatttcttccaaggatctaaccaatttgaatatgacttcctactccaacgtat-
caccaaaacactgaa
aagcaatagctggtttggttgttagaaatggtgtaattaatggtttttgttagttcacttcagcttaataag-
tatttattgcatattt
gctatgtcctcagtgtaccactacttagagatatgtatcataaaaataaaatctgtaaaccataggtaatga-
ttatataaaata
cataatatttttcaattttgaaaactctaattgtccattcttgcttgactctactattaagtttgaaaatag-
ttaccttcaaagcaag
ataattctatttgaagcatgctctgtaagttgcttcctaacatccttggactgagaaattatacttacttct-
ggcataactaaa 64 204620
tgccgtgctcccaaaacattttaaatgaaagtattggcattcaaaaagacagcagacaaaatg-
aaagaaaatgagagca _s_at
gaaagtaagcatttccagcctatctaatttctttagttttctatttgcctccagtgcagtccatttc-
ctaatgtataccagcctact
gtactatttaaaatgctcaatttcagcaccgatggccatgtaaataagatgatttaatgttgattttaatcc-
tgtatataaaataa
aaagtcacaatgagtttgggcatatttaatgatgattatggagccttagaggtctttaatcattggttcggc-
tgcttttatgtag
tttaggctggaaatggtttcacttgctctttgactgtcagcaagactgaagatggcttttcctggacagcta-
gaaaacacaa
aatcttgtaggtcattgcacctatctcagccataggtgcagtttgcttctacatgatgctaaaggctgcgaa-
tgggatcctga tggaactaaggactccaatgtcgaactcttctttgctgc 65 204702
tgctctccagtgtacccatgatggaagtatcttgatagtacccaaagaactggtggcctcagg-
ccacaaaaaggaaacc _s_at
caaaagggaaagagaaagtgagaagaaactgaagatggactctattatgtgaagtagtaatgttcag-
aaactgattatttg
gatcagaaaccattgaaactgcttcaagaattgtatctttaagtactgctacttgaataactcagttaacgc-
tgttttgaagctt
acatggacaaatgtttaggacttcaagatcacacttgtgggcaatctgggggagccacaacttttcatgaag-
tgcattgtat
acaaaattcatagttatgtccaaagaataggttaacatgaaaacccagtaagactttccatcttggcagcca-
tcctttttaag
agtaagttggttacttcaaaaagagcaaacactggggatcaaattattttaagaggtatttcagttttaaat-
gcaaaatagcc
ttattttcatttagtttgttagcactatagtgagcttttcaaacactattttaatc 66 204855
cttcgttcgcagagcttttcagattgtggaatgttggataaggaattatagacctctagtagc-
tgaaatgcaagaccccaag _at
aggaagttcagatcttaatataaattcactttcatttttgatagctgtcccatctggtcatgtggttgg-
cactagactggtggca
ggggcttctagctgactcgcacagggattctcacaatagccgatatcagaatttgtgttgaaggaacttgtc-
tcttcatctaa
tatgatagcgggaaaaggagaggaaactactgcctttagaaaatataagtaaagtgattaaagtgctcacgt-
taccttgac
acatagtttttcagtctatgggtttagttactttagatggcaagcatgtaacttatattaatagtaatttgt-
aaagttgggtggat
aagctatccctgttgccggttcatggattacactctataaaaaatatatatttaccaaaaaattttgtgaca-
ttcatctcccatc tcttccttgacatgcattgtaaataggttcttcttgttctgag 67 204885
tttccagaacatgaacgggtccgaatacttcgtgaagatccagtccttcctgggtggggcccc-
cacggaggatttgaag _s_at
gcgctcagtcagcagaatgtgagcatggacttggccacgttcatgaagctgcggacggatgcggtgc-
tgccgttgactg tggctgaggt 68 205174
gtctggcacaccatggatgacaatgaagaaaatttggatgaatcaaccattgacaatctaaac-
aaaatcctacaagtcttt _s_at
gtgttggaatatcttcatttgtaatactctgatttagtttaggataattggttctagaattgaattc-
aaaagtcaaggcatcattta
aaataatctgatttcagacaaatgctgtgtggaaacatctatcctatagatcatcctattcttatgtgtctt-
tggttatcagatca
attacagaataattgtgttgtgatattgtgtcctaaattgctcattaatttttatttacagattgaaaaaga-
ggcaccgtgtaaag
aaaatggcaaaataaatatctttccaaggatcatcatcacgatagctaaacagtacttaaatagcggttgga-
actaggtag
cctttcgaattttatgattttttcatatgtggaaatctattacatgtaatacaaaacaaacatgtagtttga-
aggcggtcagattt ctttgag 69 205361
aaggcggctgcagaagatgtcaatgttactttcgaagatcaacaaaagataaacaaatttgca-
cggaatacaagtagaat _s_at
cacagagctgaaggaagaaatagaagtaaaaaagaaacaactccaaaacctagaagatgcttgtgat-
gacatcatgctt
gcagatgatgattgcttaatgataccttatcaaattggtgatgtcttcattagccattctcaagaagaaacg-
caagaaatgtt
agaagaagcaaagaaaaatttgcaagaagaaattgacgccttagaatccagagtggaatcaattcagcgagt-
gttagca gatttgaaagttcagttgtatgcaaaattcgggagcaacataaaccttgaagctg 70
205366
cctcagcctgatcaggcttcctggtgagaactgaggagcggactcacttgatgtttcctggaa-
gcagagcaaaagttctc _s_at
ttgtccctgtcgcgtctcattttgtccatgtcccccgtgcacggttcaatggtagattcgctgtcct-
cagcgggggccttgaa
gactccctgatcccagacctggtcgtctctcccaccccctccccaaagccactggaaggagcacatactacc-
tagaagt
aagaagaggagcctcagaagaaaacaaagttctattttattaattttctatgtgttgtgtttgtagtcttgt-
cttagctctggac g 71 205470
gccaacatcaccatcattgagcaccagaagtgtgagaacgcctaccccggcaacatcacagac-
accatggtgtgtgcc _s_at
agcgtgcaggaagggggcaaggactcctgccagggtgactccgggggccctctggtctgtaaccagt-
ctcttcaagg
cattatctcctggggccaggatccgtgtgcgatcacccgaaagcctggtgtctacacgaaagtctgcaaata-
tgtggact
ggatccaggagacgatgaagaacaattagactggacccacccaccacagcccatcaccctccatttccactt-
ggtgtttg
gttcctgttcactctgttaataagaaaccctaagccaagaccctctacgaacattctttgggcctcctggac-
tacaggagat
gctgtcacttaataatcaacctggggttcgaaatcagtgagacctggattcaaattctgccttgaaatattg-
tgactctggga
atgacaacacctggtttgttctctgttgtatccccagccccaaagacagctcctggccatatatca
72 205476
ttcacacggcagctggccaatgaaggctgtgacatcaatgctatcatctttcacacaaagaaa-
aagttgtctgtgtgcgca _at
aatccaaaacagacttgggtgaaatatattgtgcgtctcctcagtaaaaaagtcaagaacatgtaaaaa-
ctgtggcttttct
ggaatggaattggacatagcccaagaacagaaagaaccttgctggggttggaggtttcacttgcacatcatg-
gagggttt
agtgcttatctaatttgtgcctcactggacttgtccaattaatgaagttgattcatattgcatcatagtttg-
ctttgtttaagcatc
acattaaagttaaactgtattttatgttatttatagctgtaggttttctgtgtttagctatttaatactaat-
tttccataagctattttgg
tttagtgcaaagtataaaattatatttgggggggaataagattatatggactttcttgcaagcaacaa
73 205479
cccgaccggtgggcatttgtgaggcccatggttgagaaatgaataatttcccaattaggaagt-
gtaagcagctgaggtct _s_at
cttgagggagcttagccaatgtgggagcagcggtttggggagcagagacactaacgacttcagggca-
gggctctgata
ttccatgaatgtatcaggaaatatatatgtgtgtgtatgtttgcacacttgttgtgtgggctgtgagtgtaa-
gtgtgagtaaga
gctggtgtctgattgttaagtctaaatatttccttaaactgtgtggactgtgatgccacacagagtggtctt-
tctggagaggtt
ataggtcactcctggggcctcttgggtcccccacgtgacagtgcctgggaatgtacttattctgcagcatga-
cctgtgacc
agcactgtctcagtttcactttcacatagatgtccctttcttggccagttatcccttccttttagcctagtt-
catccaatcctcact gggtgggg 74 205513
aacaaagactcttcttgcgtctctgcttcttggtaacttcaacatctccgctgatgagcctat-
aactgtgacacctcctgactc _at
acaatcatatatctccgtcaattactctgtgagaatcaatgaaacatatttcaccaatgtcactgtgct-
aaatggttctgtcttc
ctcagtgtgatggagaaagcccagaaaatgaatgatactatatttggtttcacaatggaggagcgctcatgg-
gggcccta
tatcacctgtattcagggcctatgtgccaacaataatgacagaacctactgggaacttctgagtggaggcga-
accactga
gccaaggagctggtagttacgttgtccgcaatggagaaaacttggaggttcgctggagcaaatactaataag-
cccaaac
tttcctcagctgcataaaatccatttgcagtggagttccatgtttattgtccttatgccttct 75
205713
caaacgtattggcaggcgaaccccttccgtgctgtggccgagcctggcatccaactcaaggct-
gtgaagtcttccacag _s_at
gccccggggaacagctgcggaacgctctgtggcatacaggagacacagagtcccaggtgcggctgct-
gtggaagga
cccgcgaaacgtgggttggaaggacaagaagtcctatcgttggttcctgcagcaccggccccaagtgggcta-
catcag
ggtgcgattctatgagggccctgagctggtggccgacagcaacgtggtcttggacacaaccatgcggggtgg-
ccgcct
gggggtcttctgcttctcccaggagaacatcatctgggccaacctgcgttaccgctgcaatgacaccatccc-
agaggact atgagacccatcagctgcggcaagcctagggacc 76 205765
caccacctacctatgatgccgtggtacagatggagtaccttgacatggtggtgaatgaaacac-
tcagattattcccagttg _at
ctattagacttgagaggacttgcaagaaagatgttgaaatcaatggggtattcattcccaaagggtcaa-
tggtggtgattcc
aacttatgctcttcaccatgacccaaagtactggacagagcctgaggagttccgccctgaaaggttcagtaa-
gaagaag
gacagcatagatccttacatatacacaccctttggaactggacccagaaactgcattggcatgaggtttgct-
ctcatgaac
atgaaacttgctctaatcagagtccttcagaacttctccttcaaaccttgtaaagaaacacagatccccttg-
aaattagacac
gcaaggacttcttcaaccagaaaaacccattgttctaaaggtggattcaagagatggaaccctaagtggaga-
atgagtta
ttctaaggacttctactttggtcttcaagaaagctgtgccccagaacaccagagatttcaacttagtca
77 205815
tgctatgccttgtttttgtcaccaaaatcctggacagatgcagatctggcctgccagaagcgg-
ccctctggaaacctggtg _at
tctgtgctcagtggggctgagggatccttcgtgtcctccctggtgaagagcattggtaacagctactca-
tacgtctggattg
ggctccatgaccccacacagggcaccgagcccaatggagaaggttgggagtggagtagcagtgatgtgatga-
attact
ttgcatgggagagaaatccctccaccatctcaagccccggccactgtgcgagcctgtcgagaagcacagcat-
ttctgag
gtggaaagattataactgtaatgtgaggttaccctatgtctgcaagttcactgactagtgcaggagggaagt-
cagcagcct
gtgtttggtgtgcaactcatcatgggcatgagaccagtgtgaggactcaccctggaagagaatattcgctta-
attccccca
acctgaccacctcattcttatctttcttctgtttcttcctccccgctgtcatttcagtctcttcattttgtc
78 205825
tttccattcccaatctagtgctagatgtataaatctttcttttgattcttcctaacaaaatat-
tttctgggttaaaaccccagccaa _at
ctcattgggttgtagccaaaggttcactctcaagaagctttaatatttaaataaaatcatattgaatgt-
ttccaacctggagtat
aatattcagatataaaacagttttgtcagtctttcttagtgcctgtgtggatttttgtgaaaatgtcaaaga-
gaaaacttatatac
tatttcccttgaaattttaaactatattttctttacaggtatttataatataccaatgcttttatcaaacag-
aattttaaagagcataa
taaattatattaaagaaccaaaagttttcctgagaataagaaagtttcacccaataaaatatttttgaaagg-
catgttcctctgt
caatgaaaaaaagtacatgtatgtgttgtgatattaaaagtgacatttgtctaatagcctaatacaacatgt-
agctgagtttaa catgtgtggtcttg 79 205828
gaaaatcgatgcagccatttctgataaggaaaagaacaaaacatatttctttgtagaggacaa-
atactggagatttgatga _at
gaagagaaattccatggagccaggctttcccaagcaaatagctgaagactttccagggattgactcaaa-
gattgatgctg
tttttgaagaatttgggttcttttatttctttactggatcttcacagttggagtttgacccaaatgcaaaga-
aagtgacacacact
ttgaagagtaacagctggcttaattgttgaaagagatatgtagaaggcacaatatgggcactttaaatgaag-
ctaataattc
ttcacctaagtctctgtgaattgaaatgttcgttttctcctgcctgtgctgtgactcgagtcacactcaagg-
gaacttgagcgt
gaatctgtatcttgccggtcatttttatgttattacagggcattcaaatgggctgctgcttagcttgcacct-
tgtcacatagagt gatctttcccaagagaaggggaagcactcgtgtgcaacagac 80 205886
cacccaggcggagggtgccttcgtggcctcactgattaaggagagtagcactgatgacagcaa-
tgtctggattggcctc _at
catgacccaaaaaagaaccgccgctggcactggagtagtgggtccctggtctcctacaagtcctgggac-
actggatcc
ccgagcagtgctaatgctggctactgtgcaagcctgacttcatgctcaggattcaagaaatggaaggatgaa-
tcttgtga
gaagaagttctcctttgtttgcaagttcaaaaactagaggaagctgaaaaatggatgtctagaactggtcct-
gcaattacta
tgaagtcaaaaattaaactagactatgtctccaactcagttcagaccatctcctccctaatgagtttgcatc-
gctgatcttcag taccttc 81 205890
gatcttaaagccacggagaagcctctcatcttatggcattgacaaagagaagaccatccacct-
taccctgaaagtggtga _s_at
agcccagtgatgaggagctgcccttgtttcttgtggagtcaggtgatgaggcaaagaggcacctcct-
ccaggtgcgaag
gtccagctcagtggcacaagtgaaagcaatgatcgagactaagacgggtataatccctgagacccagattgt-
gacttgc
aatggaaagagactggaagatgggaagatgatggcagattacggcatcagaaagggcaacttactcttcctg-
gcatctt
attgtattggagggtgaccaccctggggatggggtgttggcaggggtcaaaaagcttatttcttttaatctc-
ttactcaacg
aacacatcttctgatgatttcccaaaattaatgagaatgagatgagtagagtaagatttgggtgggatgggt-
aggatgaag tatattgcccaactctatgtttctttga 82 205910
gactccaaggaagctcagatgcctgcagtcattaggttttagcgtcccatgagccttggtatc-
aagaggccacaagagtg _s_at ggaccccaggggctc 83 205927
tccacacacggccaggcctgtttatctacactgctgcccactcctctctccagctccacatgc-
tgtacctggatcattctga _s_at
agcaaattccgagcattacatcattttgtccataaatatttctaacatccttaaatatacaatcgga-
attcaagcatctcccatt
gtcccacaaatgtttggctgtttttgtagttggattgtttgtattaggattcaagcaaggcccatatattgc-
atttatttgaaatgt
ctgtaagtctctttccatctacagagtttagcacatttgaacgttgctggttgaaatcccgaggtgtcattt-
gacatggttctct
gaacttatctttcctataaaatggtagttagatctggaggtctgattttgtggcaaaaatacttcctaggtg-
gtgctgggtactt
cttgttgcatcctgtcaggaggcagataatgctggtgcctctctattggtaatgttaagactgctgggtggg-
tttggagttctt ggc 84 205941
atactatttttcataccacgtgcatgtgaaagggactcatgtttgggtaggcctgtataagaa-
tggcacccctgtaatgtaca _s_at
cctatgatgaatacaccaaaggctacctggatcaggcttcagggagtgccatcatcgatctcacaga-
aaatgaccaggt
gtggctccagcttcccaatgccgagtcaaatggcctatactcctctgagtatgtccactcctctttctcagg-
attcctagtgg
ctccaatgtgagtacaccccacagagctaatctaaatcttgtgctagaaaaagcattctctaactctacccc-
accctacaaa
atgcatatggaggtaggctgaaaagaatgtaatttttattttctgaaatacagatttgagctatcagaccaa-
caaaccttccc cctgaaaagtgagcagcaacgtaaaaacgtatgtgaagcctctcttgaa 85
205983
gccgaccatctggatcacatcaaggaggtggcaggagccagagccgtgggttttggtggggac-
tttgatggtgttccaa _at
gggtccctgaggggctggaggacgtctccaagtatccagacctgatcgctgagctgctcaggaggaact-
ggacggag
gcggaggtcaagggcgcactggctgacaacctgctgagggtcttcgaggctgtggaacaggccagcaacctc-
acaca
ggctcccgaggaggagcccatcccgctggaccagctgggtggctcctgcaggacccattacggctactcctc-
tgggg
cttccagcctccatcgccactgggggctcctgctggcctccctcgctcccctggtcctctgtctgtctctcc-
tgtgaaacct
gggagaccagagtcccttttagggttcccggagctccgggaagacccgcccatcccaggactccagatgcca-
ggag
ccctgctgcccacatgcaaggaccagcatctcctgagaggacgcctgggcttacctggggggcaggatgcct-
gggga cagttcag 86 206224
ggaggataggataatcccgggtggcatctataacgcagacctcaatgatgagtgggtacagcg-
tgcccttcacttcgcc _at
atcagcgagtataacaaggccaccaaagatgactactacagacgtccgctgcgggtactaagagccagg-
caacagac
cgttgggggggtgaattacttcttcgacgtagaggtgggccgaaccatatgtaccaagtcccagcccaactt-
ggacacct
gtgccttccatgaacagccagaactgcagaagaaacagttgtgctctttcgagatctacgaagttccctggg-
agaacaga aggtccctggtgaaatccaggtgtcaagaatcctagggatctgtgccag 87
206239
gagacgtggtaagtgcggtgcagttttcaactgacctctggacgcagaacttcagccatgaag-
gtaacaggcatctttctt _s_at
ctcagtgccttggccctgttgagtctatctggtaacactggagctgactccctgggaagagaggcca-
aatgttacaatga
acttaatggatgcaccaagatatatgaccctgtctgtgggactgatggaaatacttatcccaatgaatgcgt-
gttatgttttg
aaggtcggaaacgccagacttctatcctcattcaaaaatctgggccttgctgagaaccaaggttttgaaatc-
ccatcaggt caccgc 88 206286
gtggaccttagaatacagttttgagtagagttgatcaaaatcaattaaaatagtctctttaaa-
aggaaagaaaacatctttaa _s_at
ggggaggaaccagagtgctgaaggaatggaagtccatctgcgtgtgtgcagggagactgggtaggaa-
agaggaagc
aaatagaagagagaggttgaaaaacaaaatgggttacttgattggtgattaggtggtggtagagaagcaagt-
aaaaagg
ctaaatggaagggcaagtttccatcatctatagaaagctatataagacaagaactcccttttttttcccaaa-
ggcattataaa
aagaatgaagcctccttagaaaaaaaattatacctcaatgtccccaacaagattgcttaataaattgtgttt-
cctccaagcta
ttcaattcttttaactgttgtagaagacaaaatgttcacaatatatttagttgtaaaccaagtgatcaaact-
acatattgtaaagc ccattttt 89 206976
aagtctgtagtctttatgatcctaaaagggaaaattgccttggtaactttcagattcctgtgg-
aattgtgaattcatactaagct _s_at
ttctgtgcagtctcaccatttgcatcactgaggatgaaactgacttttgtcttttggagaaaaaaaa-
ctgtactgttgttcaag
agggctgtgattaaaatctttaagcatttgttcctgccaaggtagttttcttgcattttgctctccattcag-
catgtgtgtgggtg
tggatgtttataaacaagactaagtctgacttcataagggctttctaaaaccatttctgtccaagagaaaat-
gactttttgcttt
gatattaaaaattcaatgagtaaaacaaaagctagtcaaatgtgttagcagcatgcagaacaaaaactttaa-
actttctctct
cactatacagtatattgtcaatgtgaaagtgtggaatggaagaaatgtcgatcctgttgtaactga
90 207158
gcaccctggtgtgactctagtgatctacgtagctcggcttttttggcacatggatcaacaaaa-
tcggcaaggtctcaggga _at
ccttgttaacagtggagtaactattcagattatgagagcatcagagtattatcactgctggaggaattt-
tgtcaactacccac
ctggggatgaagctcactggccacaatacccacctctgtggatgatgttgtacgcactggagctgcactgca-
taattctaa
gtcttccaccctgtttaaagatttcaagaagatggcaaaatcatcttacatttttcagacttcatcttcaaa-
actgccattacca
aacgattccgccacacatcatttagctacagggctgatacatccttctgtggcttggagatgaataggatga-
ttccgtgtgt
gtactgattcaagaacaagcaatgatgacccactaaagagtgaatgccatttagaatctagaaatgttcaca-
aggtacccc aaaactctgtagct 91 207173
gaacatccaagtctttcttcttttttaagttgtcaaagaagcttccacaaaattagaaaggac-
aacagttctgagctgtaatttc _x_at
gccttaaactctggacactctatatgtagtgcatttttaaacttgaaatatataatattcagccagc-
ttaaacccatacaatgta
tgtacaatacaatgtacaattatgtctcttgagcatcaatcttgttactgctgattcttgtaaatctttttg-
cttctactttcatctta
aactaatacgtgccagatataactgtcttgtttcagtgagagacgccctatttctatgtcatttttaatgta-
tctatttgtacaattt
taaagttcttattttagtatacatataaatatcagtattctgacatgtaagaaaatgttacggcatcacact-
tatatttta 92 207457
aaccgaatgcggtgctacaactgtggtggaagccccagcagttcttgcaaagaggccgtgacc-
acctgtggcgaggg _s_at
cagaccccagccaggcctggaacagatcaagctacctggaaaccccccagtgaccttgattcaccaa-
catccagcctg
cgtcgcagcccatcattgcaatcaagtggagacagagtcggtgggagacgtgacttatccagcccacaggga-
ctgcta
cctgggagacctgtgcaacagcgccgtggcaagccatgtggcccctgcaggcattttggctgcagcagctac-
cgccct
gacctgtctcttgccaggactgtggagcggatagggggagtaggagtagagaagggaacaagggagcaaggg-
aac aagggacatctgaacatct 93 207850
agaacagcagctttctagggacagctggaaagggacttaatgtgtttgactatttcttacgag-
ggttctacttatttatgtattt _at
atttttgaaagcttgtattttaatattttacatgctgttatttaaagatgtgagtgtgtttcatcaaac-
atagctcagtcctgattatt
taattggaatatgatgggttttaaatgtgtcattaaactaatatttagtgggagaccataatgtgtcagcca-
ccttgataaatg
acagggtggggaactggagggtngggggattgaaatgcaagcaattagtggatcactgttagggtaagggaa-
tgtatg
tacacatctattttttatacttttttttttaaaaaagaatgtcagttgttatttattcaaattatctcacat-
tatgtgttcaacatttttat
gctgaagtttcccttagacattttatgtcttgcttgtagggcataatgccttgtttaatgtccattctgcag-
cgttt 94 208079
ccctcaatctagaacgctacacaagaaatattttgtttttactcagcaggtgtgccttaacct-
ccctattcagaaagctccac _sat
atcaataaacatgacactctgaagtgaaagtagccacgagaattgtgctacttatactggaacataat-
ctggaggcaaggt
tcgactgcagtcgaaccttgcctccagattatgaaccagtataagtagcacaattctcgtggctactttcac-
ttcagagtgtc
atgtttattgatgtggagctttctgaatagggaggttaaggcacacctgctgagtaaaacaaatatttcttg-
tgtagcgttctt
aggaatctggtgtctgtccggccccggtaggcctgttgggtttctagtcctccttaccatcatctccatatg-
agagtgtgaa
aataggaacacgtgctctacctccatttagggatttgcttgggatacagaagaggccatgtgtctcagagct-
gttaagggc ttatttttttaaaacattggagtcatagcatgtgtgtaa 95 208712
gttttgggtatgtttaatctgttatgtactagtgttctgtttgttattgttttgttaattaca-
ccataatgctaatttaaagagactcc _at
aaatctcaatgaagccagctcacagtgctgtgtgccccggtcatctagcaagctgccgaaccaaaagaa-
tttgcacccc
gctgcgggcccacgtggttggggccctgccctggcagggtcatcctgtgctcggaggccatctcgggcacag-
gccca
ccccgccccacccctccagaacacggctcacgcttacctcaaccatcctggctgcggcgtctgtctgaacca-
cgcggg
ggccttgagggacgcttgtctgtcgtgatggggcaagggcacaagtcctggatgttgtgtgtatcgagaggc-
caaagg
ctggtggcaagtgcacggggcacagcggagtctgtcctgtgacgcgcaagtctgagggtctgggcggcg
96 209218
gattccctgcatcaactaagaaaagcctgttttctttatttcaaacttggtggcgaatgtgtt-
gcgggtcctgttgggctgcttt _at
ctgtattgtctcctaaccctctagttttaattggacacttctttgctgttgcaatctatgccgtgtatt-
tttgctttaagtcagaacc
ttggattacaaaacctcgagcccttctcagtagtggtgctgtattgtacaaagcgtgttctgtaatatttcc-
tctaatttactca
gaaatgaagtatatggttcattaagcttaaaggggaaccatttgtgaatgaatatttggaacttaccaagtc-
ctaagagactt ttggaagaggatatatatagcatagtaccataccacttata 97 209309
tgcggaaatacctgaaatacagcaaaaatatcctggaccggcaagatcctccctctgtggtgg-
tcaccagccaccaggc _at
cccaggagaaaagaagaaactgaagtgcctggcctacgacttctacccagggaaaattgatgtgcactg-
gactcgggc
cggcgaggtgcaggagcctgagttacggggagatgttcttcacaatggaaatggcacttaccagtcctgggt-
ggtggtg
gcagtgcccccgcaggacacagccccctactcctgccacgtgcagcacagcagcctggcccagcccctcgtg-
gtgcc
ctgggaggccagctaggaagcaagggttggaggcaatgtgggatctcagacccagtagctgcccttcctgcc-
tgatgt
gggagctgaaccacagaaatcacagtcaatggatccacaaggcctgaggagcagtgtggggggacagacagg-
aggt
ggatttggagaccgaagactgggatgcctgtcttgagtagacttggacccaaaaaatcatctcaccttgagc-
cca 98 209369
gaagacttactgttggccatagttaattgtgtgaggaacacgccggcctttttagccgaaaga-
ctgcatcgagccttgaag _at
ggtattggaactgatgagtttactctgaaccgaataatggtgtccagatcagaaattgaccctttggac-
attcgaacagagtt
caagaagcattatggctattccctatattcagcaattaaatcggatacttctggagactatgaaatcacact-
cttaaaaatctg
tggtggagatgactgaaccaagaagataatctccaaaggtccacgatgggcttttccaacagctccacctta-
cttcttctca tactatttaagagaacaagcaaatataaacagcaacttgtgttcctaacagg 99
209752
agagattcattgcagctcagcatggctcagaccagctcatacttcatgctgatctcctgcctg-
atgtttctgtctcagagcca _at
aggccaagaggcccagacagagttgccccaggcccggatcagctgcccagaaggcaccaatgcctatcg-
ctcctact
gctactactttaatgaagaccgcgagacctgggttgatgcagatctctattgccagaacatgaattcgggca-
acctggtgt
ctgtgctcacccaggccgagggtgcctttgtggcctcactgattaaggagagtggcactgatgacttcaatg-
tctggattg
gcctccatgaccccaaaaagaaccgccgctggcactggagcagtgggtccctggtctcctacaagtcctggg-
gcattg
gagccccaagcagtgttaatcctggctactgtgtgagcctgacctcaagcacaggattccagaaatggaagg-
atgtgcc ttgtgaagacaagttctcct 100 209773
ttttaccttggatgctgacttctaaatgaactgaagatgtgcccttacttggctgattttttt-
tttccatctcataagaaaaatcag _s_at
ctgaagtgttaccaactagccacaccatgaattgtccgtaatgttcattaacagcatctttaaaact-
gtgtagctacctcaca
accagtcctgtctgtttatagtgctggtagtatcaccctttgccagaaggcctggctggctgtgacttacca-
tagcagtgac
aatggcagtcttggctttaaagtgaggggtgaccctttagtgagcttagcacagcgggattaaacagtcctt-
taaccagca cagccagttaaaagatgcagcctcactgcttcaacgcagatt 101 209774
agagagacacagctgcagaggccacctggattgcgcctaatgtgtttgagcatcacttaggag-
aagtcttctatttatttatt _x_at
tatttatttatttatttgtttgttttagaagattctatgttaatattttatgtgtaaaataaggtta-
tgattgaatctacttgcacactct
cccattatatttattgtttattttaggtcaaacccaagttagttcaatcctgattcatatttaatttgaaga-
tagaaggtttgcagat
attctctagtcatttgttaatatttcttcgtgatgacatatcacatgtcagccactgtgatagaggctgagg-
aatccaagaaaa
tggccagtaagatcaatgtgacggcagggaaatgtatgtgtgtctattttgtaactgtaaagatgaatgtca-
gttgttatttatt
gaaatgatttcacagtgtgtggtcaacatttctcatgttgaagctttaagaactaaaatgttctaaatatcc-
cttggacattttat
gtctttcttgtaagatactgccttgtttaatgttaattatgcagtgtttccctc 102 209792
tcctctcgtggggtgtttacccctgtggctctgcccagcatccagctgtctacacccagatct-
gcaaatacatgtcctggat _s_at
caataaagtcatacgctccaactgatccagatgctacgctccagctgatccagatgttatgctcctg-
ctgatccagatgcc
cagaggctccatcgtccatcctcttcctccccagtcggctgaactctccccttgtctgcactgttcaaacct-
ctgccgccct
ccacacctctaaacatctcccctctcacctcattcccccacctatccccattctctgcctgtactgaagctg-
aaatgcagga
agtggtggcaaaggtttattccagagaagccaggaagccggtcatcacccagcctctgagagcagttactgg-
ggtcac
ccaacctgacttcctctgccactccccgctgtgtgactttgggcaagccaagtgccctctctgaacctcagt-
ttcctcatct gcaaaatgggaacaatgacgtgcctacctcttagacatgttgtg 103 209875
gaatggtgcatacaaggccatccccgttgcccaggacctgaacgcgccttctgattgggacag-
ccgtgggaaggaca _s_at
gttatgaaacgagtcagctggatgaccagagtgctgaaacccacagccacaagcagtccagattata-
taagcggaaag
ctaatgatgagagcaatgagcattccgatgtgattgatagtcaggaactttccaaagtcagccgtgaattcc-
acagccatg
aatttcacagccatgaagatatgctggttgtagaccccaaaagtaaggaagaagataaacacctgaaatttc-
gtatttctca
tgaattagatagtgcatcttctgaggtcaattaaaaggagaaaaaatacaatttctcactttgcatttagtc-
aaaagaaaaaa
tgctttatagcaaaatgaaagagaacatgaaatgcttctttctcagtttattggttgaatgtgtatctattt-
gagtctggaaataa ctgatgtgtttgataattagtttagtttgtggcttcatggaa 104
209955
acagctttccaaggtgacaaactcctctatgcagtgtatcgaaagctgggtgtttatgaagtt-
gaagaccagattacagct _s_at
gtcagaaaattcatagaaatgggtttcattgatgaaaaaagaatagccatatggggctggtcctatg-
gaggatacgtttcat
cactggcccttgcatctggaactggtcttttcaaatgtggtatagcagtggctccagtctccagctgggaat-
attacgcgtc
tgtctacacagagagattcatgggtctcccaacaaaggatgataatcttgagcactataagaattcaactgt-
gatggcaag
agcagaatatttcagaaatgtagactatcttctcatccacggaacagcagatgataatgtgcactttcagaa-
ctcagcaca
gattgctaaagctctggttaatgcacaagtggatttccaggcaatgtggtactctgaccagaaccacggctt-
atccggcct gtccacgaaccacttatacacccacatgacccacttcctaaagcagtg 105
210052
agtcaagtgaccagcctctgactgtgcctgtatctcccaaattctccactcgattccactgct-
aaactcagctgtgagctgc _s_at
ggataccgcccggcaatgggacctgctcttaacctcaaacctaggaccgtcttgctttgtcattggg-
catggagagaacc
catttctccagacttttacctacccgtgcctgagaaagcatacttgacaactgtggactccagttttgttga-
gaattgttttctt
acattactaaggctaataatgagatgtaactcatgaatgtctcgattagactccatgtagttacttccttta-
aaccatcagccg
gccttttatatgggtcttcactctgactagaatttagtctctgtgtcagcacagtgtaatctctattgctat-
tgcccc 106 210445
gctttcaccggcaagttcgagatggagagtgagaagaattatgatgagttcatgaagctcctt-
gggatctccagcgatgta _at
atcgaaaaggcccgcaacttcaagatcgtcacggaggtgcagcaggatgggcaggacttcacttggtcc-
cagcactac
tccgggggccacaccatgaccaacaagttcactgttggcaaggaaagcaacatacagacaatggggggcaag-
acgtt
caaggccactgtgcagatggagggcgggaagctggtggtgaattccccaactatcaccagacctcagagatc-
gtggg tgacaagctggtggaggtctccaccatcggaggcgtgacctatgagcgcgtgagca 107
210511
aaaggagcagtcgcacagacctttcctcatgctgcaggcccggcagtctgaagaccaccctca-
tcgccggcgtcggc _s_at
ggggcttggagtgtgatggcaaggtcaacatctgctgtaagaaacagttctttgtcagtttcaagga-
catcggctggaatg
actggatcattgctccctctggctatcatgccaactactgcgagggtgagtgcccgagccatatagcaggca-
cgtccgg
gtcctcactgtccttccactcaacagtcatcaaccactaccgcatgcggggccatagcccctttgccaacct-
caaatcgtg
ctgtgtgcccaccaagctgagacccatgtccatgttgtactatgatgatggtcaaaacatcatcaaaaagga-
cattcagaa catgatcgtggaggagtgtgggtgctcatagagttgcccagc 108 210519
cagaccttgtgatattccagttccccctgcagtggtttggagtccctgccattctgaaaggct-
ggtttgagccttcatagga _s_at
gagtttgcttacacttacgctgccatgtatgacaaaggacccttccggagtggcattctgcatttct-
gtggcttccaagtctt
agaacctcaactgacatatagcattgggcacactccagcagacgcccgaattcaaatcctggaaggatggaa-
gaaacg
cctggagaatatttgggatgagacaccactgtattttgctccaagcagcctctttgacctaaacttccaggc-
aggattcttaa
tgaaaaaagaggtacaggatgaggagaaaaacaagaaatttggcctttctgtgggccatcacttgggcaagt-
ccatccc aactgac 109 210559
gtaacactctggtacagatctccagaagtattgctggggtcagctcgttactcaactccagtt-
gacatttggagtataggca _s_at
ccatatttgctgaactagcaactaagaaaccacttttccatggggattcagaaattgatcaactctt-
caggattttcagagctt
tgggcactcccaataatgaagtgtggccagaagtggaatctttacaggactataagaatacatttcccaaat-
ggaaacca
ggaagcctagcatcccatgtcaaaaacttggatgaaaatggcttggatttgctctcgaaaatgttaatctat-
gatccagcca aacgaatttctggcaaaatggcactgaatcatccatattttaat 110 210766
ggttccatcaatggtgagcaccagcctgaatgcagaagcgctccagtatctccaagggtacct-
tcaggcagccagtgtg _s_at
acactgctttaaactgcatttttctnaatgggctaaacccagatggtttcctaggaaatcacaggct-
tctgagcacagctgc att 111 211429
tactggaacctatgatctgaagagcgtcctgggtcaactgggcatcactaaggtcttcagcaa-
tggggctgacctctccg _s_at
gggtcacagaggaggcacccctgaagctctccaaggccgtgcataaggctgtgctgaccatcgacga-
gaaagggact gaagctgctggggccatgtttttagaggcc
atacccatgtctatcccccccgaggtcaagttcaacaaaccctttgtcttctt
aatgattgaacaaaataccaagtctcccctcttcatgggaaaagtggtgaatcccacccaaaaataactgcc-
tctcgctcc tcaacccctcccctccatccctggccccctccctggatgacattaaaga 112
211506
gtgtgaaggtgcagttttgccaaggagtgctaaagaacttagatgtcagtgcataaagacata-
ctccaaacctttccaccc _s_at
caaatttatcaaagaactgagagtgattgagagtggaccacactgcgccaacacagaaattattgta-
aagctttctgatgg
aagagagctctgtctggaccccaaggaaaactgggtgcagagggttgtggagaa 113 212063
attgtaaatcttttgtgtctcctgaagacttcccttaaaattagctctgagtgaaaaatcaaa-
agagacaaaagacatcttcg _at
aatccatatttcaagcctggtagaattggcttttctagcagaacctttccaaaagttttatattgagat-
tcataacaacaccaa
gaattgattttgtagccaacattcattcaatactgttatatcagaggagtaggagagaggaaacatttgact-
tatctggaaaa
gcaaaatgtacttaagaataagaataacatggtccattcacctttatgttatagatatgtctttgtgtaaat-
catttgttttgagtt
ttcaaagaatagcccattgttcattcttgtgctgtacaatgaccactgttattgttactttgacttttcaga-
gcacaccc 114 212070
tccaaggactgagactgacctcctctggtgacactggcctagngcctgacactctcctaagag-
gttctctccaagccccc _at
aaatagctccaggcgccctcggccgcccatcatggttaattctgtccaacaaacacacacgggtagatt-
gctggcctgtt
gtaggtggtagggacacagatgaccgacctggtcactcctcctgccaacattcagtctggtatgtgaggcgt-
gcgtgaa
gcaagaactcctggagctacagggacagggagccatcattcctgcctgggaatcctggaagacttcctgcag-
gagtca gcgttcaatcttgaccttgaagatgggaaggatgttctttttacgtaccaattct 115
212190
cgatgcaagtgtttctgttctgggaggtattggagggaaaaaancaagcaggatggctggaac-
actgtactgaggaatg _at
aatagaaaggcttccagatgtctaaaagattctttaaactactgaactgttacctaggttaacaaccct-
gttgagtatttgctg
tttgtccagttcaggaatttttgttttgttttgtctatatgtgcggcttttcagaagaaatttaatcagtgt-
gacagaaaaaaaaat
gttttatggtagcttttactttttatgaaaaaaaaattatttgccttttaaattcttttcccccatccccct-
ccaaagtcttgatagc
aagcgttattttgggggtagaaacggtgaaatctctagcctctttgtgtttttgttgttgttgttgttgttg-
ttttatataatgcatgt
attcactaaaataaaatttaaaaaactcctgtcttgctagacaaggttgctgttgtgcagtgtgcctgtcac-
tactggtctgta ctccttggatttgc 116 212281
tacagccaggcataacatatccactgtgtgcatagagggtctcttcacgttgatgcttggcat-
tccatcagctttctctaagt _s_at ctttgctcaagttcaaccttaaaatgatgttag 117
212344
ggaaaacacctcatttgaccttgccagctgaccttcaaaccctgcatttgaaccgaccaacat-
taagtccagagagtaaa _at
cttgaatggaataacgacattccagaagttaatcatttgaattctgaacactggagaaaaaccgaaaaa-
tggacggggca
tgaagagactaatcatctggnaaaccgatttcagtggcgatggcatgacagagctagagctcgggcccagcc-
ccaggc
tgcagcccattcgcaggcacccgaaagaacttccccagtatggtggtcctggaaaggacatttttgaagatc-
aactatatc
ttcctgtgcattccgatggaatttcagttcatcagatgttcaccatggccaccgcagaacaccgaagtaatt-
ccagcatagc
ggggaagatgttgaccaaggtggagaagaatcacgaaaaggagaagtcacagcacctagaaggcagcgcctc-
ctctt cactctcctctgattagatgaaactgttaccttacccta 118 212353
aatatccttgttgtgtattaggtttttaaataccagctaaaggattacctcactgagtcatca-
gtaccctcctattcagctcccc _at
aagatgatgtgtttttgcttaccctaagagaggttttcttcttatttttagataattcaagtgcttaga-
taaattatgttttctttaagt
gtttatggtaaactcttttaaagaaaatttaatatgttatagctgaatctttttggtaactttaaatcttta-
tcatagactctgtacat
atgttcaaattagctgcttgcctgatgtgtgtatcatcggtgggatgacagaacaaacatatttatgatcat-
gaataatgtgct ttgtaaaaagatttcaagttattaggaagcatactctgttttttaatca 119
212354
gtgtgcacacggagactcatcgttataatttactatctgccaagagtagaaagaaaggctggg-
gatatttgggttggcttg _at
gttttgattttttgcttgtttgtttgttttgtactaaaacagtattatcttttgaatatcgtagggaca-
taagtatatacatgttatcca
atcaagatggctagaatggtgcctttctgagtgtctaaaacttgacacccctggtaaatctttcaacacact-
tccactgcctg
cgtaatgaagttttgattcatttttaaccactggaatttttcaatgccgtcattttcagttagatgattttg-
cactttgagattaaaa
tgccatgtctatttgattagtcttatttttttatttttacaggcttatcagtctcactgttggctgtcattg-
tgacaaagtcaaataaa
cccccaaggacgacacacagtatggatcacatattgtttgacattaagcttttgccagaaaatgttgcatgt-
gttttacctcg actt 120 212531
caagagctacaatgtcacctccgtcctgtttaggaaaaagaagtgtgactactggatcaggac-
ttttgttccaggttgcca _at
gcccggcgagttcacgctgggcaacattaagagttaccctggattaacgagttacctcgtccgagtggt-
gagcaccaac
tacaaccagcatgctatggtgttcttcaagaaagtttctcaaaacagggagtacttcaagatcaccctctac-
gggagaacc
aaggagctgacttcggaactaaaggagaacttcatccgcttctccaaatctctgggcctccctgaaaaccac-
atcgtcttc
cctgtcccaatcgaccagtgtatcgacggctgagtgcacaggtgccgccagntgccgcaccagcccgaacac-
cattga ggga 121 212942
ccttcttgtccacggttttgttgagttttcactcttctaatgcaagggtctcacactgtgaac-
cacttaggatgtgatcactttca _s_at
ggtggccaggaatgttgaatgtctttggctcagttcatttaaaaaagatatctatttgaaagttctc-
agagttgtacatatgttt
cacagtacaggatctgtacataaaagtttctttcctaaaccattcaccaagagccaatatctaggcattttc-
ttggtagcaca
aattttcttattgcttagaaaattgtcctccttgttatttctgtttgtaagacttaagtgagttaggtcttt-
aaggaaagcaacgct
cctctgaaatgcttgtcttttttctgagccgaaatagctggtcctttttcgggagttagatgtatagagtgt-
ttgtatgtaaacat ttcttgtaggcatcaccatg 122 213880
caatatctgacaccactttggactcaagagactcagtaacgtattatcctgtttatttagctt-
ggttttagctgtgttctctctgg _at
ataacccacttgatgttaggaacattacttctctgcttattccatattaatactgtgttaggtatttta-
agaagcaagttattaaat
aagaaaagtcaaagtattaattcttaccttctattatcctatattagcttcaatacatccaaaccaaatggc-
tgttaggtagattt
atttttatataagcatgtttattttgatcagatgttttaacttggatttgaaaaaatacatttatgagatgt-
tttataagatgtgtaaa
tatagaactgtatttattactatagtaaaggttcagtaacattaaggaccatgataatgataataaaccttg-
tacagtggcata ttctttgatttatattgtgtttctctgcccatt 123 213905
cacaaaaccccagggacagcggtctccccagcctgccctgctcangccttgcccccaaacctg-
tactgtcccggagga _x_at
ggttgggaggtggaggcccagcatcccgcgcagatgacaccggttttcctagaagcccctcaccccc-
actggcccact
ggtggctaggtctccccttatccttctggtccagcgcaaggaggggctgcttctgaggtcggtggctgtctt-
tccattaaa gaaacaccgtg 124 213975
gaaataacccagacttaatcagaatgatncgattatgcccaatattaagtananaatataaga-
aaaggttatcttaaataga _s_at
tcaaggcaaaataccagctgatgaaggcatctgatgccttcatctgttcagtcatctccaaaaacag-
taaaaataaccact
ttttgttgggcaatatgaaatttttaaaggagtagaataccaaatgatagaaacagactgcctgaattgaga-
attttgatttntt
aaagtgtgtttctttctaaattgctgttccttaatttgattaatttaattcatgtattatgattaaatctga-
ggcagatgagcttaca
agtattgaaataattactaattaatcacaaatgtgaagttatgcatgatgtaaaaaatacaaacattctaat-
taaaggctt 125 214022
tcaacaccctcttcttgaactggtgctgtctgggcttcatagcattcgcctactccgtgaagt-
ctagggacaggaagatggt _s_at
tggcgacgtgaccggggcccaggcctatgcctccaccgccaagtgcctgaacatctgggccctgatt-
ctgggcatcct
catgaccattggattcatcctgttactggtattcggctctgtgacagtctaccatattatgttacagataat-
acaggaaaaac
ggggttactagtagccgcccatagcctgcaacctttgcactccactgtgcaatgctggccctgcacngctng-
ggctgttg
cccctgcccccttggtcctgcccctagatacagcagtttatacccacacacctgtctacagtgtcattcaat-
a 126 214235
ggtgaggggatgacccctggagatgaagggaagaggtgaagccttagcaaaaatgcctcctca-
ccactccccaggag _at
aatttttataaaaagcataatcactgattccttcactgacataatgtaggaagcctctgaggagaaaaa-
caaagggagaaa
catagagaacggttgctactggcagaagcataagatctttgtacaatattgctggccctggttcacctgttt-
actgttatcac aata 127 214651
gtgattcaaacttctgtgtactgggtgatgcacccattgtgattgtggaagatagaattcaat-
ttgaactcaggttgtttatga _s_at
ggggaaaaaaacagttgcatagagtatagctctgtagtggaatatgtcttctgtataactaggctgt-
taacctatgattgtaa
agtagctgtaagaatttcccagtgaaataaaaaaaaattttaagtgttctcggggatgcatagattcatcat-
tttctccacctt
aaaaatgcgggcatttaagtctgtccattatctatatagtcctgtcttgtctattgtatatataatctatat-
gattaaagaaaatat
gcataatcagacaagcgtaatgcataatcagacaagcttgaatattgtttttgcaccagacgaacagtgagg-
aaattcgga gctatacatatgtgcag 128 214974
agtcagtgttgtcttaatatccttgataatgctgtaaagtttatttttacaaatatttctgtt-
taagctatttcacctttgtttggaaat _x_at
ccttcccttttaaagagaaaatgtgacacttgtgaaaaggcttgtaggaaagctcctcccttttttt-
nctttaaacctttaaatg
acaaacctaggtaattaatggttgtgaatttctatttttgctttgtttttaatgaacatttgtctttcagaa-
taggattctgtgataat
atttaaatggcaaaaacaaaacataattttgtgcaattaacaaagctactgcaagaaaaataaaacatttct-
tggtaaaaac
gtatgtatttatatattatatatttatatataatatatattatatatttagcattgctgagctttttagatg-
cctattgtgtatcttttaaa
ggttttgaccattttgttatgagtaattacatatatattacattcactatattaaaattgtacttttttact-
atgtgnctcattggttca tagtctttattttgtcctttgaa 129 215091
tatgtcgctgtccaagagaaggctgtggaagaacctatacaactgtgtttaatctccaaagcc-
atatcctctccttccatga _s_at
ggaaagccgcccttttgtgtgtgaacatgctggctgtggcaaaacatttgcaatgaaacaaagtctc-
actaggcatgctgt
tgtacatgatcctgacaagaagaaaatgaagctcaaagtcaaaaaatctcgtgaaaaacggagntnggcctc-
tcatctca
gtggatatatccctcccaaaaggaaacaagggcaaggcttatcnttgtgtcaaaacggagagtcacccaact-
gtgtgga agacaagatgctctcnacagttgcagtacttacccttggctaagaact 130 217430
agggcctaagggtgacagaggtgatgctggtcccaaaggtgctgatggctctcctggcaaaga-
tggcgtccgtggtct _x_at
gaccggccccattggtcctcctggccctgctggtgcccctggtgacaagggggaccccattcccgag-
gagctttatgag 131 217523
gagttattattatctcatagcgtatgttttcttgnacagccttgaataattttgattgacctc-
tgggatgttattaaagcctaacgt _at
tccttctattctcacaaattttcgttatgacttcagaaggatcattaactctggtatctgtttgtttgc-
ttgtatggcaccaataag
cagatttcttctttctaatctatggattagtatagaccaggagaaggctaatacagagactatgaaacggga-
ataagttttttt
aacgatatggcaaaattgtgactctgaaagatcattcatgtatattctaaaattaccacagtcataaaaagt-
cttggactttca
tgaggaaatagcatagctagatatgaaaaaatatagaaaatcttcatcaatggaactattcttggggtagac-
actaatcata tgaaaagacaaatgctcattccctaagatagcctga 132 217867
gcttctacgtcatcttcgacagagcccagaagagggtgggcttcgcagcgagcccctgtgcag-
aaattgcaggtgctgc _x_at
agtgtctgaaatttccgggcctttctcaacagaggatgtagccagcaactgtgtccccgctcagtct-
ttgagcgagcccat
tttgtggattgtgtcctatgcgctcatgagcgtctgtggagccatcctccttgtcttaatcgtcctgctgct-
gctgccgttccg
gtgtcagcgtcgcccccgtgaccctgaggtcgtcaatgatgagtcctctctggtcagacatcgctggaaatg-
aatagcca
ggcctgacctcaagcaaccatgaactcagctattaagaaaatcacatttccagggcagcagccgggatcgat-
ggtggc
gctttctcctgtgcccacccgtcttcaatctctgttctgctcccagatgccttctagattcactgtctt
133 217996
gaagtgggacgagcacatttctattgtcttcacttggatcaaaagcaaaacagtctctccgcc-
ccgcaccagatcaagta _at
gtttggacatcaccctactgaaaacttgcgattcttcttagttttctgcatacttttcatcacgatgca-
ggaaacgatttcgagt
caagaagacttttatttatgaacctttgaaaggatcgtcttgtatggtgaattttctaggagcgatgatgta-
ctgtaattttatttt
aatgtattttgatttatgattatttattagttttttttaaatgcttgttctaagacatttctgaatgtagac-
cattttccaaaaaggaaa
ctttattttcaaaaacctaatccgtagtaattcctaatcttggagaataaaaaagggcggtggaggggaaaa-
cattaagaat
ttattcattatttctcgagtactttcagaaagtctgacactttcattgttgtgccagctggtt 134
218086
ggcacagagcgcggagatgtaccactaccagcaccaacggcaacagatgctgtgcctggagcg-
gcataaagagcca _at
cccaaggagctggacacggcctcctcggatgaggagaatgaggacggagacttcacggtgtacgagtgc-
ccgggcc
tggccccgaccggggaaatggaggtgcgcaaccctctgttcgaccacgccgcactgtccgcgcccctgccgg-
ccccc
agctcaccgcctgcactgccatgacctggaggcagacagacgcccacctgctccccgacctcgaggcccccg-
ggga
ggggcagggcctggagcttcccactaaaaacatgttttgatgctgtgtgcttttggctgggcctcgggctcc-
aggccctg
ggaccccttgccagggagacccccgaacctttgtgccaggacacctcctggtcccctgcacctctcctgttc-
ggtttaga cccccaaactggagggggcatggagaaccgtagagcgcaggaacgggtgggtaatt
135 218211
gccacaccttcgcgaaacctgtggtggcccaccagtcctaacgggacaggacagagagacaga-
gcagccctgcact _s_at
gttttccctccaccacagccatcctgtccctcattggctctgtgctttccactatacacagtcaccg-
tcccaatgagaaacaa
gaaggagcaccctccacatggactcccacctgcaagtggacagcgacattcagtcctgcactgctcacctgg-
gtttact
gatgactcctggctgccccaccatcctctctgatctgtgagaaacagctaagctgctgtgacttccctttag-
gacaatgttg
tgtaaatctttgaaggacacaccgaagacctttatactgtgatcttttacccctttcactcttggctttctt-
atgttgc 136 218507
tggtgtatgctgtgctttcctcagcagtatggctctgacatctcttagatgtcccaacttcag-
ctgttgggagatggtgatattt _at
tcaaccctacttcctaaacatctgtctggggttcctttagtcttgaatgtcttatgctcaattatttgg-
tgttgagcctctcttcca
caagagctcctccatgtttggatagcagttgaagaggttgtgtgggtgggctgttgggagtgaggatggagt-
gttcagtg
cccatttctcattttacattttaaagtcgttcctccaacatagtgtgtattggtctgaagggggtggtggga-
tgccaaagcctg ctcaagttatggacattgtggccaccatgtggct 137 218704
gaatttctgctggactttatctgggcagaggaaggatggaatgaaggtagaaaaggcagaatt-
acagctgagcgggga _at
caacaaagagttcttctctgggaaaagttttgtcttagagcaaggatggaaaatggggacaacaaagga-
aaagcaaagt
gtgacccttgggtttggacagcccagaggcccagctccccagtataagccatacaggccagggacccacagg-
agagt
ggattagagcacaagtctggcctcactgagtggacaagagctgatgggcctcatcagggtgacattcacccc-
agggca
gcctgaccactcttggcccctcaggcattatcccatttggaatgtgaatgtggtggcaaagtgggcagagga-
ccccacct
gggaacccttttccctcagttagtggggagactagcacctaggtacccacatgggtatttatatctgaacca-
gacagacgc ttgaatcaggcactat 138 218796
gagacagacttggcaagggaccccctggttctgagccagtagctgccatctggaaattcctct-
tttagcctctccttagag _at
gtgaatgtgaatgaagcctcccaggcacccgctgaatttctgaggccttgcttaaagctcagaagtggt-
ttaggcatttgg
aaaatctggttcacatcataaagaacttgatttgaaatgttttctatagaaacaagtgctaagtgtaccgta-
ttatacttgatgtt
ggtcatttctcagtcctatttctcagttctattattttagaacctagtcagttctttaagattataactggt-
cctacattaaaataat
gcttctcgatgtcagattttacctgtttgctgctgagaacatctctgcctaatttaccaaagccagaccttc-
agttcaacatgc
ttccttagcttttcatagttgtctgacatttccatgaaaacaaaggaaccaactttgttttaaccaaacttt-
gtttggttacagtttt caggggagcgtttcttccatgaca 139 218872
catgtacgactcggacagcgacggccgcatcactctggaagaatatcgaaatgtaaagtggtc-
gaggagctgctgtcg _at
ggaaaccctcacatctagaaggagtccgctcgctccatcgccgacggggccatgatggaggcggccagc-
gtgtgcat
ggggcagatggagcctgatcaggtgtacgaggggatcaccacgaggacttcctgaagatctggcaggggatc-
gacat
tgagaccaagatgcacgtccgcttccttaacatggaaaccatggccctctgccactgacccaccgccacctc-
cgcgga
gagactgcactttgcaatggggccgcctccccgcgtagctggagcagcccaggcccggcggacagcctcttc-
ctgca
gcgccggtacatagccaaggctcgtctgcgcaccttgtgtcttgtagggtatggtatgtgggacttcgct
140 218963
gaggaggaactgacgcagctacgccacgaactggagcggcagaacaatgaataccaagtgctg-
ctgggcatcaaaa _s_at
cccacctggagaaggaaatcaccacgtaccgacggctcctggagggagagagtgaagggacacggga-
agaatcaa
agtcgagcatgaaagtgtctgcaactccaaagatcaaggccataacccaggagaccatcaacggaagattag-
ttctttgt
caagtgaatgaaatccaaaagcacgcatgagaccaatgaaagtttccgcctgttgtaaagtctattttcccc-
caaggaaa
gtccttgcacagacaccagtgagtgagttctaaaagatacccttggaattatcagactcagaaacttttatt-
tttttttttctgta
acagtctcaccagacttctcataatgctcttaatatattgcacttttctaatcaaagtgcgagtttatgagg-
gtaaagctctact ttcctactg 141 218984
aatcctgcaattctcaatcttgcactgcagcctcgacctcccaggctccagtgactctcccac-
ctcagcctcctaagtagct _at
gggagtacaggcgcgcaccaccacgcctagctgatttttgtatttttttgtagagacgggggtttggcc-
atgttgccgagg
ctaactcctgggattacaggcatgagctgtgctggccgggtttttttttcttgatgtaaacgtgtacagctg-
ttttattagttaa
ggtctaatttttactctaggtgccttttatgttcagaactctttccactggactggtatttgctcaaaaata-
aataatggtagaga
agaaaactataaaaatggacaaggctttcttctatcagtagcgtttaccctttgtcaccagtggctttggta-
tttccatgtctg
gcattgcataaacttctctggtgtgaaaggataaatatgcctttctaaagttgtatatcaaaattgtatcaa-
tttttattttctatga
tttctagaaacaaatgtaataaatatttttaaaatctcctttctactggttatgta 142 219630
ctcgttgcaatcgcctttgcagtcaaccacttctggtgccaggaggagccggagcctgcacac-
atgatcctgaccgtcg _at
gaaacaaggcagatggagtcctggtgggaacagatggaaggtactcttcgatggcggccagtttcaggt-
ccagtgagc
atgagaatgcctatgagaatgtgcccgaggaggaaggcaaggtccgcagcaccccgatgtaaccttctctgt-
ggctcc
aaccccaagactcccaggcacatgggatggatgtccagtgctaccacccaagccccctccttctttgtgtgg-
aatctgca
atagtgggctgactccctccagccccatgccggccctacccgcccttgaagtatagccagccaaggttggag-
ctcaga ccgtgtctaggttggggctcg 143 219682
gagagaaaacaatatagccccctacccttttcccaatcctttgccctcaaatcagtgacccaa-
gggagggggggatttaa _s_at
agggaaggagtgggcaaaacacataaaatgaatttattatatctaagctctgtagcaggattcatgt-
cgttctttgacagttc
tttctctttcctgtatatgcaataacaaggttttaaaaaaaaaaaaaaaaagtgagactattagacaaagta-
tttatgtaattatt
tgataactcagtaaataggtggaatatgaatgatggaaaattaaactttaatttattgacattgtacatagc-
tctgtgtaaata
gaattgcaactgtcaggttttgtgttcttgttttcctttagttgggtttatttccaggtcacagaattgctg-
ttaacactagaaaac
acacttcctgcaccaacaccaataccctttcaaaagagttgtctgcaacatttttgttttcttttttaatgt-
ccaaaagtggggg
aaagtgctatttcctattttcaccaaaattggggaaggagtgccactttccagc 144 219727
ttagcactgaaagtctcttgccccaggaaaccccatcagtcccaggcagattgggacagctgg-
tcaccttacgcaagag _at
ccaggctgaaacatcccctccatactcagctctttaacttttcttttcctttttcatcgggctctttcc-
taaaaagctgagctgta
aaatattttacatcgaggtataataaataatcatgtacatgttttaccaccacccaggtcaagacatagaat-
gtttcaacatttc
catcaccccagaaactccccttgtacccccttccacttcgtctcccctagctcctagaagcaaccactgatg-
tgatttctac
caaatccagttttggtcctactaaatatactcttttgagactggcctcttttactcaccataatgcctttgt-
aattc 145 219787
tagctgtttcagagagagtacggtatatttatggtaattttatccactagcaaatcttgattt-
agtttgatagtgtgtggaatttta _s_at
ttttgaaggataagaccatgggaaaattgtggtaaagactgtttgtacccttcatgaaataattctg-
aagttgccatcagtttt
actaatcttctgtgaaatgcatagatatgcgcatgttcaactttttattgtggtcttataattaaatgtaaa-
attgaaaattcatttg
ctgtttcaaagtgtgatatctttcacaatagcctttttatagtcagtaattcagaataatcaagttcatatg-
gataaatgcattttt
atttcctatttctttagggagtgctacaaatgtttgtcacttaaatttcaagtttctgttttaatagttaac-
tgactatagattgttttc
tatgccatgtatgtgccacttctgagagtagtaaatgactctttgctacatttta 146 219911
gtgtaccagaattcggccatgagccgctacatactcatcatggggctcctgtacaaggtgctg-
ggcgtcctcttctttgcc _s_at
atagcctgcttcttatacaagcccctgtcggagtcttcagatggcctggaaacttgtctgcccagcc-
agtcctcagcccct
gacagtgccacagatagccagctccagagcagcgtctgaccaccgcccgcgcccacccggccacggcgggca-
ctc
agcatttcctgatgacagaacagtgccgttgggtgatgcaatcacacgggaacttctatttgacctgcaacc-
ttctacttaa
cctgtggtttaaagtcggctgtgacctcctgtccccagagctgtacggccctgcagtgggtgggaggaactt-
gcataaat
atatatttatggacacacagtttgcatcagaacgtgtttatagaatgtgttttatacccgatcgtgtgtggt-
gtgcgtgaggac
aaactccgcaggggctgtgaatcccactgggagggcggtgggcctgcagcccgaggaaggcttgtgtgtcct-
cagtta a 147 219955
gaagttgcaacattcgtttgataggaattccagaaaaggagagttatgagaatagggcagagg-
acataattaaagaaata _at
attgatgaaaactttgcagaactaaagaaaggttcaagtcttgagattgtcagtgcttgtcgagtacct-
agtaaaattgatga
aaagagactgactcctagacacatcttggtgaaattttggaattctagtgataaagagaaaataataagggc-
ttctagaga
gagaagagaaattacctaccaaggaacaagaatcaggttgacagcagacttatcactggacacactggatgc-
tagaagt
aaatggagcaatgtcttcaaagttctgctggaaaaaggctttaatcctagaatcctatatccagccaaaatg-
gcatttgatttt
aggggcaaaacaaaggtatttcttagtattgaagaatttagagattatgttttgcatatgcccaccttgaga-
gaattactggg gaataatataccttagcacgccagggtgactaca 148 219956
ttgcttgttccccggaggttgaagctacagtgagccttgattgtgtcactgcactccagcctg-
ggcaacaggtaagactct _at
gtctcaaaaaaaaaacaaaaaagaagaagaaaagtacttctacagccatgtcctattccttgatcatcc-
aaagcacctgc agagtccagtgaaatgatatattctggctgggc 149 221577
gacggcgtcaaggtcgtgggacgtgacacgaccgctgcggcgtcagctcagccttgcaagacc-
ccaggcgcccgcg _x_at
ctgcacctgcgactgtcgccgccgccgtcgcagtcggaccaactgctggcagaatcttcgtccgcac-
ggccccagctg
gagttgcacttgcggccgcaagccgccagggggcgccgcagagcgcgtgcgcgcaacggggaccactgtccg-
ctc
gggcccgggcgttgctgccgtctgcacacggtccgcgcgtcgctggaagacctgggctgggccgattgggtg-
ctgtc
gccacgggaggtgcaagtgaccatgtgcatcggcgcgtgcccgagccagttccgggcggcaaacatgcacgc-
gcag
atcaagacgagcctgcaccgcctgaagcccgacacggtgccagcgccctgctgcgtgcccgccagctacaat-
cccat
ggtgctcattcaaaagaccgacaccggggtgtcgctccagacctatgatgacttgttagccaaagactgcca-
ctgca 150 221729
tggaattagaccatttggcttttgaactacataggaaaaatgacccaacatttcttagcatga-
gctacctcatctctagaag _at
ctgggatggacttactattcttgtttatattttagatactgaaaggtgctatgcttctgttattattcc-
aagactggagataggca
gggctaaaaaggtattattatttttcctttaatgatggtgctaaaattcttcctataaaattccttaaaaat-
aaagatggtttaatc
actaccattgtgaaaacataactgttagacttcccgtttctgaaagaaagagcatcgttccaatgcttgttc-
actgttcctctg
tcatactgtatctggaatgctttgtaatacttgcatgcttcttagaccagaacatgtaggtccccttgtgtc-
tcaatacttttttttt cttaattgcatttgttggctctattttaattt 151 221730
tagattccggtatatcgttcttcaagacacttgctctaagcggaatggaaatgtgggcaagac-
tgtctttgaatatagaaca _at
cagaatgtggcacgcttgcccatcatagatcttgctcctgtggatgttggcggcacagaccaggaattc-
ggcgttgaaatt
gggccagtttgttttgtgtaaagtaagccaagacacatcgacaatgagcaccaccatcaatgaccaccgcca-
ttcacaag
aactttgactgtttgaagttgatcctgagactcttgaagtaatggctgatcctgcatcagcattgtatatat-
ggtcttaagtgcc
tggcctccttatccttcagaatatttattttacttacaatcctcaagttttaattgattttaaatatttttc-
aatacaacagtttaggtt taagatgaccaatgacaatgaccacctt 152 221731
tacagcaccgatggccatgtaaataagatgatttaatgagatataatcctgtatataaantaa-
aaagtncncaatgagat _x_at
ngggcatatttaatgatgattatggagccttagaggtctttaatcattggttcnggctgcttttatg-
tagtttaggctggaaatg
gtttcacttgctctttgactgtcagcaagactgaagatggcttttcctggacagctagaaaacacaaaatct-
tgtaggtcatt
gcacctatctcagccataggtgcagtttgcttctacatgatgctaaaggctgcgaatgggatcctgatggaa-
ctaaggact
ccaatgtcgaactcttctttgctgcattcctttttcttcacttacaagaaaggcctgaatggaggacttttc-
tgtaaccaggaa
cattttttaggggtcaaagtgctaataattaactcaaccaggtctactttttaatggctttcataacactaa-
ctcataaggttac cgatcaatgcatttcatacggatatagacctagggctctggagggtgggg
153 221922
gtaaatagttaaccacagtagtctattaaggcattaatacttctctggacatgcgcgtttgag-
ggtggaggggtcctgtaag _at
gtgcttcatcgtctgtgattactgcttgggatgtgttctttggcagcttgtgagattactttacctagt-
gtttataaagtaggaag
ttaagtgaatcatagattagaatttaatactcttatggaaataattttttaacatcttaattgacaatggcg-
tttttttataca 154 221923
tagtccatactgagtgtcatcaacaatccagactgaagtcttctattttaatctcaatcccct-
tttctgatttgccacccatgcct _s_at
cttcaggctggaaacaatctcttggttccctaaagcactttcttctgactgctgtgattcagtgaac-
cttgccctttgctttctat
tacttgtgcatttgcctcacctgacaatgttttaaatcgcctttgtatctccttagctgctcaataa
155 222449
aatatgtcagtgcttgcttgatggaaacttctcttgtgtctgttgagactttaagggagaaat-
gtcggaatttcagagtcgcct _at
gacggcagagggtgagcccccgtggagtctgcagagaggccttggccaggagcggcgggctttcccgag-
gggcca
ctgtccctgcagagtggatgcttctgcctagtgacaggttatcaccacgttatatattccctaccgaaggag-
acaccttttcc
cccctgacccagaacagcctttaaatcacaagcaaaataggaaagttaaccacggaggcaccgagttccag
156 222450
ggctgggggagagccgggttcattccctgtcctcattggtcgtccctatgaattgtacgtttc-
agagaaattttttttcctatgt _at
gcaacacgaagcttccagaaccataaaatatcccgtcgataaggaaagaaaatgtcgttgttgttgttt-
ttctggaaactgc
ttgaaatcttgctgtactatagagctcagaaggacacagcccgtcctcccctgcctgcctgattccatggct-
gttgtgctga
ttccaatgctttcacgttggttcctggcgtgggaactgctctcctttgcagccccatttcccaagctctgtt-
caagttaaactta
tgtaagctttccgtggcatgcggggcgcgcacccacgtccccgctgcgtaagactctgtatttggatgccaa-
tccacagg cctgaagaaactgcttgttgtg 157 222549
gtgagtatggcccaatgctttctgtggctaaacagatgtaatgggaagaaataaaagcctacg-
tgttggtaaatccaacag _at
caagggagatttttgaatcataataactcataaggtgctatctgttcagtgatgccctcagagctcttg-
ctgttagctggcag
ctgacgctgctaggatagttagtttggaaatggtacttcataataaactacacaaggaaagtcagccaccgt-
gtcttatgag
gaattggacctaataaattttagtgtgccttccaaacctgagaatatatgcttttggaagttaaaatttaaa-
tggcttttgccac
atacatagatcttcatgatgtgtgagtgtaattccatgtggatatcagttaccaaacattacaaaaaaattt-
tatggcccaaaa
tgaccaacgaaattgttacaatagaatttatccaattttgatctttttatattcttctaccacacctggaaa-
cagacc 158 222608
catggtttacatttactcagctactatatatgcagtgtggtgcacattttcacagaattctgg-
cttcattaagatcattatttttgn _s_at
ctgcgtagcttacagacttagcatattagttttttctactcctacaagtgtaaattgaaaaatcttt-
atattaaaaaagtaaactg
ttatgaagctgctatgtactaataatactttgcttgccaaagtgtttgggttttgttgttgtttgtttgttt-
gtttgtttttggttcatga
acaacagtgtctagaaacccattttgaaagtggaaaattattaagtcacctatcacctttaaacgccttttt-
ttaaaattataaa
atattgtaaagcagggtctcaacttttaaatacactttgaacttcttctctgaattattaaagttctttatg-
acctcatttataaaca ctaaattctgtcacctcctg 159 222696
gccgctgtgctttcgtggaaatgacagttccttgttttttttgtttctgtttttgttttacat-
tagtcattggaccacagccattcag _at
gaactaccccctgccccacaaagaaatgaacagttgtagggagacccagcagcacctttcctccacaca-
ccttcattttg
angttcgggtttttgtgttaagttaatctgtacattctgtttgccattgttacttgtactatacatctgtat-
atagtgtacggcaaa
agagtattaatccactatctctagtgcttgactttaaatcagtacagtacctgtacctgcacggtcacccgc-
tccgtgtgtcg
ccctatattgagggctcaagctttcccttgttttttgaaaggggtttatgtataaatatattttatgccttt-
ttattacaagtcttgt 160 223062
ggagtggtttaagagtgccaggcgaagggcaaactgtagatcgatctttatgctgttattaca-
ggagaagtgacatacttt _s_at
atatatgtttatattagcaaggtctgtttttaataccatatactttatatttctatacatttatatt-
tctaataatacagttatcactgat
atatgtagacacttttagaatttattaaatccttgaccttgtgcattatagcattccattagcaagagttgt-
accccctccccag
tcttcgccttcctctttttaagctgttttatgaaaaagacctagaagttcttgattcatttttaccattctt-
tccataggtagaagag
aaagttgattggttggttgtttttcaattatgccattaaactaaacatttctgttaaattaccctatccttt-
gttctctactgttttcttt
gtaatgtatgactacgagagtgatactttgctgaaaagtctttcccctattgtttatctattgtca
161 223447
ttcctgtgcaagtaccgaccatagagcaagaatcaagattctgctaactcctgcacagccccg-
tcctcttcctttctgctag _at
cctggctaaatctgctcattatttcagaggggaaacctagcaaactaagagtgataagggccctactac-
actggctttttta
ggcttagagacagaaactttagcattggcccagtagtggcttctagctctaaatgtttgccccgccatccct-
ttccacagtat
ccttcttccctcctcccctgtctctggctgtctcgagcagtctagaagagtgcatctccagcctatgaaaca-
gctgggtcttt
ggccataagaagtaaagatttgaagacagaaggaagaaactcaggagtaagcttctagaccccttcagatct-
acaccct
tctgccctctctccattgcctgcaccccaccccagccactcaactcctgcttgtttttcctttggccatagg
162 223970
ggagctcagagatctaagctgctttccatcttttctcccagccccaggacactgactctgtac-
aggatggggccgtcctctt _at
gcctccttctcatcctaatcccccttctccagctgatcaacccggggagtactcagtgttccttagact-
ccgttatggataag
aagatcaaggatgttctcaacagtctagagtacagtccctctcctataagcaagaagctctcgtgtgctagt-
gtcaaaagc
caaggcagaccgtcctcctgccctgctgggatggctgtcactggctgtgcttgtggctatggctgtggttcg-
tgggatgtt
cagctggaaaccacctgccactgccagtgcagtgtggtggactggaccactgcccgctgctgccacctgacc-
tgacag
ggaggaggctgagaactcagttttgtgaccatgacagtaatgaaaccagggtcccaaccaagaaatctaact-
caaacgt cccact 163 224428
gcaaagtttatttcagttcacatgtaaggtattgcaaataaattcttggacaattttgtatgg-
aaacttgatattaaaaactagtc _s_at
tgtggttctttgcagtttcttgtaaatttataaaccaggcacaaggttcaagtttagattttaagca-
cttttataacaatgataagt
gcctttttggagatgtaacttttagcagtttgttaacctgacatctctgccagtctagtttctgggcaggtt-
tcctgtgtcagtat
tccccctcctctttgcattaatcaaggtatttggtagaggtggaatctaagtgtttgtatgtccaatttact-
tgcatatgtaaacc attgctgtgccattcaa 164 224646
agacggccttgagtctcagtacgagtgtgcgtgagtgtgagccaccttggcaagtgcctg _x_at
165 224915
ggagtgtggtacttctcctagttgcagtcaggcttcatacgctnttgtcctgcccgttagagc-
agccagcgggtacagaat _x_at
ggattttggaagagggagtcaccactggacctccaaggaagccacgtgcagacatctacaaccttcg-
atctcctgacga
gtttattgttggccaaaaccaggctttgattgaaccaggatgaatgcgggtgttggaagtagaatatatata-
tacatataaaa
ttggttgggagccacgtgtaccagtgtgtgttgatcttggcttgattcagtctgccttgtaacagaaactgg-
cgatggaatat
gagaggagccctctggaaagaaaaggacagaccctgtgctttcatgaaagtgaagatctggctgaaccagtt-
ccacaa
ggttactgtatacatagcctgagtttaaaaggctgtgcccacttcaagaatgtcattgttagactttgaaat-
ttctaactgccta cctgca 166 225295
agggctgtaacagttgctgctagtattagggttccacatcattctaatgtatagtttcaagtc-
ttaatagacaatctgaattcca _at
ctacatttcttttggctccaacattccttttagcttgaccagtctaatttaaaatgtgtttgttggagg-
tcattaacgttacttgtac
aatgctgtcactgtgtgacatccatatgaattttggtatatatcaatcaatcaatcaatcannnncattgca-
ttcaatcaatca
gctgtgattgattnnnnatgcttagaaatactatagtaactagatgcagtgtgaattttttccattaacaaa-
caaacaagtca
gtggcttaaatgtgattatggtcctgcaaggtgattcttgctaaaatatctaaacttttgttttgttttaac-
tgaatcattttttaact
taaaaagctggaaaatatcaaatgctgttttttttttnncattgtcaacagtggtgtgtcattttatgtatg-
ttcctaatgcttatg gaactcctcca 167 225520
ggaacgatgagcaccatgccaggactgcccacccggccctgatttatgacatagatcttgata-
ccgaaacagaacaag _at
ttaaaggcttgttctaagtggacaaggctctcacaggacccgatgcagactcctgaaacagactactct-
ttgcctttttgct
gcagttggagaagaaactgaatttgaaaaatgtctgttatgcaatgctggagacatggtgaaataggccaaa-
gatttcttct
tcgttcaagatgaattctgttcacagtggagtatggtgttcggcaaaaggacctccaccaagactgaaagaa-
actaatttat
ttctgtttctgtggagtttccattatttctactgcttacactttagaatgtttattttatggggactaaggg-
attangagtgtgaac
taaaaggtaacattttccactctcaagttttctactttgtctttgaactgaa 168 225541
gaaacacaaccaagacgcgaggatcnnnnnctntnnnnnnnnnnnnnctngcaagatggcgcc-
gcagaaagac _at
aggaagcccaagaggtcaacctggaggtttaatttggaccttactcatccagtagaagatggaattttt-
gattctggaaattt
tgagcaatttctacgggagaaggttaaagtcaatggcaaaactggaaatctcgggaatgttgttcacattga-
acgcttcaa
gaataaaatcacagttgtttctgagaaacagttctctaaaaggtatttgaaataccttaccaagaaatacct-
taagaagaac
aatcttcgtgattggcttcgagtggttgcatctgacaaggagacctacgaacttcgttacttccagattagt-
caagatgaag atgaatcagagtcggaggactaggcaaaggctccccttacagggctttgcttatt
169 225664
ggaacccagagctgctgtgtatttcgagcgggcagtttatcttttgctatacttattttcaat-
tcaattacaccacgattcaaat _at
aattcccctcctaaaaccaaaaaggagggaaacgtcaactccattgcaattacttatcttcctcttcta-
tctctgttatacgcc
ggggcatagaatgctcgtatacatctctttaacaaccacaaaccttaagccatgtagatgaagttagtgcat-
caacgggat
acagttccatattgccttaaacctccttgttttagacacactaacatttataccaaattgcagattattctg-
cagagagggaatt gcatgtttgtgttgta 170 225681
aattaatattcatcgcacttcttctgtggaaggactttgtgaaggaattggtgctggattagt-
ggatgttgctatctgggttgg _at
cacttgttcagattacccaaaaggagatgcttctactggatggaattcagtttctcgcatcattattga-
agaactaccaaaat
aaatgctttaattttcatttgctacctctttttttattatgccttggaatggttcacttaaatgacatttta-
aataagtttatgtatacat
ctgaatgaaaagcaaagctaaatatgtttacagaccaaagtgtgatttcacactgtttttaaatctagcatt-
attcattttgcttc
aatcaaaagtggtttcaatattttttttagttggttagaatactttcttcatagtcacattctctcaaccta-
taatttggaatattgtt
gtggtcttttgttttttctcttagtatagcatttttaaaaaaatataaaagctaccaatctttgtacaattt-
g 171 225767
ccgtgtgagcgatcgcggtgggttcgggccggtgtgacgcgtgcgccggccggccgccgaggg-
gctgccgttctgc _at
ctccgaccggtcgtgtgtgggttgacttcggaggcgctctgcctcggaaggaaggaggtgggtggacgg-
gggggcct
ggtggggttgcgcgcacgcgcgcaccggccgggcccccngccctgaacgcgaacgctcgaggtggccgcgcg-
ca
ggtgtttcctcgtaccgcagggccccctcccttccccaggcgtccctcggcgcctctgcgggcccgaggagg-
agcgg
ctggcgggtggggggagtgtgacccaccctcggtgagaaaagccttctctagcgatctgagaggcgtgcctt-
gggggt ac 172 225799
aaatgactggatggtcgctgctttttaagtttcaaattgacattccagacaagcggtgcctga-
gcccgtgcctgtcttcagat _at
cttcacagcacagttcctgggaaggtggagccaccagcctctccntgaataactgggagatgaaacagg-
aagctctatg
acacacttgatcgaatatgacagacacngaaaatcacgactcanccccctccagcacctctacctgttgccc-
gccgatc
acagccggaatgcagctgaaagattccctggggcctggttccaaccgcccactgtggactctgaggcctctg-
catttgc gggtggtctgcctgtgatattttggtcatgggctggtctg 173 225806
tcttctcaggtcacttgtacacttggtttcctagtagaagctcacttgccacctctcaggggg-
gtcccggattgcatccatca _at
caatcccaaaactngagttggggggaactggagggagcaaaacactgatttgatactagtcagtttgct-
tgaaactagtt
cacctaaagctagatctcttaaaaccaatttactgaaaacttgtttgcttaaagttaatgacttaatgacta-
atttgccaaaagc
tcaattcctattttggtgtgtttatatccatttaggtgtcctattcttttttgtcatgctttggatatttca-
aggatttatatctattcatc
caagagtacttctgagntattatcagcaacataaatttatcaaatttgcagcactttgtaaatgatgagatt-
gcttcctaccttt atggatgtcttt 174 225835
aatgcattactttcacttaacactagacaccaggtcgaaaattttcaaggttatagtacttat-
ttcaacaattcttagagatgct _at
agctagtgttgaagctaaaaatagctttatttatgctgaattgtgatttttttatgccaaanttttttt-
agttctaatcattgatgata
gcttggaaataaataattatgccatggcatttgacagttcattattcctataagaattaaattgagtttaga-
gagaatggtggt
gttgagctgattattaacagttactgaaatcaaatatttatttgaacattattccatttgtattttaggttt-
ccttttacattctttttat
atgcattctgacattacatattttttaagactatggaaataatttaaagatttaagctctggtggatgatta-
tctgctaagtaagt
ctgaaaatgtaatattttgataatactgtaatatacctgtcacacaaatgcttttctaatgttttaaccttg-
agtattgcagttgct gctttgtacagaggtt 175 226227
gtacttctcctagttgcagtcaggcttcatacgctattgtcctgcccgttagagcagccagcg-
ggtacagaatggattttgg _x_at
aagagggagtcaccactggacctccaaggaagccacgtgcagacatctacaaccttcgatctcctga-
cgagtttattgtt
ggccaaaaccaggctttgattgaaccaggatgaatgcgggtgttggaagtagaatatatatatacatataaa-
attggttgg
gagccacgtgtaccagtgtgtgttgatcttggcttgattcagtctgccttgtaacagaaactggcgatggaa-
tatgagagg
agccctctggaaagaaaaggacagaccctgtgctttcatgaaagtgaagatctggctgaaccagttccacaa-
ggttactg
tatacatagcctgagtttaaaaggctgtgcccacttcaagaatgtcattgttagactttgaaatttctaact-
gcctacctgca 176 226237
gaagaggagcaacatctatgccaaatactgtgcattctacaatggtgctaatctcagacctaa-
atgatactccatttaattta _at
aaaaagagttttaaataattatctatgtgcctgtatttcccttttgagtgctgcacaacatgttaacat-
attagtgtaaaagcag
atgaaacaaccacgtgttctaaagtctagggattgtgctataatccctatttagacaaaattaaccagaatt-
cttccatgtga
aatggaccaaactcatattattgttatgtaaatacagagttttaatgcagtatgacatcccacaggggaaaa-
gaatgtctgta
gtgggtgactgttatcaaatattttatagaatacaatgaacggtgaacagactggtaacttgtttgagttcc-
catgacagattt gagacttg 177 226311
aaacgacgcaaatctctgagctggggaccacttggagaaccggcttagtaacagtcctgatct-
tcgcaagccagcttctt _at
ctgcatctgaggggctcctggcgcccagaggaggcagacagatgtcttctagctgagtttctaaccgca-
tgatgagact
cagaccttccgctgcactagaaaatctgcaacagtgtccctgagtcacttctccttagtgggcagactcgtg-
ttagatttgt
ggaacccagctctctgatttactccttttggaaaacccatggaatttcatgtataaggctttcatttgtatt-
ttaaggtttttctgtt
tgttttgagtatatacatggtgctcaatagcaacatcttagcagatgaagcagtttatgattccactccctc-
ctgtatgacagg
tagccactatactgaatcaaggtgctgaactcaaatcacaaaattctggcttaccgatacaacaaccaatac
178 226360
gtcccactgctcacatacttatgtgctgctagtctctactcgaagttcgtgcaggactaatgc-
ttttaaaatgaggtctaaaa _at
aataattactagtcgagactattattctttaaacagaactgcctttttctactctttatgtaaactctt-
tctattgtgttggtctaacn
aggcactattttaaaattttttaatttttcccatagcacttaaaagagattttgtaaagaccttgctgtaaa-
gattttgtaataaaa
tggtctaagggctctttttccaacattaccatttttaaaaaatgttttaaaagctagaagacaacttatgta-
tattctntatatgta
tagcagcacatttcatttatggaaatatgttctcagaatatttatttactaatatatttatcttaagccatg-
tcttatgttgagagtg
tgacattgttggaataatcattgaaaatgactaacacaagaccctgtaaatacatgataattgcacacagat-
tttacatatttg cagaccaaaaatgatttaaaacaagttgtagtcttctatggttttg 179
226777
tataaggtaactctttagtcctccatttagcacattttaaatcctccaaagaataagtatcat-
gtgattattttagctttacaaaaa _at
aaaagttgaatggcgttttattttcatggcctataagcaggtaccttagtagggcagatataggaaaaa-
caaattagagcaa
aacaaatcctctacaaatccaaggcaggaaaagtggtggcagagtgactcattctcctgtccctcccatcag-
gtcaaatc
aggaggctgcagtgaatgcctgttctttgaatgtgtagcagttgttncctgtaactctttaaaacttggcta-
taggctgtttag
cacagtacagattaaagatacagttacgtaaacagcaaagtaattttatagtgcttcatccatttatcatgc-
tttggtttgctaa
ttttttcacatacctttttctatcacagtctgttgcttttgtacacatttctcatattggggttcgaca
180 226835
ggagtgtggtacttctcctagttgcagtcaggcttcatacgctattgtcctgcccgttagagc-
agccagcgggtacagaat _s_at
ggattttggaagagggagtcaccactggacctccaaggaagccacgtgcagacatctacaaccttcg-
atctcctgacga
gtttattgttggccaaaaccaggctttgattgaaccaggatgaatgcgggtgttggaagtag 181
227140
ttaccctctatttaaatgctttgaaaaacagtgcattgacaatgggttgatatttttctttaa-
aagaaaaatataattatgaaagc _at
caagataatctgaagcctgttttattttaaaactttttatgttctgtggttgatgttgtttgtttgttt-
gtttctattttgttggttttttac
tttgttttttgttttgttttgttttgttttgcatactacatgcagttctttaaccaatgtctgtttggctaa-
tgtaattaaagttgttaattt
atatgagtgcatttcaactatgtcaatggtttcttaatatttattgtgtagaagtactggtaatttttttat-
ttacaatatgtttaaag
agataacagtttgatatgttttcatgtgtttatagcagaagttatttatttctatggcattccagcggatat-
tttggtgtttgcgag
gcatgcagtcaatattttgtacagttagtggacagtattcagcaacgcctgatagcttctttggcctt
182 227174
ctggcacaaccctgacattactaagtggaaatgttaggatttttcggcatcgcatgttagaat-
ctctaaaatttaaacattcct _at
gttaaatgactaaggtttgcttttatcaatatgaattctgaaggccaatatcataccattaactatgaa-
agcttttaattcctaaa
aatagttttagagatattcaagcaatgctctcctaatatccatacgcaagtgtgtttatgacacaaattcac-
tagtctgtttaaa
aatgaattctttatattgactggtgttccacatatttcagtaatttctgttatgagaggacttgaaatagca-
aattgccacacag
ttaactggatagaccangtacgtggtgatcataaccacttggtactacacccagaaactcaaaattgtcttt-
ctcctgatga
gatatgggtgtccttttgtacgtctaggcctaggtaaccagtggagtgattatattagcaaatgtgtttgta-
tccagagtcttc c 183 227475
ccaggcttcgtcttatttctactgtttttgtcgcaacttccattgatttatgtcccttccctc-
ccccctaagtacatcagggaacc _at
tttccacactataaatgatatgactactgtttggggtttctgggcccccatccgtgtacgtatgtggca-
tttccaggtatgact
gagtgtgagagacatgtcagaggctcttcagtgatttcttgctattgaccgatgcttcactgtgccaaaaga-
gaaaaaaaa
tgttgggttttgtaattaaattatttatatatttttgaaacccgaattgaaaatgttgcaggcaacgggcta-
cagctttattagtg
gttctctaactgtggtctccttgggccaagcaatttctttaaaggaaaagttgattatgtatgtggggtgcc-
aggaccactgc cttgaaagca 184 228303
tagcccaaccctatcattttcatattatgaaactgagtccaggtaagtgaatctgtccaaggt-
cacccagcaaggtatcagt _at
agccctgagggtaaggactctgataaggctcgggagggtcctggaaagcctgaggcggcaggaagagtg-
tgcagag
ttgagcgtgtctggaaggctgatccactgctgggcccacatcaaagcccccatggggagcagacccgactgc-
acatgg
ctcttttgctggaagaagagcatngctgcgcagaggactaaaatttcatctgggaaggcttcttttgactgt-
cagtagcag
gatgtcaccagatgagggtgctatgggaccacagctgtctttgttcccattgcaactcaaccctgcnggagg-
ccgcctgc
atccctgagagccttctggagcctacagaggagacattggccagccaaaaggaaaggagtggccagggtacg-
acct 185 228653
aattatcccttatcattccaaaaatgaaatgctgtgttaaatatctccagggcaaagtggtat-
gttgactgggacaaacgtta _at
gaaattgtattgttcattgcacttgttgccctgttccccaagcttgtcaatgtttagagatactattcg-
ggttgctaaagccatta
ttcatagaaaatttctgcccctacagaagtgtgtgcatgggccttggaaaatctacatgtgtatatctgagt-
agcgaagcac
agattcactctaattgaaagcagcagtttggttttgtaaatgtaattgcaattgacactttcttttcccttt-
cagttattatttttttta
aaggacgttatgagaaggcactatgaaaagcctaattggaatagcattatgaaccatgtaatgcatgcccat-
gcacactgt gatttgcaaacatatgtccgctcttcaat 186 228754
ggtgggtgtcactacagacatgttctggcgtgttctccgagggatggagcatcctgttatata-
tttgacttcaaattgagatg _at
ttggcttcattttttttttttacccaattaatctcccaatccctagcaactgtgactctgtatttagca-
caagagaaagctgagaa
tgtgggtcttgcctccttccagaaatatgtctggctcatcaggacatttttttaaaacttcaaaatattttt-
aagatattttaaactt
ttataaaaaaaaaatcaaccaacaagagacttttctgaggaggaacatttgtatttgaacaagatccttggt-
gtgtagttcag
tcttgcagtatacaagcttttgtgtataaatgttttatgatatgattccctgtnttttgcaggggttttttt-
ctcttttgctttttagata
aatatgtatatcaatattttaaattcatctttgctttttttagaggagtttgtaatcaccttataac
187 228915
gaaaaaagctatcagctgtatgttaagagagactcttactaacatgttgtaaatattacaatt-
catgaaatgttattgtaagtct _at
gtaacttaattttttccctgttttagttatacaggttggtttggaaatttgtgttttggcataaacaag-
taaaatgtgcccattttat
ggtttccatgcttttgtaatcctaaaaatattaatgtctagttgttctatattataaccacatttgcgctct-
atgcaagcccttgga
acagaacatactcatcttcatgtaggacctatgaaaattgtctatttttatctatatatttaaagttttcta-
aaaatgataaaaggt
tattacgaattttgttgtacaaaatctgtacaaaaatctgtttttacatcataatgcaagaattggaaattt-
ttctatggtagccta gttatttgagcctggtttcaatgtgaga 188 229215
gccgcggtggaaacgggcttggagctggccccataangggctngcggcttcctccgacgccgc-
ccctccccacagct _at
tctcgactgcagtggggcggggggcaccaacacttggagatttttccggaggggagaggattttctaag-
ggcacagag
aatccattttctacacattaacttgagctgctggagggacactgctggcaaacggagacctatttttgtaca-
aagaaccctt
gacctggggcgtaataaagatgacctggacccctgcccccactatctgnngnnnnnnntgctggccaagatc-
tggac
acgagcagtccctgaggggcggggtccctggcgtgaggcccccgtgacagcccaccctggggtgggtttgtg-
ggca ctgctgctctgctagggagaagcctgtgtggggcacacctcttcaagggagcgtga 189
229802
gacatgattgtctataatctcgctagccttgtactgtgtgtgcatagcaattacagggaagta-
atctagctcctgactattatg _at
ttgaactatgtcgctgctttttacaaacttgtcttgatccaaagcagtcacaatgataaccctgcatat-
ctgggaatcataagt
caactatgtatctctgtgtgtgtatatatatgtatgtatgtatctattttcaaactgtgatttaatatttaa-
atattcctactgccattt
ttgtgactgaaaaactacacatgaggaaacgtcttagaattttccaatagaggaaaaataacacttgggcaa-
tctgtcatgt
ttcacaacagttctcatttttctcatgatttgtgtagcgtggaatgtgtttgctcaatgtgaagggttttca-
ttgctcaatttctctg tgtaa 190 231766
ggttccggctaacacattttctaagtcgccagtgctgcttacagtttgaatacatgaaaatcc-
tgtttctnagatgtttgcgca _s_at
cgtgcttattaggaaatgagtctgtatggaaatctcaccacagataatggttaacgaaccgggtcga-
catcacaaaggag
ggtggagactctttttactaacttgaatgagacaaaagcagtggtgtcagtttataatcctgatgcatttca-
gtaataatgtag
aaaaacattattttaaaaaagttccaacacacagccatgaggagccnnnnnnnnnntcagttttgaaagagg-
tgcataa taaaactactaaccagaggagtctatgccatttt 191 231832
gagtttcaactttaaatgttcactatgtcatttagtgtccanctttacggataggttgactat-
ctaaataggcatttttagtcatta _at
aaaaaaantctagtcaccaggaggatccctataactcaaaataacttgtttgtaaaagaaaatttgttt-
acttacccattagta
agttcctgcatattcattataagatggcaaatcaaacttttctaggatgaagacagcttatttttaagttgt-
atagtcttagttgg
tttagggtctcaattttaattaataaaatacttggtttttatttgcttgtccttttgaattcctgttttaat-
aattttaaaatgagcaca
aagaangttgaagttcagattaatctcttctgaatgatgtttttttcctctgtgatgagttgtttctg
192 231941
caccaagttacgtcaaagtctcaggagcagctccggtctccatagaggctgggtcagcagtgg-
gcaaaacaacttccttt _s_at
gctgggagctctgcttcctcctacagcccctcggaanncncnctcaagaacttcaccccttcagaga-
caccgaccatgg
acatcncaaccaaggggnccttccccaccagcanggaccctcttccttctgtccctccgactacaaccaaca-
gcagcc ganngacgaacagcacntnnnnnaagatcacaacctcagcgaagaccacgatgaagcccc
193 232151
gtacagcatgaaaggcttcctctacaagacactagtcaaagagttgagagctgcggtttctaa-
tctttgtccattactccctt _at
actccctatgagactgtggacctgtcacttggcctctctggtcttcagttttctcaccagtaaaacaag-
gaacttgaaccaa
atgacctctagtgttccccttgggtttaaatgtctataaatgttcaatgactagaannnantgcgtttttct-
ttattctttttgcttt
gagaaaagagaatgtgatttaagagtaataatttgaataccaattatccacattaaaattgtgtcctctatg-
tgtaaggcata
gcacatttagcacacatacataagcacactaagcaccttacaaatatcctcatttattctttacataatctt-
ttgaaatngattat
gtaatacacacngttttnnaacaatnggtgacttccagctgtttaaaacaaactacagtatggtgcttgagt-
actgacttag gaggtcagcatnggtttcactaggagcttctcaaagcacgctgcc 194 232176
gggatcactgggagaagccatggcattatcttcaggcaatttagtctgtcccaaataaaataa-
atccttgcatgtaaatcatt _at
caagggttatagtaatatttcatatactgaaaagtgtctcataggagtcctcttgcacatctaaaaagg-
ctgaacatttaagta
tcccgaattttcttgaattgctttccctatagattaattacaattggatttcatcatttaaaaaccatactt-
gtatatgtagttataat
atgtaaggaatacattgtttataaccagtatgtacttcaaaaatgtgtattgtcaaacatacctaactttct-
tgcaataaatgca
aaagaaactggaacttgacaattataaatagtaatagtgaagaaaaaatagaaaggttgcaattatataggc-
catgggtg gctcaaaactttgaa 195 232252
ggacgatgaagccatcattgctgcttggagacgccggcaagaagaaaccaggaccaagctgca-
gaaaaggaggga _at
ggactgagctggggaaaatctgagaacactgaaagaaaccactcacgttagcatagggctcagggcaca-
cgttgcca
ccactcatcgcaggatgaggatacagagaggatcttccagaggggcagagccaaaatgagagntaccaagca-
tnng
ggcannngaggtggagtagggaggaggcaaggagggggagaaccatcaatacgaatacgaggtccgaatgcg-
ga
ccaactgataccattttctgttgctcagcgccctctaagctttggtgtttcacttaatgtatttgacagtgt-
tcatcacaggcta
gagaggtgagcttggaaaagcactgtagtttgtcagagactccagtttacatccagaaaggccatgaacata-
ggacacg
cttctgtctgtagaggcttcatatgagacccagaaagtctatcctatggcaagtctgacctctcctggcaat-
gctcagttctg att 196 232481 gaagtccatcctttggtccaaagc
atctggaagaggaagaagagaggaatgagaaagaaggaagtgatgcaaaacat _s_at
ctccaaagaagtcttttggaacaggaaaatcattcaccactcacagggtcaaatatgaaatacaaaa-
ccacgaaccaatc
aacagaatttttatccttccaagatgccagctcattgtacagaaacattttagaaaaagaaagggaacttca-
gcaactggg
aatcacagaatacctaaggaaaaacattgctcagctccagcctgatatggaggcacattatcctggagccca-
cgaagag
ctgaagttaatggaaacattaatgtactcacgtccaaggaaggtattagtggaacagacaaaaaatgagtat-
tttgaactta
aagctaatttacatgctgaacctgactatttagaagtcctggagcagcaaacatagatggagagtttgaggg-
ctttcgcag
aaatgctgtgattctgttttaagtccataccttgtaaataagtgccttacgtgagtgtgtcatcaatcagaa-
cctaagc 197 234331
accaagatggtgcaagttccctttgcagatggcgtgggcacacttgatttttattatgagtga-
atgtaatctttctgtattttac _s_at
cagagttacagcaattacctgaaaagtttcctaacattttaataatgttagggatttcgttttggtt-
ttagttgtcctcaagagac
aacaggttcacagtaatttccatgatgttgggtgtggctaagctggggattggttctgttccccctgctccc-
gtgtagagaa
aagctatatttatactgcattctttctcaactttcaggtaaaacaaactatgatttaaaaaaagaaaaaaga-
aaagacaggta
cttttacttcaaagagtgctttgctacatttttatttaaaccaaaaatcaaataaaataaggaggggggctg-
ggtatactttaa acaaaaccagtcctgaaatgctgttatt 198 235210
ttcttgtccagctgttcacagttttatttttatatagatggtgatataaatatttccaaatgc-
atttgtaaacattctaaatattctca _s_at
agtcatgttcaatgtttcctaaaccttcaattttggccaaagtccccaaacacatcattgccacact-
ctgaagtagagaaag
aaaatttaggggccagttctcaaggaacacaggtcctttatttttattttaactaagttgaagacccactca-
aaaagctcttgt
ggttttatgttcttgacctttcaactggagtcctctcattcagcaggtggcccgtgagacacagaatac
199 235976
cagtgctgctgtgaactaaagtatgtcatttatgctcaaagtttaattcttcttcttgggata-
ttttaaaaatgctactgagattct _at
gctgtaaatatgactagagaatatattgggtttgctttatttcataggcttaattctttgtaaatctga-
atgaccataatagaaat
acatttcttgtggcaagtaattcacagttgtaaagtaaataggaaaaattattttatttttattgatgtaca-
ttgatagatgccata
aatcagtagcaaaaggcacttctaaaggtaagtggtttaagttgcctcaanagagggacaatgtagctttat-
tttacaagaa
ggcatagttagatttctatgaaatatttattctgtacagttttatatanttttggttcacaaaagtaattat-
tcttgggtgcctttca a 200 236894
aaagtatattgtgctagcttgtctaagaataaacttnnatactgttgggggagggctgcacct-
gtcaagataacctgtcaat _at
gtagtaggaaaacaggaggggacagtaacagaaaagcacgggaaaagatggcaaggttagttaaaatag-
aaaagtg
ctcagttcctcatacctgtaatcccagcagtttagggggccaaggaaggtgggtcacttgagcccaagagtt-
caaggcc
atcctgggcaatgtggcgaaagtgtctacaaaaaaatacaaaaagaggaagaaatgatatttcacaagtttg-
tatcatttgt cat 201 238017
caaaaccacgattgtgtgccccttttttatnaaanctggnatgtttgaangttgtantacang-
ctntncttctntgttgccaat _at
tctgnnacnnnnntnnnnannngaaaaaatagtagaagctattctacaagaaaaaatgtacttgtatat-
gccaaagttgt
tatacttcatgatgtttcttaaaagctttttgcccctcaagacaggactgcttatagctgactatttgggca-
tccttcatgcaat
ggatggctttgttgaccaaaagaagaagctctaaagaccaactctatggctaaggtcatctgatacacagtg-
ttacataat
gcgtacttcaatgaagaaaagtatttttgtctgacagtggaatatatctggagaccacaagtaccactccta-
ttctgttatctg g 202 238021
agccgttggtctttgaaatttcctgtgatgtgtttcaatctagatgcaaagaacatggaaaaa-
tcaaagtgctcgagtggttt _s_at
aaatatgttttgggtattcctgtttatagactataatacttttccaattaaaatcctcagttgtcac-
gcagaagaaggttaagct
gtatttgattgccagttttactgaaaatgcttagtattttacagtatcaccaaatatattttgtttagccaa-
ggtatagga 203 238984
acccaacaagagctgtgcggctccctgattcctcgccagtgttgctaccgcccttggctcttc-
ttgcatggctggctcttga _at
gacccctggaagctgatggaggcaacgtgagaagcacatggacatccgnccntgagcttgagaggcaga-
ggcctga
gttctagttacagccccagcagtaccagttgtgtggactgggagggaggcnatcacgtacatactccaagcc-
tccaagc
ctgtttccccttctgacacaggatcttttgtggctggtatanagtgggcactcaataaatgctgtctggtcg-
tctggctggca
tgcctnatgggcctgagaattgaatagaattacagtgatagaagcatgctggtattgtaagtggtttgtaag-
tgtgaggact
aaattattattaaatagtaatcacatctaatcttggataaattagtaaaagcaagaatgggagcagtaaaaa-
cctaagcaac
ccgaactaaaattttattgaattaattcaatttcttgtcatgtaacacaaccccaga 204
241031
gtttctgtttcagtcacaaattagggttattgtgatgtgtatttatgatgaccnttgaacaaa-
tgtgaagaatactgtgaattcta _at
tgactttatcaaaatcagccacatccaggagcttgcagttgttgaccaaatgaatgatgacatagagta-
gttcagatctatc
atgtgctcttctatctaatcagtcaatatttccttggccctcaagccaacattcattttttatgtataacct-
tcttcatgattttgaa
attttgatagggtaactgctaatgagttcacaaatgtagcactttaaaaggaaaataaatggagagtgaaaa-
caacttggct acgtataattgtgggt 205 37892_
caacccattttgtgccacatgcaagttttgaataaggatggtatagaaaacaacgctgcatat-
acaggtaccatttaggna at
nnancngatgcctttntgggggcagaatcacatggcaaaagctttgaaaatcataaagatataagttggt-
gtggctaaga
tggaaacagggctgattcttgattcccaattctcaactctccttttcctatttgaatttctttggtgctgta-
gaaaacaaaaaaa
gaaaaatatatattcataaaaaatatggtgctcattctcatccatccaggatgtactaaaacagtgtgttta-
ataaattgtaatt
attttgtgtacagttctatactgttatctgtgtccatttccaaaacttgcacgtgtccctgaattcc
206 60474_
acagacttggcaagggaccccctggttctgagccagtagctgccatctggaaattcctctttt-
nnnnnnnnnnnnnnn at
nnnnnnnnnnnnnnnnnctcccaggnacccgctgaatttctgaggccttgcttaaagctcagaagtggtt-
taggcatt
tggaaaatctggttcacatcataaagaacttgatttgaaatgttttctatagaaacaagtgctaagtgtnac-
cgtattatacttg
atgttggtcatttctcagtcctatttctcagttctattattttagaacctagtcagttctttaagattataa-
ctggtcctacattaaaa
taatgcttctcgangtcagattttacctgtttgctgctgagaacatctctgcctaannnnnnnnnnnnnnnn-
cttcagttc aacatgcttccttagcttttcatagttgtctgacatttccatgaaa
BIBLIOGRAPHY
[0388] Affymetrix. GeneChip expression data analysis fundamentals.
Affymetrix, Santa Clara, Calif. USA, 2001. [0389] Alon et al.,
Proc. Natl. Acad. Sci. USA: 96, 6745-6750, June 1999 [0390]
Ausubel, F. et al., "Current Protocols in Molecular Biology", John
Wiley & Sons, (1998) [0391] Bonner et al (1973) J. Mol. Biol.
81:123 [0392] DeRisi, et al., Nature Genetics 14:457-460 (1996)
[0393] Germer et al., Genome Res. 10:258-266 (2000) [0394] Guo et
al., Nucleic Acids Res. 22:5456-5465 (1994) [0395] Heid et al.,
Genome Res. 6:986-994 (1996) [0396] Hubbell E. W., W. M. Liu, and
R. Mei. Robust estimators for expression analysis. Bioinformatics,
18:1585-1592, 2002. [0397] Irizarry R. W., B. M. Bolstad, F.
Collin, L. M. Cope, B. Hobbs, and T. P. Speed. Summaries of
affymetrix genechip probe level data. Nucleic Acid Research, 31,
2003. [0398] Kraus, M. and Aaronson, S., 1991. Methods Enzymol.,
200:546-556 [0399] Maskos and Southern, Nuc. Acids Res. 20:1679-84,
1992 [0400] Moore et al., BBA, 1402:239-249, 1988 [0401] Nielsen
(1999) Curr. Opin. Biotechnol. 10:71-75 [0402] Nielsen et al.
(1991) Science 254: 1497-1500 [0403] Pease et al., Proc. Natl.
Acad. Sci. USA 91(11):5022-5026 (1994) [0404] Pevzner et al., J.
Biomol. Struc. & Dyn. 9:399-410, 1991 [0405] Schena, et al.
Science 270:467-470 (1995) [0406] Smith et al., Science
258:1122-1126 (1992) [0407] Smyth G. K. Bioinformatics and
Computational Biology Solutions using R and Bioconductor. Springer,
N.Y., 2005. [0408] Smyth G. K. Linear models and empirical bayes
methods for assessing differential expression in microarray
experiments. Statistical Applications in Genetics and Molecular
Biology, 3(1):Article 3, 2004. [0409] T. Sano and C. R. Cantor,
Bio/Technology 9:1378-81 (1991) [0410] Urdea et al., Nucleic Acids
Symp. Ser., 24:197-200 (1991) [0411] Wedemeyer et al., Clinical
Chemistry 48:9 1398-1405, 2002) [0412] Weissleder et al., Nature
Medicine 6:351-355, 2000
Sequence CWU 1
1
2061441DNAhuman 1caaggctggg ccgggaaggg cgtgggttga ggagaggctc
cagacccgca cgccgcgcgc 60acagagctct cagcgccgct cccagccaca gcctcccgcg
cctcgctcag ctccaacatg 120gcaaaaatct ccagccctac agagactgag
cggtgcatcg agtccctgat tgctgtcttc 180cagaagtatg ctggaaagga
tggttataac tacactctct ccaagacaga gttcctaagc 240ttcatgaata
cagaactagc tgccttcaca aagaaccaga aggaccctgg tgtccttgac
300cgcatgatga agaaactgga caccaacagt gatggtcagc tagatttctc
agaatttctt 360aatctgattg gtggcctagc tatggcttgc catgactcct
tcctcaaggc tgtcccttcc 420cagaagcgga cctgaggacc c 4412416DNAhuman
2gttggttcaa acttttggga gcacggactg tcagttctct gggaagtggt cagcgcatcc
60tgcagggctt ctcctcctct gtcttttgga gaaccagggc tcttctcagg ggctctaggg
120actgccaggc tgtttcagcc aggaaggcca aaatcaagag tgagatgtag
aaagttgtaa 180aatagaaaaa gtggagttgg tgaatcggtt gttctttcct
cacatttgga tgattgtcat 240aaggttttta gcatgttcct ccttttcttc
accctcccct ttgttcttct attaatcaag 300agaaacttca aagttaatgg
gatggtcgga tctcacaggc tgagaactcg ttcacctcca 360agcatttcat
gaaaaagctg cttcttatta atcatacaaa ctctcaccat gatgtg 4163541DNAhuman
3aaaagcgagg tggccatgtt atgctggtgg ttgccagggc ctccaaccac tgtgccactg
60acttgctgtg tgaccctggg caagtcactt aactataagg tgcctcagtt ttccttctgt
120taaaatgggg ataataatac tgacctacct caaagggcag ttttgaggca
tgactaatgc 180tttttagaaa gcattttggg atccttcagc acaggaattc
tcaagacctg agtatttttt 240ataataggaa tgtccaccat gaacttgata
cgtccgtgtg tcccagatgc tgtcattagt 300ctatatggtt ctccaagaaa
ctgaatgaat ccattggaga agcggtggat aactagccag 360acaaaatttg
agaatacata aacaacgcat tgccacggaa acatacagag gatgcctttt
420ctgtgattgg gtgggatttt ttcccttttt atgtgggata tagtagttac
ttgtgacaag 480aataattttg gaataatttc tattaatatc aactctgaag
ctaattgtac taatctgaga 540t 5414357DNAhuman 4gcagcgggaa cagagtaccc
tcttcaagcc ccggtcatga tggaggtccc agccacaggg 60aaccatgagc tcagtggtct
tggaacagct cactaagtca gtccttcctt agcctggaag 120ccagtagtgg
agtcacaaag cccatgtgtt ttgccatcta ggccttcacc tggtctgtgg
180acttatacct gtgtgcttgg tttacaggtc cagtggttct tcagcccatg
acagatgaga 240aggggctata ttgaagggca aagaggaact gttgtttgaa
ttttcctgag agcctggctt 300agtgctgggc cttctcttaa acctcattac
aatgaggtta gtacttttag tccctgt 3575241DNAhuman 5agtgttgatg
ggctctactt ctgatcttgg tcactgtgaa aaaatcaaga aggcctgtgg 60aaattttggc
attccatgtg aacttcgagt aacatctgcg cataaaggac cagatgaaac
120tctgaggatt aaagctgagt atgaagggga tggcattcct actgtatttg
tggcagtggc 180aggcagaagt aatggtttgg gaccagtgat gtctgggaac
actgcatatc cagttatcag 240c 2416312DNAhuman 6agatctgtgc ggttggcata
accaacttac taacagaatg tcccccaatg atggacactg 60agtataccaa actgtggact
ccattattac agtctttgat tggtcttttt gagttacccg 120aagatgatac
cattcctgat gaggaacatt ttattgacat agaagataca ccaggatatc
180agactgcctt ctcacagttg gcatttgctg ggaaaaaaga gcatgatcct
gtaggtcaaa 240tggtgaataa ccccaaaatt cacctggcac agtcacttca
catgttgtct accgcctgtc 300caggaagggt tc 3127522DNAhuman 7tcagaaggta
ggggccgtgt cccgcggtgc tgactgaggc ctgcttcccc ctccccctcc 60tgctgtgctg
gaattccaca gggaccaggg ccaccgcagg ggactgtctc agaagacttg
120atttttccgt ccctttttct ccacactcca ctgacaaacg tccccagcgg
tttccacttg 180tgggcttcag gtgttttcaa gcacaaccca ccacaacaag
caagtgcatt ttcagtcgtt 240gtgctttttt gttttgtgct aacgtcttac
taatttaaag atgctgtcgg caccatgttt 300atttatttcc agtggtcatg
ctcagccttg ctgctctgcg tggcgcaggt gccatgcctg 360ctccctgtct
gtgtcccagc cacgcagggc catccactgt gacgtcggcc gaccaggctg
420gacaccctct gccgagtaat gacgtgtgtg gctgggacct tctttattct
gtgttaatgg 480ctaacctgtt acactgggct gggttgggta gggtgttctg gc
5228479DNAhuman 8tctctctttc tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg
tgtgtgtgtc ttgtgcttcc 60tcagaccttt ctcgcttctg agcttggtgg cctgttccct
ccatctctcc gaacctggct 120tcgcctgtcc ctttcactcc acaccctctg
gccttctgcc ttgagctggg actgctttct 180gtctgtccgg cctgcaccca
gcccctgccc acaaaacccc agggacagcg gtctccccag 240cctgccctgc
tcaggccttg cccccaaacc tgtactgtcc cggaggaggt tgggaggtgg
300aggcccagca tcccgcgcag atgacaccat caaccgccag agtcccagac
accggttttc 360ctagaagccc ctcaccccca ctggcccact ggtggctagg
tctcccctta tccttctggt 420ccagcgcaag gaggggctgc ttctgaggtc
ggtggctgtc tttccattaa agaaacacc 4799407DNAhuman 9tacagatact
ctactacact cagcctctta tgtgccaagt ttttctttaa gcaatgagaa 60attgctcatg
ttcttcatct tctcaaatca tcagaggccg aagaaaaaca ctttggctgt
120gtctataact tgacacagtc aatagaatga agaaaattag agtagttatg
tgattatttc 180agctcttgac ctgtcccctc tggctgcctc tgagtctgaa
tctcccaaag agagaaacca 240atttctaaga ggactggatt gcagaagact
cggggacaac atttgatcca agatcttaaa 300tgttatattg ataaccatgc
tcagcaatga gctattagat tcattttggg aaatctccat 360aatttcaatt
tgtaaacttt gttaagacct gtctacattg ttatatg
40710547DNAhumanmisc_feature(97)..(99)n is a, c, g, or
tmisc_feature(135)..(135)n is a, c, g, or
tmisc_feature(258)..(258)n is a, c, g, or t 10agcatcggag ccattcattc
ggagaaaacg ttttgatcaa aatggagact tttgtagtcg 60tttcaaaaga gcacctgagt
catgtgtatt cccggcnnnc tttataaatg acccggtcaa 120gttggtttca
aagtncgaca ggcttgtctg tttactagct gcgtggcctt ggacgggtgg
180ctgacatctg taaagaatcc tcctgtgatg aaactgagga atcgggtggc
cgggcaagct 240gggaagagca aagccagnag ctgcgctgcc tcaataccca
caaaagacca ttcccagtat 300acataagcac aggatgtttt tctcaagagg
gatgtattta tcacttggac atctgtttat 360aatataaaca gacatgtgac
tgggaacatc ttgctgccaa aagaatccta ggcagtggct 420cattgtatgt
gaggttgaac cacgtgaaat tgccaatatt aggctggctt ttatctacaa
480agaaggagtt tcatggggtt cagcctaaca gttatggaaa ctacagtcct
tataaaccat 540tggcatg 54711424DNAhuman 11gatgtatgtc gctgtccaag
agaaggctgt ggaagaacct atacaactgt gtttaatctc 60caaagccata tcctctcctt
ccatgaggaa agccgccctt ttgtgtgtga acatgctggc 120tgtggcaaaa
catttgcaat gaaacaaagt ctcactaggc atgctgttgt acatgatcct
180gacaagaaga aaatgaagct caaagtcaaa aaatctcgtg aaaaacggga
gtttggcctc 240tcatctcagt ggatatatcc tcccaaaagg aaacaagggc
aaggcttatc tttgtgtcaa 300aacggagagt cacccaactg tgtggaagac
aagatgctct cgacagttgc agtacttacc 360cttggctaag aactgcactg
ctttgtttaa aggactgcag accaaggagt cgagctttct 420ctca
42412375DNAhuman 12ggtctgttct tgaatcctct attaattact gtgtgtgagc
cagagggagc tgtggtaagg 60gttgggcccc cagcctgtag ggaactttct ggactcccac
tctttgaatc gatataggca 120tttggtctca ctacttgacc attctcaccc
tgtgaaacgt cccacacttt gaagcaaata 180caattcacag cacagtacac
acaaaaacct tggcataaga cagagaaggt tcttcttatt 240ttgtgggctg
gttgctgtag aaacatataa caaagggcag ccctccactt ctggtataat
300tgtgtagccc cttttctttg ggcttgacac ctgtcttgaa taagagtgat
tagagctgca 360taatgtccct ctctt
37513533DNAhumanmisc_feature(360)..(361)n is a, c, g, or t
13gaggtcagat ttggagcttc tcattgcacg cggagattat tattgcatcg ggttccaagc
60caatgggaag cccgggggag gggtttggca tgaggaagcg ttggttacag cagctgattg
120gctgcagcca agactgtgaa aggataaaga ggcgcgaggc ggaattgggg
tctgctctaa 180gctgcagcaa gagaaactgt gtgtgagggg aagaggcctg
tttcgctgtc gggtctctag 240ttcttgcacg ctctttaaga gtctgcactg
gaggaactcc tgccattacc agctcccttc 300ttgcagaagg gagggggaaa
catacattta ttcatgccag tctgttgcat gcaggctttn 360nggcttccta
ccttgcaaca aaataattgc accaactcct tagtgccgat tccgcccaca
420gagagtcctg gagccacagt cttttttgct ttgcattgta ggagagggac
taagtgctag 480agactatgtc gctttcctga gctaccgaga gcgctcgtga
actggaatca act 53314408DNAhuman 14gtaaaccaca tcttttttgc acttttttta
taagcaaaaa cgtgccgttt aaaccactgg 60atctatctaa atgccgattt gagttcgcga
cactatgtac tgcgtttttc attcttgtat 120ttgactattt aatcctttct
acttgtcgct aaatataatt gttttagtct tatggcatga 180tgatagcata
tgtgttcagg tttatagctg ttgtgtttaa aaattgaaaa aagtggaaaa
240catctttgta catttaagtc tgtattataa taagcaaaaa gattgtgtgt
atgtatgttt 300aatataacat gacaggcact aggacgtctg cctttttaag
gcagttccgt taagggtttt 360tgtttttaaa cttttttttg ccatccatcc
tgtgcaatat gccgtgta 40815414DNAhuman 15gatgacttac catgggatgg
ggtccagtcc catgaccttg gggtacaatt gtaaacctag 60agttttatca actttggtga
acagttttgg cataatagtc aatttctact tctggaagtc 120atctcattcc
actgttggta ttatataatt caaggagaat atgataaaac actgccctct
180tgtggtgcat tgaaagaaga gatgagaaat gatgaaaagg ttgcctgaaa
aatgggagac 240agcctcttac ttgccaagaa aatgaaggga ttggaccgag
ctggaaaacc tcctttacca 300gatgctgact ggcactggtg gtttttgctc
tcgacatatc cacaatagct gacggctggg 360tgtttcagtt tgcaaaatat
tttgttgcct tcatcttcac tgcaattttg tgta 41416481DNAhuman 16ttcagaccca
gtaactgtcc gcagctgtct gctagtggtt gtcttaacat cgtagtccta 60gtttgcattt
tttaaatccc ctctgtttaa aaggtttgta aaacaaaaac aaaaaactaa
120gtctgctcag tgaaatgctg tagaacccta aataagtggt agaagagtgt
cactgaattt 180tgtctctgaa ttcagtataa ctgagttttg tccatgctgg
tgtctgggtt ataggcctga 240tgggcctggt agttttccat cttgttctgg
cctagaggtc agtcctttgc acttcctcaa 300agcttgtgta cagtgctcac
ctaaatccat ctgactactt gttcctgtgc cctcttgttt 360taggcctcgt
ttacttttaa aaaatgaaat tgttcattgc tgggagaaga atgttgtaat
420ttttacttat taaagtcaac ttgttaagtt ttttatgtat tcctgttggg
ttttcttgtt 480g 48117545DNAhuman 17acaggaggaa tgcaccacgg cagctctccg
ccaatttctc tcagatttcc acagagactg 60tttgaatgtt ttcaaaacca agtatcacac
tttaatgtac atgggccgca ccataatgag 120atgtgagcct tgtgcatgtg
ggggaggagg gagagagatg tactttttaa atcatgttcc 180ccctaaacat
ggctgttaac ccactgcatg cagaaacttg gatgtcactg cctgacattc
240acttccagag aggacctatc ccaaatgtgg aattgactgc ctatgccaag
tccctggaaa 300aggagcttca gtattgtggg gctcataaaa catgaatcaa
gcaatccagc ctcatgggaa 360gtcctggcac agtttttgta aagcccttgc
acagctggag aaatggcatc attataagct 420atgagttgaa atgttctgtc
aaatgtgtct cacatctaca cgtggcttgg aggcttttat 480ggggccctgt
ccaggtagaa aagaaatggt atgtagagct tagatttccc tattgtgaca 540gagcc
54518446DNAhuman 18aggaaactgc tacttgtgga cctcaccaga gaccaggagg
gtttggttag ctcacaggac 60ttcccccacc ccagaagatt agcatcccat actagactca
tactcaactc aactaggctc 120atactcaatt gatggttatt agacaattcc
atttctttct ggttattata aacagaaaat 180ctttcctctt ctcattacca
gtaaaggctc ttggtatctt tctgttggaa tgatttctat 240gaacttgtct
tattttaatg gtgggttttt tttctggtaa gatttagacc taaatcgcat
300catgccaact tgtgactttg agactattca tcaagaatga ggatatagta
gccatgacat 360agcttgagct atagccttta attccttact ttggctatgg
gtggagggtg agtttgaaga 420ggttctgatt ttcttgtaac ctggga
44619521DNAhuman 19gattccgcct tgttggtctg aaattcatgc aagcttccga
agatcttctc aaggaacact 60acgttgacct gaaggaccgt ccattctttg ccggcctggt
gaaatacatg cactcagggc 120cggtagttgc catggtctgg gaggggctga
atgtggtgaa gacgggccga gtcatgctcg 180gggagaccaa ccctgcagac
tccaagcctg ggaccatccg tggagacttc tgcatacaag 240ttggcaggaa
cattatacat ggcagtgatt ctgtggagag tgcagagaag gagatcggct
300tgtggtttca ccctgaggaa ctggtagatt acacgagctg tgctcagaac
tggatctatg 360aatgacagga gggcagacca cattgctttt cacatccatt
tcccctcctt cccatgggca 420gaggaccagg ctgtaggaaa tctagttatt
tacaggaact tcatcataat ttggagggaa 480gctcttggag ctgtgagttc
tccctgtaca gtgttaccat c 52120482DNAhuman 20agaaaaccac acttctcata
ccttcactca acacttcctt ccccaaagcc agaagatgca 60caaggaggaa catgaggtgg
ctgtgctggg ggcacccccc agcaccatcc ttccaaggtc 120caccgtgatt
aacatccaca gcgagacctc cgtgcccgac catgtcgtct ggtccctgtt
180caacaccctc ttcttgaact ggtgctgtct gggcttcata gcattcgcct
actccgtaaa 240gtctagggac aggaagatgg ttggcgacgt gaccggggcc
caggcctatg cctccaccgc 300caagtgcctg aacatctggg ccctgattct
gggcatcctc atgaccattg gattcatcct 360gttactggta ttcggctctg
taacagtcta ccatattatg ttacagataa tacaggaaaa 420acggggttac
tagtagccgc ccatagcctg caacctttgc actccactgt gcaatgctgg 480cc
48221515DNAhuman 21gtagtgccac tgttgttttg gggggggctt tttttctttt
tccggaaaat ccttaaacct 60taagatacta aggacgttgt tttggttgta cttggaattc
ttagtcacaa aatatatttt 120gtttacaaaa atttctgtaa aacaggttat
aacagtgttt aaagtctcag tttcttgctt 180ggggaacttg tgtccctaat
gtgttagatt gctagattgc taaggagctg atacttgaca 240gttttttaga
cctgtgttac taaaaaaaag atgaatgtcg gaaaagggtg ttgggagggt
300ggtcaacaaa gaaacaaaga tgttatggtg tttagactta tggttgttaa
aaatgtcatc 360tcaagtcaag tcactggtct gtttgcattt gatacatttt
tgtactaact agcattgtaa 420aattatttca tgattagaaa ttacctgtgg
atatttgtat aaaagtgtga aataaatttt 480ttataaaagt gttcattgtt
tcgtaacaca gcatt 51522393DNAhuman 22tcagggccaa gttcgtgggg
acaccagaag tcaaccagac caccttatac cagcgttatg 60agatcaagat gaccaagatg
tataaagggt tccaagcctt aggggatgcc gctgacatcc 120ggttcgtcta
cacccccgcc atggagagtg tctgcggata cttccacagg tcccacaacc
180gcagcgagga gtttctcatt gctggaaaac tgcaggatgg actcttgcac
atcactacct 240gcagtttcgt ggctccctgg aacagcctga gcttagctca
gcgccggggc ttcaccaaga 300cctacactgt tggctgtgag gaatgcacag
tgtttccctg tttatccatc ccctgcaaac 360tgcagagtgg cactcattgc
ttgtggacgg acc 39323432DNAhuman 23gtgatttttt tccacaagat ctgtaatgtt
atttccactt ataaaggaaa taaaaaatga 60aaaacattat ttggatatca aaagcaaata
aaaacccaat tcagtctctt ctaagcaaaa 120ttgctaaaga gagatgaacc
acattataaa gtaatctttg gctgtaaggc attttcatct 180ttccttcggg
ttggcaaaat attttaaagg taaaacatgc tggtgaacca ggggtgttga
240tggtgataag ggaggaatat agaatgaaag actgaatctt cctttgttgc
acaaatagag 300tttggaaaaa gcctgtgaaa ggtgtcttct ttgacttaat
gtctttaaaa gtatccagag 360atactacaat attaacataa gaaaagatta
tatattattt ctgaatcgag atgtccatag 420tcaaatttgt aa 43224429DNAhuman
24gagagcactc tatttattgt actgtgaata atgatgaagg agagtggagt ggcccaccac
60ctgaatgcag aggaaaatct ctaacttcca aggtcccacc aacagttcag aaacctacca
120cagtaaatgt tccaactaca gaagtctcac caacttctca gaaaaccacc
acaaaaacca 180ccacaccaaa tgctcaagca acacggagta cacctgtttc
caggacaacc aagcattttc 240atgaaacaac cccaaataaa ggaagtggaa
ccacttcagg tactacccgt cttctatctg 300ggcacacgtg tttcacgttg
acaggtttgc ttgggacgct agtaaccatg ggcttgctga 360cttagccaaa
gaagagttaa gaagaaaata cacacaagta tacagactgt tcctagtttc 420ttagactta
42925324DNAhuman 25gtatgacaac ccgggatcgt ttgcaagtaa ctgaatccat
tgcgacattg tgaaggctta 60aatgagttta gatgggaaat agcgttgtta tcgccttggg
tttaaattat ttgatgagtt 120ccacttgtat catggcctac ccgaggagaa
gaggagtttg ttaactgggc ctatgtagta 180gcctcattta ccatcgtttg
tattactgac cacatatgct tgtcactggg aaagaagcct 240gtttcagctg
cctgaacgca gtttggatgt ctttgaggac agacattgcc cggaaactca
300gtctatttat tcttcagctt gccc 32426473DNAhuman 26tggcctacat
ggaccagcag actggcaacc tcaagaaggc cctgctcctc cagggctcca 60acgagatcga
gatccgcgcc gagggcaaca gccgcttcac ctacagcgtc actgtcgatg
120gctgcacgag tcacaccgga gcctggggca agacagtgat tgaatacaaa
accaccaaga 180cctcccgcct gcccatcatc gatgtggccc ccttggacgt
tggtgcccca gaccaggaat 240tcggcttcga cgttggccct gtctgcttcc
tgtaaactcc ctccatccca acctggctcc 300ctcccaccca accaactttc
cccccaaccc ggaaacagac aagcaaccca aactgaaccc 360cctcaaaagc
caaaaaatgg gagacaattt cacatggact ttggaaaata tttttttcct
420ttgcattcat ctctcaaact tagtttttat ctttgaccaa ccgaacatga cca
47327472DNAhumanmisc_feature(149)..(149)n is a, c, g, or
tmisc_feature(153)..(153)n is a, c, g, or
tmisc_feature(428)..(428)n is a, c, g, or t 27gctccccatt tttataccaa
aggtgctaca tctatgtgat gggtggggtg gggagggaat 60cactggtgct atagaaattg
agatgccccc ccaggccagc aaatgttcct ttttgttcaa 120agtctatttt
tattccttga tattttttnt ttnttttttt ttttttttgt ggatggggac
180ttgtgaattt ttctaaaggt gctatttaac atgggaggag agcgtgtgcg
gctccagccc 240agcccgctgc tcactttcca ccctctctcc acctgcctct
ggcttctcag gcctctgctc 300tccgacctct ctcctctgaa accctcctcc
acagctgcag cccatcctcc cggctccctc 360ctagtctgtc ctgcgtcctc
tgtccccggg tttcagagac aacttcccaa agcacaaagc 420agtttttncc
cctaggggtg ggaggaagca aaagactctg tacctatttt gt 47228474DNAhuman
28aacctgaaaa catcccagcc aagaactggt ataggagctc caaggacaag aaacacgtct
60ggctaggaga aactatcaat gctggcagcc agtttgaata taatgtagaa ggagtgactt
120ccaaggaaat ggctacccaa cttgccttca tgcgcctgct ggccaactat
gcctctcaga 180acatcaccta ccactgcaag aacagcattg catacatgga
tgaggagact ggcaacctga 240aaaaggctgt cattctacag ggctctaatg
atgttgaact tgttgctgag ggcaacagca 300ggttcactta cactgttctt
gtagatggct gctctaaaaa gacaaatgaa tggggaaaga 360caatcattga
atacaaaaca aataagccat cacgcctgcc cttccttgat attgcacctt
420tggacatcgg tggtgctgac caggaattct ttgtggacat tggcccagtc tgtt
47429356DNAhuman 29actttcccat gagtgtgatc cacattgtta ggtgctgacc
tagacagaga tgaactgagg 60tccttgtttt gttttgttca taatacaaag gtgctaatta
atagtatttc agatacttga 120agaatgttga tggtgctaga agaatttgag
aagaaatact cctgtattga gttgtatcgt 180gtggtgtatt ttttaaaaaa
tttgatttag cattcatatt ttccatctta ttcccaatta 240aaagtatgca
gattatttgc ccaaagttgt cctcttcttc agattcagca tttgttcttt
300gccagtctca ttttcatctt cttccatggt tccacagaag ctttgtttct tgggca
35630418DNAhuman 30gcaacaaccg aaaatgcacc agccccaggt cctcggacac
cgaggagaat gtcaagaggc 60gaacacacaa cgtcttggag cgccagagga ggaacgagct
aaaacggagc ttttttgccc 120tgcgtgacca gatcccggag ttggaaaaca
atgaaaaggc ccccaaggta gttatcctta 180aaaaagccac agcatacatc
ctgtccgtcc aagcagagga gcaaaagctc atttctgaag 240aggacttgtt
gcggaaacga cgagaacagt tgaaacacaa acttgaacag ctacggaact
300cttgtgcgta aggaaaagta aggaaaacga ttccttctaa cagaaatgtc
ctgagcaatc 360acctatgaac ttgtttcaaa tgcatgatca aatgcaacct
cacaaccttg gctgagtc 41831380DNAhuman 31ggaaacctct cagtgtcttg
acatcaccct acccaggcgg tgggtctcca ccacagccac 60tttgagtctg tggtccctgg
agggtggctt ctcctgactg gcaggatgac cttagccaag 120atattcctct
gttccctctg ctgagataaa gaattccctt aacatgatat aatccaccca
180tgcaaatagc tactggccca gctaccattt accatttgcc tacagaattt
cattcagtct 240acactttggc attctctctg gcgatggagt
gtggctgggc tgaccgcaaa aggtgcctta 300cacactgccc ccaccctcag
ccgttgcccc atcagaggct gcctcctcct tctgattacc 360ccccatgttg
catatcaggg 38032289DNAhuman 32atccccaact gtgacaagca tggcctgtac
aacctcaaac agtgcaagat gtctctgaac 60gggcagcgtg gggagtgctg gtgtgtgaac
cccaacaccg ggaagctgat ccagggagcc 120cccaccatcc ggggggaccc
cgagtgtcat ctcttctaca atgagcagca ggaggcttgc 180ggggtgcaca
cccagcggat gcagtagacc gcagccagcc ggtgcctggc gcccctgccc
240cccgcccctc tccaaacacc ggcagaaaac ggagagtgct tgggtggtg
28933212DNAhuman 33ccgaacgtgg gcgccaatgg cgagatctgc gtcaacgtgc
tcaagaggga ctggacggct 60gagctgggca tccgacacgt actgctgacc atcaagtgcc
tgctgatcca ccctaacccc 120gagtctgcac tcaacgagga ggcgggccgc
ctgctcttgg agaactacga ggagtatgcg 180gctcgggccc gtctgctcac
agagatccac gg 21234464DNAhuman 34ctacccttat gatgacccat tttccctcat
gaccgatccc aagctcatca tttggagccc 60tgtgcgccgc tcagatgtgg cctggaactt
tgagaagttc ctcatagggc cggagggaga 120gcccttccga cgctacagcc
gcaccttccc aaccatcaac attgagcctg acatcaagcg 180cctccttaaa
gttgccatat agatgtgaac tgctcaacac acagatctcc tactccatcc
240agtcctgagg agccttagga tgcagcatgc cttcaggaga cactgctgga
cctcagcatt 300cccttgatat cagtcccctt cactgcagag ccttgccttt
cccctctgcc tgtttccttt 360tcctctccca accctctggt tggtgattca
acttgggctc caagacttgg gtaagctctg 420ggccttcaca gaatgatggc
accttcctaa accctcatgg gtgg 46435224DNAhuman 35gaagcgttta ggcatgttta
acatccagca ctgtaagaag ctgtccagct gggtactgct 60aatgaaatac ctgggcaatg
ccaccgccat cttcttccta cctgatgagg ggaaactaca 120gcacctggaa
aatgaactca cccacgatat catcaccaag ttcctggaaa atgaagacag
180aaggtctgcc agcttacatt tacccaaact gtccattact ggaa
22436364DNAhuman 36gtacccagtt aaattttcat ttcagataaa caacaaataa
ttttttagta taagtacatt 60attgtttatc tgaaagtttt aattgaacta acaatcctag
tttgatactc ccagtcttgt 120cattgccagc tgtgttggta gtgctgtgtt
gaattacgga ataatgagtt agaactatta 180aaacagccaa aactccacag
tcaatattag taatttcttg ctggttgaaa cttgtttatt 240atgtacaaat
agattcttat aatattattt aaatgactgc atttttaaat acaaggcttt
300atatttttaa ctttaagatg tttttatgtg ctctccaaat tttttttact
gtttctgatt 360gtat 36437529DNAhuman 37gagaggacca accagaattc
cctttggaca tttgtgtttt tttgtttttt tattttgttt 60tgttttttct tcttcttctt
cttccttaaa gacatttaag ctaaaggcaa ctcgtaccca 120aatttccaag
acacaaacat gacctatcca agcgcattac ccacttgtgg ccaatcagtg
180gccaggccaa ccttggctaa atggagcagc gaaatcaacg agaaactgga
ctttttaaac 240cctcttcaga gcaagcgtgg aggatgatgg agaatcgtgt
gatcagtgtg ctaaatctct 300ctgcctgttt ggactttgta attatttttt
tagcagtaat taaagaaaaa agtcctctgt 360gaggaatatt ctctatttta
aatattttta gtatgtactg tgtatgattc attaccattt 420tgaggggatt
tatacatatt tttagataaa attaaatgct cttatttttc caacagctaa
480actactctta gttgaacagt gtgccctagc ttttcttgca accagagta
52938516DNAhuman 38gtagtgtatc actgagtcat ttgcagtgtt ttctgccaca
gacctttggg ctgccttata 60ttgtgtgtgt gtgtgggtgt gtgtgtgttt tgacacaaaa
acaatgcaag catgtgtcat 120ccatatttct ctacatcttc tcttggagtg
agggaggcta cctggagggg atcagcccac 180tgacagacct taatcttaat
tactgctgtg gctagagagt ttgaggattg ctttttaaaa 240aagacagcaa
actttttttt ttatttaaaa aaagatatat taacagtttt agaagtcagt
300agaataaaat cttaaagcac tcataatatg gcatccttca atttctgtat
aaaagcagat 360ctttttaaaa aagatacttc tgtaacttaa gaaacctggc
atttaaatca tattttgtct 420ttaggtaaaa gctttggttt gtgttcgtgt
tttgtttgtt tcacttgttt ccctcccagc 480cccaaacctt ttgttctctc
cgtgaaactt accttt 51639459DNAhuman 39gccttccctg aatcagacaa
ccttttcaaa tgggtaggga ccatccatgg agcagctgga 60acagtatatg aagacctgag
gtataagctc tcgctagagt tccccagtgg ctacccttac 120aatgcgccca
cagtgaagtt cctcacgccc tgctatcacc ccaacgtgga cacccagggt
180aacatatgcc tggacatcct gaaggaaaag tggtctgccc tgtatgatgt
caggaccatt 240ctgctctcca tccagagcct tctaggagaa cccaacattg
atagtccctt gaacacacat 300gctgccgagc tctggaaaaa ccccacagct
tttaagaagt acctgcaaga aacctactca 360aagcaggtca ccagccagga
gccctgaccc aggctgccca gcctgtcctt gtgtcgtctt 420tttaattttt
ccttagatgg tctgtccttt ttgtgattt 45940557DNAhuman 40gccagtcttg
accgggatga ggcccacaga caggttgtca tcagcttgtc ccattcaagc 60caccgagctc
accacagaca cagtggagcc gcgctcttct ccagtgacac gtggacaaat
120gcgggctcat cagccccccc agagagggtc aggccgaacc ccatttctcc
tcctcttagg 180tcattttcag caaacttgaa tatctagacc tctcttccaa
tgaaaccctc cagtctatta 240tagtcacata gataatggtg ccacgtgttt
tctgatttgg tgagctcaga cttggtgctt 300ccctctccac aacccccacc
ccttgttttt caagatacta ttattatatt ttcacagact 360tttgaagcac
aaatttattg gcatttaata ttggacatct gggcccttgg aagtacaaat
420ctaaggaaaa accaacccac tgtgtaagtg actcatcttc ctgttgttcc
aattctgtgg 480gtttttgatt caacggtgct ataaccaggg tcctgggtga
cagggcgctc actgagcacc 540atgtgtcatc acagaca 55741546DNAhuman
41caggaaatag tcactcatcc cactccacat aaggggttta gtaagagaag tctgtctgtc
60tgatgatgga tagggggcaa atctttttcc cctttctgtt aatagtcatc acatttctat
120gccaaacagg aacgatccat aactttagtc ttaatgtaca cattgcattt
tgataaaatt 180aattttgttg tttcctttga ggttgatcgt tgtgttgttt
tgctgcactt tttacttttt 240tgcgtgtgga gctgtattcc cgagacaacg
aagcgttggg atacttcatt aaatgtagcg 300actgtcaaca gcgtgcaggt
tttctgtttc tgtgttgtgg ggtcaaccgt acaatggtgt 360gggaatgacg
atgatgtgaa tatttagaat gtaccatatt ttttgtaaat tatttatgtt
420tttctaaaca aatttatcgt ataggttgat gaaacgtcat gtgttttgcc
aaagactgta 480aatatttatt tatgtgttca catggtcaaa atttcaccac
tgaaaccctg cacttagcta 540gaacct 54642520DNAhuman 42atggtaacat
gtatctttgc cctgggtctg ggtgggtcca gtcagtctca gatttacaag 60catttaggag
cctaggtaaa agctgctagt attcttttaa aagttatatt tatgacttgc
120aatgatagaa aactccttcc aattaaatgg cattttataa tattatgtgt
gtacttcaca 180gtgttaaaaa taccctcata cgttattgca tttgatcttc
acagaaagtg cattttaacc 240agtactctgg gtgcaataaa taatatgtag
aaatttaagt cctccaattc cagcatatcc 300agtgagtttt gacagtgtgt
ttatgtggaa tgtttaagga tatacaattg tactttatat 360aaattggttc
ttgttcttct taaatgtgac atgaaataat tgtgctgcta cattatactg
420gaaattaaca ggggaaaagg gaagagctct tggctccctt gaggttctgc
tagtggtgtt 480aggagtggtt acaactgagc ttttagtaac catttaaccg
52043468DNAhumanmisc_feature(399)..(399)n is a, c, g, or t
43tgctaagttc aagtttcgta atgctttgaa gtatttttat gctctgaatg tttaaatgtt
60ctcatcagtt tcttgccatg ttgttaacta tacaacctgg ctaaagatga atatttttct
120actggtattt taatttttga cctaaatgtt taagcattcg gaatgagaaa
actatacaga 180tttgagaaat gatgctaaat ttataggagt tttcagtaac
ttaaaaagct aacatgagag 240catgccaaaa tttgctaagt cttacaaaga
tcaagggctg tccgcaacag ggaagaacag 300ttttgaaaat ttatgaacta
tcttattttt aggtaggttt tgaaagcttt ttgtctaagt 360gaattcttat
gccttggtca gagtaataac tgaaggagnt gcttatcttg gctttcgagt
420ctgagtttaa aactacacat tttgacatag tgtttattag cagccatc
46844477DNAhuman 44gtggccgtag caacttggcg gagacaggct atgagtctga
cgttagagtg gttgcttcct 60tagcctttca ggatggagga atgtgggcag tttgacttca
gcactgaaaa cctctccacc 120tgggccaggg ttgcctcaga ggccaagttt
ccagaagcct cttacctgcc gtaaaatgct 180caaccctgtg tcctgggcct
gggcctgctg tgactgacct acagtggact ttctctctgg 240aatggaacct
tcttaggcct cctggtgcaa cttaattttt ttttttaatg ctatcttcaa
300aacgttagag aaagttcttc aaaagtgcag cccagagctg ctgggcccac
tggccgtcct 360gcatttctgg tttccagacc ccaatgcctc ccattcggat
ggatctctgc gtttttatac 420tgagtgtgcc taggttgccc cttatttttt
attttccctg ttgcgttgct atagatg 47745517DNAhuman 45agagtggtct
tttcaacact cctcccccta ctccaccgga cctcaaccag gacttcagtg 60gatttcagct
tctagtggat gttgcactca aacgggctgc agagatggag cttcaggcaa
120aacttacagc ttaacccatt ttcaagcaaa acagttctca gaaatgtcat
gattgccggg 180gtgaaggcaa gagatgaatt gcattatttt atatattttt
tattaatatt tgcacatggg 240attgctaaaa cagcttcctg ttactgagat
gtcttcaatg gaatacagtc attccaagaa 300ctataaactt aaagctactg
tagaaacaaa gggttttctt ttttaaatgt ttcttggtag 360attattcata
atgtgagatg gttcccaata tcatgtgatt tttttttttc ctccccttcc
420ctttttttgt tattttttca gactgtgcaa tacttagaga acctatagca
tcttctcatt 480cccatgtgga acaggatgcc cacatactgt ctaatta
51746513DNAhuman 46gaagccaagg gttaacccag caagctacaa agagggtgtg
tcacactgaa actcaatagt 60tgagtttggc tgttgttgca ggaaaatgat tataactaaa
agctctctga tagtgcagag 120acttaccaga agacacaagg aattgtactg
aagagctatt acaatccaaa tattgccgtt 180tcataaatgt aataagtaat
actaattcac agagtattgt aaatggtgga tgacaaaaga 240aaatctgctc
tgtggaaaga aagaactgtc tctaccaggg tcaagagcat gaacgcatca
300atagaaagaa ctcggggaaa catcccatca acaggactac acacttgtat
atacattctt 360gagaacactg caatgtgaaa atcacgtttg ctatttataa
acttgtcctt agattaatgt 420gtctggacag attgtgggag taagtgattc
ttctaagaat tagatacttg tcactgccta 480tacctgcagc tgaactgaat
ggtacttcgt atg 51347546DNAhuman 47gaagcaggtg gaaacatgag cattcagttt
cttggtacag tgtacaaggt gaatatctta 60accagacttg ccgcagaatt gaacaaattt
atgctggaaa aagtgactga ggacacaagc 120agtgttctgc gttccccgat
gcccggagtg gtggtggccg tctctgtcaa gcctggagac 180gcggtagcag
aaggtcaaga aatttgtgtg attgaagcca tgaaaatgca gaatagtatg
240acagctggga aaactggcac ggtgaaatct gtgcactgtc aagctggaga
cacagttgga 300gaaggggatc tgctcgtgga gctggaatga aggatttata
acctttcagt catcacccaa 360tttaattagc catttgcatg atgctttcac
acacaattga ttcaagcatt atacaggaac 420acccctgtgc agctacgttt
acgtcgtcat ttattccaca gagtcaagac caatattctg 480ccaaaaaatc
accaatggaa attttcatga tataaatact tgtactatag atgtacttct 540gctgtg
54648539DNAhuman 48tgccagcgac tgtctcagac tgggcaggga ggctttggca
tgacttaaga ggaagggcag 60tcttgggacc cgctatgcag gtcctggcaa acctggctgc
cctgtctcat ccctgtccct 120cagggtagca ccatggcagg actgggggaa
ctggagtgtc cttgctgtat ccctgttgtg 180aggttccttc caggggctgg
cactgaagca agggtgctgg ggccccatgg ccttcagccc 240tggctgagca
actgggctgt agggcagggc cacttcctga ggtcaggtct tggtaggtgc
300ctgcatctgt ctgccttctg gctgacaatc ctggaaatct gttctccaga
atccaggcca 360aaaagttcac agtcaaatgg ggaggggtat tcttcatgca
ggagacccca ggccctggag 420gctgcaacat acctcaatcc tgtcccaggc
cggatcctcc tgaagccctt ttcgcagcac 480tgctatcctc caaagccatt
gtaaatgtgt gtacagtgtg tataaacctt cttcttctt 53949508DNAhuman
49gactaatcca tacacagtta acctaatgcc aaataaatac tggttaaata aatgtatggc
60acagaatata atttgactat caagactttt agcataatga aaaaccctct ctctatatat
120atatgtgtat atgaattatg tgggcattct tgatacttca agttctagtt
tgaaaaaaat 180acataactaa tttaatttta cacaaaaata tttatgcaga
ttttcagaat ttcatatcag 240gaaatgacct ttttatgtct gttaaatatc
aaaacaattt gctacagtgt taatctgcat 300ggtctttaag cctgctgtag
ttgagttgca gacagtgcat gaaaaagtat tccgctggga 360attgagccat
gccaccaaag ccaagaggag cgcatggaaa cccggtagtc tagaactaat
420cagattactg attttagggc acagcaccag atgaattgtt gtatatgctt
gtaaaaattg 480attctgtgtg ttcctctgaa caaagcgg 50850466DNAhuman
50gtccagcttg aacatctaga attcctagag aaacagaatg agcaggcgaa ggagatgcag
60cagatggtga aattggaagc cgagatggac cgcagaccag caacagtagt atgaaactcc
120aaaatgcaaa ctgaagcagc aaacccacaa agcatcaaaa gactcactca
caaaacttct 180gaacacaaac tccatggatg aaagctgttt attttgtttc
ctttatgtgt aaacaagatg 240atatctgaaa ccagagagac ttggaatgtc
tgactgactt ctatttaaca gcttgagtat 300tgcatttcct tggccaaaca
aaaatagcta caaatccaca aaaatttact attccagtaa 360ggcagagtcc
aaccattgat aatacaactt aaacatgttt gctataaaat accatcacaa
420gtaaatgagc ttggtgtgaa caactcttcc tttgtgatgc cttagg
46651440DNAhumanmisc_feature(331)..(331)n is a, c, g, or t
51ggactagagc aacatcgtgc tgcccaaagg actaacctat gcaaactagt tcacatttta
60gtggatgtcg cagttaatgt gtaataagac attatttccc ctgcataatg tacaacagca
120ttgaaatgac acattaagcc tagcatcaca ttgtatagta cagtcactca
caaacccttc 180aaggctaccc taatcattaa cattaatatt tgtttaaaag
caaatcaccg atttatctat 240tgaaactact taaatgacgg caaaccagga
atgacagatg gctgtgtcag caatggcttt 300aatgtgttcc ctgcaagtgg
tctcctatga ntagaactgc gttctcaaat gcactctctt 360cagggtctta
atattctgtg ttttctctct gtatttgtaa aacattataa cacattaatt
420tcctatctct acacatttgg 44052505DNAhuman 52gtcaaggcat tgtatgttgc
ttctgtggtt attattctgt gatgcttaga ctacttgaac 60ccataaactt ggaagaatct
ttgagcaaat tttctcagtt gtctgtatga cttcagtata 120ttcctgggaa
tgccatagga ttttttgtgc ttgatacatg gtatccagtt tgcatagtat
180cacttctttg taatccagtt gctgttaaga atgatgtact ttaaaggaaa
agagaaaact 240gcatcacagt cccattctcc agtgtccatg caatgaattg
ctgagcattt aggaagcagc 300accaagtcta ttacaggcat ggtgtgaaac
ttgatgtttg acctgtgatc aaaattgaac 360cattgtacag tttggcttct
gtttgcttca aaatatgtag aattgtggtt gatgattaat 420ttgcgagact
aactttgaga gtgtaacagt tttgaagaaa acattgaatg ttttacaaat
480gaaggggctt cacggaatgt tacaa 50553291DNAhuman 53aaccagccag
tcccaagaag aacattaaaa ctaggagtgc ccagaagaga acaaacccga 60aaagagtgtg
agctaactag tttccaaagc ggagacttcc gacttcctta caggatgagg
120ctgggcattg cctgggacag cctatgtaag gccatgtgcc ccttgcccta
acaactcact 180gcagtgctct tcatagacac atcttgcagc atttttctta
aggctatgct tcagtttttc 240tttgtaagcc atcacaagcc atagtggtag
gtttgccctt tggtacagaa g 29154468DNAhuman 54ttgtgttttg tcattagctc
tgcccttttt aattaaatat tttggttcat ggaccaaagg 60gtttacttga caaatttgtg
tgacagactc cgaacaattc ctttactacg aagtataatt 120tataaaataa
aatataccca ttttaagggt acagtttgat ttttgaccag tgaaactatg
180atcccaatca aggtatagat gccgtcaccc caaaaagttc cctccatatc
cctttgcagt 240cagttcatcc ctaccctggc ccagatgatc actgatcttg
tcattataga tgagttttgc 300cagttcaaga atttaatgga atcagatatt
gtaagcattc ttgtgtaata cttcattctc 360tctcattatt gagattcatc
catattgttg aatgtttcac tagttaatgt ttattgttca 420atatttttgt
atatactttt aaagcctatt cacttgctga tggatctt 46855496DNAhuman
55cgctctcgtt tcattttctg cagcgcgcca cgaggatggc ccacaagcag atctactact
60cggacaagta cttcgacgaa cactacgagt accggcatgt tatgttaccc agagaacttt
120ccaaacaagt acctaaaact catctgatgt ctgaagagga gtggaggaga
cttggtgtcc 180aacagagtct aggctgggtt cattacatga ttcatgagcc
agaaccacat attcttctct 240ttagacgacc tcttccaaaa gatcaacaaa
aatgaagttt atctggggat cgtcaaatct 300ttttcaaatt taatgtatat
gtgtatataa ggtagtattc agtgaatact tgagaaatgt 360acaaatcttt
catccatacc tgtgcatgag ctgtattctt cacagcaaca gagctcagtt
420aaatgcaact gcaagtaggt tactgtaaga tgtttaagat aaaagttctt
ccagtcagtt 480tttctcttaa gtgcct 49656543DNAhuman 56ctcatgggga
ctcctaccca tttgatgggc caggaaacac gctggctcat gcctttgcgc 60ctgggacagg
tctcggagga gatgctcact tcgatgagga tgaacgctgg acggatggta
120gcagtctagg gattaacttc ctgtatgctg caactcatga acttggccat
tctttgggta 180tgggacattc ctctgatcct aatgcagtga tgtatccaac
ctatggaaat ggagatcccc 240aaaattttaa actttcccag gatgatatta
aaggcattca gaaactatat ggaaagagaa 300gtaattcaag aaagaaatag
aaacttcagg cagaacatcc attcattcat tcattggatt 360gtatatcatt
gttgcacaat cagaattgat aagcactgtt cctccactcc atttagcaat
420tatgtcaccc ttttttattg cagttggttt ttgaatgtct ttcactcctt
ttattggtta 480aactccttta tggtgtgact gtgtcttatt ccatctatga
gctttgtcag tgcgcgtaga 540tgt 54357507DNAhuman 57gaaaatgtac
cttggtgcca ccaacccatt ttgtgccaca tgcaagtttt gaataaggat 60gtatggaaaa
caacgctgca tatacaggta ccatttagga aataccgatg cctttgtggg
120ggcagaatca cagacaaaag ctttgaaaat cataaagata taagttggtg
tggctaagat 180ggaaacaggg ctgattcttg attcccaatt ctcaactctc
cttttcctat ttgaatttct 240ttggtgctgt agaaaacaaa aaaagaaaaa
tatatattca taaaaaatat ggtgctcatt 300ctcatccatc caggatgtac
taaaacagtg tgtttaataa attgtaatta ttttgtgtac 360agttctatac
tgttatctgt gtccatttcc aaaacttgca cgtgtccctg aattccgctg
420actctaattt atgaggatgc cgaactctga tggcaataat atatgtatta
tgaaaatgaa 480gttatgattt ccgatgaccc taagtcc 50758406DNAhuman
58gggtctgaat ctagcaccat gacggaacta gagacagcca tgggcatgat catagacgtc
60ttttcccgat attcgggcag cgagggcagc acgcagaccc tgaccaaggg ggagctcaag
120gtgctgatgg agaaggagct accaggcttc ctgcagagtg gaaaagacaa
ggatgccgtg 180gataaattgc tcaaggacct ggacgccaat ggagatgccc
aggtggactt cagtgagttc 240atcgtgttcg tggctgcaat cacgtctgcc
tgtcacaagt actttgagaa ggcaggactc 300aaatgatgcc ctggagatgt
cacagattcc tgcagagcca tggtcccagg cttcccaaaa 360gtgtttgttg
gcaattattc ccctaggctg agcctgctca tgtacc 40659485DNAhuman
59gtagctggac ccacgaggag gaaccaggct actttcccca gtactgaggt ggtggacatc
60gtctctgcca ctcctgaccc agccctgaac aaagcacctc aagtgcaagg accaaagggg
120gccctggctt ggagtgggtt ggcttgctga tggctgctgg aggggacgct
ggctaaagtg 180ggtaggcctt ggcccacctg aggccccagg tgggaacatg
gtcaccccca ctctgcatac 240cctcatcaaa aacactctca ctatgctgct
atggacgacc tccagctctc agttacaagt 300gcaggcgact ggaggcagga
ctcctgggtc cctgggaaag agggtactag gggcccggat 360ccaggattct
gggaggcttc agttaccgct ggccgagctg aagaactggg tatgaggctg
420gggcggggct ggaggtggcg ccccctggtg ggacaacaaa gaggacacca
tttttccaga 480gctgc 48560410DNAhuman 60agaccaagac ataccggcag
atcaggttaa atgagttatt aaaggaacat tcaagcacag 60ctaatattat tgtcatgagt
ctcccagttg cacgaaaagg tgctgtgtct agtgctctct 120acatggcatg
gttagaagct ctatctaagg acctaccacc aatcctccta gttcgtggga
180atcatcagag tgtccttacc ttctattcat aaatgttcta tacagtggac
agccctccag 240aatggtactt cagtgcctag tgtagtaacc tgaaatcttc
aatgacacat taacatcaca 300atggcgaatg gtgacttttc tttcacgatt
tcattaattt gaaagcacac aggaaagctt 360gctccattga taacgtgtat
ggagacttcg gttttagtca attccatatc 41061433DNAhuman 61tatgattaac
tctacctgca cactgtccta ttatattcat tctttttgaa atgtcaaccc 60caagttagtt
caatctggat tcatatttaa tttgaaggta gaatgttttc aaatgttctc
120cagtcattat gttaatattt ctgaggagcc tgcaacatgc cagccactgt
gatagaggct 180ggcggatcca agcaaatggc caatgagatc attgtgaagg
caggggaatg
tatgtgcaca 240tctgttttgt aactgtttag atgaatgtca gttgttattt
attgaaatga tttcacagtg 300tgtggtcaac atttctcatg ttgaaacttt
aagaactaaa atgttctaaa tatcccttgg 360acattttatg tctttcttgt
aaggcatact gccttgttta atggtagttt tacagtgttt 420ctggcttaga aca
43362386DNAhuman 62gaagaactgt ctattttctc agtcattttt aacctctaga
gtcactgata cacagaatat 60aatcttattt atacctcagt ttgcatattt ttttactatt
tagaatgtag ccctttttgt 120actgatataa tttagttcca caaatggtgg
gtacaaaaag tcaagtttgt ggcttatgga 180ttcatatagg ccagagttgc
aaagatcttt tccagagtat gcaactctga cgttgatccc 240agagagcagc
ttcagtgaca aacatatcct ttcaagacag aaagagacag gagacatgag
300tctttgccgg aggaaaagca gctcaagaac acatgtgcag tcactggtgt
caccctggat 360aggcaaggga taactcttct aacaca 38663510DNAhuman
63agatgatgga ccctggttat cccaaactga ttaccaagaa cttccaagga atcgggccta
60aaattgatgc agtcttctat tctaaaaaca aatactacta tttcttccaa ggatctaacc
120aatttgaata tgacttccta ctccaacgta tcaccaaaac actgaaaagc
aatagctggt 180ttggttgtta gaaatggtgt aattaatggt ttttgttagt
tcacttcagc ttaataagta 240tttattgcat atttgctatg tcctcagtgt
accactactt agagatatgt atcataaaaa 300taaaatctgt aaaccatagg
taatgattat ataaaataca taatattttt caattttgaa 360aactctaatt
gtccattctt gcttgactct actattaagt ttgaaaatag ttaccttcaa
420agcaagataa ttctatttga agcatgctct gtaagttgct tcctaacatc
cttggactga 480gaaattatac ttacttctgg cataactaaa 51064541DNAhuman
64tgccgtgctc ccaaaacatt ttaaatgaaa gtattggcat tcaaaaagac agcagacaaa
60atgaaagaaa atgagagcag aaagtaagca tttccagcct atctaatttc tttagttttc
120tatttgcctc cagtgcagtc catttcctaa tgtataccag cctactgtac
tatttaaaat 180gctcaatttc agcaccgatg gccatgtaaa taagatgatt
taatgttgat tttaatcctg 240tatataaaat aaaaagtcac aatgagtttg
ggcatattta atgatgatta tggagcctta 300gaggtcttta atcattggtt
cggctgcttt tatgtagttt aggctggaaa tggtttcact 360tgctctttga
ctgtcagcaa gactgaagat ggcttttcct ggacagctag aaaacacaaa
420atcttgtagg tcattgcacc tatctcagcc ataggtgcag tttgcttcta
catgatgcta 480aaggctgcga atgggatcct gatggaacta aggactccaa
tgtcgaactc ttctttgctg 540c 54165549DNAhuman 65tgctctccag tgtacccatg
atggaagtat cttgatagta cccaaagaac tggtggcctc 60aggccacaaa aaggaaaccc
aaaagggaaa gagaaagtga gaagaaactg aagatggact 120ctattatgtg
aagtagtaat gttcagaaac tgattatttg gatcagaaac cattgaaact
180gcttcaagaa ttgtatcttt aagtactgct acttgaataa ctcagttaac
gctgttttga 240agcttacatg gacaaatgtt taggacttca agatcacact
tgtgggcaat ctgggggagc 300cacaactttt catgaagtgc attgtataca
aaattcatag ttatgtccaa agaataggtt 360aacatgaaaa cccagtaaga
ctttccatct tggcagccat cctttttaag agtaagttgg 420ttacttcaaa
aagagcaaac actggggatc aaattatttt aagaggtatt tcagttttaa
480atgcaaaata gccttatttt catttagttt gttagcacta tagtgagctt
ttcaaacact 540attttaatc 54966547DNAhuman 66cttcgttcgc agagcttttc
agattgtgga atgttggata aggaattata gacctctagt 60agctgaaatg caagacccca
agaggaagtt cagatcttaa tataaattca ctttcatttt 120tgatagctgt
cccatctggt catgtggttg gcactagact ggtggcaggg gcttctagct
180gactcgcaca gggattctca caatagccga tatcagaatt tgtgttgaag
gaacttgtct 240cttcatctaa tatgatagcg ggaaaaggag aggaaactac
tgcctttaga aaatataagt 300aaagtgatta aagtgctcac gttaccttga
cacatagttt ttcagtctat gggtttagtt 360actttagatg gcaagcatgt
aacttatatt aatagtaatt tgtaaagttg ggtggataag 420ctatccctgt
tgccggttca tggattactt ctctataaaa aatatatatt taccaaaaaa
480ttttgtgaca ttccttctcc catctcttcc ttgacatgca ttgtaaatag
gttcttcttg 540ttctgag 54767168DNAhuman 67tttccagaac atgaacgggt
ccgaatactt cgtgaagatc cagtccttcc tgggtggggc 60ccccacggag gatttgaagg
cgctcagtca gcagaatgtg agcatggact tggccacgtt 120catgaagctg
cggacggatg cggtgctgcc gttgactgtg gctgaggt 16868514DNAhuman
68gtctggcaca ccatggatga caatgaagaa aatttggatg aatcaaccat tgacaatcta
60aacaaaatcc tacaagtctt tgtgttggaa tatcttcatt tgtaatactc tgatttagtt
120taggataatt ggttctagaa ttgaattcaa aagtcaaggc atcatttaaa
ataatctgat 180ttcagacaaa tgctgtgtgg aaacatctat cctatagatc
atcctattct tatgtgtctt 240tggttatcag atcaattaca gaataattgt
gttgtgatat tgtgtcctaa attgctcatt 300aatttttatt tacagattga
aaaagaggca ccgtgtaaag aaaatggcaa aataaatatc 360tttccaagga
tcatcatcac gatagctaaa cagtacttaa atagcggttg gaactaggta
420gcctttcgaa ttttatgatt ttttcatatg tggaaatcta ttacatgtaa
tacaaaacaa 480acatgtagtt tgaaggcggt cagatttctt tgag
51469376DNAhuman 69aaggcggctg cagaagatgt caatgttact ttcgaagatc
aacaaaagat aaacaaattt 60gcacggaata caagtagaat cacagagctg aaggaagaaa
tagaagtaaa aaagaaacaa 120ctccaaaacc tagaagatgc ttgtgatgac
atcatgcttg cagatgatga ttgcttaatg 180ataccttatc aaattggtga
tgtcttcatt agccattctc aagaagaaac gcaagaaatg 240ttagaagaag
caaagaaaaa tttgcaagaa gaaattgacg ccttagaatc cagagtggaa
300tcaattcagc gagtgttagc agatttgaaa gttcagttgt atgcaaaatt
cgggagcaac 360ataaaccttg aagctg 37670328DNAhuman 70cctcagcctg
atcaggcttc ctggtgagaa ctgaggagcg gactcacttg atgtttcctg 60gaagcagagc
aaaagttctc ttgtccctgt cgcgtctcat tttgtccatg tcccccgtgc
120acggttcaat ggtagattcg ctgtcctcag cgggggcctt gaagactccc
tgatcccaga 180cctggtcgtc tctcccaccc cctccccaaa gccactggaa
ggagcacata ctacctagaa 240gtaagaagag gagcctcaga agaaaacaaa
gttctatttt attaattttc tatgtgttgt 300gtttgtagtc ttgtcttagc tctggacg
32871546DNAhuman 71gccaacatca ccatcattga gcaccagaag tgtgagaacg
cctaccccgg caacatcaca 60gacaccatgg tgtgtgccag cgtgcaggaa gggggcaagg
actcctgcca gggtgactcc 120gggggccctc tggtctgtaa ccagtctctt
caaggcatta tctcctgggg ccaggatccg 180tgtgcgatca cccgaaagcc
tggtgtctac acgaaagtct gcaaatatgt ggactggatc 240caggagacga
tgaagaacaa ttagactgga cccacccacc acagcccatc accctccatt
300tccacttggt gtttggttcc tgttcactct gttaataaga aaccctaagc
caagaccctc 360tacgaacatt ctttgggcct cctggactac aggagatgct
gtcacttaat aatcaacctg 420gggttcgaaa tcagtgagac ctggattcaa
attctgcctt gaaatattgt gactctggga 480atgacaacac ctggtttgtt
ctctgttgta tccccagccc caaagacagc tcctggccat 540atatca
54672489DNAhuman 72ttcacacggc agctggccaa tgaaggctgt gacatcaatg
ctatcatctt tcacacaaag 60aaaaagttgt ctgtgtgcgc aaatccaaaa cagacttggg
tgaaatatat tgtgcgtctc 120ctcagtaaaa aagtcaagaa catgtaaaaa
ctgtggcttt tctggaatgg aattggacat 180agcccaagaa cagaaagaac
cttgctgggg ttggaggttt cacttgcaca tcatggaggg 240tttagtgctt
atctaatttg tgcctcactg gacttgtcca attaatgaag ttgattcata
300ttgcatcata gtttgctttg tttaagcatc acattaaagt taaactgtat
tttatgttat 360ttatagctgt aggttttctg tgtttagcta tttaatacta
attttccata agctattttg 420gtttagtgca aagtataaaa ttatatttgg
gggggaataa gattatatgg actttcttgc 480aagcaacaa 48973502DNAhuman
73cccgaccggt gggcatttgt gaggcccatg gttgagaaat gaataatttc ccaattagga
60agtgtaagca gctgaggtct cttgagggag cttagccaat gtgggagcag cggtttgggg
120agcagagaca ctaacgactt cagggcaggg ctctgatatt ccatgaatgt
atcaggaaat 180atatatgtgt gtgtatgttt gcacacttgt tgtgtgggct
gtgagtgtaa gtgtgagtaa 240gagctggtgt ctgattgtta agtctaaata
tttccttaaa ctgtgtggac tgtgatgcca 300cacagagtgg tctttctgga
gaggttatag gtcactcctg gggcctcttg ggtcccccac 360gtgacagtgc
ctgggaatgt acttattctg cagcatgacc tgtgaccagc actgtctcag
420tttcactttc acatagatgt ccctttcttg gccagttatc ccttcctttt
agcctagttc 480atccaatcct cactgggtgg gg 50274470DNAhuman
74aacaaagact cttcttgcgt ctctgcttca ggtaacttca acatctccgc tgatgagcct
60ataactgtga cacctcctga ctcacaatca tatatctccg tcaattactc tgtgagaatc
120aatgaaacat atttcaccaa tgtcactgtg ctaaatggtt ctgtcttcct
cagtgtgatg 180gagaaagccc agaaaatgaa tgatactata tttggtttca
caatggagga gcgctcatgg 240gggccctata tcacctgtat tcagggccta
tgtgccaaca ataatgacag aacctactgg 300gaacttctga gtggaggcga
accactgagc caaggagctg gtagttacgt tgtccgcaat 360ggagaaaact
tggaggttcg ctggagcaaa tactaataag cccaaacttt cctcagctgc
420ataaaatcca tttgcagtgg agttccatgt ttattgtcct tatgccttct
47075425DNAhuman 75caaacgtatt ggcaggcgaa ccccttccgt gctgtggccg
agcctggcat ccaactcaag 60gctgtgaagt cttccacagg ccccggggaa cagctgcgga
acgctctgtg gcatacagga 120gacacagagt cccaggtgcg gctgctgtgg
aaggacccgc gaaacgtggg ttggaaggac 180aagaagtcct atcgttggtt
cctgcagcac cggccccaag tgggctacat cagggtgcga 240ttctatgagg
gccctgagct ggtggccgac agcaacgtgg tcttggacac aaccatgcgg
300ggtggccgcc tgggggtctt ctgcttctcc caggagaaca tcatctgggc
caacctgcgt 360taccgctgca atgacaccat cccagaggac tatgagaccc
atcagctgcg gcaagcctag 420ggacc 42576555DNAhuman 76caccacctac
ctatgatgcc gtggtacaga tggagtacct tgacatggtg gtgaatgaaa 60cactcagatt
attcccagtt gctattagac ttgagaggac ttgcaagaaa gatgttgaaa
120tcaatggggt attcattccc aaagggtcaa tggtggtgat tccaacttat
gctcttcacc 180atgacccaaa gtactggaca gagcctgagg agttccgccc
tgaaaggttc agtaagaaga 240aggacagcat agatccttac atatacacac
cctttggaac tggacccaga aactgcattg 300gcatgaggtt tgctctcatg
aacatgaaac ttgctctaat cagagtcctt cagaacttct 360ccttcaaacc
ttgtaaagaa acacagatcc ccttgaaatt agacacgcaa ggacttcttc
420aaccagaaaa acccattgtt ctaaaggtgg attcaagaga tggaacccta
agtggagaat 480gagttattct aaggacttct actttggtct tcaagaaagc
tgtgccccag aacaccagag 540atttcaactt agtca 55577554DNAhuman
77tgctatgcct tgtttttgtc accaaaatcc tggacagatg cagatctggc ctgccagaag
60cggccctctg gaaacctggt gtctgtgctc agtggggctg agggatcctt cgtgtcctcc
120ctggtgaaga gcattggtaa cagctactca tacgtctgga ttgggctcca
tgaccccaca 180cagggcaccg agcccaatgg agaaggttgg gagtggagta
gcagtgatgt gatgaattac 240tttgcatggg agagaaatcc ctccaccatc
tcaagccccg gccactgtgc gagcctgtcg 300agaagcacag catttctgag
gtggaaagat tataactgta atgtgaggtt accctatgtc 360tgcaagttca
ctgactagtg caggagggaa gtcagcagcc tgtgtttggt gtgcaactca
420tcatgggcat gagaccagtg tgaggactca ccctggaaga gaatattcgc
ttaattcccc 480caacctgacc acctcattct tatctttctt ctgtttcttc
ctccccgctg tcatttcagt 540ctcttcattt tgtc 55478530DNAhuman
78tttccattcc caatctagtg ctagatgtat aaatctttct tttgattctt cctaacaaaa
60tattttctgg gttaaaaccc cagccaactc attgggttgt agccaaaggt tcactctcaa
120gaagctttaa tatttaaata aaatcatatt gaatgtttcc aacctggagt
ataatattca 180gatataaaac agttttgtca gtctttctta gtgcctgtgt
ggatttttgt gaaaatgtca 240aagagaaaac ttatatacta tttcccttga
aattttaaac tatattttct ttacaggtat 300ttataatata ccaatgcttt
tatcaaacag aattttaaag agcataataa attatattaa 360agaaccaaaa
gttttcctga gaataagaaa gtttcaccca ataaaatatt tttgaaaggc
420atgttcctct gtcaatgaaa aaaagtacat gtatgtgttg tgatattaaa
agtgacattt 480gtctaatagc ctaatacaac atgtagctga gtttaacatg
tgtggtcttg 53079540DNAhuman 79gaaaatcgat gcagccattt ctgataagga
aaagaacaaa acatatttct ttgtagagga 60caaatactgg agatttgatg agaagagaaa
ttccatggag ccaggctttc ccaagcaaat 120agctgaagac tttccaggga
ttgactcaaa gattgatgct gtttttgaag aatttgggtt 180cttttatttc
tttactggat cttcacagtt ggagtttgac ccaaatgcaa agaaagtgac
240acacactttg aagagtaaca gctggcttaa ttgttgaaag agatatgtag
aaggcacaat 300atgggcactt taaatgaagc taataattct tcacctaagt
ctctgtgaat tgaaatgttc 360gttttctcct gcctgtgctg tgactcgagt
cacactcaag ggaacttgag cgtgaatctg 420tatcttgccg gtcattttta
tgttattaca gggcattcaa atgggctgct gcttagcttg 480caccttgtca
catagagtga tctttcccaa gagaagggga agcactcgtg tgcaacagac
54080410DNAhuman 80cacccaggcg gagggtgcct tcgtggcctc actgattaag
gagagtagca ctgatgacag 60caatgtctgg attggcctcc atgacccaaa aaagaaccgc
cgctggcact ggagtagtgg 120gtccctggtc tcctacaagt cctgggacac
tggatccccg agcagtgcta atgctggcta 180ctgtgcaagc ctgacttcat
gctcaggatt caagaaatgg aaggatgaat cttgtgagaa 240gaagttctcc
tttgtttgca agttcaaaaa ctagaggaag ctgaaaaatg gatgtctaga
300actggtcctg caattactat gaagtcaaaa attaaactag actatgtctc
caactcagtt 360cagaccatct cctccctaat gagtttgcat cgctgatctt
cagtaccttc 41081508DNAhuman 81gatcttaaag ccacggagaa gcctctcatc
ttatggcatt gacaaagaga agaccatcca 60ccttaccctg aaagtggtga agcccagtga
tgaggagctg cccttgtttc ttgtggagtc 120aggtgatgag gcaaagaggc
acctcctcca ggtgcgaagg tccagctcag tggcacaagt 180gaaagcaatg
atcgagacta agacgggtat aatccctgag acccagattg tgacttgcaa
240tggaaagaga ctggaagatg ggaagatgat ggcagattac ggcatcagaa
agggcaactt 300actcttcctg gcatcttatt gtattggagg gtgaccaccc
tggggatggg gtgttggcag 360gggtcaaaaa gcttatttct tttaatctct
tactcaacga acacatcttc tgatgatttc 420ccaaaattaa tgagaatgag
atgagtagag taagatttgg gtgggatggg taggatgaag 480tatattgccc
aactctatgt ttctttga 5088295DNAhuman 82gactccaagg aagctcagat
gcctgcagtc attaggtttt agcgtcccat gagccttggt 60atcaagaggc cacaagagtg
ggaccccagg ggctc 9583511DNAhuman 83tccacacacg gccaggcctg tttatctaca
ctgctgccca ctcctctctc cagctccaca 60tgctgtacct ggatcattct gaagcaaatt
ccgagcatta catcattttg tccataaata 120tttctaacat ccttaaatat
acaatcggaa ttcaagcatc tcccattgtc ccacaaatgt 180ttggctgttt
ttgtagttgg attgtttgta ttaggattca agcaaggccc atatattgca
240tttatttgaa atgtctgtaa gtctctttcc atctacagag tttagcacat
ttgaacgttg 300ctggttgaaa tcccgaggtg tcatttgaca tggttctctg
aacttatctt tcctataaaa 360tggtagttag atctggaggt ctgattttgt
ggcaaaaata cttcctaggt ggtgctgggt 420acttcttgtt gcatcctgtc
aggaggcaga taatgctggt gcctctctat tggtaatgtt 480aagactgctg
ggtgggtttg gagttcttgg c 51184459DNAhuman 84atactatttt tcataccacg
tgcatgtgaa agggactcat gtttgggtag gcctgtataa 60gaatggcacc cctgtaatgt
acacctatga tgaatacacc aaaggctacc tggatcaggc 120ttcagggagt
gccatcatcg atctcacaga aaatgaccag gtgtggctcc agcttcccaa
180tgccgagtca aatggcctat actcctctga gtatgtccac tcctctttct
caggattcct 240agtggctcca atgtgagtac accccacaga gctaatctaa
atcttgtgct agaaaaagca 300ttctctaact ctaccccacc ctacaaaatg
catatggagg taggctgaaa agaatgtaat 360ttttattttc tgaaatacag
atttgagcta tcagaccaac aaaccttccc cctgaaaagt 420gagcagcaac
gtaaaaacgt atgtgaagcc tctcttgaa 45985553DNAhuman 85gccgaccatc
tggatcacat caaggaggtg gcaggagcca gagccgtggg ttttggtggg 60gactttgatg
gtgttccaag ggtccctgag gggctggagg acgtctccaa gtatccagac
120ctgatcgctg agctgctcag gaggaactgg acggaggcgg aggtcaaggg
cgcactggct 180gacaacctgc tgagggtctt cgaggctgtg gaacaggcca
gcaacctcac acaggctccc 240gaggaggagc ccatcccgct ggaccagctg
ggtggctcct gcaggaccca ttacggctac 300tcctctgggg cttccagcct
ccatcgccac tgggggctcc tgctggcctc cctcgctccc 360ctggtcctct
gtctgtctct cctgtgaaac ctgggagacc agagtcccct ttagggttcc
420cggagctccg ggaagacccg cccatcccag gactccagat gccaggagcc
ctgctgccca 480catgcaagga ccagcatctc ctgagaggac gcctgggctt
acctgggggg caggatgcct 540ggggacagtt cag 55386365DNAhuman
86ggaggatagg ataatcccgg gtggcatcta taacgcagac ctcaatgatg agtgggtaca
60gcgtgccctt cacttcgcca tcagcgagta taacaaggcc accaaagatg actactacag
120acgtccgctg cgggtactaa gagccaggca acagaccgtt gggggggtga
attacttctt 180cgacgtagag gtgggccgaa ccatatgtac caagtcccag
cccaacttgg acacctgtgc 240cttccatgaa cagccagaac tgcagaagaa
acagttgtgc tctttcgaga tctacgaagt 300tccctgggag aacagaaggt
ccctggtgaa atccaggtgt caagaatcct agggatctgt 360gccag
36587331DNAhuman 87gagacgtggt aagtgcggtg cagttttcaa ctgacctctg
gacgcagaac ttcagccatg 60aaggtaacag gcatctttct tctcagtgcc ttggccctgt
tgagtctatc tggtaacact 120ggagctgact ccctgggaag agaggccaaa
tgttacaatg aacttaatgg atgcaccaag 180atatatgacc ctgtctgtgg
gactgatgga aatacttatc ccaatgaatg cgtgttatgt 240tttgaaggtc
ggaaacgcca gacttctatc ctcattcaaa aatctgggcc ttgctgagaa
300ccaaggtttt gaaatcccat caggtcaccg c 33188498DNAhuman 88gtggacctta
gaatacagtt ttgagtagag ttgatcaaaa tcaattaaaa tagtctcttt 60aaaaggaaag
aaaacatctt taaggggagg aaccagagtg ctgaaggaat ggaagtccat
120ctgcgtgtgt gcagggagac tgggtaggaa agaggaagca aatagaagag
agaggttgaa 180aaacaaaatg ggttacttga ttggtgatta ggtggtggta
gagaagcaag taaaaaggct 240aaatggaagg gcaagtttcc atcatctata
gaaagctata taagacaaga actccccttt 300ttttcccaaa ggcattataa
aaagaatgaa gcctccttag aaaaaaaatt atacctcaat 360gtccccaaca
agattgctta ataaattgtg tttcctccaa gctattcaat tcttttaact
420gttgtagaag acaaaatgtt cacaatatat ttagttgtaa accaagtgat
caaactacat 480attgtaaagc ccattttt 49889489DNAhuman 89aagtctgtag
tctttatgat cctaaaaggg aaaattgcct tggtaacttt cagattcctg 60tggaattgtg
aattcatact aagctttctg tgcagtctca ccatttgcat cactgaggat
120gaaactgact tttgtctttt ggagaaaaaa aactgtactg ttgttcaaga
gggctgtgat 180taaaatcttt aagcatttgt tcctgccaag gtagttttct
tgcattttgc tctccattca 240gcatgtgtgt gggtgtggat gtttataaac
aagactaagt ctgacttcat aagggctttc 300taaaaccatt tctgtccaag
agaaaatgac tttttgcttt gatattaaaa attcaatgag 360taaaacaaaa
gctagtcaaa tgtgttagca gcatgcagaa caaaaacttt aaactttctc
420tctcactata cagtatattg tcaatgtgaa agtgtggaat ggaagaaatg
tcgatcctgt 480tgtaactga 48990508DNAhuman 90gcaccctggt gtgactctag
tgatctacgt agctcggctt ttttggcaca tggatcaaca 60aaatcggcaa ggtctcaggg
accttgttaa cagtggagta actattcaga ttatgagagc 120atcagagtat
tatcactgct ggaggaattt tgtcaactac ccacctgggg atgaagctca
180ctggccacaa tacccacctc tgtggatgat gttgtacgca ctggagctgc
actgcataat 240tctaagtctt ccaccctgtt taaagatttc aagaagatgg
caaaatcatc ttacattttt 300cagacttcat cttcaaaact gccattacca
aacgattccg ccacacatcc ttttagctac 360agggctgata catccttctg
tggcttggag atgaatagga tgattccgtg tgtgtactga 420ttcaagaaca
agcaatgatg acccactaaa gagtgaatgc catttagaat ctagaaatgt
480tcacaaggta ccccaaaact ctgtagct
50891428DNAhuman 91gaacatccaa gtctttcttc ttttttaagt tgtcaaagaa
gcttccacaa aattagaaag 60gacaacagtt ctgagctgta atttcgcctt aaactctgga
cactctatat gtagtgcatt 120tttaaacttg aaatatataa tattcagcca
gcttaaaccc atacaatgta tgtacaatac 180aatgtacaat tatgtctctt
gagcatcaat cttgttactg ctgattcttg taaatctttt 240tgcttctact
ttcatcttaa actaatacgt gccagatata actgtcttgt ttcagtgaga
300gacgccctat ttctatgtca tttttaatgt atctatttgt acaattttaa
agttcttatt 360ttagtataca tataaatatc agtattctga catgtaagaa
aatgttacgg catcacactt 420atatttta 42892405DNAhuman 92aaccgaatgc
ggtgctacaa ctgtggtgga agccccagca gttcttgcaa agaggccgtg 60accacctgtg
gcgagggcag accccagcca ggcctggaac agatcaagct acctggaaac
120cccccagtga ccttgattca ccaacatcca gcctgcgtcg cagcccatca
ttgcaatcaa 180gtggagacag agtcggtggg agacgtgact tatccagccc
acagggactg ctacctggga 240gacctgtgca acagcgccgt ggcaagccat
gtggcccctg caggcatttt ggctgcagca 300gctaccgccc tgacctgtct
cttgccagga ctgtggagcg gataggggga gtaggagtag 360agaagggaac
aagggagcaa gggaacaagg gacatctgaa catct
40593505DNAhumanmisc_feature(281)..(281)n is a, c, g, or t
93agaacagcag ctttctaggg acagctggaa agggacttaa tgtgtttgac tatttcttac
60gagggttcta cttatttatg tatttatttt tgaaagcttg tattttaata ttttacatgc
120tgttatttaa agatgtgagt gtgtttcatc aaacatagct cagtcctgat
tatttaattg 180gaatatgatg ggttttaaat gtgtcattaa actaatattt
agtgggagac cataatgtgt 240cagccacctt gataaatgac agggtgggga
actggagggt ngggggattg aaatgcaagc 300aattagtgga tcactgttag
ggtaagggaa tgtatgtaca catctatttt ttatactttt 360ttttttaaaa
aagaatgtca gttgttattt attcaaatta tctcacatta tgtgttcaac
420atttttatgc tgaagtttcc cttagacatt ttatgtcttg cttgtagggc
ataatgcctt 480gtttaatgtc cattctgcag cgttt 50594533DNAhuman
94ccctcaatct agaacgctac acaagaaata ttttgttttt actcagcagg tgtgccttaa
60cctccctatt cagaaagctc cacatcaata aacatgacac tctgaagtga aagtagccac
120gagaattgtg ctacttatac tggaacataa tctggaggca aggttcgact
gcagtcgaac 180cttgcctcca gattatgaac cagtataagt agcacaattc
tcgtggctac tttcacttca 240gagtgtcatg tttattgatg tggagctttc
tgaataggga ggttaaggca cacctgctga 300gtaaaacaaa tatttcttgt
gtagcgttct taggaatctg gtgtctgtcc ggccccggta 360ggcctgttgg
gtttctagtc ctccttacca tcatctccat atgagagtgt gaaaatagga
420acacgtgctc tacctccatt tagggatttg cttgggatac agaagaggcc
atgtgtctca 480gagctgttaa gggcttattt ttttaaaaca ttggagtcat
agcatgtgtg taa 53395471DNAhuman 95gttttgggta tgtttaatct gttatgtact
agtgttctgt ttgttattgt tttgttaatt 60acaccataat gctaatttaa agagactcca
aatctcaatg aagccagctc acagtgctgt 120gtgccccggt catctagcaa
gctgccgaac caaaagaatt tgcaccccgc tgcgggccca 180cgtggttggg
gccctgccct ggcagggtca tcctgtgctc ggaggccatc tcgggcacag
240gcccaccccg ccccacccct ccagaacacg gctcacgctt acctcaacca
tcctggctgc 300ggcgtctgtc tgaaccacgc gggggccttg agggacgctt
tgtctgtcgt gatggggcaa 360gggcacaagt cctggatgtt gtgtgtatcg
agaggccaaa ggctggtggc aagtgcacgg 420ggcacagcgg agtctgtcct
gtgacgcgca agtctgaggg tctgggcggc g 47196382DNAhuman 96gattccctgc
atcaactaag aaaagcctgt tttctttatt tcaaacttgg tggcgaatgt 60gttgcgggtc
ctgttgggct gctttctgta ttgtctccta accctctagt tttaattgga
120cacttctttg ctgttgcaat ctatgccgtg tatttttgct ttaagtcaga
accttggatt 180acaaaacctc gagcccttct cagtagtggt gctgtattgt
acaaagcgtg ttctgtaata 240tttcctctaa tttactcaga aatgaagtat
atggttcatt aagcttaaag gggaaccatt 300tgtgaatgaa tatttggaac
ttaccaagtc ctaagagact tttggaagag gatatatata 360gcatagtacc
ataccactta ta 38297542DNAhuman 97tgcggaaata cctgaaatac agcaaaaata
tcctggaccg gcaagatcct ccctctgtgg 60tggtcaccag ccaccaggcc ccaggagaaa
agaagaaact gaagtgcctg gcctacgact 120tctacccagg gaaaattgat
gtgcactgga ctcgggccgg cgaggtgcag gagcctgagt 180tacggggaga
tgttcttcac aatggaaatg gcacttacca gtcctgggtg gtggtggcag
240tgcccccgca ggacacagcc ccctactcct gccacgtgca gcacagcagc
ctggcccagc 300ccctcgtggt gccctgggag gccagctagg aagcaagggt
tggaggcaat gtgggatctc 360agacccagta gctgcccttc ctgcctgatg
tgggagctga accacagaaa tcacagtcaa 420tggatccaca aggcctgagg
agcagtgtgg ggggacagac aggaggtgga tttggagacc 480gaagactggg
atgcctgtct tgagtagact tggacccaaa aaatcatctc accttgagcc 540ca
54298382DNAhuman 98gaagacttac tgttggccat agttaattgt gtgaggaaca
cgccggcctt tttagccgaa 60agactgcatc gagccttgaa gggtattgga actgatgagt
ttactctgaa ccgaataatg 120gtgtccagat cagaaattga ccttttggac
attcgaacag agttcaagaa gcattatggc 180tattccctat attcagcaat
taaatcggat acttctggag actatgaaat cacactctta 240aaaatctgtg
gtggagatga ctgaaccaag aagataatct ccaaaggtcc acgatgggct
300tttccaacag ctccacctta cttcttctca tactatttaa gagaacaagc
aaatataaac 360agcaacttgt gttcctaaca gg 38299499DNAhuman
99agagattcat tgcagctcag catggctcag accagctcat acttcatgct gatctcctgc
60ctgatgtttc tgtctcagag ccaaggccaa gaggcccaga cagagttgcc ccaggcccgg
120atcagctgcc cagaaggcac caatgcctat cgctcctact gctactactt
taatgaagac 180cgcgagacct gggttgatgc agatctctat tgccagaaca
tgaattcggg caacctggtg 240tctgtgctca cccaggccga gggtgccttt
gtggcctcac tgattaagga gagtggcact 300gatgacttca atgtctggat
tggcctccat gaccccaaaa agaaccgccg ctggcactgg 360agcagtgggt
ccctggtctc ctacaagtcc tggggcattg gagccccaag cagtgttaat
420cctggctact gtgtgagcct gacctcaagc acaggattcc agaaatggaa
ggatgtgcct 480tgtgaagaca agttctcct 499100375DNAhuman 100ttttaccttg
gatgctgact tctaaatgaa ctgaagatgt gcccttactt ggctgatttt 60ttttttccat
ctcataagaa aaatcagctg aagtgttacc aactagccac accatgaatt
120gtccgtaatg ttcattaaca gcatctttaa aactgtgtag ctacctcaca
accagtcctg 180tctgtttata gtgctggtag tatcaccttt tgccagaagg
cctggctggc tgtgacttac 240catagcagtg acaatggcag tcttggcttt
aaagtgaggg gtgacccttt agtgagctta 300gcacagcggg attaaacagt
cctttaacca gcacagccag ttaaaagatg cagcctcact 360gcttcaacgc agatt
375101571DNAhuman 101agagagacac agctgcagag gccacctgga ttgcgcctaa
tgtgtttgag catcacttag 60gagaagtctt ctatttattt atttatttat ttatttattt
gtttgtttta gaagattcta 120tgttaatatt ttatgtgtaa aataaggtta
tgattgaatc tacttgcaca ctctcccatt 180atatttattg tttattttag
gtcaaaccca agttagttca atcctgattc atatttaatt 240tgaagataga
aggtttgcag atattctcta gtcatttgtt aatatttctt cgtgatgaca
300tatcacatgt cagccactgt gatagaggct gaggaatcca agaaaatggc
cagtaagatc 360aatgtgacgg cagggaaatg tatgtgtgtc tattttgtaa
ctgtaaagat gaatgtcagt 420tgttatttat tgaaatgatt tcacagtgtg
tggtcaacat ttctcatgtt gaagctttaa 480gaactaaaat gttctaaata
tcccttggac attttatgtc tttcttgtaa gatactgcct 540tgtttaatgt
taattatgca gtgtttccct c 571102531DNAhuman 102tcctctcgtg gggtgtttac
ccctgtggct ctgcccagca tccagctgtc tacacccaga 60tctgcaaata catgtcctgg
atcaataaag tcatacgctc caactgatcc agatgctacg 120ctccagctga
tccagatgtt atgctcctgc tgatccagat gcccagaggc tccatcgtcc
180atcctcttcc tccccagtcg gctgaactct ccccttgtct gcactgttca
aacctctgcc 240gccctccaca cctctaaaca tctcccctct cacctcattc
ccccacctat ccccattctc 300tgcctgtact gaagctgaaa tgcaggaagt
ggtggcaaag gtttattcca gagaagccag 360gaagccggtc atcacccagc
ctctgagagc agttactggg gtcacccaac ctgacttcct 420ctgccactcc
ccgctgtgtg actttgggca agccaagtgc cctctctgaa cctcagtttc
480ctcatctgca aaatgggaac aatgacgtgc ctacctctta gacatgttgt g
531103529DNAhuman 103gaatggtgca tacaaggcca tccccgttgc ccaggacctg
aacgcgcctt ctgattggga 60cagccgtggg aaggacagtt atgaaacgag tcagctggat
gaccagagtg ctgaaaccca 120cagccacaag cagtccagat tatataagcg
gaaagctaat gatgagagca atgagcattc 180cgatgtgatt gatagtcagg
aactttccaa agtcagccgt gaattccaca gccatgaatt 240tcacagccat
gaagatatgc tggttgtaga ccccaaaagt aaggaagaag ataaacacct
300gaaatttcgt atttctcatg aattagatag tgcatcttct gaggtcaatt
aaaaggagaa 360aaaatacaat ttctcacttt gcatttagtc aaaagaaaaa
atgctttata gcaaaatgaa 420agagaacatg aaatgcttct ttctcagttt
attggttgaa tgtgtatcta tttgagtctg 480gaaataactg atgtgtttga
taattagttt agtttgtggc ttcatggaa 529104536DNAhuman 104acagctttcc
aaggtgacaa actcctctat gcagtgtatc gaaagctggg tgtttatgaa 60gttgaagacc
agattacagc tgtcagaaaa ttcatagaaa tgggtttcat tgatgaaaaa
120agaatagcca tatggggctg gtcctatgga ggatacgttt catcactggc
ccttgcatct 180ggaactggtc ttttcaaatg tggtatagca gtggctccag
tctccagctg ggaatattac 240gcgtctgtct acacagagag attcatgggt
ctcccaacaa aggatgataa tcttgagcac 300tataagaatt caactgtgat
ggcaagagca gaatatttca gaaatgtaga ctatcttctc 360atccacggaa
cagcagatga taatgtgcac tttcagaact cagcacagat tgctaaagct
420ctggttaatg cacaagtgga tttccaggca atgtggtact ctgaccagaa
ccacggctta 480tccggcctgt ccacgaacca cttatacacc cacatgaccc
acttcctaaa gcagtg 536105409DNAhuman 105agtcaagtga ccagcctctg
actgtgcctg tatctcccaa attctccact cgattccact 60gctaaactca gctgtgagct
gcggataccg cccggcaatg ggacctgctc ttaacctcaa 120acctaggacc
gtcttgcttt gtcattgggc atggagagaa cccatttctc cagactttta
180cctacccgtg cctgagaaag catacttgac aactgtggac tccagttttg
ttgagaattg 240ttttcttaca ttactaaggc taataatgag atgtaactca
tgaatgtctc gattagactc 300catgtagtta cttcctttaa accatcagcc
ggccttttat atgggtcttc actctgacta 360gaatttagtc tctgtgtcag
cacagtgtaa tctctattgc tattgcccc 409106370DNAhuman 106gctttcaccg
gcaagttcga gatggagagt gagaagaatt atgatgagtt catgaagctc 60cttgggatct
ccagcgatgt aatcgaaaag gcccgcaact tcaagatcgt cacggaggtg
120cagcaggatg ggcaggactt cacttggtcc cagcactact ccgggggcca
caccatgacc 180aacaagttca ctgttggcaa ggaaagcaac atacagacaa
tggggggcaa gacgttcaag 240gccactgtgc agatggaggg cgggaagctg
gtggtgaatt tccccaacta tcaccagacc 300tcagagatcg tgggtgacaa
gctggtggag gtctccacca tcggaggcgt gacctatgag 360cgcgtgagca
370107441DNAhuman 107aaaggagcag tcgcacagac ctttcctcat gctgcaggcc
cggcagtctg aagaccaccc 60tcatcgccgg cgtcggcggg gcttggagtg tgatggcaag
gtcaacatct gctgtaagaa 120acagttcttt gtcagtttca aggacatcgg
ctggaatgac tggatcattg ctccctctgg 180ctatcatgcc aactactgcg
agggtgagtg cccgagccat atagcaggca cgtccgggtc 240ctcactgtcc
ttccactcaa cagtcatcaa ccactaccgc atgcggggcc atagcccctt
300tgccaacctc aaatcgtgct gtgtgcccac caagctgaga cccatgtcca
tgttgtacta 360tgatgatggt caaaacatca tcaaaaagga cattcagaac
atgatcgtgg aggagtgtgg 420gtgctcatag agttgcccag c 441108412DNAhuman
108cagaccttgt gatattccag ttccccctgc agtggtttgg agtccctgcc
attctgaaag 60gctggtttga gccttcatag gagagtttgc ttacacttac gctgccatgt
atgacaaagg 120acccttccgg agtggcattc tgcatttctg tggcttccaa
gtcttagaac ctcaactgac 180atatagcatt gggcacactc cagcagacgc
ccgaattcaa atcctggaag gatggaagaa 240acgcctggag aatatttggg
atgagacacc actgtatttt gctccaagca gcctctttga 300cctaaacttc
caggcaggat tcttaatgaa aaaagaggta caggatgagg agaaaaacaa
360gaaatttggc ctttctgtgg gccatcactt gggcaagtcc atcccaactg ac
412109372DNAhuman 109gtaacactct ggtacagatc tccagaagta ttgctggggt
cagctcgtta ctcaactcca 60gttgacattt ggagtatagg caccatattt gctgaactag
caactaagaa accacttttc 120catggggatt cagaaattga tcaactcttc
aggattttca gagctttggg cactcccaat 180aatgaagtgt ggccagaagt
ggaatcttta caggactata agaatacatt tcccaaatgg 240aaaccaggaa
gcctagcatc ccatgtcaaa aacttggatg aaaatggctt ggatttgctc
300tcgaaaatgt taatctatga tccagccaaa cgaatttctg gcaaaatggc
actgaatcat 360ccatatttta at
372110164DNAhumanmisc_feature(105)..(105)n is a, c, g, or t
110ggttccatca atggtgagca ccagcctgaa tgcagaagcg ctccagtatc
tccaagggta 60ccttcaggca gccagtgtga cactgcttta aactgcattt ttctnaatgg
gctaaaccca 120gatggtttcc taggaaatca caggcttctg agcacagctg catt
164111370DNAhuman 111tactggaacc tatgatctga agagcgtcct gggtcaactg
ggcatcacta aggtcttcag 60caatggggct gacctctccg gggtcacaga ggaggcaccc
ctgaagctct ccaaggccgt 120gcataaggct gtgctgacca tcgacgagaa
agggactgaa gctgctgggg ccatgttttt 180agaggccata cccatgtcta
tcccccccga ggtcaagttc aacaaaccct ttgtcttctt 240aatgattgaa
caaaatacca agtctcccct cttcatggga aaagtggtga atcccaccca
300aaaataactg cctctcgctc ctcaacccct cccctccatc cctggccccc
tccctggatg 360acattaaaga 370112216DNAhuman 112gtgtgaaggt gcagttttgc
caaggagtgc taaagaactt agatgtcagt gcataaagac 60atactccaaa cctttccacc
ccaaatttat caaagaactg agagtgattg agagtggacc 120acactgcgcc
aacacagaaa ttattgtaaa gctttctgat ggaagagagc tctgtctgga
180ccccaaggaa aactgggtgc agagggttgt ggagaa 216113417DNAhuman
113attgtaaatc ttttgtgtct cctgaagact tcccttaaaa ttagctctga
gtgaaaaatc 60aaaagagaca aaagacatct tcgaatccat atttcaagcc tggtagaatt
ggcttttcta 120gcagaacctt tccaaaagtt ttatattgag attcataaca
acaccaagaa ttgattttgt 180agccaacatt cattcaatac tgttatatca
gaggagtagg agagaggaaa catttgactt 240atctggaaaa gcaaaatgta
cttaagaata agaataacat ggtccattca cctttatgtt 300atagatatgt
ctttgtgtaa atcatttgtt ttgagttttc aaagaatagc ccattgttca
360ttcttgtgct gtacaatgac cactgttatt gttactttga cttttcagag cacaccc
417114372DNAhumanmisc_feature(43)..(43)n is a, c, g, or t
114tccaaggact gagactgacc tcctctggtg acactggcct agngcctgac
actctcctaa 60gaggttctct ccaagccccc aaatagctcc aggcgccctc ggccgcccat
catggttaat 120tctgtccaac aaacacacac gggtagattg ctggcctgtt
gtaggtggta gggacacaga 180tgaccgacct ggtcactcct cctgccaaca
ttcagtctgg tatgtgaggc gtgcgtgaag 240caagaactcc tggagctaca
gggacaggga gccatcattc ctgcctggga atcctggaag 300acttcctgca
ggagtcagcg ttcaatcttg accttgaaga tgggaaggat gttcttttta
360cgtaccaatt ct 372115525DNAhumanmisc_feature(44)..(44)n is a, c,
g, or t 115cgatgcaagt gtttctgttc tgggaggtat tggagggaaa aaancaagca
ggatggctgg 60aacactgtac tgaggaatga atagaaaggc ttccagatgt ctaaaagatt
ctttaaacta 120ctgaactgtt acctaggtta acaaccctgt tgagtatttg
ctgtttgtcc agttcaggaa 180tttttgtttt gttttgtcta tatgtgcggc
ttttcagaag aaatttaatc agtgtgacag 240aaaaaaaaat gttttatggt
agcttttact ttttatgaaa aaaaaattat ttgcctttta 300aattcttttc
ccccatcccc ctccaaagtc ttgatagcaa gcgttatttt gggggtagaa
360acggtgaaat ctctagcctc tttgtgtttt tgttgttgtt gttgttgttg
ttttatataa 420tgcatgtatt cactaaaata aaatttaaaa aactcctgtc
ttgctagaca aggttgctgt 480tgtgcagtgt gcctgtcact actggtctgt
actccttgga tttgc 525116116DNAhuman 116tacagccagg cataacatat
ccactgtgtg catagagggt ctcttcacgt tgatgcttgg 60cattccatca gctttctcta
agtctttgct caagttcaac cttaaaatga tgttag
116117517DNAhumanmisc_feature(181)..(181)n is a, c, g, or t
117ggaaaacacc tcatttgacc ttgccagctg accttcaaac cctgcatttg
aaccgaccaa 60cattaagtcc agagagtaaa cttgaatgga ataacgacat tccagaagtt
aatcatttga 120attctgaaca ctggagaaaa accgaaaaat ggacggggca
tgaagagact aatcatctgg 180naaaccgatt tcagtggcga tggcatgaca
gagctagagc tcgggcccag ccccaggctg 240cagcccattc gcaggcaccc
gaaagaactt ccccagtatg gtggtcctgg aaaggacatt 300tttgaagatc
aactatatct tcctgtgcat tccgatggaa tttcagttca tcagatgttc
360accatggcca ccgcagaaca ccgaagtaat tccagcatag cggggaagat
gttgaccaag 420gtggagaaga atcacgaaaa ggagaagtca cagcacctag
aaggcagcgc ctcctcttca 480ctctcctctg attagatgaa actgttacct tacccta
517118397DNAhuman 118aatatccttg ttgtgtatta ggtttttaaa taccagctaa
aggattacct cactgagtca 60tcagtaccct cctattcagc tccccaagat gatgtgtttt
tgcttaccct aagagaggtt 120ttcttcttat ttttagataa ttcaagtgct
tagataaatt atgttttctt taagtgttta 180tggtaaactc ttttaaagaa
aatttaatat gttatagctg aatctttttg gtaactttaa 240atctttatca
tagactctgt acatatgttc aaattagctg cttgcctgat gtgtgtatca
300tcggtgggat gacagaacaa acatatttat gatcatgaat aatgtgcttt
gtaaaaagat 360ttcaagttat taggaagcat actctgtttt ttaatca
397119518DNAhuman 119gtgtgcacac ggagactcat cgttataatt tactatctgc
caagagtaga aagaaaggct 60ggggatattt gggttggctt ggttttgatt ttttgcttgt
ttgtttgttt tgtactaaaa 120cagtattatc ttttgaatat cgtagggaca
taagtatata catgttatcc aatcaagatg 180gctagaatgg tgcctttctg
agtgtctaaa acttgacacc cctggtaaat ctttcaacac 240acttccactg
cctgcgtaat gaagttttga ttcattttta accactggaa tttttcaatg
300ccgtcatttt cagttagatg attttgcact ttgagattaa aatgccatgt
ctatttgatt 360agtcttattt ttttattttt acaggcttat cagtctcact
gttggctgtc attgtgacaa 420agtcaaataa acccccaagg acgacacaca
gtatggatca catattgttt gacattaagc 480ttttgccaga aaatgttgca
tgtgttttac ctcgactt 518120404DNAhumanmisc_feature(374)..(374)n is
a, c, g, or t 120caagagctac aatgtcacct ccgtcctgtt taggaaaaag
aagtgtgact actggatcag 60gacttttgtt ccaggttgcc agcccggcga gttcacgctg
ggcaacatta agagttaccc 120tggattaacg agttacctcg tccgagtggt
gagcaccaac tacaaccagc atgctatggt 180gttcttcaag aaagtttctc
aaaacaggga gtacttcaag atcaccctct acgggagaac 240caaggagctg
acttcggaac taaaggagaa cttcatccgc ttctccaaat ctctgggcct
300ccctgaaaac cacatcgtct tccctgtccc aatcgaccag tgtatcgacg
gctgagtgca 360caggtgccgc cagntgccgc accagcccga acaccattga ggga
404121448DNAhuman 121ccttcttgtc cacggttttg ttgagttttc actcttctaa
tgcaagggtc tcacactgtg 60aaccacttag gatgtgatca ctttcaggtg gccaggaatg
ttgaatgtct ttggctcagt 120tcatttaaaa aagatatcta tttgaaagtt
ctcagagttg tacatatgtt tcacagtaca 180ggatctgtac ataaaagttt
ctttcctaaa ccattcacca agagccaata tctaggcatt 240ttcttggtag
cacaaatttt cttattgctt agaaaattgt cctccttgtt atttctgttt
300gtaagactta agtgagttag gtctttaagg aaagcaacgc tcctctgaaa
tgcttgtctt 360ttttctgttg ccgaaatagc tggtcctttt tcgggagtta
gatgtataga gtgtttgtat 420gtaaacattt cttgtaggca tcaccatg
448122465DNAhuman 122caatatctga caccactttg gactcaagag actcagtaac
gtattatcct gtttatttag 60cttggtttta gctgtgttct ctctggataa cccacttgat
gttaggaaca ttacttctct 120gcttattcca tattaatact gtgttaggta
ttttaagaag caagttatta aataagaaaa 180gtcaaagtat taattcttac
cttctattat cctatattag cttcaataca tccaaaccaa 240atggctgtta
ggtagattta tttttatata agcatgttta ttttgatcag atgttttaac
300ttggatttga aaaaatacat ttatgagatg ttttataaga tgtgtaaata
tagaactgta 360tttattacta tagtaaaggt tcagtaacat taaggaccat
gataatgata ataaaccttg 420tacagtggca tattctttga tttatattgt
gtttctctgc ccatt 465123248DNAhumanmisc_feature(45)..(45)n is a, c,
g, or t 123cacaaaaccc cagggacagc ggtctcccca gcctgccctg ctcangcctt
gcccccaaac 60ctgtactgtc ccggaggagg ttgggaggtg gaggcccagc atcccgcgca
gatgacaccg 120gttttcctag aagcccctca cccccactgg cccactggtg
gctaggtctc cccttatcct 180tctggtccag cgcaaggagg ggctgcttct
gaggtcggtg gctgtctttc cattaaagaa 240acaccgtg
248124419DNAhumanmisc_feature(30)..(30)n is a, c, g, or
tmisc_feature(53)..(53)n is a, c, g, or tmisc_feature(55)..(55)n is
a, c, g, or tmisc_feature(248)..(248)n is a, c, g, or t
124gaaataaccc agacttaatc ttgaatgatn cgattatgcc caatattaag
tananaatat 60aagaaaaggt tatcttaaat agatcttagg caaaatacca gctgatgaag
gcatctgatg 120ccttcatctg ttcagtcatc tccaaaaaca gtaaaaataa
ccactttttg ttgggcaata 180tgaaattttt aaaggagtag aataccaaat
gatagaaaca gactgcctga attgagaatt 240ttgatttntt aaagtgtgtt
tctttctaaa ttgctgttcc ttaatttgat taatttaatt 300catgtattat
gattaaatct gaggcagatg agcttacaag tattgaaata attactaatt
360aatcacaaat gtgaagttat gcatgatgta aaaaatacaa acattctaat taaaggctt
419125396DNAhumanmisc_feature(310)..(310)n is a, c, g, or
tmisc_feature(314)..(314)n is a, c, g, or t 125tcaacaccct
cttcttgaac tggtgctgtc tgggcttcat agcattcgcc tactccgtga 60agtctaggga
caggaagatg gttggcgacg tgaccggggc ccaggcctat gcctccaccg
120ccaagtgcct gaacatctgg gccctgattc tgggcatcct catgaccatt
ggattcatcc 180tgttactggt attcggctct gtgacagtct accatattat
gttacagata atacaggaaa 240aacggggtta ctagtagccg cccatagcct
gcaacctttg cactccactg tgcaatgctg 300gccctgcacn gctngggctg
ttgcccctgc ccccttggtc ctgcccctag atacagcagt 360ttatacccac
acacctgtct acagtgtcat tcaata 396126245DNAhuman 126ggtgagggga
tgacccctgg agatgaaggg aagaggtgaa gccttagcaa aaatgcctcc 60tcaccactcc
ccaggagaat ttttataaaa agcataatca ctgattcctt cactgacata
120atgtaggaag cctctgagga gaaaaacaaa gggagaaaca tagagaacgg
ttgctactgg 180cagaagcata agatctttgt acaatattgc tggccctggt
tcacctgttt actgttatca 240caata 245127436DNAhuman 127gtgattcaaa
cttctgtgta ctgggtgatg cacccattgt gattgtggaa gatagaattc 60aatttgaact
caggttgttt atgaggggaa aaaaacagtt gcatagagta tagctctgta
120gtggaatatg tcttctgtat aactaggctg ttaacctatg attgtaaagt
agctgtaaga 180atttcccagt gaaataaaaa aaaattttaa gtgttctcgg
ggatgcatag attcatcatt 240ttctccacct taaaaatgcg ggcatttaag
tctgtccatt atctatatag tcctgtcttg 300tctattgtat atataatcta
tatgattaaa gaaaatatgc ataatcagac aagcgtaatg 360cataatcaga
caagcttgaa tattgttttt gcaccagacg aacagtgagg aaattcggag
420ctatacatat gtgcag 436128551DNAhumanmisc_feature(158)..(158)n is
a, c, g, or tmisc_feature(516)..(516)n is a, c, g, or t
128agtcagtgtt gtcttaatat ccttgataat gctgtaaagt ttatttttac
aaatatttct 60gtttaagcta tttcaccttt gtttggaaat ccttcccttt taaagagaaa
atgtgacact 120tgtgaaaagg cttgtaggaa agctcctccc tttttttnct
ttaaaccttt aaatgacaaa 180cctaggtaat taatggttgt gaatttctat
ttttgctttg tttttaatga acatttgtct 240ttcagaatag gattctgtga
taatatttaa atggcaaaaa caaaacataa ttttgtgcaa 300ttaacaaagc
tactgcaaga aaaataaaac atttcttggt aaaaacgtat gtatttatat
360attatatatt tatatataat atatattata tatttagcat tgctgagctt
tttagatgcc 420tattgtgtat cttttaaagg ttttgaccat tttgttatga
gtaattacat atatattaca 480ttcactatat taaaattgta cttttttact
atgtgnctca ttggttcata gtctttattt 540tgtcctttga a
551129370DNAhumanmisc_feature(227)..(227)n is a, c, g, or
tmisc_feature(229)..(229)n is a, c, g, or
tmisc_feature(287)..(287)n is a, c, g, or
tmisc_feature(338)..(338)n is a, c, g, or t 129tatgtcgctg
tccaagagaa ggctgtggaa gaacctatac aactgtgttt aatctccaaa 60gccatatcct
ctccttccat gaggaaagcc gcccttttgt gtgtgaacat gctggctgtg
120gcaaaacatt tgcaatgaaa caaagtctca ctaggcatgc tgttgtacat
gatcctgaca 180agaagaaaat gaagctcaaa gtcaaaaaat ctcgtgaaaa
acggagntng gcctctcatc 240tcagtggata tatccctccc aaaaggaaac
aagggcaagg cttatcnttg tgtcaaaacg 300gagagtcacc caactgtgtg
gaagacaaga tgctctcnac agttgcagta cttacccttg 360gctaagaact
370130157DNAhuman 130agggcctaag ggtgacagag gtgatgctgg tcccaaaggt
gctgatggct ctcctggcaa 60agatggcgtc cgtggtctga ccggccccat tggtcctcct
ggccctgctg gtgcccctgg 120tgacaagggg gaccccattc ccgaggagct ttatgag
157131460DNAhumanmisc_feature(35)..(35)n is a, c, g, or t
131gagttattat tatctcatag cgtatgtttt cttgnacagc cttgaataat
tttgattgac 60ctctgggatg ttattaaagc ctaacgttcc ttctattctc acaaattttc
gttatgactt 120cagaaggatc attaactctg gtatctgttt gtttgcttgt
atggcaccaa taagcagatt 180tcttctttct aatctatgga ttagtataga
ccaggagaag gctaatacag agactatgaa 240acgggaataa gtttttttaa
cgatatggca aaattgtgac tctgaaagat cattcatgta 300tattctaaaa
ttaccacagt cataaaaagt cttggacttt catgaggaaa tagcatagct
360agatatgaaa aaatatagaa aatcttcatc aatggaacta ttcttggggt
agacactaat 420catatgaaaa gacaaatgct cattccctaa gatagcctga
460132471DNAhuman 132gcttctacgt catcttcgac agagcccaga agagggtggg
cttcgcagcg agcccctgtg 60cagaaattgc aggtgctgca gtgtctgaaa tttccgggcc
tttctcaaca gaggatgtag 120ccagcaactg tgtccccgct cagtctttga
gcgagcccat tttgtggatt gtgtcctatg 180cgctcatgag cgtctgtgga
gccatcctcc ttgtcttaat cgtcctgctg ctgctgccgt 240tccggtgtca
gcgtcgcccc cgtgaccctg aggtcgtcaa tgatgagtcc tctctggtca
300gacatcgctg gaaatgaata gccaggcctg acctcaagca accatgaact
cagctattaa 360gaaaatcaca tttccagggc agcagccggg atcgatggtg
gcgctttctc ctgtgcccac 420ccgtcttcaa tctctgttct gctcccagat
gccttctaga ttcactgtct t 471133487DNAhuman 133gaagtgggac gagcacattt
ctattgtctt cacttggatc aaaagcaaaa cagtctctcc 60gccccgcacc agatcaagta
gtttggacat caccctactg aaaacttgcg attcttctta 120gttttctgca
tacttttcat cacgatgcag gaaacgattt cgagtcaaga agacttttat
180ttatgaacct ttgaaaggat cgtcttgtat ggtgaatttt ctaggagcga
tgatgtactg 240taattttatt ttaatgtatt ttgatttatg attatttatt
agtttttttt aaatgcttgt 300tctaagacat ttctgaatgt agaccatttt
ccaaaaagga aactttattt tcaaaaacct 360aatccgtagt aattcctaat
cttggagaat aaaaaagggc ggtggagggg aaaacattaa 420gaatttattc
attatttctc gagtactttc agaaagtctg acactttcat tgttgtgcca 480gctggtt
487134521DNAhuman 134ggcacagagc gcggagatgt accactacca gcaccaacgg
caacagatgc tgtgcctgga 60gcggcataaa gagccaccca aggagctgga cacggcctcc
tcggatgagg agaatgagga 120cggagacttc acggtgtacg agtgcccggg
cctggccccg accggggaaa tggaggtgcg 180caaccctctg ttcgaccacg
ccgcactgtc cgcgcccctg ccggccccca gctcaccgcc 240tgcactgcca
tgacctggag gcagacagac gcccacctgc tccccgacct cgaggccccc
300ggggaggggc agggcctgga gcttcccact aaaaacatgt tttgatgctg
tgtgcttttg 360gctgggcctc gggctccagg ccctgggacc ccttgccagg
gagacccccg aacctttgtg 420ccaggacacc tcctggtccc ctgcacctct
cctgttcggt ttagaccccc aaactggagg 480gggcatggag aaccgtagag
cgcaggaacg ggtgggtaat t 521135399DNAhuman 135gccacacctt cgcgaaacct
gtggtggccc accagtccta acgggacagg acagagagac 60agagcagccc tgcactgttt
tccctccacc acagccatcc tgtccctcat tggctctgtg 120ctttccacta
tacacagtca ccgtcccaat gagaaacaag aaggagcacc ctccacatgg
180actcccacct gcaagtggac agcgacattc agtcctgcac tgctcacctg
ggtttactga 240tgactcctgg ctgccccacc atcctctctg atctgtgaga
aacagctaag ctgctgtgac 300ttccctttag gacaatgttg tgtaaatctt
tgaaggacac accgaagacc tttatactgt 360gatcttttac ccctttcact
cttggctttc ttatgttgc 399136370DNAhuman 136tggtgtatgc tgtgctttcc
tcagcagtat ggctctgaca tctcttagat gtcccaactt 60cagctgttgg gagatggtga
tattttcaac cctacttcct aaacatctgt ctggggttcc 120tttagtcttg
aatgtcttat gctcaattat ttggtgttga gcctctcttc cacaagagct
180cctccatgtt tggatagcag ttgaagaggt tgtgtgggtg ggctgttggg
agtgaggatg 240gagtgttcag tgcccatttc tcattttaca ttttaaagtc
gttcctccaa catagtgtgt 300attggtctga agggggtggt gggatgccaa
agcctgctca agttatggac attgtggcca 360ccatgtggct 370137489DNAhuman
137gaatttctgc tggactttat ctgggcagag gaaggatgga atgaaggtag
aaaaggcaga 60attacagctg agcggggaca acaaagagtt cttctctggg aaaagttttg
tcttagagca 120aggatggaaa atggggacaa caaaggaaaa gcaaagtgtg
acccttgggt ttggacagcc 180cagaggccca gctccccagt ataagccata
caggccaggg acccacagga gagtggatta 240gagcacaagt ctggcctcac
tgagtggaca agagctgatg ggcctcatca gggtgacatt 300caccccaggg
cagcctgacc actcttggcc cctcaggcat tatcccattt ggaatgtgaa
360tgtggtggca aagtgggcag aggaccccac ctgggaacct ttttccctca
gttagtgggg 420agactagcac ctaggtaccc acatgggtat ttatatctga
accagacaga cgcttgaatc 480aggcactat 489138532DNAhuman 138gagacagact
tggcaaggga ccccctggtt ctgagccagt agctgccatc tggaaattcc 60tcttttagcc
tctccttaga ggtgaatgtg aatgaagcct cccaggcacc cgctgaattt
120ctgaggcctt gcttaaagct cagaagtggt ttaggcattt ggaaaatctg
gttcacatca 180taaagaactt gatttgaaat gttttctata gaaacaagtg
ctaagtgtac cgtattatac 240ttgatgttgg tcatttctca gtcctatttc
tcagttctat tattttagaa cctagtcagt 300tctttaagat tataactggt
cctacattaa aataatgctt ctcgatgtca gattttacct 360gtttgctgct
gagaacatct ctgcctaatt taccaaagcc agaccttcag ttcaacatgc
420ttccttagct tttcatagtt gtctgacatt tccatgaaaa caaaggaacc
aactttgttt 480taaccaaact ttgtttggtt acagttttca ggggagcgtt
tcttccatga ca 532139458DNAhuman 139catgtacgac tcggacagcg acggccgcat
cactctggaa gaatatcgaa atgtaaagtg 60gtcgaggagc tgctgtcggg aaaccctcac
atctagaagg agtccgctcg ctccatcgcc 120gacggggcca tgatggaggc
ggccagcgtg tgcatggggc agatggagcc tgatcaggtg 180tacgagggga
tcaccttcga ggacttcctg aagatctggc aggggatcga cattgagacc
240aagatgcacg tccgcttcct taacatggaa accatggccc tctgccactg
acccaccgcc 300acctccgcgg agagactgca ctttgcaatg gggccgcctc
cccgcgtagc tggagcagcc 360caggcccggc ggacagcctc ttcctgcagc
gccggtacat agccaaggct cgtctgcgca 420ccttgtgtct tgtagggtat
ggtatgtggg acttcgct 458140491DNAhuman 140gaggaggaac tgacgcagct
acgccacgaa ctggagcggc agaacaatga ataccaagtg 60ctgctgggca tcaaaaccca
cctggagaag gaaatcacca cgtaccgacg gctcctggag 120ggagagagtg
aagggacacg ggaagaatca aagtcgagca tgaaagtgtc tgcaactcca
180aagatcaagg ccataaccca ggagaccatc aacggaagat tagttctttg
tcaagtgaat 240gaaatccaaa agcacgcatg agaccaatga aagtttccgc
ctgttgtaaa gtctattttc 300ccccaaggaa agtccttgca cagacaccag
tgagtgagtt ctaaaagata cccttggaat 360tatcagactc agaaactttt
attttttttt ttctgtaaca gtctcaccag acttctcata 420atgctcttaa
tatattgcac ttttctaatc aaagtgcgag tttatgaggg taaagctcta
480ctttcctact g 491141562DNAhuman 141aatcctgcaa ttctcaatct
tgcactgcag cctcgacctc ccaggctcca gtgactctcc 60cacctcagcc tcctaagtag
ctgggagtac aggcgcgcac caccacgcct agctgatttt 120tgtatttttt
tgtagagacg ggggtttggc catgttgccg aggctaactc ctgggattac
180aggcatgagc tgtgctggcc gggttttttt ttcttgatgt aaacgtgtac
agctgtttta 240ttagttaagg tctaattttt actctaggtg ccttttatgt
tcagaactct ttccactgga 300ctggtatttg ctcaaaaata aataatggta
gagaagaaaa ctataaaaat ggacaaggct 360ttcttctatc agtagcgttt
accctttgtc accagtggct ttggtatttc catgtctggc 420attgcataaa
cttctctggt gtgaaaggat aaatatgcct ttctaaagtt gtatatcaaa
480attgtatcaa tttttatttt ctatgatttc tagaaacaaa tgtaataaat
atttttaaaa 540tctcctttct actggttatg ta 562142414DNAhuman
142ctcgttgcaa tcgcctttgc agtcaaccac ttctggtgcc aggaggagcc
ggagcctgca 60cacatgatcc tgaccgtcgg aaacaaggca gatggagtcc tggtgggaac
agatggaagg 120tactcttcga tggcggccag tttcaggtcc agtgagcatg
agaatgccta tgagaatgtg 180cccgaggagg aaggcaaggt ccgcagcacc
ccgatgtaac cttctctgtg gctccaaccc 240caagactccc aggcacatgg
gatggatgtc cagtgctacc acccaagccc cctccttctt 300tgtgtggaat
ctgcaatagt gggctgactc cctccagccc catgccggcc ctacccgccc
360ttgaagtata gccagccaag gttggagctc agaccgtgtc taggttgggg ctcg
414143561DNAhuman 143gagagaaaac aatatagccc cctacccttt tcccaatcct
ttgccctcaa atcagtgacc 60caagggaggg ggggatttaa agggaaggag tgggcaaaac
acataaaatg aatttattat 120atctaagctc tgtagcagga ttcatgtcgt
tctttgacag ttctttctct ttcctgtata 180tgcaataaca aggttttaaa
aaaaaaaaaa aaaagtgaga ctattagaca aagtatttat 240gtaattattt
gataactctt gtaaataggt ggaatatgaa tgcttggaaa attaaacttt
300aatttattga cattgtacat agctctgtgt aaatagaatt gcaactgtca
ggttttgtgt 360tcttgttttc ctttagttgg gtttatttcc aggtcacaga
attgctgtta acactagaaa 420acacacttcc tgcaccaaca ccaataccct
ttcaaaagag ttgtctgcaa catttttgtt 480ttctttttta atgtccaaaa
gtgggggaaa gtgctatttc ctattttcac caaaattggg 540gaaggagtgc
cactttccag c 561144409DNAhuman 144ttagcactga aagtctcttg ccccaggaaa
ccccatcagt cccaggcaga ttgggacagc 60tggtcacctt acgcaagagc caggctgaaa
catcccctcc atactcagct ctttaacttt 120tcttttcctt tttcatcggg
ctctttccta aaaagctgag ctgtaaaata ttttacatcg 180aggtataata
aataatcatg tacatgtttt accaccaccc aggtcaagac atagaatgtt
240tcaacatttc catcacccca gaaactcccc ttgtaccccc ttccacttcg
tctcccctag 300ctcctagaag caaccactga tgtgatttct accaaatcca
gttttggtcc tactaaatat 360actcttttga gactggcctc ttttactcac
cataatgcct ttgtaattc 409145491DNAhuman 145tagctgtttc agagagagta
cggtatattt atggtaattt tatccactag caaatcttga 60tttagtttga tagtgtgtgg
aattttattt tgaaggataa gaccatggga aaattgtggt 120aaagactgtt
tgtacccttc atgaaataat tctgaagttg ccatcagttt tactaatctt
180ctgtgaaatg catagatatg cgcatgttca actttttatt gtggtcttat
aattaaatgt 240aaaattgaaa attcatttgc tgtttcaaag tgtgatatct
ttcacaatag cctttttata 300gtcagtaatt cagaataatc aagttcatat
ggataaatgc atttttattt cctatttctt 360tagggagtgc tacaaatgtt
tgtcacttaa atttcaagtt tctgttttaa tagttaactg 420actatagatt
gttttctatg ccatgtatgt gccacttctg agagtagtaa atgactcttt
480gctacatttt a 491146562DNAhuman 146gtgtaccaga attcggccat
gagccgctac atactcatca tggggctcct gtacaaggtg 60ctgggcgtcc tcttctttgc
catagcctgc ttcttataca agcccctgtc ggagtcttca 120gatggcctgg
aaacttgtct gcccagccag tcctcagccc ctgacagtgc cacagatagc
180cagctccaga gcagcgtctg accaccgccc gcgcccaccc ggccacggcg
ggcactcagc 240atttcctgat gacagaacag tgccgttggg tgatgcaatc
acacgggaac ttctatttga 300cctgcaacct tctacttaac ctgtggttta
aagtcggctg tgacctcctg tccccagagc 360tgtacggccc tgcagtgggt
gggaggaact tgcataaata tatatttatg gacacacagt 420ttgcatcaga
acgtgtttat agaatgtgtt ttatacccga tcgtgtgtgg tgtgcgtgag
480gacaaactcc gcaggggctg tgaatcccac tgggagggcg gtgggcctgc
agcccgagga 540aggcttgtgt gtcctcagtt aa 562147524DNAhuman
147gaagttgcaa cattcgtttg ataggaattc cagaaaagga gagttatgag
aatagggcag 60aggacataat taaagaaata attgatgaaa actttgcaga actaaagaaa
ggttcaagtc 120ttgagattgt cagtgcttgt cgagtaccta gtaaaattga
tgaaaagaga ctgactccta 180gacacatctt ggtgaaattt tggaattcta
gtgataaaga gaaaataata agggcttcta 240gagagagaag agaaattacc
taccaaggaa caagaatcag gttgacagca gacttatcac 300tggacacact
ggatgctaga agtaaatgga gcaatgtctt caaagttctg ctggaaaaag
360gctttaatcc tagaatccta tatccagcca aaatggcatt tgattttagg
ggcaaaacaa 420aggtatttct tagtattgaa gaatttagag attatgtttt
gcatatgccc accttgagag 480aattactggg gaataatata ccttagcacg
ccagggtgac taca 524148194DNAhuman 148ttgcttgttc cccggaggtt
gaagctacag tgagccttga ttgtgtcact gcactccagc 60ctgggcaaca ggtaagactc
tgtctcaaaa aaaaaacaaa aaagaagaag aaaagtactt 120ctacagccat
gtcctattcc ttgatcatcc aaagcacctg cagagtccag tgaaatgata
180tattctggct gggc 194149536DNAhuman 149gacggcgtca aggtcgtggg
acgtgacacg accgctgcgg cgtcagctca gccttgcaag 60accccaggcg cccgcgctgc
acctgcgact gtcgccgccg ccgtcgcagt cggaccaact 120gctggcagaa
tcttcgtccg cacggcccca gctggagttg cacttgcggc cgcaagccgc
180cagggggcgc cgcagagcgc gtgcgcgcaa cggggaccac tgtccgctcg
ggcccgggcg 240ttgctgccgt ctgcacacgg tccgcgcgtc gctggaagac
ctgggctggg ccgattgggt 300gctgtcgcca cgggaggtgc aagtgaccat
gtgcatcggc gcgtgcccga gccagttccg 360ggcggcaaac atgcacgcgc
agatcaagac gagcctgcac cgcctgaagc ccgacacggt 420gccagcgccc
tgctgcgtgc ccgccagcta caatcccatg gtgctcattc aaaagaccga
480caccggggtg tcgctccaga cctatgatga cttgttagcc aaagactgcc actgca
536150460DNAhuman 150tggaattaga ccatttggcc tttgaacttt cataggaaaa
atgacccaac atttcttagc 60atgagctacc tcatctctag aagctgggat ggacttacta
ttcttgttta tattttagat 120actgaaaggt gctatgcttc tgttattatt
ccaagactgg agataggcag ggctaaaaag 180gtattattat ttttccttta
atgatggtgc taaaattctt cctataaaat tccttaaaaa 240taaagatggt
ttaatcacta ccattgtgaa aacataactg ttagacttcc cgtttctgaa
300agaaagagca tcgttccaat gcttgttcac tgttcctctg tcatactgta
tctggaatgc 360tttgtaatac ttgcatgctt cttagaccag aacatgtagg
tccccttgtg tctcaatact 420ttttttttct taattgcatt tgttggctct
attttaattt 460151446DNAhuman 151tagattccgg tatatcgttc ttcaagacac
ttgctctaag cggaatggaa atgtgggcaa 60gactgtcttt gaatatagaa cacagaatgt
ggcacgcttg cccatcatag atcttgctcc 120tgtggatgtt ggcggcacag
accaggaatt cggcgttgaa attgggccag tttgttttgt 180gtaaagtaag
ccaagacaca tcgacaatga gcaccaccat caatgaccac cgccattcac
240aagaactttg actgtttgaa gttgatcctg agactcttga agtaatggct
gatcctgcat 300cagcattgta tatatggtct taagtgcctg gcctccttat
ccttcagaat atttatttta 360cttacaatcc tcaagtttta attgatttta
aatatttttc aatacaacag tttaggttta 420agatgaccaa tgacaatgac cacctt
446152552DNAhumanmisc_feature(63)..(63)n is a, c, g, or
tmisc_feature(72)..(72)n is a, c, g, or tmisc_feature(74)..(74)n is
a, c, g, or tmisc_feature(85)..(85)n is a, c, g, or
tmisc_feature(138)..(138)n is a, c, g, or t 152tttcagcacc
gatggccatg taaataagat gatttaatgt tgattttaat cctgtatata 60aantaaaaag
tncncaatga gtttngggca tatttaatga tgattatgga gccttagagg
120tctttaatca ttggttcngg ctgcttttat gtagtttagg ctggaaatgg
tttcacttgc 180tctttgactg tcagcaagac tgaagatggc ttttcctgga
cagctagaaa acacaaaatc 240ttgtaggtca ttgcacctat ctcagccata
ggtgcagttt gcttctacat gatgctaaag 300gctgcgaatg ggatcctgat
ggaactaagg actccaatgt cgaactcttc tttgctgcat 360tcctttttct
tcacttacaa gaaaggcctg aatggaggac ttttctgtaa ccaggaacat
420tttttagggg tcaaagtgct aataattaac tcaaccaggt ctacttttta
atggctttca 480taacactaac tcataaggtt accgatcaat gcatttcata
cggatataga cctagggctc 540tggagggtgg gg 552153253DNAhuman
153gtaaatagtt aaccttcagt agtctattaa ggcattaata cttctctgga
catgcgcgtt 60tgagggtgga ggggtcctgt aaggtgcttc atcgtctgtg attactgctt
gggatgtgtt 120ctttggcagc ttgtgagatt actttaccta gtgtttataa
agtaggaagt taagtgaatc 180atagattaga atttaatact cttatggaaa
taatttttta acatcttaat tgacaatggc 240gtttttttat aca
253154239DNAhuman 154tagtccatac tgagtgtcat caacaatcca gactgaagtc
ttctatttta atctcaatcc 60ccttttctga tttgccaccc atgcctcttc aggctggaaa
caatctcttg gttccctaaa 120gcactttctt ctgactgctg tgattcagtg
aaccttgccc tttgctttct attacttgtg 180catttgcctc acctgacaat
gttttaaatc gcctttgtat ctccttagct gctcaataa 239155313DNAhuman
155aatatgtcag tgcttgcttg atggaaactt ctcttgtgtc tgttgagact
ttaagggaga 60aatgtcggaa tttcagagtc gcctgacggc agagggtgag cccccgtgga
gtctgcagag 120aggccttggc caggagcggc gggctttccc gaggggccac
tgtccctgca gagtggatgc 180ttctgcctag tgacaggtta tcaccacgtt
atatattccc taccgaagga gacacctttt 240cccccctgac ccagaacagc
ctttaaatca caagcaaaat aggaaagtta accacggagg 300caccgagttc cag
313156436DNAhuman 156ggctggggga gagccgggtt cattccctgt cctcattggt
cgtccctatg aattgtacgt 60ttcagagaaa ttttttttcc tatgtgcaac acgaagcttc
cagaaccata aaatatcccg 120tcgataagga aagaaaatgt cgttgttgtt
gtttttctgg aaactgcttg aaatcttgct 180gtactataga gctcagaagg
acacagcccg tcctcccctg cctgcctgat tccatggctg 240ttgtgctgat
tccaatgctt tcacgttggt tcctggcgtg ggaactgctc tcctttgcag
300ccccatttcc caagctctgt tcaagttaaa cttatgtaag ctttccgtgg
catgcggggc 360gcgcacccac gtccccgctg cgtaagactc tgtatttgga
tgccaatcca caggcctgaa 420gaaactgctt gttgtg 436157493DNAhuman
157gtgagtatgg cccaatgctt tctgtggcta aacagatgta atgggaagaa
ataaaagcct 60acgtgttggt aaatccaaca gcaagggaga tttttgaatc ataataactc
ataaggtgct 120atctgttcag tgatgccctc agagctcttg ctgttagctg
gcagctgacg ctgctaggat 180agttagtttg gaaatggtac ttcataataa
actacacaag gaaagtcagc caccgtgtct 240tatgaggaat tggacctaat
aaattttagt gtgccttcca aacctgagaa tatatgcttt 300tggaagttaa
aatttaaatg gcttttgcca catacataga tcttcatgat gtgtgagtgt
360aattccatgt ggatatcagt taccaaacat tacaaaaaaa ttttatggcc
caaaatgacc 420aacgaaattg ttacaataga atttatccaa ttttgatctt
tttatattct tctaccacac 480ctggaaacag acc
493158457DNAhumanmisc_feature(87)..(87)n is a, c, g, or t
158catggtttac atttactcag ctactatata tgcagtgtgg tgcacatttt
cacagaattc 60tggcttcatt aagatcatta tttttgnctg cgtagcttac agacttagca
tattagtttt 120ttctactcct acaagtgtaa attgaaaaat ctttatatta
aaaaagtaaa ctgttatgaa 180gctgctatgt actaataata ctttgcttgc
caaagtgttt gggttttgtt gttgtttgtt 240tgtttgtttg tttttggttc
atgaacaaca gtgtctagaa acccattttg aaagtggaaa 300attattaagt
cacctatcac ctttaaacgc ctttttttaa aattataaaa tattgtaaag
360cagggtctca acttttaaat acactttgaa cttcttctct gaattattaa
agttctttat 420gacctcattt ataaacacta aattctgtca cctcctg
457159426DNAhumanmisc_feature(170)..(170)n is a, c, g, or t
159gccgctgtgc tttcgtggaa atgacagttc cttgtttttt ttgtttctgt
ttttgtttta 60cattagtcat tggaccacag ccattcagga actaccccct gccccacaaa
gaaatgaaca 120gttgtaggga gacccagcag cacctttcct ccacacacct
tcattttgan gttcgggttt 180ttgtgttaag ttaatctgta cattctgttt
gccattgtta cttgtactat acatctgtat 240atagtgtacg gcaaaagagt
attaatccac tatctctagt gcttgacttt aaatcagtac 300agtacctgta
cctgcacggt cacccgctcc gtgtgtcgcc ctatattgag ggctcaagct
360ttcccttgtt ttttgaaagg ggtttatgta taaatatatt ttatgccttt
ttattacaag 420tcttgt 426160502DNAhuman 160ggagtggttt aagagtgcca
ggcgaagggc aaactgtaga tcgatcttta tgctgttatt 60acaggagaag tgacatactt
tatatatgtt tatattagca aggtctgttt ttaataccat 120atactttata
tttctataca tttatatttc taataataca gttatcactg atatatgtag
180acacttttag aatttattaa atccttgacc ttgtgcatta tagcattcca
ttagcaagag 240ttgtaccccc tccccagtct tcgccttcct ctttttaagc
tgttttatga aaaagaccta 300gaagttcttg attcattttt accattcttt
ccataggtag aagagaaagt tgattggttg 360gttgtttttc aattatgcca
ttaaactaaa catttctgtt aaattaccct atcctttgtt 420ctctactgtt
ttctttgtaa tgtatgacta cgagagtgat actttgctga aaagtctttc
480ccctattgtt tatctattgt ca 502161482DNAhuman 161ttcctgtgca
agtaccgacc atagagcaag aatcaagatt ctgctaactc ctgcacagcc 60ccgtcctctt
cctttctgct agcctggcta aatctgctca ttatttcaga ggggaaacct
120agcaaactaa gagtgataag ggccctacta cactggcttt tttaggctta
gagacagaaa 180ctttagcatt ggcccagtag tggcttctag ctctaaatgt
ttgccccgcc atccctttcc 240acagtatcct tcttccctcc tcccctgtct
ctggctgtct cgagcagtct agaagagtgc 300atctccagcc tatgaaacag
ctgggtcttt ggccataaga agtaaagatt tgaagacaga 360aggaagaaac
tcaggagtaa gcttctagac cccttcagct tctacaccct tctgccctct
420ctccattgcc tgcaccccac cccagccact caactcctgc ttgtttttcc
tttggccata 480gg 482162490DNAhuman 162ggagctcaga gatctaagct
gctttccatc ttttctccca gccccaggac actgactctg 60tacaggatgg ggccgtcctc
ttgcctcctt ctcatcctaa tcccccttct ccagctgatc 120aacccgggga
gtactcagtg ttccttagac tccgttatgg ataagaagat caaggatgtt
180ctcaacagtc tagagtacag tccctctcct ataagcaaga agctctcgtg
tgctagtgtc 240aaaagccaag gcagaccgtc ctcctgccct gctgggatgg
ctgtcactgg ctgtgcttgt 300ggctatggct gtggttcgtg ggatgttcag
ctggaaacca cctgccactg ccagtgcagt 360gtggtggact ggaccactgc
ccgctgctgc cacctgacct gacagggagg aggctgagaa 420ctcagttttg
tgaccatgac agtaatgaaa ccagggtccc aaccaagaaa tctaactcaa
480acgtcccact 490163362DNAhuman 163gcaaagttta tttcagttca catgtaaggt
attgcaaata aattcttgga caattttgta 60tggaaacttg atattaaaaa ctagtctgtg
gttctttgca gtttcttgta aatttataaa 120ccaggcacaa ggttcaagtt
tagattttaa gcacttttat aacaatgata agtgcctttt 180tggagatgta
acttttagca gtttgttaac ctgacatctc tgccagtcta gtttctgggc
240aggtttcctg tgtcagtatt ccccctcctc tttgcattaa tcaaggtatt
tggtagaggt 300ggaatctaag tgtttgtatg tccaatttac ttgcatatgt
aaaccattgc tgtgccattc 360aa 36216460DNAhuman 164agacggcctt
gagtctcagt acgagtgtgc gtgagtgtga gccaccttgg caagtgcctg
60165495DNAhumanmisc_feature(44)..(44)n is a, c, g, or t
165ggagtgtggt acttctccta gttgcagtca ggcttcatac gctnttgtcc
tgcccgttag 60agcagccagc gggtacagaa tggattttgg aagagggagt caccactgga
cctccaagga 120agccacgtgc agacatctac aaccttcgat ctcctgacga
gtttattgtt ggccaaaacc 180aggctttgat tgaaccagga tgaatgcggg
tgttggaagt agaatatata tatacatata 240aaattggttg ggagccacgt
gtaccagtgt gtgttgatct tggcttgatt cagtctgcct 300tgtaacagaa
actggcgatg gaatatgaga ggagccctct ggaaagaaaa ggacagaccc
360tgtgctttca tgaaagtgaa gatctggctg aaccagttcc acaaggttac
tgtatacata 420gcctgagttt aaaaggctgt gcccacttca agaatgtcat
tgttagactt tgaaatttct 480aactgcctac ctgca
495166527DNAhumanmisc_feature(235)..(238)n is a, c, g, or
tmisc_feature(271)..(274)n is a, c, g, or
tmisc_feature(467)..(468)n is a, c, g, or t 166agggctgtaa
cagttgctgc tagtattagg gttccacatc attctaatgt atagtttcaa 60gtcttaatag
acaatctgaa ttccactaca tttcttttgg ctccaacatt ccttttagct
120tgaccagtct aatttaaaat gtgtttgttg gaggtcatta acgttacttg
tacaatgctg 180tcactgtgtg acatccatat gaattttggt atatatcaat
caatcaatca atcannnnca 240ttgcattcaa tcaatcagct gtgattgatt
nnnnatgctt agaaatacta tagtaactag 300atgcagtgtg aattttttcc
attaacaaac aaacaagtca gtggcttaaa tgtgattatg 360gtcctgcaag
gtgattcttg ctaaaatatc taaacttttg ttttgtttta actgaatcat
420tttttaactt aaaaagctgg aaaatatcaa atgctgtttt ttttttnnca
ttgtcaacag 480tggtgtgtca ttttatgtat gttcctaatg cttatggaac tcctcca
527167464DNAhumanmisc_feature(402)..(402)n is a, c, g, or t
167ggaacgatga gcaccatgcc aggactgccc acccggccct gcttttatga
catagatctt 60gataccgaaa cagaacaagt taaaggcttg ttctaagtgg acaaggctct
cacaggaccc 120gatgcagact cctgaaacag actactcttt gcctttttgc
tgcagttgga gaagaaactg 180aatttgaaaa atgtctgtta tgcaatgctg
gagacatggt gaaataggcc aaagatttct 240tcttcgttca agatgaattc
tgttcacagt ggagtatggt gttcggcaaa aggacctcca 300ccaagactga
aagaaactaa tttatttctg tttctgtgga gtttccatta tttctactgc
360ttacacttta gaatgtttat tttatgggga ctaagggatt angagtgtga
actaaaaggt 420aacattttcc actctcaagt tttctacttt gtctttgaac tgaa
464168456DNAhumanmisc_feature(26)..(30)n is a, c, g, or
tmisc_feature(33)..(33)n is a, c, g, or tmisc_feature(35)..(47)n is
a, c, g, or tmisc_feature(50)..(50)n is a, c, g, or t 168gaaacacaac
caagacgcga ggatcnnnnn ctntnnnnnn nnnnnnnctn gcaagatggc 60gccgcagaaa
gacaggaagc ccaagaggtc aacctggagg tttaatttgg accttactca
120tccagtagaa gatggaattt ttgattctgg aaattttgag caatttctac
gggagaaggt 180taaagtcaat ggcaaaactg gaaatctcgg gaatgttgtt
cacattgaac gcttcaagaa 240taaaatcaca gttgtttctg agaaacagtt
ctctaaaagg tatttgaaat accttaccaa 300gaaatacctt aagaagaaca
atcttcgtga ttggcttcga gtggttgcat ctgacaagga 360gacctacgaa
cttcgttact tccagattag tcaagatgaa gatgaatcag agtcggagga
420ctaggcaaag gctcccctta cagggctttg cttatt 456169351DNAhuman
169ggaacccaga gctgctgtgt atttcgagcg ggcagtttat cttttgctat
acttattttc 60aattcaatta caccacgatt caaataattc ccctcctaaa accaaaaagg
agggaaacgt 120caactccatt gcaattactt atcttcctct tctatctctg
ttatacgccg gggcatagaa 180tgctcgtata catctcttta acaaccacaa
accttaagcc atgtagatga agttagtgca 240tcaacgggat acagttccat
attgccttaa acctccttgt tttagacaca ctaacattta 300taccaaattg
cagattattc tgcagagagg gaattgcatg tttgtgttgt a 351170506DNAhuman
170aattaatatt catcgcactt cttctgtgga aggactttgt gaaggaattg
gtgctggatt 60agtggatgtt gctatctggg ttggcacttg ttcagattac ccaaaaggag
atgcttctac 120tggatggaat tcagtttctc gcatcattat tgaagaacta
ccaaaataaa tgctttaatt 180ttcatttgct acctcttttt ttattatgcc
ttggaatggt tcacttaaat gacattttaa 240ataagtttat gtatacatct
gaatgaaaag caaagctaaa tatgtttaca gaccaaagtg 300tgatttcaca
ctgtttttaa atctagcatt attcattttg cttcaatcaa aagtggtttc
360aatatttttt ttagttggtt agaatacttt cttcatagtc acattctctc
aacctataat 420ttggaatatt gttgtggtct tttgtttttt ctcttagtat
agcattttta aaaaaatata 480aaagctacca atctttgtac aatttg
506171384DNAhumanmisc_feature(192)..(192)n is a, c, g, or t
171ccgtgtgagc gatcgcggtg ggttcgggcc ggtgtgacgc gtgcgccggc
cggccgccga 60ggggctgccg ttctgcctcc gaccggtcgt gtgtgggttg acttcggagg
cgctctgcct 120cggaaggaag gaggtgggtg gacggggggg cctggtgggg
ttgcgcgcac gcgcgcaccg 180gccgggcccc cngccctgaa cgcgaacgct
cgaggtggcc gcgcgcaggt gtttcctcgt 240accgcagggc cccctccctt
ccccaggcgt ccctcggcgc ctctgcgggc ccgaggagga 300gcggctggcg
ggtgggggga gtgtgaccca ccctcggtga gaaaagcctt ctctagcgat
360ctgagaggcg tgccttgggg gtac
384172360DNAhumanmisc_feature(128)..(128)n is a, c, g, or
tmisc_feature(190)..(190)n is a, c, g, or
tmisc_feature(206)..(206)n is a, c, g, or t 172aaatgactgg
atggtcgctg ctttttaagt ttcaaattga cattccagac aagcggtgcc 60tgagcccgtg
cctgtcttca gatcttcaca gcacagttcc tgggaaggtg gagccaccag
120cctctccntg aataactggg agatgaaaca ggaagctcta tgacacactt
gatcgaatat 180gacagacacn gaaaatcacg actcancccc ctccagcacc
tctacctgtt gcccgccgat 240cacagccgga atgcagctga aagattccct
ggggcctggt tccaaccgcc cactgtggac 300tctgaggcct ctgcatttgc
gggtggtctg cctgtgatat tttggtcatg ggctggtctg
360173437DNAhumanmisc_feature(97)..(97)n is a, c, g, or
tmisc_feature(357)..(357)n is a, c, g, or t 173tcttctcagg
tcacttgtac acttggtttc ctagtagaag ctcacttgcc acctctcagg 60ggggtcccgg
attgcatcca tcacaatccc aaaactngag ttggggggaa ctggagggag
120caaaacactg atttgatact agtcagtttg cttgaaacta gttcacctaa
agctagatct 180cttaaaacca atttactgaa aacttgtttg cttaaagtta
atgacttaat gactaatttg 240ccaaaagctc aattcctatt ttggtgtgtt
tatatccatt taggtgtcct attctttttt 300gtcatgcttt ggatatttca
aggatttata tctattcatc caagagtact tctgagntat 360tatcagcaac
ataaatttat caaatttgca gcactttgta aatgatgaga ttgcttccta
420cctttatgga tgtcttt 437174539DNAhumanmisc_feature(147)..(147)n is
a, c, g, or t 174aatgcattac tttcacttaa cactagacac caggtcgaaa
attttcaagg ttatagtact 60tatttcaaca attcttagag atgctagcta gtgttgaagc
taaaaatagc tttatttatg 120ctgaattgtg atttttttat gccaaanttt
ttttagttct aatcattgat gatagcttgg 180aaataaataa ttatgccatg
gcatttgaca gttcattatt cctataagaa ttaaattgag 240tttagagaga
atggtggtgt tgagctgatt attaacagtt actgaaatca aatatttatt
300tgttacatta ttccatttgt attttaggtt tccttttaca ttctttttat
atgcattctg 360acattacata ttttttaaga ctatggaaat aatttaaaga
tttaagctct ggtggatgat 420tatctgctaa gtaagtctga aaatgtaata
ttttgataat actgtaatat acctgtcaca 480caaatgcttt tctaatgttt
taaccttgag tattgcagtt gctgctttgt acagaggtt 539175487DNAhuman
175gtacttctcc tagttgcagt caggcttcat acgctattgt cctgcccgtt
agagcagcca 60gcgggtacag aatggatttt ggaagaggga gtcaccactg gacctccaag
gaagccacgt 120gcagacatct acaaccttcg atctcctgac gagtttattg
ttggccaaaa ccaggctttg 180attgaaccag gatgaatgcg ggtgttggaa
gtagaatata tatatacata taaaattggt 240tgggagccac gtgtaccagt
gtgtgttgat cttggcttga ttcagtctgc cttgtaacag 300aaactggcga
tggaatatga gaggagccct ctggaaagaa aaggacagac cctgtgcttt
360catgaaagtg aagatctggc tgaaccagtt ccacaaggtt actgtataca
tagcctgagt 420ttaaaaggct gtgcccactt caagaatgtc attgttagac
tttgaaattt ctaactgcct 480acctgca 487176427DNAhuman 176gaagaggagc
aacatctatg ccaaatactg tgcattctac aatggtgcta atctcagacc 60taaatgatac
tccatttaat ttaaaaaaga gttttaaata attatctatg tgcctgtatt
120tcccttttga gtgctgcaca acatgttaac atattagtgt aaaagcagat
gaaacaacca 180cgtgttctaa agtctaggga ttgtgctata atccctattt
agttcaaaat taaccagaat 240tcttccatgt gaaatggacc aaactcatat
tattgttatg taaatacaga gttttaatgc 300agtatgacat cccacagggg
aaaagaatgt ctgtagtggg tgactgttat caaatatttt 360atagaataca
atgaacggtg aacagactgg taacttgttt gagttcccat gacagatttg 420agacttg
427177485DNAhuman 177aaacgacgca aatctctgag ctggggacca cttggagaac
cggcttagta acagtcctga 60tcttcgcaag ccagcttctt ctgcatctga ggggctcctg
gcgcccagag gaggcagaca 120gatgtcttct agctgagttt ctaaccgcat
gatgagactc agaccttccg ctgcactaga 180aaatctgcaa cagtgtccct
gagtcacttc tccttagtgg gcagactcgt gttagatttg 240tggaacccag
ctctctgatt tactcctttt ggaaaaccca tggaatttca tgtataaggc
300tttcatttgt attttaaggt ttttctgttt gttttgagta tatacatggt
gctcaatagc 360aacatcttag cagatgaagc agtttatgat tccactccct
cctgtatgac aggtagccac 420tatactgaat caaggtgctg aactcaaatc
acaaaattct ggcttaccga tacaacaacc 480aatac
485178564DNAhumanmisc_feature(172)..(172)n is a, c, g, or
tmisc_feature(338)..(338)n is a, c, g, or t 178gtcccactgc
tcacatactt atgtgctgct agtctctact cgaagttcgt gcaggactaa 60tgcttttaaa
atgaggtcta aaaaataatt actagtcgag actattattc tttaaacaga
120actgcctttt tctactcttt atgtaaactc tttctattgt gttggtctaa
cnaggcacta 180ttttaaaatt ttttaatttt tcccatagca cttaaaagag
attttgtaaa gaccttgctg 240taaagatttt gtaataaaat ggtctaaggg
ctctttttcc aacattacca tttttaaaaa 300atgttttaaa agctagaaga
caacttatgt atattctnta tatgtatagc agcacatttc 360atttatggaa
atatgttctc agaatattta tttactaata tatttatctt aagccatgtc
420ttatgttgag agtgtgacat tgttggaata atcattgaaa atgactaaca
caagaccctg 480taaatacatg ataattgcac acagatttta catatttgca
gaccaaaaat gatttaaaac 540aagttgtagt cttctatggt tttg
564179487DNAhumanmisc_feature(296)..(296)n is a, c, g, or t
179tataaggtaa ctctttagtc ctccatttag cacattttaa atcctccaaa
gaataagtat 60catgtgatta ttttagcttt acaaaaaaaa agttgaatgg cgttttattt
tcatggccta 120taagcaggta ccttagtagg gcagatatag gaaaaacaaa
ttagagcaaa acaaatcctc 180tacaaatcca aggcaggaaa agtggtggca
gagtgactca ttctcctgtc cctcccatca 240ggtcaaatca ggaggctgca
gtgaatgcct gttctttgaa tgtgtagcag ttgttncctg 300taactcttta
aaacttggct ataggctgtt tagcacagta cagattaaag atacagttac
360gtaaacagca aagtaatttt atagtgcttc atccatttat catgctttgg
tttgctaatt 420ttttcacata cctttttcta tcacagtctg ttgcttttgt
acacatttct catattgggg 480ttcgaca 487180222DNAhuman 180ggagtgtggt
acttctccta gttgcagtca ggcttcatac gctattgtcc tgcccgttag 60agcagccagc
gggtacagaa tggattttgg aagagggagt caccactgga cctccaagga
120agccacgtgc agacatctac aaccttcgat ctcctgacga gtttattgtt
ggccaaaacc 180aggctttgat tgaaccagga tgaatgcggg tgttggaagt ag
222181516DNAhuman 181ttaccctcta tttaaatgct ttgaaaaaca gtgcattgac
aatgggttga tatttttctt 60taaaagaaaa atataattat gaaagccaag ataatctgaa
gcctgtttta ttttaaaact 120ttttatgttc tgtggttgat gttgtttgtt
tgtttgtttc tattttgttg gttttttact 180ttgttttttg ttttgttttg
ttttgttttg catactacat gcagttcttt aaccaatgtc 240tgtttggcta
atgtaattaa agttgttaat ttatatgagt gcatttcaac tatgtcaatg
300gtttcttaat atttattgtg tagaagtact ggtaattttt
ttatttacaa tatgtttaaa 360gagataacag tttgatatgt tttcatgtgt
ttatagcaga agttatttat ttctatggca 420ttccagcgga tattttggtg
tttgcgaggc atgcagtcaa tattttgtac agttagtgga 480cagtattcag
caacgcctga tagcttcttt ggcctt
516182507DNAhumanmisc_feature(357)..(357)n is a, c, g, or t
182ctggcacaac cctgacatta ctaagtggaa atgttaggat ttttcggcat
cgcatgttag 60aatctctaaa atttaaacat tcctgttaaa tgactaaggt ttgcttttat
caatatgaat 120tctgaaggcc aatatcatac cattaactat gaaagctttt
aattcctaaa aatagtttta 180gagatattca agcaatgctc tcctaatatc
catacgcaag tgtgtttatg acacaaattc 240actagtctgt ttaaaaatga
attctttata ttgactggtg ttccacatat ttcagtaatt 300tctgttatga
gaggacttga aatagcaaat tgccacacag ttaactggat agaccangta
360cgtggtgatc ataaccactt ggtactacac ccagaaactc aaaattgtct
ttctcctgat 420gagatatggg tgtccttttg tacgtctagg cctaggtaac
cagtggagtg attatattag 480caaatgtgtt tgtatccaga gtcttcc
507183430DNAhuman 183ccaggcttcg tcttatttct actgtttttg tcgcaacttc
cattgattta tgtcccttcc 60ctccccccta agtacatcag ggaacctttc cacactataa
atgatatgac tactgtttgg 120ggtttctggg cccccatccg tgtacgtatg
tggcatttcc aggtatgact gagtgtgaga 180gacatgtcag aggctcttca
gtgatttctt gctattgacc gatgcttcac tgtgccaaaa 240gagaaaaaaa
atgttgggtt ttgtaattaa attatttata tatttttgaa acccgaattg
300aaaatgttgc aggcaacggg ctacagcttt attagtggtt ctctaactgt
ggtctccttg 360ggccaagcaa tttctttaaa ggaaaagttg attatgtatg
tggggtgcca ggaccactgc 420cttgaaagca
430184473DNAhumanmisc_feature(260)..(260)n is a, c, g, or
tmisc_feature(384)..(384)n is a, c, g, or t 184tagcccaacc
ctatcatttt catattatga aactgagtcc aggtaagtga atctgtccaa 60ggtcacccag
caaggtatca gtagccctga gggtaaggac tctgataagg ctcgggaggg
120tcctggaaag cctgaggcgg caggaagagt gtgcagagtt gagcgtgtct
ggaaggctga 180tccactgctg ggcccacatc aaagccccca tggggagcag
acccgactgc acatggctct 240tttgctggaa gaagagcatn gctgcgcaga
ggactaaaat ttcatctggg aaggcttctt 300ttgactgtca gtagcaggat
gtcaccagat gagggtgcta tgggaccaca gctgtctttg 360ttcccattgc
aactcaaccc tgcnggaggc cgcctgcatc cctgagagcc ttctggagcc
420tacagaggag acattggcca gccaaaagga aaggagtggc cagggtacga cct
473185451DNAhuman 185aattatccct tatcattcca aaaatgaaat gctgtgttaa
atatctccag ggcaaagtgg 60tatgttgact gggacaaacg ttagaaattg tattgttcat
tgcacttgtt gccctgttcc 120ccaagcttgt caatgtttag agatactatt
cgggttgcta aagccattat tcatagaaaa 180tttctgcccc tacagaagtg
tgtgcatggg ccttggaaaa tctacatgtg tatatctgag 240tagcgaagca
cagattcact ctaattgaaa gcagcagttt ggttttgtaa atgtaattgc
300aattgacact ttcttttccc tttcagttat tatttttttt aaaggacgtt
atgagaaggc 360actatgaaaa gcctaattgg aatagcatta tgaaccatgt
aatgcatgcc catgcacact 420gtgatttgca aacatatgtc cgctcttcaa t
451186498DNAhumanmisc_feature(394)..(394)n is a, c, g, or t
186ggtgggtgtc actacagaca tgttctggcg tgttctccga gggatggagc
atcctgttat 60atatttgact tcaaattgag atgttggctt catttttttt ttttacccaa
ttaatctccc 120aatccctagc aactgtgact ctgtatttag cacaagagaa
agctgagaat gtgggtcttg 180cctccttcca gaaatatgtc tggctcatca
ggacattttt ttaaaacttc aaaatatttt 240taagatattt taaactttta
taaaaaaaaa atcaaccaac aagagacttt tctgaggagg 300aacatttgta
tttgaacaag atccttggtg tgtagttcag tcttgcagta tacaagcttt
360tgtgtataaa tgttttatga tatgattccc tgtnttttgc aggggttttt
ttctcttttg 420ctttttagat aaatatgtat atcaatattt taaattcatc
tttgcttttt ttagaggagt 480ttgtaatcac cttataac 498187462DNAhuman
187gaaaaaagct atcagctgta tgttaagaga gactcttact aacatgttgt
aaatattaca 60attcatgaaa tgttattgta agtctgtaac ttaatttttt ccctgtttta
gttatacagg 120ttggtttgga aatttgtgtt ttggcataaa caagtaaaat
gtgcccattt tatggtttcc 180atgcttttgt aatcctaaaa atattaatgt
ctagttgttc tatattataa ccacatttgc 240gctctatgca agcccttgga
acagaacata ctcatcttca tgtaggacct atgaaaattg 300tctattttta
tctatatatt taaagttttc taaaaatgat aaaaggttat tacgaatttt
360gttgtacaaa atctgtacaa aaatctgttt ttacatcata atgcaagaat
tggaaatttt 420tctatggtag cctagttatt tgagcctggt ttcaatgtga ga
462188446DNAhumanmisc_feature(37)..(37)n is a, c, g, or
tmisc_feature(43)..(43)n is a, c, g, or tmisc_feature(286)..(287)n
is a, c, g, or tmisc_feature(289)..(295)n is a, c, g, or t
188gccgcggtgg aaacgggctt ggagctggcc ccataanggg ctngcggctt
cctccgacgc 60cgcccctccc cacagcttct cgactgcagt ggggcggggg gcaccaacac
ttggagattt 120ttccggaggg gagaggattt tctaagggca cagagaatcc
attttctaca cattaacttg 180agctgctgga gggacactgc tggcaaacgg
agacctattt ttgtacaaag aacccttgac 240ctggggcgta ataaagatga
cctggacccc tgcccccact atctgnngnn nnnnntgctg 300gccaagatct
ggacacgagc agtccctgag gggcggggtc cctggcgtga ggcccccgtg
360acagcccacc ctggggtggg tttgtgggca ctgctgctct gctagggaga
agcctgtgtg 420gggcacacct cttcaaggga gcgtga 446189433DNAhuman
189gacatgattg tctataatct cgctagcctt gtactgtgtg tgcatagcaa
ttacagggaa 60gtaatctagc tcctgactat tatgttgaac tatgtcgctg ctttttacaa
acttgtcttg 120atccaaagca gtcacaatga taaccctgca tatctgggaa
tcataagtca actatgtatc 180tctgtgtgtg tatatatatg tatgtatgta
tctattttca aactgtgatt taatatttaa 240atattcctac tgccattttt
gtgactgaaa aactacacat gaggaaacgt cttagaattt 300tccaatagag
gaaaaataac acttgggcaa tctgtcatgt ttcacaacag ttctcatttt
360tctcatgatt tgtgtagcgt ggaatgtgtt tgctcaatgt gaagggtttt
cattgctcaa 420tttctctgtg taa
433190361DNAhumanmisc_feature(71)..(71)n is a, c, g, or
tmisc_feature(295)..(304)n is a, c, g, or t 190ggttccggct
aacacatttt ctaagtcgcc agtgctgctt acagtttgaa tacatgaaaa 60tcctgtttct
nagatgtttg cgcacgtgct tattaggaaa tgagtctgta tggaaatctc
120accacagata atggttaacg aaccgggtcg acatcacaaa ggagggtgga
gactcttttt 180actaacttga atgagacaaa agcagtggtg tcagtttata
atcctgatgc atttcagtaa 240taatgtagaa aaacattatt ttaaaaaagt
tccaacacac agccatgagg agccnnnnnn 300nnnntcagtt ttgaaagagg
tgcataataa aactactaac cagaggagtc tatgccattt 360t
361191415DNAhumanmisc_feature(42)..(42)n is a, c, g, or
tmisc_feature(95)..(95)n is a, c, g, or tmisc_feature(353)..(353)n
is a, c, g, or t 191gagtttcaac tttaaatgtt cactatgtca tttagtgtcc
anctttacgg ataggttgac 60tatctaaata ggcattttta gtcattaaaa aaaantctag
tcaccaggag gatccctata 120actcaaaata acttgtttgt aaaagaaaat
ttgtttactt acccattagt aagttcctgc 180atattcatta taagatggca
aatcaaactt ttctaggatg aagacagctt atttttaagt 240tgtatagtct
tagttggttt agggtctcaa ttttaattaa taaaatactt ggtttttatt
300tgcttgtcct tttgaattcc tgttttaata attttaaaat gagcacaaag
aangttgaag 360ttcagattaa tctcttctga atgatgtttt tttcctctgt
gatgagttgt ttctg 415192297DNAhumanmisc_feature(117)..(118)n is a,
c, g, or tmisc_feature(120)..(120)n is a, c, g, or
tmisc_feature(122)..(122)n is a, c, g, or
tmisc_feature(165)..(165)n is a, c, g, or
tmisc_feature(177)..(177)n is a, c, g, or
tmisc_feature(193)..(193)n is a, c, g, or
tmisc_feature(240)..(241)n is a, c, g, or
tmisc_feature(254)..(254)n is a, c, g, or
tmisc_feature(256)..(260)n is a, c, g, or t 192caccaagtta
cgtcaaagtc tcaggagcag ctccggtctc catagaggct gggtcagcag 60tgggcaaaac
aacttccttt gctgggagct ctgcttcctc ctacagcccc tcggaanncn
120cnctcaagaa cttcacccct tcagagacac cgaccatgga catcncaacc
aaggggncct 180tccccaccag canggaccct cttccttctg tccctccgac
tacaaccaac agcagccgan 240ngacgaacag cacntnnnnn aagatcacaa
cctcagcgaa gaccacgatg aagcccc
297193549DNAhumanmisc_feature(222)..(224)n is a, c, g, or
tmisc_feature(226)..(226)n is a, c, g, or
tmisc_feature(416)..(416)n is a, c, g, or
tmisc_feature(434)..(434)n is a, c, g, or
tmisc_feature(440)..(441)n is a, c, g, or
tmisc_feature(448)..(448)n is a, c, g, or
tmisc_feature(516)..(516)n is a, c, g, or t 193gtacagcatg
aaaggcttcc tctacaagac actagtcaaa gagttgagag ctgcggtttc 60taatctttgt
ccattactcc cttactccct atgagactgt ggacctgtca cttggcctct
120ctggtcttca gttttctcac cagtaaaaca aggaacttga accaaatgac
ctctagtgtt 180ccccttgggt ttaaatgtct ataaatgttc aatgactaga
annnantgcg tttttcttta 240ttctttttgc tttgagaaaa gagaatgtga
tttaagagta ataatttgaa taccaattat 300ccacattaaa attgtgtcct
ctatgtgtaa ggcatagcac atttagcaca catacataag 360cacactaagc
accttacaaa tatcctcatt tattctttac ataatctttt gaaatngatt
420atgtaataca cacngttttn naacaatngg tgacttccag ctgtttaaaa
caaactacag 480tatggtgctt gagtactgac ttaggaggtc agcatnggtt
tcactaggag cttctcaaag 540cacgctgcc 549194436DNAhuman 194gggatcactg
ggagaagcca tggcattatc ttcaggcaat ttagtctgtc ccaaataaaa 60taaatccttg
catgtaaatc attcaagggt tatagtaata tttcatatac tgaaaagtgt
120ctcataggag tcctcttgca catctaaaaa ggctgaacat ttaagtatcc
cgaattttct 180tgaattgctt tccctataga ttaattacaa ttggatttca
tcatttaaaa accatacttg 240tatatgtagt tataatatgt aaggaataca
ttgtttataa ccagtatgta cttcaaaaat 300gtgtattgtc aaacatacct
aactttcttg caataaatgc aaaagaaact ggaacttgac 360aattataaat
agtaatagtg aagaaaaaat agaaaggttg caattatata ggccatgggt
420ggctcaaaac tttgaa 436195552DNAhumanmisc_feature(215)..(215)n is
a, c, g, or tmisc_feature(226)..(227)n is a, c, g, or
tmisc_feature(233)..(235)n is a, c, g, or t 195ggacgatgaa
gccatcattg ctgcttggag acgccggcaa gaagaaacca ggaccaagct 60gcagaaaagg
agggaggact gagctgggga aaatctgaga acactgaaag aaaccactca
120cgttagcata gggctcaggg cacacgttgc caccactcat cgcaggatga
ggatacagag 180aggatcttcc agaggggcag agccaaaatg agagntacca
agcatnnggg cannngaggt 240ggagtaggga ggaggcaagg agggggagaa
ccatcaatac gaatacgagg tccgaatgcg 300gaccaactga taccattttc
tgttgctcag cgccctctaa gctttggtgt ttcacttaat 360gtatttgaca
gtgttcatca caggctagag aggtgagctt ggaaaagcac tgtagtttgt
420cagagactcc agtttacatc cagaaaggcc atgaacatag gacacgcttc
tgtctgtaga 480ggcttcatat gagacccaga aagtctatcc tatggcaagt
ctgacctctc ctggcaatgc 540tcagttctga tt 552196559DNAhuman
196gaagtccatc ctttggtcca aagcatctgg aagaggaaga agagaggaat
gagaaagaag 60gaagtgatgc aaaacatctc caaagaagtc ttttggaaca ggaaaatcat
tcaccactca 120cagggtcaaa tatgaaatac aaaaccacga accaatcaac
agaattttta tccttccaag 180atgccagctc attgtacaga aacattttag
aaaaagaaag ggaacttcag caactgggaa 240tcacagaata cctaaggaaa
aacattgctc agctccagcc tgatatggag gcacattatc 300ctggagccca
cgaagagctg aagttaatgg aaacattaat gtactcacgt ccaaggaagg
360tattagtgga acagacaaaa aatgagtatt ttgaacttaa agctaattta
catgctgaac 420ctgactattt agaagtcctg gagcagcaaa catagatgga
gagtttgagg gctttcgcag 480aaatgctgtg attctgtttt aagtccatac
cttgtaaata agtgccttac gtgagtgtgt 540catcaatcag aacctaagc
559197448DNAhuman 197accaagatgg tgcaagttcc ctttgcagat ggcgtgggca
cacttgattt ttattatgag 60tgaatgtaat ctttctgtat tttaccagag ttacagcaat
tacctgaaaa gtttcctaac 120attttaataa tgttagggat ttcgttttgg
ttttagttgt cctcaagaga caacaggttc 180acagtaattt ccatgatgtt
gggtgtggct aagctgggga ttggttctgt tccccctgct 240cccgtgtaga
gaaaagctat atttatactg cattctttct caactttcag gtaaaacaaa
300ctatgattta aaaaaagaaa aaagaaaaga caggtacttt tacttcaaag
agtgctttgc 360tacattttta tttaaaccaa aaatcaaata aaataaggag
gggggctggg tatactttaa 420acaaaaccag tcctgaaatg ctgttatt
448198324DNAhuman 198ttcttgtcca gctgttcaca gttttatttt tatatagatg
gtgatataaa tatttccaaa 60tgcatttgta aacattctaa atattctcaa gtcatgttca
atgtttccta aaccttcaat 120tttggccaaa gtccccaaac acatcattgc
cacactctga agtagagaaa gaaaatttag 180gggccagttc tcaaggaaca
caggtccttt atttttattt taactaagtt gaagacccac 240tcaaaaagct
cttgtggttt tatgttcttg acctttcaac tggagtcctc tcattcagca
300ggtggcccgt gagacacaga atac
324199431DNAhumanmisc_feature(311)..(311)n is a, c, g, or
tmisc_feature(391)..(391)n is a, c, g, or t 199cagtgctgct
gtgaactaaa gtatgtcatt tatgctcaaa gtttaattct tcttcttggg 60atattttaaa
aatgctactg agattctgct gtaaatatga ctagagaata tattgggttt
120gctttatttc ataggcttaa ttctttgtaa atctgaatga ccataataga
aatacatttc 180ttgtggcaag taattcacag ttgtaaagta aataggaaaa
attattttat ttttattgat 240gtacattgat agatgccata aatcagtagc
aaaaggcact tctaaaggta agtggtttaa 300gttgcctcaa nagagggaca
atgtagcttt attttacaag aaggcatagt tagatttcta 360tgaaatattt
attctgtaca gttttatata nttttggttc acaaaagtaa ttattcttgg
420gtgcctttca a 431200322DNAhumanmisc_feature(37)..(38)n is a, c,
g, or t 200aaagtatatt gtgctagctt gtctaagaat aaacttnnat actgttgggg
gagggctgca 60cctgtcaaga taacctgtca atgtagtagg aaaacaggag gggacagtaa
cagaaaagca 120cgggaaaaga tggcaaggtt agttaaaata gaaaagtgct
cagttcctca tacctgtaat 180cccagcagtt tagggggcca aggaaggtgg
gtcacttgag cccaagagtt caaggccatc 240ctgggcaatg tggcgaaagt
gtctacaaaa aaatacaaaa agaggaagaa atgatatttc 300acaagtttgt
atcatttgtc at 322201415DNAhumanmisc_feature(31)..(31)n is a, c, g,
or tmisc_feature(35)..(35)n is a, c, g, or tmisc_feature(40)..(40)n
is a, c, g, or tmisc_feature(50)..(50)n is a, c, g, or
tmisc_feature(57)..(57)n is a, c, g, or tmisc_feature(62)..(62)n is
a, c, g, or tmisc_feature(66)..(66)n is a, c, g, or
tmisc_feature(68)..(68)n is a, c, g, or tmisc_feature(74)..(74)n is
a, c, g, or tmisc_feature(89)..(90)n is a, c, g, or
tmisc_feature(93)..(97)n is a, c, g, or tmisc_feature(99)..(102)n
is a, c, g, or tmisc_feature(104)..(106)n is a, c, g, or t
201caaaaccacg attgtgtgcc ccttttttat naaanctggn atgtttgaan
gttgtantac 60angctntnct tctntgttgc caattctgnn acnnnnntnn nnannngaaa
aaatagtaga 120agctattcta caagaaaaaa tgtacttgta tatgccaaag
ttgttatact tcatgatgtt 180tcttaaaagc tttttgcccc tcaagacagg
actgcttata gctgactatt tgggcatcct 240tcatgcaatg gatggctttg
ttgaccaaaa gaagaagctc taaagaccaa ctctatggct 300aaggtcatct
gatacacagt gttacataat gcgtacttca atgaagaaaa gtatttttgt
360ctgacagtgg aatatatctg gagaccacaa gtaccactcc tattctgtta tctgg
415202249DNAhuman 202agccgttggt ctttgaaatt tcctgtgatg tgtttcaatc
tagatgcaaa gaacatggaa 60aaatcaaagt gctcgagtgg tttaaatatg ttttgggtat
tcctgtttat agactataat 120acttttccaa ttaaaatcct cagttgtcac
gcagaagaag gttaagctgt atttgattgc 180cagttttact gaaaatgctt
agtattttac agtatcacca aatatatttt gtttagccaa 240ggtatagga
249203541DNAhumanmisc_feature(131)..(131)n is a, c, g, or
tmisc_feature(134)..(134)n is a, c, g, or
tmisc_feature(209)..(209)n is a, c, g, or
tmisc_feature(279)..(279)n is a, c, g, or
tmisc_feature(326)..(326)n is a, c, g, or t 203acccaacaag
agctgtgcgg ctccctgatt cctcgccagt gttgctaccg cccttggctc 60ttcttgcatg
gctggctctt gagacccctg gaagctgatg gaggcaacgt gagaagcaca
120tggacatccg nccntgagct tgagaggcag aggcctgagt tctagttaca
gccccagcag 180taccagttgt gtggactggg agggaggcna tcacgtacat
actccaagcc tccaagcctg 240tttccccttc tgacacagga tcttttgtgg
ctggtatana gtgggcactc aataaatgct 300gtctggtcgt ctggctggca
tgcctnatgg gcctgagaat tgaatagaat tacagtgata 360gaagcatgct
ggtattgtaa gtggtttgta agtgtgagga ctaaattatt attaaatagt
420aatcacatct aatcttggat aaattagtaa aagcaagaat gggagcagta
aaaacctaag 480caacccgaac taaaatttta ttgaattaat tcaatttctt
gtcatgtaac acaaccccag 540a 541204354DNAhumanmisc_feature(54)..(54)n
is a, c, g, or t 204gtttctgttt cagtcacaaa ttagggttat tgtgatgtgt
atttatgatg accnttgaac 60aaatgtgaag aatactgtga attctatgac tttatcaaaa
tcagccacat ccaggagctt 120gcagttgttg accaaatgaa tgatgacata
gagtagttca gatctatcat gtgctcttct 180atctaatcag tcaatatttc
cttggccctc aagccaacat tcatttttta tgtataacct 240tcttcatgat
tttgaaattt tgatagggta actgctaatg agttcacaaa tgtagcactt
300taaaaggaaa ataaatggag agtgaaaaca acttggctac gtataattgt gggt
354205398DNAhumanmisc_feature(80)..(80)n is a, c, g, or
tmisc_feature(82)..(83)n is a, c, g, or tmisc_feature(85)..(85)n is
a, c, g, or tmisc_feature(87)..(87)n is a, c, g, or
tmisc_feature(97)..(97)n is a, c, g, or t 205caacccattt tgtgccacat
gcaagttttg aataaggatg gtatagaaaa caacgctgca 60tatacaggta ccatttaggn
annancngat gcctttntgg gggcagaatc acatggcaaa 120agctttgaaa
atcataaaga tataagttgg tgtggctaag atggaaacag ggctgattct
180tgattcccaa ttctcaactc tccttttcct atttgaattt ctttggtgct
gtagaaaaca 240aaaaaagaaa aatatatatt cataaaaaat atggtgctca
ttctcatcca tccaggatgt 300actaaaacag tgtgtttaat aaattgtaat
tattttgtgt acagttctat actgttatct 360gtgtccattt ccaaaacttg
cacgtgtccc tgaattcc 398206457DNAhumanmisc_feature(64)..(95)n is a,
c, g, or tmisc_feature(104)..(104)n is a, c, g, or
tmisc_feature(226)..(226)n is a, c, g, or
tmisc_feature(344)..(344)n is a, c, g, or
tmisc_feature(387)..(402)n is a, c, g, or t 206acagacttgg
caagggaccc cctggttctg agccagtagc tgccatctgg aaattcctct 60tttnnnnnnn
nnnnnnnnnn nnnnnnnnnn nnnnnctccc aggnacccgc tgaatttctg
120aggccttgct taaagctcag aagtggttta ggcatttgga aaatctggtt
cacatcataa 180agaacttgat ttgaaatgtt ttctatagaa acaagtgcta
agtgtnaccg tattatactt 240gatgttggtc atttctcagt cctatttctc
agttctatta ttttagaacc tagtcagttc 300tttaagatta taactggtcc
tacattaaaa taatgcttct cgangtcaga ttttacctgt 360ttgctgctga
gaacatctct gcctaannnn nnnnnnnnnn nncttcagtt caacatgctt
420ccttagcttt tcatagttgt ctgacatttc catgaaa 457
* * * * *
References