U.S. patent application number 14/540583 was filed with the patent office on 2015-06-11 for method of diagnosing neoplasms.
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 | 20150159223 14/540583 |
Document ID | / |
Family ID | 40578971 |
Filed Date | 2015-06-11 |
United States Patent
Application |
20150159223 |
Kind Code |
A1 |
LAPOINTE; Lawrence Charles ;
et al. |
June 11, 2015 |
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 |
|
|
Family ID: |
40578971 |
Appl. No.: |
14/540583 |
Filed: |
November 13, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12739580 |
Jul 28, 2010 |
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PCT/AU2008/001571 |
Oct 23, 2008 |
|
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14540583 |
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60982114 |
Oct 23, 2007 |
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Current U.S.
Class: |
506/9 |
Current CPC
Class: |
C12Q 2600/158 20130101;
C12Q 2600/16 20130101; C12Q 2600/112 20130101; G01N 2800/06
20130101; C12Q 1/6886 20130101; G01N 33/57446 20130101 |
International
Class: |
C12Q 1/68 20060101
C12Q001/68 |
Claims
1. 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: (i) the gene, genes or transcripts
detected by Affymetrix probeset ID: 227475_at (ii) FOXQ1 in a
biological sample from said individual wherein a higher level of
expression of the genes or transcripts of group (i) 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, wherein control levels are expression levels of the genes or
transcripts of group (i) and/or group (ii) in a non-neoplastic
cell.
2.-6. (canceled)
7. The method according to claim 1, wherein said neoplastic cell is
an adenoma or an adenocarcinoma.
8.-23. (canceled)
24. The method according to claim 1, wherein said cell is a
colorectal cell.
25. The method according to claim 1, wherein said biological sample
is a fecal sample, enema wash, surgical resection, tissue biopsy or
blood sample.
26. The method according to claim 1, wherein said level of
expression is mRNA expression or protein expression.
27. The method according to claim 1, wherein said individual is a
human.
28.-30. (canceled)
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.
BACKGROUND OF THE INVENTION
[0002] Bibliographic details of the publications referred to by
author in this specification are collected alphabetically at the
end of the description.
[0003] 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.
[0004] 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.
[0005] 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.
[0006] 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.
[0007] Once a sporadic adenoma has developed, the chance of a new
adenoma occurring is approximately 30% within 26 months.
[0008] 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.
[0009] 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.
[0010] 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.
[0011] 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.
[0012] 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.
[0013] 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
[0014] 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.
[0015] 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.
[0016] 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.
[0017] 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.
[0018] 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: [0019] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00001 [0019] 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 23248l_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
TABLE-US-00002 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, MMPI, 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: [0037] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00003 [0037] 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
[0038] (ii)
TABLE-US-00004 [0038] 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.
[0039] 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: [0040] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00005 [0040] 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
[0041] (ii)
TABLE-US-00006 [0041] 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.
[0042] 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: [0043] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00007 [0043] 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
[0044] (ii)
TABLE-US-00008 [0044] 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.
[0045] 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: [0046] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00009 [0046] 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
[0047] (ii)
TABLE-US-00010 [0047] 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.
[0048] 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: [0049] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00011 [0049] 204885_s_at 217523_at 236894_at 205174_s_at
228915_at 238984_at 205825_at 235976_at 241031_at; and/or
[0050] (ii)
TABLE-US-00012 [0050] 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.
[0051] 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: [0052] (i) the gene or genes detected by
Affymetrix probeset IDs:
TABLE-US-00013 [0052] 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
[0053] (ii)
TABLE-US-00014 [0053] 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.
[0054] 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: [0055] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00015 [0055] 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
[0056] (ii)
TABLE-US-00016 [0056] 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.
[0057] 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:
[0058] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00017 [0058] 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 20229l_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
[0059] (ii)
TABLE-US-00018 [0059] 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.
[0060] 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:
[0061] (i) the gene or genes detected by Affymetrix probeset IDs:
[0062] 210107_at; and/or [0063] (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.
[0064] 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:
[0065] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00019 [0065] 203240_at 219955_at 242601_at 204607_at
232481_s_at 227725_at 223969_s_at 228232_s_at; and/or
[0066] (ii)
TABLE-US-00020 [0066] 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.
[0067] 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:
[0068] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs: [0069] 202404_s_at, 210809_s_at, 227140_at,
225681_at, 209875_s_at, 204475_at, 212464_s_at; and/or, [0070] (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.
[0071] 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: [0072] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs: [0073] 200665_s_at, 218468_s_at,
211959_at, 201744_s_at, 202859_x_at; and/or, [0074] (ii) SPARC,
GREM1, IGFBPS, 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.
[0075] 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: [0076] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs:
TABLE-US-00021 [0076] 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
[0077] (ii)
TABLE-US-00022 [0077] 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.
[0078] 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: [0079] (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs:
TABLE-US-00023 [0079] 235976_at 236894_at; and/or
[0080] (ii)
TABLE-US-00024 [0080] 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.
[0081] 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: [0082] (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs: [0083] 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 [0084] (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.
[0085] A related aspect of the present invention provides a
molecular array, which array comprises a plurality of: [0086] (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 [0087] (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 [0088] (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
[0089] (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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0090] FIG. 1 is a graphical representation of nuclear factor
(erythroid-derived-2)-like 2. Blk=normal, grn=inflamed,
red=adenoma,blue=cancer
[0091] FIG. 2 is a graphical representation of SLIT and NTRK-like
family, member 6 (left) and LINE1 type transposase domain
containing 1 (right).
[0092] FIG. 3 is a graphical representation of collagen type XI,
alpha 1.
[0093] FIG. 4 is an image of the immunohistochemical staining for
MSLN in a normal tissue shows mild staining in the cytoplasm of the
colonocytes.
[0094] 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.
[0095] FIG. 6 is an image of the immunohistochemical staining of
MSLN in a moderately differentiated adenoma shows strong staining
in the multilayered colonic epithelium.
[0096] 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).
[0097] 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 1x 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).
[0098] 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).
[0099] FIG. 10 is a schematic representation of predicted RNA
variants derived from hCG.sub.--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
[0100] 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.
[0101] 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".
[0102] 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: [0103] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00025 [0103] 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
[0104] (ii)
TABLE-US-00026 [0104] 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.
[0105] 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: [0106] (i) the cecum; [0107] (ii)
the ascending colon; [0108] (iii) the transverse colon; [0109] (iv)
the descending colon; [0110] (v) the sigmoid colon; and [0111] (vi)
the rectum.
[0112] 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.
[0113] Preferably, said neoplastic cell is an adenoma or
adenocarcinoma and even more preferably a colorectal adenoma or
adenocarcinoma.
[0114] 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.
[0115] 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.
[0116] 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.
[0117] 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.
[0118] 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.
[0119] 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.
[0120] 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-00027 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
[0121] 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: [0122] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0123] 225681_at;
227140_at; and/or [0124] (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.
[0125] Preferably, said control level is a non-neoplastic
level.
[0126] 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: [0127] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0128] 227475_at,
204475_at, 202859_x_at, 202404_s_at; and/or [0129] (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.
[0130] Preferably, said control level is a non-neoplastic
level.
[0131] 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: [0132] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs: [0133] 205513_at,
204259_at, 227174_at, 210511_s_at, 37892_at; and/or [0134] (ii)
TCN1, MMPI, 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.
[0135] Preferably, said control level is a non-neoplastic
level.
[0136] 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: [0137] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00028 [0137] 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
[0138] (ii)
TABLE-US-00029 [0138] 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.
[0139] Preferably, said control level is a non-neoplastic
level.
[0140] According to these aspects of the present invention, said
large intestine tissue is preferably colorectal tissue.
[0141] 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.
[0142] 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).
[0143] 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.
[0144] 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.
[0145] 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: [0146] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00030 [0146] 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
[0147] (ii)
TABLE-US-00031 [0147] 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.
[0148] 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:
[0149] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00032 [0149] 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
[0150] (ii)
TABLE-US-00033 [0150] 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.
[0151] 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.
[0152] 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.
[0153] 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: [0154] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00034 [0154] 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
[0155] (ii)
TABLE-US-00035 [0155] 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.
[0156] In a most preferred embodiment, said genes or transcripts
are selected from: [0157] (i) the gene, genes or transcripts
detected by Affymetrix probeset IDs:
TABLE-US-00036 [0157] 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
[0158] (ii)
TABLE-US-00037 [0158] MMP1 COL11A1 IL8 MMP7 COL1A1 TACSTD2 LGR5
DUSP27 COL8A1 WDR72 NLF1
[0159] Preferably, said neoplasm is an adenoma or an adenocarcinoma
and said gastrointestinal tissue is colorectal tissue.
[0160] 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.
[0161] 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: [0162] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00038 [0162] 204885_s_at 217523_at 236894_at 205174_s_at
228915_at 238984_at 205825_at 235976_at 241031_at; and/or
[0163] (ii)
TABLE-US-00039 [0163] 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.
[0164] 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: [0165] (i) the gene or genes detected
by Affymetrix probeset IDs:
TABLE-US-00040 [0165] 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
[0166] (ii)
TABLE-US-00041 [0166] 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.
[0167] Preferably, said large intestine tissue is colorectal
tissue.
[0168] More preferably, said biological sample is a blood sample or
stool sample.
[0169] 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.
[0170] 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.
[0171] 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-00042 The gene or genes detected by Affymetrix probe Nos:
200600_at 20396_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 203860_at
211964_at 223235_s_at 241031_at 203878_s_at 211966_at 224428_s_at
37892_at 203895_at 212063_at 224646_x_at 60474_at 203896_s_at
212070_at 224694_at ACTA2 DUOX2 LOC541471 S100A11 AHCY DUSP27 MAFB
S100A8 ANLN ECT2 MLPH S100P ANTXR1 ELOVL5 MMP11 SCD ANXA3 ENC1 MMP2
SLC11A2 APOBEC1 ETS2 MSLN SLC12A2 APOE FABP6 MSN SLC39A10 ASCL2
FAM84A MTHFD1L SLC6A6 AURKA FAP MXRA5 SLC7A5 BACE2 FCGR3B MYC
SLCO4A1 C14orf94 FLJ37644 MYL9 SLITRK6 C20orf199 FOXQ1 NEBL SMOC2
C20orf42 FSTL1 NFE2L3 SORD CALD1 GOS2 NLF1 SOX4 CCND1 GALNT6 NNMT
SOX9 CD163 GJA1 NPDC1 SQLE CD44 GPR56 NPM1 SULF1 CD55 GPSM2 NQO1
SULF2 CD93 GPX2 OLFML2B TACSTD2 CDC2 H19 PALM2- TAGLN CDCA7 AKAP2
TBX3 CDH11 HNT PCCA TDGF1 CDH3 HOXA9 PCSK1 TESC CKS2 HOXB6 PDZK1IP1
TGIF1 CLDN1 HSPH1 PFDN4 THY1 COL10A1 IFITM1 PHLDA1 TMEM97 COL11A1
ISLR PLCB4 TMEPAI COL12A1 ITGA6 PLOD2 TPX2 COL4A2 KCNN4 PSAT1
TRIM29 COL6A2 KIAA1199 PUS7 TYROBP CSE1L KIAA1913 RAB31 UBD CTSE
KRT23 RDHE2 UBE2C CTSK L1TD1 RFC3 UBE2S CYP3A5 LBH RNF43 VIM
CYP3A5P2 LGALS1 RP5-875H10.1 WDR51B DACH1 LGR5 RPESP WDR72 DKC1
LOC387763 RPL22L1 ZNRF3 DPEP1 RRM2
[0172] 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.
[0173] 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.
[0174] 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.
[0175] 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.
[0176] 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.
[0177] 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.
[0178] 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.
[0179] 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.
[0180] 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.
[0181] 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: [0182] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs:
TABLE-US-00043 [0182] 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
[0183] (ii)
TABLE-US-00044 [0183] 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.
[0184] 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:
[0185] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00045 [0185] 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
[0186] (ii)
TABLE-US-00046 [0186] 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.
[0187] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0188] 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.
[0189] 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.
[0190] 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-00047 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
[0191] 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-00048 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
[0192] 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: [0193] (i) the gene or genes detected by Affymetrix probeset
IDs: [0194] 210107_at; and/or [0195] (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.
[0196] 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:
[0197] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00049 [0197] 203240_at 219955_at 242601_at 204607_at
232481_s_at 227725_at 223969_s_at 228232_s_at; and/or
[0198] (ii)
TABLE-US-00050 [0198] 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.
[0199] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0200] Still more preferably, said biological sample is a tissue
sample.
[0201] 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: [0202] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs:
TABLE-US-00051 [0202] 202404_s_at 210809_s_at 227140_at 225681_at
209875_s_at 204475_at 212464_s_at; and/or
[0203] (ii)
TABLE-US-00052 [0203] 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.
[0204] 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: [0205] (i) the gene, genes or transcripts detected
by Affymetrix probeset IDs:
TABLE-US-00053 [0205] 200665_s_at 218468_s_at 211959_at 201744_s_at
202859_x_at; and/or
[0206] (ii)
TABLE-US-00054 [0206] 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.
[0207] 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: [0208] (i) the gene, genes or
transcripts detected by Affymetrix probeset IDs:
TABLE-US-00055 [0208] 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
[0209] (ii)
TABLE-US-00056 [0209] 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.
[0210] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0211] Even more preferably, said biological sample is a tissue
sample.
[0212] 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.
[0213] 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: [0214] (i) the gene, genes or transcripts detected by
Affymetrix probeset IDs:
TABLE-US-00057 [0214] 235976_at 236894_at; and/or
[0215] (ii)
TABLE-US-00058 [0215] 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.
[0216] 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:
[0217] (i) the gene, genes or transcripts detected by Affymetrix
probeset IDs:
TABLE-US-00059 [0217] 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
[0218] (ii)
TABLE-US-00060 [0218] 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.
[0219] Preferably, said gastrointestinal tissue is colorectal
tissue.
[0220] Still more preferably, said biological sample is a tissue
sample.
[0221] 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.
[0222] 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.
[0223] 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.
[0224] 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: [0225] (i) In vivo detection. [0226]
Molecular Imaging may be used following administration of imaging
probes or reagents capable of disclosing altered expression of the
markers in the intestinal tissues. [0227] 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. [0228] (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). [0229] (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). [0230] 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. [0231] 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. [0232] 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)). [0233] 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. [0234] 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). [0235] 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. [0236] 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. [0237] 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. [0238] 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. [0239] 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.
[0240] 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. [0241] 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. [0242] 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. [0243] 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.
[0244] 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. [0245] 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. [0246] 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. [0247] 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).
[0248] (iv) Measurement of altered neoplastic marker protein levels
in cell extracts, for example by immunoassay. [0249] 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. [0250] 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. [0251] 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. [0252] 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. [0253] 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. [0254] 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. [0255] 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.
[0256] 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. [0257] (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, 5 meC) 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. [0258] 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. [0259]
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. [0260] (vi) Determining altered expression of protein
neoplastic markers on the cell surface, for example by
immunohistochemistry. [0261] (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.
[0262] 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.
[0263] 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.
[0264] 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.
[0265] 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.
[0266] 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).
[0267] A related aspect of the present invention provides a
molecular array, which array comprises a plurality of: [0268] (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 [0269] (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 [0270] (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
[0271] (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.
[0272] Preferably, said percent identity is at least 85%, 90%, 91%,
92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%.
[0273] 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).
[0274] 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.
[0275] In terms of the probes which are used to detect the subject
proteins, they may take any suitable form including antibodies and
aptamers.
[0276] 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.
[0277] 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.
[0278] 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.
[0279] 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.
[0280] The present invention is further described by the following
non-limiting examples:
Example 1
Methods and Materials
[0281] Affymetrix GeneChip data
[0282] 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.
[0283] 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.
Univariate Differential Expression
[0284] 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, New York,
2005). Significance estimates (p-values) were corrected to adjust
for multiple hypothesis testing using the Bonferonni
correction.
Tissue Specific Expression Patterns
[0285] 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.
Gene Symbol Annotations
[0286] 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.
Estimates of Performance Characteristics
[0287] 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.
Results
[0288] 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.
Genes Differentially Expressed in Neoplastic Tissues
[0289] 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.
[0290] 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-00061 .DELTA.-expression ProbeSet ID Gene Symbol Maps UP
205 157
Hypothetical Markers Specific for Colorectal Neoplasia
[0291] 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.
Genes Differentially Expressed Between Adenomas and Cancer
Tissues
[0292] 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.
[0293] 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
[0294] 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.
[0295] 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.
Validation/Hypothesis Testing
[0296] 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.
[0297] 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.
Conclusion
[0298] 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
[0299] 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: [0300] 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 [0301] 2. That
microarray binding intensity for such `off` probesets to labelled
cRNA will reflect technical assay background, i.e. non-specific
oligonucleotide binding.
[0302] 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. By design, 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.
Validation/Hypothesis Testing
[0303] 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.
[0304] 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.
[0305] 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
[0306] 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.
Validation/Hypothesis Testing
[0307] 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.
[0308] 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.
Conclusion
[0309] 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
[0310] 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.
Hypothesis Testing
[0311] 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.
Colorectal Tissue Specimens
[0312] 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.
[0313] 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 -150 C until
processing.
RNA Extraction
[0314] 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 7,500 g 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.
Gene Chip Processing
[0315] 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).
Statistical Software and Data Processing
[0316] 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.
Hypothesis Testing of Differentially Expressed Biomarkers
[0317] 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.
Discovery of Tissue-Specific Gene Expression Patterns
[0318] 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.
[0319] 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.
[0320] 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.
[0321] 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.
[0322] 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
[0323] BLAST the sequence of interest using online available Basic
Local Alignment Search Tools [BLAST]. e.g. NCBI/BLAST [0324]
(http://blast.ncbi.nlm.nih.gov/Blast.cgi) [0325] (a) Select "Human"
in BLAST ASSEMBLED GENOMES on the web page
http://blast.ncbi.nlm.nih.gov/Blast.cgi [0326] (b) Leave the
default settings, i.e.: [0327] Database: Genome (all assemblies)
[0328] Program: megaBLAST: compare highly related nucleotide
sequences [0329] Optional parameters: Expect: 0.01, Filter:
default, Descriptions: 100, Alignments: 100 [0330] (c) Copy/Paste
Sequence into the "BLAST" window [0331] (d) Click "Begin Search"
[0332] (e) Click "View Report"
Assessment of the Open BLAST Search Results
[0333] Multiple significant sequence alignments may be identified
when "blasting" the sequence.
Identify gene nomenclature of the identified sequence match [0334]
(a) Click the link to one of the identified hits [0335] (b) The new
page will schematically depict the position of the hit on one
chromosome. It will be apparent which gene is hit. [0336] (c)
Retrieve the "hit" sequence clicking on the link [0337] (d) Do a
search for the gene in the provided "search" window. This provides
the gene nucleotide coordinates for the gene. Determine promiscuity
of Sequence [0338] (a) Open the NCBI/BLAST tool,
(http://blast.ncbi.nlm.nih.gov/Blast.cgi) [0339] (b) Click on
"nucleotide Blast" under "basic BLAST" [0340] (c) Copy/paste the
sequence of interest into the "Query Sequence" window [0341] (d)
Click "Blast". Assessment of the nBLAST Search Results of the
Sequence [0342] (a) The nBLAST exercise with the Sequence may
result in multiple Blast hits of which some accession entry numbers
are listed in "Description". [0343] (b) These hits should be
reviewed. Determine location of the Sequence in the Gene
[0344] The Ensembl database is an online database, which produces
and maintains automatic annotation selected eukaryotic genomes
(www.ensembl.orq/index.html)
Identify Location of the Sequence in the Gene
[0345] (a) Set "Search" to Homo Sapiens, Type "the gene name" in
the provided Search Field Ensemble.org/index.html) [0346] (b) Click
"Go" [0347] (c) Click the "vega protein_coding Gene:
OTTHUMG000000144184" link to get an annotation report [0348] (d)
Click on "Gene DAS Report" to retrieve information regarding
Alternative splice site database: Type "the gene name" in search
field [0349] Click on "the gene entry" [0350] Scroll down to
"evidence" [0351] Review alternative splice sites [0352] Click
"Confirmed intron/exons" to get a list of coordinates for the exons
& introns. Alternative Splicing and/or Transcription
[0353] 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/
Further Investigation of the Gene mRNA Transcripts [0354] (a) Type
"the gene name" into the provided "search" field [0355] (b) Click
"Go" [0356] (c) The following information is available from the
resulting entry in AceView: [0357] The number of cDNA clones from
which the gene is constructed (ie originated-from experimental work
involving isolation of mRNA) [0358] The mRNAs predicted to be
produced by the gene [0359] The existence of non-overlapping
alternative exons and validated alternative polyadenylation sites
[0360] The existence of truncations [0361] The possibility of
regulated alternate expression [0362] Introns recorded as
participating in alternatively splicing of the gene [0363] (d)
Classic splice site motives Application of Method to
LOC643911/hCG.sub.--1815491
Materials and Methods
Extraction of RNA
[0364] 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. 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. 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.
Gene Chip Processing
[0365] 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 16-18 hours.
[0366] 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.
SYBR Green Based Quantitative Real Time-PCR
[0367] Quantitative real time polymerase chain reaction was
performed on RNA isolated from clinical samples for the
amplification and detection of the various hCG.sub.--1815491
transcripts.
[0368] Firstly cDNA was synthesized from 2 ug 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.
[0369] PCR was performed in a 25 ul volume using 12.5 ul Promega 2x
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.
[0370] Cycling conditions for amplification were 95.degree. for 2
minutes.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.sub.--1815491
transcripts being calculated relative to the expression level of
the endogenous house keeping gene HPRT.
End-Point PCR
[0371] End point PCR was performed on RNA isolated from clinical
samples for the various hCG.sub.--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.
Results
[0372] The nucleotide structure and expression levels of
transcripts related to hCG.sub.--1815491 was analysed based on the
identification of diagnostic utility of Affymetrix probesets
238021_s_at and 238022_at from the gene chip analysis.
[0373] The gene hCG.sub.--1815491 is currently represented in NCBI
as a single RefSeq sequence, XM.sub.--93911. The RefSeq sequence of
hCG.sub.--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.sub.--1815491 (earlier references to hCG.sub.--1815491 are:
LOC388279, LOC643911, LOC650242, XM.sub.--944116, AF275804,
XM.sub.--373688).
[0374] 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.sub.--010498.15|Hs16.sub.--10655, NCBI 36 Mar. 2006 genome
encompasses hCG.sub.--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.sub.--1815491 RefSeq XM.sub.--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.sub.--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
[0375] Immunohistochemistry is a useful method for evaluating
changes in local expression of up or down-regulated markers in
human tissue.
Materials and Methods:
[0376] 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.
Result:
[0377] 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.
Conclusion:
[0378] 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
[0379] 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.sub.--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.
Materials and Methods
[0380] 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.
Results
[0381] 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).
Conclusion
[0382] Measurement of MMP3 protein in bodily fluids such as stool
samples is useful for diagnosing colorectal neoplasia.
TABLES
[0383] Probeset designations include both HG-133plus2 probeset IDs
and Human Gene 1.0ST 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.s-
ub.--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.
Table 1
[0384] 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.
Table 2
[0385] 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
Table 3
[0386] 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.
Table 4
[0387] 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.
Table 5
[0388] 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.
Table 6
[0389] 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.
Table 7
[0390] 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.
Table 8
[0391] 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.
[0392] 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-00062 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: LOC730278: 2.68E-27 3.8969 3.83 97.4
93.9-99.1 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: LOC729194: MYC 5.19E-25 3.6014 4.11 96.4
92.2-98.6 221577_x_at GDF15 5.51E-25 3.5554 5.84 96.2 91.8-98.5
204702_s_at LOC650331: NFE2L3: LOC642996 1.51E-24 3.52 4.57 96.1
91.6-98.4 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: LOC729599: TMEM97
1.88E-16 2.583 2.77 90.2 83.4-94.7 202831_at GPX2 4.00E-16 2.397
3.56 88.5 81.2-93.5 225541_at LOC442108: RPL22L1 4.37E-16 2.5983
4.19 90.3 83.5-94.8 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: LOC389173: 3.32E-15 2.4895
5.52 89.3 82.3-94.1 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: LOC645313 1.23E-13 2.2759 4.28 87.2 79.8-92.6
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: HDAC9 1.69E-12
2.2328 2.24 86.8 79.2-92.3 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 1.61
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, UBE2S: 5.62E-11 1.9821 2.4 83.9
75.8-90 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, C6orf21: 1.34E-07 1.5549
6.64 78.2 69.3-85.4 LY16G6D, C6orf21: LY6G6D 210052_s_at TPX2
1.56E-07 1.6655 2.03 79.8 71.1-86.7 202859_x_ LOC652128: IGHG1:
IGHM: 1.99E-07 1.6331 3.1 79.3 70.6-86.3 at IGHV4-31: LOC647189:
IGHV1-69: IGHA1: IL8: EXOC7: SIX6: IGHD: IGH@: IGHG3: C12orf32:
ZCWPW2: IFI6: IGHG4: IGHA2: IGHG2: RAC1 211506_s_at LOC652128:
IGHG1: IGHM: 1.99E-07 1.6324 3.1 79.3 70.6-86.4 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, MGC4677: LOC541471 7.40E-07
1.4933 2.04 77.2 68.3-84.6 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 0.0001 1.1279 1.9 71.4 62.1-79.5 219955_at L1TD1
0.0001 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: LOC728628 0.1891 0.6492 1.9 62.7 53.1-71.6
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: CYP3A5P2 0.9932 0.3165 1.16
56.3 46.7-65.6
TABLE-US-00063 TABLE 2 Gene Signif. D.val Sens- CI Symbol
ValidPS_UP Symbol FDR 5 FC Spec (95) CDH3 802708-HuGene_st:
280037-HuGene_st: 1019645-HuGene_st: 119416- CDH3 3.75E-31 4.2474
37.54 98.3 95.5- HuGene_st: 642035-HuGene_st: 665706-HuGene_st:
249831- 99.5 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-HuGene_st: 1015647- ENC1 1.44E-26 3.6666
3.93 96.7 92.6- HuGene_st: 524348-HuGene_st: 291883-HuGene_st:
154485- 98.7 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-HuGene_st: 599371-
MAPK10: 3.35E-26 3.7114 7.06 96.8 92.9- HuGene_st:
391296-HuGene_st: 1031797-HuGene_st: 314340- CD44 98.8 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-HuGene_st: 566899- SORD 3.44E-25 3.4665 4.36 95.8 91.3-
HuGene_st: 339498-HuGene_st: 91263-HuGene_st: 256497- 98.3
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-HuGene_st: 517374- LOC731404: 5.19E-25 3.5977 4.11 96.4
92.2- HuGene_st: 869576-HuGene_st: 1099727-HuGene_st: 33994-
LOC729194: 98.6 HuGene_st: 781657-HuGene_st: 509634-HuGene_st:
273419- MYC 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: 1032661- GDF15 5.51E-25 3.5534 5.84
96.2 91.9- HuGene_st: 430762-HuGene_st: 392223-HuGene_st: 325978-
98.5 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-HuGene_st: 1093456- LOC650331: 1.51E-24 3.523 4.57 96.1 91.7-
HuGene_st: 347351-HuGene_st: 878719-HuGene_st: 880179- NFE2L3: 98.4
HuGene_st: 240089_at: 822197-HuGene_st: 873612-HuGene_st: 517821-
LOC642996 HuGene_st: 489354-HuGene_st: 20603-HuGene_st: 204702_s_at
NEBL 923272-HuGene_st: 580150-HuGene_st: 925039-HuGene_st: 451073-
NEBL 5.41E-24 3.5322 5.52 96.1 91.7- HuGene_st: 23015-HuGene_st:
714203-HuGene_st: 479241- 98.4 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-HuGene_st: 147251- GTF3A
1.74E-22 3.2254 2.92 94.7 89.5- HuGene_st: 27776-HuGene_st:
88229-HuGene_st: 508903- 97.6 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-HuGene_st: 517610- CLDN1 6.10E-22 3.2528
13.09 94.8 89.7- HuGene_st: 737746-HuGene_st: 847409-HuGene_st:
100345- 97.7 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-HuGene_st: 876922- MMP7 7.61E-22 3.2633 69.29 94.9 89.8-
HuGene_st: 669567-HuGene_st: 1039935-HuGene_st: 514120- 97.7
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-HuGene_st: 475923- SLC6A6: 1.15E-21 3.2313
5.02 94.7 89.6- HuGene_st: 249964-HuGene_st: 362002-HuGene_st:
126399- LOC728721 97.6 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-HuGene_st: 256806- CXCL2: 1.88E-21 3.2911 7.85 95 90-
HuGene_st: 261067-HuGene_st: 448247-HuGene_st: 666569- CXCL3 97.8
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:
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HuGene_st: 261067-HuGene_st: 448247-HuGene_st: 666569- CXCL3 97.8
HuGene_st: 222646-HuGene_st: 262117-HuGene_st: 798675- HuGene_st:
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33632-HuGene_st: 965957-HuGene_st: 556939- HuGene_st:
26460-HuGene_st: 796450-HuGene_st: 230101_at: 541868- HuGene_st:
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260925-HuGene_st: 515662-HuGene_st: 258081- HuGene_st: 1569203_at:
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7.85 95 90.1- HuGene_st: 261067-HuGene_st: 448247-HuGene_st:
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798675- HuGene_st: 391369-HuGene_st: 865299-HuGene_st: 877897-
HuGene_st: 575433-HuGene_st: 43120-HuGene_st: 42070- HuGene_st:
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26460-HuGene_st: 796450-HuGene_st: 230101_at: 541868- HuGene_st:
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HuGene_st: 107953-HuGene_st: 765929-HuGene_st: 948263- 97.6
HuGene_st: 78061-HuGene_st: 808895-HuGene_st: 69258- HuGene_st:
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KIAA1199 8.12E-21 3.0498 25.16 93.6 88- HuGene_st:
442314-HuGene_st: 14957-HuGene_st: 16406- 97 HuGene_st:
742741-HuGene_st: 115371-HuGene_st: 864695- HuGene_st:
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972252-HuGene_st: 822568-HuGene_st: 55289- HuGene_st:
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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-HuGene_st: 469415- ANXA3 1.15E-20 3.0459
3.34 93.6 88- HuGene_st: 506093-HuGene_st: 78819-HuGene_st: 149613-
97 HuGene_st: 48457-HuGene_st: 316401-HuGene_st: 35420- HuGene_st:
165320-HuGene_st: 987987-HuGene_st: 437259- HuGene_st:
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1018751-HuGene_st: 358834-HuGene_st: 1097138- HuGene_st:
931805-HuGene_st: 796166-HuGene_st: 209369_at: 358455- HuGene_st
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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:
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1008518-HuGene_st: 1087950- 97.1 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:
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787388-HuGene_st: 629934- SOX9 1.63E-20 3.0954 3.85 93.9 88.4-
HuGene_st: 1026354-HuGene_st: 863993-HuGene_st: 573850- 97.2
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:
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HuGene_st: 1567906_at: 213665_at: 1001159-HuGene_st: 1082118- 96.9
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:
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210671-HuGene_st: 693250-HuGene_st: 850876-HuGene_st: 140311- CCND1
7.06E-20 2.9073 2.85 92.7 86.8- HuGene_st: 1002162-HuGene_st:
1018086-HuGene_st: 407388- 96.4
HuGene_st: 984437-HuGene_st: 141586-HuGene_st: 647830- HuGene_st:
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179331-HuGene_st: 208712_at: 592143- HuGene_st: 583936-HuGene_st:
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763699-HuGene_st: 567459-HuGene_st: 447803-HuGene_st: 319823- FOXQ1
4.85E-19 2.9444 10.97 93 87.1- HuGene_st: 304771-HuGene_st:
1086901-HuGene_st: 444851- 96.6 HuGene_st: 742304-HuGene_st:
301921-HuGene_st: 227475_at: 541230- HuGene_st: 894028-HuGene_st:
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293941-HuGene_st: 55647-HuGene_st DPEP1 195459-HuGene_st:
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23.9 92.6 86.5- HuGene_st: 450442-HuGene_st: 414432-HuGene_st:
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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:
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769185-HuGene_st: 478322-HuGene_st: 1089212-HuGene_st: 427722- LCN2
5.68E-19 2.9407 14.6 92.9 87- HuGene_st: 341012-HuGene_st:
277123-HuGene_st: 866455- 96.6 HuGene_st: 545638-HuGene_st:
974940-HuGene_st: 942257- HuGene_st: 446106-HuGene_st:
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374635-HuGene_st: 924701- HuGene_st: 899307-HuGene_st:
911350-HuGene_st: 586877-HuGene_st BACE2 790683-HuGene_st:
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3.8 92.7 86.7- HuGene_st: 159264-HuGene_st: 718321-HuGene_st:
211932- 96.4 HuGene_st: 705852-HuGene_st: 1090860-HuGene_st:
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HuGene_st: 217867_x_at: 222446_s_at: 733284-HuGene_st: 378351-
HuGene_st: 525711-HuGene_st: 834444-HuGene_st: 889532- HuGene_st:
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686187-HuGene_st: 985190-HuGene_st: 1011822-HuGene_st: 1092705-
DACH1 1.05E-18 2.9243 5.81 92.8 86.8- HuGene_st: 693255-HuGene_st:
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49101-HuGene_st: 290879- HuGene_st: 646013-HuGene_st:
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303920-HuGene_st: 338273- HuGene_st: 20454- HuGene_st: 1567100_at:
205472_s_at: 228915_at: 1562342_at: 169641- HuGene_st:
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3.24 92.8 86.9- HuGene_st: 246870-HuGene_st: 542187-HuGene_st:
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HuGene_st: 292965-HuGene_st: 228826_at: 228828_at: 581833-
HuGene_st: 205211-HuGene_st: 292037-HuGene_st: 297431- HuGene_st:
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11.01 92.1 85.9- HuGene_st: 304181-HuGene_st: 245405-HuGene_st:
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653465-HuGene_st: 693258- HuGene_st: 211002_s_at: 393591-HuGene_st:
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269939-HuGene_st: 314919-HuGene_st: 552234-HuGene_st: 622058- NLF1
3.12E-18 2.7997 8.12 91.9 85.7- HuGene_st: 68900-HuGene_st:
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745661-HuGene_st: 996995- HuGene_st: 534469-HuGene_st:
560627-HuGene_st: 711203- HuGene_st: 24103 l_at: 93378-HuGene_st:
611899-HuGene_st: 57671- HuGene_st: 443570-HuGene_st:
231416-HuGene_st SLC7A5 496060-HuGene_st: 951443-HuGene_st:
212037-HuGene_st: 766877- SLC7A5: 5.11E-18 2.7527 6.31 91.6 85.2-
HuGene_st: 54540-HuGene_st: 467618-HuGene_st: 663825- LAT1-3TM 95.7
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-HuGene_st: 853536- ASCL2 7.76E-18 2.7559
7.73 91.6 85.3- HuGene_st: 945534-HuGene_st: 295182-HuGene_st:
1038742- 95.7 HuGene_st: 1100969-HuGene_st: 940755-HuGene_st:
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236012- HuGene_st: 474427-HuGene_st: 207607_at: 272814-HuGene_st:
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HuGene_st: 792089-HuGene_st: 623773-HuGene_st: 1085101-HuGene_st
PHLDA1 810737-HuGene_st: 617999-HuGene_st: 84013-HuGene_st: 972772-
PHLDA1 1.34E-17 2.701 5.27 91.2 84.7- HuGene_st: 843746-HuGene_st:
217999_s_at: 218000_s_at: 865439- 95.4 HuGene_st: 949246-HuGene_st:
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10.14 90.5 83.8- HuGene_st: 733349-HuGene_st: 609947-HuGene_st:
437757- 94.9 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:
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4.91 91.4 84.9- HuGene_st: 364904-HuGene_st: 157166-HuGene_st:
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HuGene_st: 732465-HuGene_st: 426052-HuGene_st: 244820_at: 31672-
HuGene_st: 226360_at: 149994-HuGene_st: 620378- HuGene_st:
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458988-HuGene_st: 845548-HuGene_st: 184387-HuGene_st: 583199-
LOC731966: 1.88E-16 2.5821 2.77 90.2 83.4- HuGene_st:
1045327-HuGene_st: 568790-HuGene_st: 52799- LOC729599: 94.7
HuGene_st: 1018996-HuGene_st: 212279_at: 980043-HuGene_st: 942215-
TMEM97 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-HuGene_st: 249710-
GPX2 4.00E-16 2.3996 3.56 88.5 81.2- HuGene_st: 1052500-HuGene_st:
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772808-HuGene_st: 181084-HuGene_st: 494932-HuGene_st: 1058299-
LOC442108: 4.37E-16 2.6007 4.19 90.3 83.6- HuGene_st:
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188478-HuGene_st: 676751-HuGene_st: 364450-HuGene_st: 323572- PUS7:
5.26E-16 2.6017 3.06 90.3 83.6- HuGene_st: 1073917-HuGene_st:
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38904-HuGene_st: 243458-HuGene_st: 233716- HuGene_st:
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327351-HuGene_st: 692667-HuGene_st: 61336-HuGene_st: 120414-
PDZK1IP1 5.38E-16 2.5049 4.22 89.5 82.5- HuGene_st:
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301666-HuGene_st: 976408-HuGene_st: 1003400- HuGene_st:
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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-HuGene_st:
1009798- KCNN4 1.85E-15 2.4698 3.07 89.2 82.1- HuGene_st:
306542-HuGene_st: 945226-HuGene_st: 489209- 94 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-HuGene_st: 855558- AXIN2
1.90E-15 2.4309 4.44 88.8 81.7- HuGene_st: 201699-HuGene_st:
717222-HuGene_st: 650014- 93.7 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-HuGene_st: 808147- NPM1
2.22E-15 2.6004 2.18 90.3 83.6- HuGene_st: 1046029-HuGene_st:
740084- 94.8 HuGene_st: 221691_x_at: 200063_s_at TIMP1
676809-HuGene_st: 14950-HuGene_st: 152072-HuGene_st: 1042197- TIMP1
2.44E-15 2.4307 3.01 88.8 81.6- HuGene_st: 480229-HuGene_st:
344184-HuGene_st: 1032497- 93.7 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-HuGene_st: 363337- INHBA 2.80E-15 2.5141 3.76 89.6 82.7-
HuGene_st: 344276-HuGene_st: 874496-HuGene_st: 395552- 94.3
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: 210511_s_at: 746887-
HuGene_st: 909672-HuGene_st: 204926_at: 548889-HuGene_st PSAT1
139416-HuGene_st: 795030-HuGene_st: 160439-HuGene_st: 322148-
LOC651255: 3.32E-15 2.4893 5.52 89.3 82.3- HuGene_st:
85375-HuGene_st: 223335-HuGene_st: 2658- PSAT1: 94.2 HuGene_st:
399855-HuGene_st: 220892_s_at: 941491-HuGene_st: LOC389173:
1017348- HuGene_st: 856207-HuGene_st: 194347-HuGene_st: 553133-
LOC729779: HuGene_st: 223062_s_at: 987517-HuGene_st:
336174-HuGene_st C8orf62 MTHFD1L 478940-HuGene_st:
729886-HuGene_st: 826803-HuGene_st: 504735- MTHFD1L 4.46E-15 2.4849
4.04 89.3 82.3- HuGene_st: 632092-HuGene_st: 926226-HuGene_st:
417984- 94.1 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-HuGene_st: 102028- CST1 7.04E-15 2.4183 13.01 88.7 81.6-
HuGene_st: 291462-HuGene_st: 206224_at: 906914-HuGene_st: 936009-
93.7 HuGene_st: 1055285-HuGene_st PAICS 426927-HuGene_st:
871276-HuGene_st: 297278-HuGene_st: 832875- PAICS 1.19E-14 2.3937
2.49 88.4 81.2- HuGene_st: 287760-HuGene_st: 667051-HuGene_st:
1057511- 93.5 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-HuGene_st: 741747- AZGP1: 1.31E-14 2.3989
6.19 88.5 81.3- HuGene_st: 28018-HuGene_st: 594026-HuGene_st:
222884- LOC401393 93.5 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: 60228-HuGene_st: 754922- C20orf42 1.38E-14 2.4573
2.78 89 82- HuGene_st: 444538-HuGene_st: 733591-HuGene_st: 159372-
93.9 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-HuGene_st: 52318- ECT2
1.42E-14 2.4271 2.82 88.8 81.6- HuGene_st: 530079-HuGene_st:
288145-HuGene_st: 234992_x_at: 64803- 93.7 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-HuGene_st: 222145- WDR51B: 1.79E-14 2.4266
2.12 88.7 81.6- HuGene_st: 67663-HuGene_st: 359031-HuGene_st:
36172- GALNT4 93.7 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-HuGene_st: 674772- HIG2
2.50E-14 2.366 4.25 88.2 80.9- HuGene_st: 761463-HuGene_st:
977422-HuGene_st: 470541- 93.3 HuGene_st: 82081-HuGene_st:
266176-HuGene_st: 127241- HuGene_st: 833078-HuGene_st: 218507_at:
766773-HuGene_st: 153456- HuGene_st: 1554452_s_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-HuGene_st: 567105- TACSTD2 3.13E-14 2.3686
15.71 88.2 80.9- HuGene_st: 8281-HuGene_st: 1041491-HuGene_st:
339450- 93.3 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-HuGene_st: 178742- TCN1 4.81E-14 2.3035 15.22 87.5 80-
HuGene_st: 286092-HuGene_st: 479663-HuGene_st: 464294- 92.8
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-HuGene_st: 164226- CDCA7:
6.41E-14 2.2638 4.27 87.1 79.6- HuGene_st: 268581-HuGene_st:
1038532-HuGene_st: 418719- LOC442172 92.5 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-HuGene_st: 221382-
SLC11A2 7.07E-14 2.362 2.18 88.1 80.7- HuGene_st: 774882-HuGene_st:
752508-HuGene_st: 132318- 93.2 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-HuGene_st: 1054693- SCD: 1.23E-13 2.2789 4.28 87.3 79.8-
HuGene_st: 698268-HuGene_st: 1088784-HuGene_st: 87215- LOC651109:
92.6 HuGene_st: 64902-HuGene_st: 211708_s_at: 1019041-HuGene_st:
749928- LOC645313 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-HuGene_st: 318195- CKS2 2.13E-13 2.2406 4.15 86.9 79.2-
HuGene_st: 744649-HuGene_st: 710242-HuGene_st: 221677- 92.3
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- HuGene_st: 228344_s_at: 91464-HuGene_st:
185883-HuGene_st: 152524- 92.4 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-HuGene_st: 766409- CSE1L 7.98E-13 2.2314
2.28 86.8 79.2- HuGene_st: 353842-HuGene_st: 248622-HuGene_st:
173835- 92.3 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-HuGene_st: 587633-
TMEM23: 1.69E-12 2.2333 2.24 86.8 79.1- HuGene_st:
918571-HuGene_st: 547690-HuGene_st: 702390- PFDN4: 92.3 HuGene_st:
291601-HuGene_st: 218399-HuGene_st: 990433- HDAC9 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-HuGene_st: 845513- NPDC1
2.66E-12 2.1699 2.53 86.1 78.3- HuGene_st: 273361-HuGene_st:
1018950-HuGene_st: 398079- 91.7 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-HuGene_st: 764617- TDGF1: 3.07E-12 2.1179
6.33 85.5 77.7- HuGene_st: 287790-HuGene_st: 206286_s_at:
1012920-HuGene_st: TDGF3 91.3 633937- HuGene_st: 2464-HuGene_st:
85190-HuGene_st IL8 1044664-HuGene_st: 714746-HuGene_st:
442029-HuGene_st: 119200- AHNAK: 3.28E-12 2.3281 1.73 87.8 80.3-
HuGene_st: 550444-HuGene_st: 493978-HuGene_st: 713906- IGHG1 93
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-HuGene_st: 690681-
SERPINB5 4.80E-12 2.1258 10.36 85.6 77.8- HuGene_st:
536963-HuGene_st: 923557-HuGene_st: 183189- 91.4 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-HuGene_st: 935371- MMP11
6.30E-12 2.0946 4.55 85.3 77.4- HuGene_st: 514533-HuGene_st:
213602_s_at: 671549-HuGene_st: 858774- 91.1 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-HuGene_st: 515713-
SERPINA1 7.12E-12 2.0812 3.43 85.1 77.1- HuGene_st:
853812-HuGene_st: 1018939-HuGene_st: 52824- 91 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-HuGene_st: 297045- LGR5
1.10E-11 2.0623 7.89 84.9 76.9- HuGene_st: 796093-HuGene_st:
783411-HuGene_st: 876648- 90.8 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-HuGene_st: 450049-
KLK11 3.11E-11 2.0091 6.04 84.2 76.1- HuGene_st: 1004334-HuGene_st:
1069590-HuGene_st: 300088- 90.4 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-HuGene_st: 184578- QPCT 3.46E-11 2.0418
3.03 84.6 76.6- HuGene_st: 454020-HuGene_st: 202482-HuGene_st:
1012784- 90.6 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-HuGene_st: 949819-
TMEPAI 3.73E-11 2.0603 2.2 84.9 76.9- HuGene_st: 38546-HuGene_st:
576310-HuGene_st: 1043092- 90.8 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- HuGene_st: 227174_at:
36564-HuGene_st: 236741_at: 604794- 90.1 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-HuGene_st: 403161- UBE2S: 5.62E-11 1.9793
2.4 83.9 75.8- HuGene_st: 202779_s_at: 588403-HuGene_st:
235992-HuGene_st: 261249- LOC731049, 90.1 HuGene_st:
692372-HuGene_st: 86733-HuGene_st: 892371- UBE2S: HuGene_st:
415931-HuGene_st: 285497-HuGene_st: 1092919- LOC731049 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:
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301512- 89.6 HuGene_st: 541945-HuGene_st: 793215-HuGene_st: 791778-
HuGene_st: 737640-HuGene_st: 246083-HuGene_st: 798367- HuGene_st:
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1015396-HuGene_st: 79359-HuGene_st: 587684- HuGene_st:
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FABP6 1.28E-10 1.9367 3.01 83.4 75.2- HuGene_st: 123214-HuGene_st:
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791516-HuGene_st: 221287- HuGene_st: 288462-HuGene_st: 210445_at:
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542596-HuGene_st: 149350-HuGene_st: 35444-HuGene_st: 200029- MMP3
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701539-HuGene_st: 945713- HuGene_st: 766524-HuGene_st:
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890494-HuGene_st: 274715- HuGene_st: 218963_s_at: 501017-HuGene_st:
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622653- 88.4 HuGene_st: 958445-HuGene_st: 445730-HuGene_st: 914223-
HuGene_st: 693724-HuGene_st: 673683-HuGene_st: 524115- HuGene_st:
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473664-HuGene_st: 732367-HuGene_st: 204475_at: 353235- HuGene_st
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89.1 HuGene_st: 488462-HuGene_st: 964336-HuGene_st: 498480-
HuGene_st: 1047616-HuGene_st: 187658-HuGene_st: 201892- HuGene_st:
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HuGene_st: 1078790-HuGene_st: 969948-HuGene_st: 868781- HuGene_st:
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PLCB4 2.29E-09 1.8407 2.37 82.1 73.8- HuGene_st: 770342-HuGene_st:
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87.7 HuGene_st: 207100-HuGene_st: 842538-HuGene_st: 343961-
HuGene_st: 899690-HuGene_st: 705871-HuGene_st: 42619- HuGene_st:
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HuGene_st: 891581-HuGene_st: 980059-HuGene_st: 907061- 87.8
HuGene_st: 536297-HuGene_st: 31908-HuGene_st: 1051267- HuGene_st:
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HuGene_st: 1555950_a_at: 201926_s_at: 201925_s_at: 241616_at:
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HuGene_st: 49079-HuGene_st: 989700-HuGene_st: 941779- UBE2C 86.5
HuGene_st: 9599-HuGene_st: 736605-HuGene_st: 814147- HuGene_st:
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HuGene_st: 209792_s_at: 279985-HuGene_st: 679337-HuGene_st: 542814-
86.1 HuGene_st: 238963-HuGene_st: 910249-HuGene_st: 1009566-
HuGene_st: 989821-HuGene_st: 167404-HuGene_st: 140675- HuGene_st:
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428218-HuGene_st: 196226-HuGene_st UBD 918426-HuGene_st:
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HuGene_st: 871149-HuGene_st: 374784-HuGene_st: 205890_s_at: 757108-
HuGene_st RRM2 158317-HuGene_st: 573546-HuGene_st: 788577- RRM2
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126031-HuGene_st: 1064973-HuGene_st: 86 456984- HuGene_st:
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78.9 70- HuGene_st: 412010-HuGene_st: 1032585-HuGene_st: 254221-
LOC653602 86 HuGene_st: 948951-HuGene_st: 252448-HuGene_st: 968035-
HuGene_st: 367165-HuGene_st: 1079872-HuGene_st: 641006- HuGene_st:
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HuGene_st: 208744_x_at: 398393-HuGene_st: 315510-HuGene_st: 957456-
HuGene_st: 468891-HuGene_st: 669816-HuGene_st: 1086868- HuGene_st:
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171694-HuGene_st: 643594-HuGene_st: 201262_s_at: 85.8 1090822-
HuGene_st: 497499-HuGene_st: 1051954-HuGene_st: 381650- HuGene_st:
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78.1 69.2- HuGene_st: 837611-HuGene_st: 815998-HuGene_st: 697366-
85.3 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:
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1.5536 6.64 78.1 69.3- HuGene_st: 290348-HuGene_st: 207457_s_at:
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HuGene_st: 218832-HuGene_st: 835196-HuGene_st: 865389- 86.7
HuGene_st: 784001-HuGene_st: 653583-HuGene_st: 150197- HuGene_st:
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HuGene_st: 1076162-HuGene_st: 186016-HuGene_st: 156254- HuGene_st:
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HuGene_st: 390198-HuGene_st: 1043179-HuGene_st: 708663- HuGene_st:
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HuGene_st: 229834-HuGene_st: 178723-HuGene_st: 795130- 85.3
HuGene_st: 850113-HuGene_st: 964061-HuGene_st: 314806- HuGene_st:
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HuGene_st: 302174-HuGene_st: 127098-HuGene_st DUSP27
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LOC541471 HuGene_st: 129947-HuGene_st: 569637-HuGene_st: 916693-
HuGene_st: 469295-HuGene_st SPINK1 366191-HuGene_st:
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HuGene_st: 942952-HuGene_st: 82798-HuGene_st: 218383_at: 165751-
HuGene_st: 965936-HuGene_st: 31043-HuGene_st: 650638- HuGene_st:
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HuGene_st: 765000-HuGene_st: 44188-HuGene_st: 59621- 83.8
HuGene_st: 465236-HuGene_st: 559922-HuGene_st: 82252-
HuGene_st: 1039687-HuGene_st: 1053735- HuGene_st: 204885_s_at:
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2.19 75.4 66.3- HuGene_st: 202998_s_at: 1074111-HuGene_st:
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HuGene_st: 237979-HuGene_st: 708999-HuGene_st: 293863- 83.1
HuGene_st: 372914-HuGene_st: 237042-HuGene_st: 207158_at: 1080489-
HuGene_st: 815110-HuGene_st: 417875-HuGene_st: 745636- HuGene_st:
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HuGene_st: 337433-HuGene_st: 128794-HuGene_st: 824637- 83.6
HuGene_st: 131043-HuGene_st: 702794-HuGene_st: 533212- HuGene_st:
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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-HuGene_st: 746940- HOXB6 1.33E-05 1.3346
1.87 74.8 65.6- HuGene_st: 103632-HuGene_st: 883931-HuGene_st:
552163- 82.4 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-HuGene_st: 385407- CTHRC1 1.83E-05 1.2895
2.57 74 64.9- HuGene_st: 647908-HuGene_st: 756615-HuGene_st:
978256- 81.8 HuGene_st: 651961-HuGene_st: 193568-HuGene_st: 310105-
HuGene_st: 393578-HuGene_st REG3A 290546-HuGene_st:
265033-HuGene_st: 385905-HuGene_st: 459677- REG3A 2.22E-05 1.2218
12.09 72.9 63.7- HuGene_st: 230871-HuGene_st: 214805-HuGene_st:
1060074- 80.8 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-HuGene_st: 968572- CXCL5 2.79E-05 1.2805
4.48 73.9 64.8- HuGene_st: 1054472-HuGene_st: 394185-HuGene_st:
181128- 81.7 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-HuGene_st: 583244- CDH11 3.44E-05 1.2652 2.25 73.7 64.4-
HuGene_st: 863670-HuGene_st: 599824-HuGene_st: 142981- 81.5
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-
HuGene_st: 209955_s_at: 600137-HuGene_st: 284881-HuGene_st: 40379-
FAP 81.3 HuGene_st REG1B 796972-HuGene_st: 1089426-HuGene_st:
762519-HuGene_st: 270006- REG1B 8.08E-05 1.1728 13.15 72.1 62.8-
HuGene_st: 553619-HuGene_st: 279169-HuGene_st: 342759- 80.1
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-HuGene_st: 348725- COMP
0.0001 1.1565 1.69 71.8 62.6- HuGene_st: 492440-HuGene_st:
307171-HuGene_st: 121009- 79.9 HuGene_st: 205713_s_at AURKA
147919-HuGene_st: 826493-HuGene_st: 453415-HuGene_st: 126529-
AURKA: 0.0001 1.1173 1.81 71.2 61.8- HuGene_st: 799451-HuGene_st:
673418-HuGene_st: 571370- STK6P 79.3 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-HuGene_st: 367103- SQLE 0.0001 1.1354 2.69 71.5
62.1- HuGene_st: 827097-HuGene_st: 213562_s_at: 819545-HuGene_st:
354972- 79.6 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- HuGene_st: 236894_at: 715579-HuGene_st:
540230-HuGene_st: 414266- 79.9 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-HuGene_st: 664848- SERPINE2 0.0002 1.1283
1.9 71.4 62.1- HuGene_st: 1052179-HuGene_st: 227487_s_at:
902213-HuGene_st: 79.4 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-HuGene_st: 456577- CEL 0.0006 1.0863 1.46 70.6 61.3-
HuGene_st: 1035054-HuGene_st: 539061-HuGene_st: 788693- 78.8
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- LILRB1 78.7 COL1A1 487433-HuGene_st:
719132- COL1A1 0.0018 1.0063 2.5 69.3 59.9- HuGene_st:
1556499_s_at: 202311_s_at: 202310_s_at: 1003153- 77.6 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-HuGene_st: 673651- PCSK1 0.0029 1.1077 1.48 71 61.7-
HuGene_st: 166044-HuGene_st: 989024-HuGene_st: 1039153- 79.1
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-HuGene_st: 203860_at
PCCA 0.0038 0.939 1.42 68.1 58.6- 76.5 H19 634871-HuGene_st:
51379-HuGene_st: 803516-HuGene_st: 336451- RPS12: 0.0051 1.0228
1.47 69.5 60.2- HuGene_st: 254511-HuGene_st: 632993-HuGene_st H19
77.8 COL10A1 288876-HuGene_st: 815716-HuGene_st: 615071-HuGene_st:
865385- COL10A1 0.0143 0.8493 2.05 66.4 56.9- HuGene_st:
1067078-HuGene_st 74.9 CYP3A5 NA CYP3A5: 0.0562 0.8249 1.58 66
56.5- CYP3A7 74.6 CYP3A5P2 NA CYP3A5: 0.0562 0.8246 1.58 66 56.5-
CYP3A7 74.6 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- LOC728628 71.6 THBS2 NA
THBS2 0.9844 0.2782 1.26 55.5 45.9- 64.8
TABLE-US-00064 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:
3.32E-15 2.4882 5.52 89.3 82.3-94.2 LOC389173:LOC729779: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:S1X6: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-00065 TABLE 4 Gene Signif. D. val Sens- CI Symbol
ValidPS_UP Symbol FDR 5 FC Spec (95) CD44
366106-HuGene_st:314808-HuGene_st:59730- MAPK10: 3.35E-26 3.7136
7.06 96.8 92.9- HuGene_st:599371-HuGene_st:391296- CD44 98.8
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: 1.51E-24 3.5213
4.57 96.1 91.6- HuGene_st:1093456-HuGene_st:347351- NFE2L3: 98.4
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 MMP7
267137-HuGene_st:1068392- MMP7 7.61E-22 3.2652 69.29 94.9 89.8-
HuGene_st:794865-HuGene_st:876922- 97.8
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: 1.95E-21 3.2907
7.85 95 90- HuGene_st:256806-HuGene_st:261067- CXCL3 97.8
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-
HuGene_st:1011822-HuGene_st:1092705- 96.5
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 NLF1
269939-HuGene_st:314919- NLF1 3.12E-18 2.8001 8.12 91.9 85.7-
HuGene_st:552234-HuGene_st:622058- 95.9
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: 3.32E-15 2.4883 5.52 89.3 82.3-
HuGene_st:160439-HuGene_st:322148- PSAT1: 94.1
HuGene_st:85375-HuGene_st:223335- LOC389173:
HuGene_st:2658-HuGene_st:399855- LOC729779:
HuGene_st:220892_s_at:941491- C8orf62
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- HuGene_st:102028-HuGene_st:291462- 93.7
HuGene_st:206224_at:906914- HuGene_st:936009-HuGene_st:1055285-
HuGene_st AZGP1 363333-HuGene_st:620891- AZGP1: 1.31E-14 2.3984
6.19 88.5 81.3- HuGene_st:619378-HuGene_st:741747- LOC401393 93.5
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- HuGene_st:52318-HuGene_st:530079- 93.7 HuGene_st:288145-
HuGene_stat: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-
HuGene_st:815649-HuGene_st:567105- 93.3
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: 3.28E-12 2.3273 1.73 87.8 80.3-
HuGene_st:442029-HuGene_st:119200- IGHG1 93
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-
HuGene_st:937559-HuGene_st:297045- 90.8
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:210393at:241266_at:213880_at QPCT
261837-HuGene_st:108729- QPCT 3.46E-11 2.0415 3.03 84.6 76.7-
HuGene_st:942514-HuGene_st:184578- 90.6
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-
HuGene_st:725768- 90 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-
HuGene_st:931162-HuGene_st:400261- 88.3
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-
HuGene_st:1020786-HuGene_st:437171- 88.4
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-
HuGene_st:477118-HuGene_st:858635- 87.7
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-
HuGene_st:869898-HuGene_st:755872- 85.6
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-
HuGene_st:124098-HuGene_st:102948- 84.8
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-
HuGene_st:537586-HuGene_st:973643- 86.5
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- HuGene_st:192667-HuGene_st:765000- 83.7
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 CXCL5
264137-HuGene_st:272626- CXCL5 2.79E-05 1.2814 4.48 73.9 64.7-
HuGene_st:745715-HuGene_st:968572- 81.7
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-
HuGene_st:1010927- 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:219955at: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- HuGene_st:456577-HuGene_st:1035054- 78.8
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-
HuGene_st:1556499_s_at:202311s_at:202310_ 77.6
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- HuGene_st:673651-HuGene_st:166044- 79.1
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
COL8A1 713455-HuGene_st COL8A1 2.54E-02 0.8325 1.43 66.1 56.6-
74.7
TABLE-US-00066 TABLE 5 Signif. Sens- TargetPS Symbol FDR D. val5 FC
Spec CI (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 232481_s_at
SLITRK6 0.0016 1.3607 5.96 75.2 62.9-85 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: 4.53E-02 1.1998 1.31 72.6 60.1-82.8 LOC650855:LOC645744
217109_at MUC4:TAF5L: 4.53E-02 1.2028 1.31 72.6 60.2-82.8
LOC650855:LOC645744 217110_s_at MUC4:TAF5L: 4.53E-02 1.198 1.31
72.5 60-82.8 LOC650855:LOC645744 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 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-00067 TABLE 6 Signif. D. val Sens- TargetPS Symbol FDR 5
FC Spec CI (95) 200665_s_ SPARC 3.05E-09 2.3771 3.24 88.3 78-94.6
at 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 211966_at COL4A2
5.5315E-09 2.4321 2.87 88.8 78.8-95 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_ SPON2 1.9471E-08 2.3321 3.38 87.8
77.5-94.3 at 221729_at COL5A2 5.7658E-08 2.2145 3.31 86.6 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_ BGN 9.6881E-08
2.2253 2.99 86.7 76-93.6 at 213905_x_ BGN 9.6881E-08 2.2232 2.99
86.7 76.1-93.6 at 209955_s_ IFIH1:FAP 1.358E-07 2.2261 4.88 86.7
76.2-93.6 at 226237_at COL8A1 3.6053E-07 2.1456 3.09 85.8 75-93
202310_s_ COL1A1 5.44E-07 2.0121 3.29 84.3 73-92 at 202311_s_
COL1A1 5.44E-07 2.0131 3.29 84.3 73.1-92 at 217430_x_ COL1A1
5.4426E-07 2.015 3.29 84.3 73.2-92 at 201438_at COL6A3 5.7026E-07
2.0286 2.73 84.5 73.5-92.1 202403_s_ COL1A2:LOC728628 8.85E-07
2.0609 2.62 84.9 73.9-92.4 at 202404_s_ COL1A2:LOC728628 8.85E-07
2.0621 2.62 84.9 73.7-92.4 at 229218_at COL1A2:LOC728628 8.8466E-07
2.0618 2.62 84.9 73.9-92.4 208850_s_ THY1 1.0326E-06 1.9159 3.34
83.1 71.8-91.1 at 208851_s_ THY1 1.0326E-06 1.915 3.34 83.1
71.7-91.1 at 213869_x_ THY1 1.0326E-06 1.9132 3.34 83.1 71.7-91.1
at 203477_at COL15A1 1.0611E-06 2.0121 3.37 84.3 73.2-91.9
201616_s_ CALD1 1.11E-06 2.1136 1.7 85.5 74.6-92.8 at 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_ IGFBP7 1.16E-06
1.999 1.91 84.1 73-91.9 at 210511_s_ INHBA 1.1943E-06 2.0027 3.38
84.2 73-91.9 at 225664_at TMEM30A:COL12A1 1.2492E-06 2.0313 4.16
84.5 73.4-92.1 231766_s_ TMEM30A:COL12A1 1.2492E-06 2.0303 4.16
84.5 73.4-92.1 at 231879_at TMEM30A:COL12A1 1.2492E-06 2.0325 4.16
84.5 73.5-92.1 203325_s_ COL5A1 1.6076E-06 1.934 2.75 83.3
72.1-91.3 at 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 72-91.2 203083_at
THBS2 2.3382E-06 1.9081 6.5 83 71.6-91 202291_s_ MGP:C12orf46
2.50E-06 1.9993 2.62 84.1 73-91.9 at 201645_at TNC 3.74E-06 1.9608
2.14 83.7 72.5-91.5 201852_x_ COL3A1 9.29E-06 1.8472 2.32 82.2
70.7-90.5 at 211161_s_ COL3A1 9.2906E-06 1.8501 2.32 82.3 70.7-90.5
at 215076_s_ COL3A1 9.2906E-06 1.8495 2.32 82.2 70.7-90.5 at
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_ ENTPD4:LOXL2 1.99E-05 1.7754 2.45 81.3
69.6-89.7 at 224724_at SULF2 2.0766E-05 1.6837 2.25 80 68.2-88.7
233555_s_ SULF2 2.0766E-05 1.6795 2.25 79.9 68-88.7 at 201069_at
MMP2 2.5409E-05 1.7345 3.02 80.7 69-89.3 201147_s_ TIMP3 2.62E-05
1.7776 2.56 81.3 69.6-89.7 at 201150_s_ TIMP3 2.62E-05 1.7774 2.56
81.3 69.6-89.7 at 209156_s_ COL6A2 2.9551E-05 1.7373 1.67 80.7
69-89.4 at 227099_s_ LOC387763 0.00003052 1.8968 1.43 82.9
71.4-90.9 at 214247_s_ DKK3 3.1838E-05 1.7434 1.86 80.8 69.1-89.5
at 202450_s_ CTSK 3.98E-05 1.7153 2.16 80.4 68.7-89.1 at 225799_at
MGC4677,MGC4677: 4.1139E-05 1.8003 1.45 81.6 70-90 LOC541471
209395_at CHI3L1:MYBPH 5.1515E-05 1.6358 3.06 79.3 67.4-88.2
209396_s_ CHI3L1:MYBPH 5.1515E-05 1.6352 3.06 79.3 67.4-88.2 at
202878_s_ CD93 5.19E-05 1.6674 2.36 79.8 67.9-88.6 at 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_ LBH 6.3299E-05 1.6771
1.9 79.9 68.1-88.7 at 213125_at OLFML2B 6.6557E-05 1.7057 1.97 80.3
68.5-89 204475_at MMP1 7.0616E-05 1.6759 3.91 79.9 68-88.8
226694_at AKAP2:PALM2:PALM2- 7.4206E-05 1.7231 1.58 80.6 68.8-89.2
AKAP2 202766_s_ FBN1 0.0001 1.5984 1.48 78.8 66.7-87.9 at 205828_at
MMP3 0.0001 1.6223 6.68 79.1 67.3-88.1 207191_s_ ISLR 0.0001 1.6448
1.87 79.5 67.5-88.4 at 213428_s_ COL6A1 0.0001 1.7301 1.58 80.6
68.8-89.3 at 226930_at FNDC1 0.0001 1.521 3.14 77.7 65.6-87
201792_at AEBP1 0.0002 1.4772 2.11 77 64.8-86.5 203878_s_ MMP11
0.0002 1.6971 1.28 80.2 68.4-88.9 at 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_ PLAU 0.0003 1.484 2.11 77.1
64.9-86.5 at 210495_x_ FN1 0.0003 1.494 2.87 77.2 65.1-86.6 at
211719_x_ FN1 0.0003 1.4894 2.87 77.2 65.1-86.7 at 212464_s_ FN1
0.0003 1.493 2.87 77.2 65-86.7 at 216442_x_ FN1 0.0003 1.4935 2.87
77.2 65-86.6 at 217762_s_ RAB31 0.0003 1.4864 2.08 77.1 65-86.6 at
217763_s_ RAB31 0.0003 1.4848 2.08 77.1 64.9-86.6 at 217764_s_
RAB31 0.0003 1.4882 2.08 77.2 65-86.5 at 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 64-85.8 210095_s_ IGFBP3 0.0006 1.5538 1.38
78.1 66-87.4 at 201426_s_ VIM 8.00E-04 1.4819 1.48 77.1 64.9-86.4
at 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 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 65-86.7
204051_s_ SFRP4 0.0015 1.4056 2.2 75.9 63.6-85.6 at 209101_at CTGF
0.0015 1.3331 1.78 74.7 62.4-84.6 204620_s_ CSPG2 0.0016 1.21 1.38
72.7 60.3-83 at 211571_s_ CSPG2 0.0016 1.2123 1.38 72.8 60.1-82.9
at 215646_s_ CSPG2 0.0016 1.2095 1.38 72.7 60.3-83 at 221731_x_
CSPG2 0.0016 1.2115 1.38 72.8 60.3-83 at 204006_s_ FCGR3B 0.0026
1.2308 2.14 73.1 60.6-83.2 at 203570_at LOXL1 0.0027 1.4048 1.33
75.9 63.7-85.6 201744_s_ LUM 2.90E-03 1.3418 2.18 74.9 62.5-84.7 at
202283_at SERPINF1 3.10E-03 1.2121 1.76 72.8 60.2-83 209596_at
MXRA5 0.0034 1.2974 1.62 74.2 61.7-84.1 210809_s_ POSTN 0.005
1.3011 2.58 74.2 61.8-84.2 at 205547_s_ TAGLN 0.0051 1.1829 2.19
72.3 59.7-82.6 at 202237_at NNMT 5.40E-03 1.223 1.44 73 60.4-83.1
202238_s_ NNMT 5.40E-03 1.2259 1.44 73 60.5-83.1 at 218468_s_ GREM1
0.007 1.3017 1.31 74.2 61.8-84.2 at 218469_at GREM1 0.007 1.3027
1.31 74.3 61.9-84.2 208747_s_ C1S 0.0088 1.3575 1.77 75.1 62.9-85
at 224560_at TIMP2 0.0097 1.1629 1.72 72 59.4-82.3 231579_s_ TIMP2
0.0097 1.1641 1.72 72 59.5-82.4 at 209875_s_ SPP1 0.0109 1.0673
3.91 70.3 57.6-80.9 at 202859_x_ IL8 0.0112 1.3238 4.54 74.6
62.2-84.5 at 200832_s_ SCD:LOC651109: 1.27E-02 1.0749 2.33 70.5
57.9-81.1 at LOC645313 201058_s_ MYL9 0.0131 1.1765 1.37 72.2
59.6-82.5 at 203645_s_ CD163 0.0146 1.1655 2.19 72 59.4-82.3 at
215049_x_ CD163 0.0146 1.1664 2.19 72 59.4-82.3 at 202917_s_ S100A8
1.48E-02 1.0979 3.17 70.8 58.3-81.4 at 201289_at CYR61 0.015 1.0919
1.69 70.7 58.1-81.2 210764_s_ CYR61 0.015 1.0938 1.69 70.8
58.2-81.2 at 218559_s_ MAFB 0.0182 1.162 1.48 71.9 59.3-82.3 at
203382_s_ APOE 0.0285 1.1124 1.43 71.1 58.5-81.6 at 201893_x_ DCN
3.64E-02 1.0821 1.29 70.6 58-81.1 at 211813_x_ DCN 0.0364 1.0838
1.29 70.6 57.8-81.1 at 211896_s_ DCN 0.0364 1.0814 1.29 70.6
58-81.1 at 213524_s_ GOS2 0.0383 0.994 1.53 69 56.3-79.8 at
207173_x_ CDH11 0.0384 1.0121 1.98 69.4 56.6-80.1 at 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_ SFRP2
0.1336 0.968 1.24 68.6 55.9-79.4 at 223235_s_ SMOC2 0.2175 0.6547
2.06 62.8 50-74.4 at 200986_at SERPING1 0.2636 0.7831 1.26 65.2
52.4-76.4 201842_s_ EFEMP1 4.91E-01 0.6821 1.27 63.3 50.5-74.8 at
204122_at TYROBP 0.4923 0.7066 1.23 63.8 51.1-75.3 202620_s_ PLOD2
5.15E-01 0.7784 1.51 65.1 52.3-76.4 at
TABLE-US-00068 TABLE 7 Gene Signif. D. val Sens- CI Symbol
ValidPS_UP Symbol FDR 5 FC Spec (95) ATP8A1 231484_at:792569-
ATP8A1 6.60E-08 2.2854 3.11 87.3 76.9- HuGene_st:210192_at:393806-
94 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- HuGene_st:622359-HuGene_st:523802- 93.1
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- HuGene_st:356782-HuGene_st:70395- 88.5
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- HuGene_st:708431-HuGene_st:231770- 88.5
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- HuGene_st:343187-HuGene_st:223925- 87.6
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- HuGene_st:463072-HuGene_st:749900- 87.7
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- HuGene_st:338164-HuGene_st:71797- 86.7
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- HuGene_st:446764-HuGene_st:548266- 86.4
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- HuGene_st:227676_at:741172- 83.8
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-
HuGene_st:214234_s_at:941416- 87 HuGene_st:238807-HuGene_st:611620-
HuGene_st CYP3A5P2 205765_at:67735- CYP3A5 0.0012 1.5297 1.8 77.8
65.6- HuGene_st:214234_s_at:941416- 87
HuGene_st:238807-HuGene_st:611620- HuGene_st SLITRK6
936650-HuGene_st:921047- SLITRK6 0.0016 1.36 5.96 75.2 62.8-
HuGene_st:371185-HuGene_st:510939- 85
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- HuGene_st:893707-HuGene_st:597814- 84.5
HuGene_st:585604-HuGene_st:240530- HuGene_st HMGCS2
616916-HuGene_st:283650- HMGCS2 0.0052 1.234 3.59 73.1 60.6-
HuGene_st:204607_at:43162- 83.3 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- 203963_at:638145-HuGene_st:1013062- 82.6 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- HuGene_st:372293-HuGene_st:247017- 82
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- HuGene_st:480007-HuGene_st:396007- 82.1
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- HuGene_st:1058922-HuGene_st:572495- 83.5
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- HuGene_st 82.7 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- 232654_s_at 80.8 MUC4 NA MUC4: 0.0453
1.1986 1.31 72.6 60.1- TAF5L: 82.8 LOC650855: 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 PBLD NA PBLD 0.1655
0.8731 1.89 66.9 54.1- 78 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-00069 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-
HuGene_st:1041514-HuGene_st:868223- 94.6
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-
HuGene_st:1009411-HuGene_st:245530- 95
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:211964at:316644- HuGene_st:1015712-HuGene_st COL4A1
831741-HuGene_st:634068- COL4A1 1.243E-08 2.3004 3.03 87.5 77-
HuGene_st:816476-HuGene_st:1030276- 94.2
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-
HuGene_st:170898-HuGene_st:6411- 94.3
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-
COLSA2 5.7658E-08 2.2164 3.31 86.6 76-
HuGene_st:260654-HuGene_st:125943- 93.5
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- HuGene_st:964097-HuGene_st:874354- 93.6
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-
HuGene_st:45294-HuGene_st:381650- 93.6
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-
HuGene_st:284881-HuGene_st:1022038- 93.6
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- HuGene_st:103513-HuGene_st:651142- 93
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- HuGene_st:52480-HuGene_st:975188- 92
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: 155699_s_at:202311_s_at COL6A3
312177-HuGene_st:24239- COL6A3 5.7026E-07 2.0313 2.73 84.5 73.5-
HuGene_st:337032-HuGene_st:31627- 92.1
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: 8.8466E-07 2.0613 2.62 84.9 73.9-
HuGene_st:240155-HuGene_st:1079758- LOC728628 92.3
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-
HuGene_st:287669-HuGene_st:329513- 91.1
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:
908785-HuGene_st:516398-HuGene_st COL15A1 330621-HuGene_st:910395-
COL15A1 1.0611E-06 2.0128 3.37 84.3 73.2-
HuGene_st:811192-HuGene_st:294092- 92
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-
HuGene_st:558226-HuGene_st:755661- 92.8
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-
HuGene_st:86333-HuGene_st:882867- 91.8
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 73- HuGene_st:363337-HuGene_st:874496-
91.9 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: 1.2492E-06 2.03 4.16 84.5
73.4- HuGene_st:1063560-HuGene_st:567963- COL12A1 92.1
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 72-
HuGene_st:299983-HuGene_st:751853- 91.3
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:212489at: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- HuGene_st:807449-HuGene_st:895973- 91
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-
HuGene_st:1030770-HuGene_st:767997- 91.6
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:
5.8225E-06 1.9994 2.62 84.1 73- C12orf46 91.9 COL3A1
410491-HuGene_st:718613- COL3A1 9.2906E-06 1.8484 2.32 82.2 70.8-
HuGene_st:1083201-HuGene_st:364429- 90.5
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-
HuGene_st:933799-HuGene_st:72604- 89.6
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-
HuGene_st:299850-HuGene_st:317595- 89.3
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: 0.000019895 1.7774 2.45 81.3 69.6-
HuGene_st:346541-HuGene_st:271051- LOXL2 89.7
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- HuGene_st:43751-HuGene_st:395846- 88.8
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-
HuGene_st:168982-HuGene_st:598990- 89.3
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- HuGene_st:231888_at:201148_s_at:326731- 89.8
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
69- HuGene_st:536399-HuGene_st:813295- 89.4
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:213290at 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- HuGene_st:829432-HuGene_st:425906- 89.5
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:86457- HuGene_st CTSK
592586-HuGene_st:682010- CTSK 0.000039778 1.7156 2.16 80.4 68.8-
HuGene_st:30909-HuGene_st:235976- 89.1
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-
HuGene_st:916693-HuGene_st:569637- MGC4677: 90
HuGene_st:868769-HuGene_st:469295- LOC541471
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: 0.000051515 1.6351 3.06
79.3 67.4- HuGene_st:261087-HuGene_st:57128- MYBPH 88.3
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-
HuGene_st:900048-HuGene_st:1024597- 88.6
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-
HuGene_st:360139-HuGene_st:64257- 89.5
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-
HuGene_st:766856-HuGene_st:1083711- 88.7
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-
HuGene_st:682043-HuGene_st:249054- 89
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-
HuGene_st:300572-HuGene_st:914223- 88.7
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: 0.000074206 1.724 1.58 80.6
68.9- AKAP2 HuGene_st:799637-HuGene_st:91787- PALM2: 89.2
HuGene_st:448601-HuGene_st:839008- PALM2-
HuGene_st:1044350-HuGene_st:327679- AKAP2
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-
HuGene_st:427611-HuGene_st:921008- 87.8
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-
HuGene_st:483424-HuGene_st:634624- 88.1
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-
HuGene_st:864958-HuGene_st:599962- 88.4
HuGene_st:864958-HuGene_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- HuGene_st:694215-HuGene_st:133534-
89.3 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-
HuGene_st:959100-HuGene_st:187071- 87
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- HuGene_st:209682-HuGene_st:285969- 86.4
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:324921- MMP11 0.0002 1.6993 1.28
80.2 68.3- HuGene_st:718792-HuGene_st:514533- 89
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-
HuGene_st:323206-HuGene_st:941332- 87.5
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-
HuGene_st:783863-HuGene_st:1027344- 86.5
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-
HuGene_st:86783-HuGene_st:756615- 86.2
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 65-
HuGene_st:338536-HuGene_st:586400- 86.6
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 65-
HuGene_st:936297-HuGene_st:576193- 86.6
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-
HuGene_st:289133-HuGene_st:775286- 86.5
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- HuGene_st:211457-HuGene_st:551828- 87.2
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-
HuGene_st:799524-HuGene_st:85875- 86.9
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-
HuGene_st:1070983-HuGene_st:548186- 85.8
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 66-
HuGene_st:585931-HuGene_st:145671- 87.3
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-
HuGene_st:837477-HuGene_st:1079757- 86.5
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-
HuGene_st:224396_s_at:640448- 85.6
HuGene_st:1055545-HuGene_st:447994-
HuGene_st:835521-HuGene_st:567513- HuGene_st:546047-
HuGene_st:219087_at:673620-HuGene_st HNT 291569-HuGene_st:1099035-
HNT 0.001 1.425 2.26 76.2 63.8- HuGene_st:237480- 85.8
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-
HuGene_st:100706-HuGene_st:202715- 85.6
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-
HuGene_st:1038630-HuGene_st:555838- 86.7
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-
HuGene_st:321583-HuGene_st:784119- 85.5
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-
HuGene_st:661089-HuGene_st:338622- 84.6
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 775320-HuGene_st:483078- FCGR3B 0.0026 1.232 2.14 73.1 60.5-
HuGene_st:897088-HuGene_st:891504- 83.3
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-
HuGene_st:999775-HuGene_st 85.5 LUM 253522-HuGene_st:646969- LUM
0.0029 1.3426 2.18 74.9 62.5- HuGene_st:566007-HuGene_st:629878-
84.7 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 MXRA5
319799-HuGene_st:432137- MXRA5 0.0034 1.2959 1.62 74.1 61.6-
HuGene_st:408065-HuGene_st:291182- 84.1
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-
HuGene_st:538299-HuGene_st:649547- 84.3
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-
HuGene_st:898711-HuGene_st:505391- 82.6
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- HuGene_st:591616-HuGene_st:968910- 83.2
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: 0.0062
1.6808 1.33 80 68.1- C6orf142: 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-
HuGene_st:639839-HuGene_st:326978- 84.2
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 C1S
947234-HuGene_st:962144- C1S 0.0088 1.3551 1.77 75.1 62.8-
HuGene_st:567397-HuGene_st:490300- 84.9
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-
HuGene_st:965142-HuGene_st:463158- 82.3
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-
HuGene_st:809583-HuGene_st:44881- 80.9
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: 1.27E-02 1.073 2.33 70.4 57.7-
HuGene_st:433956-HuGene_st:1088784- LOC651109: 81
HuGene_st:1019041-HuGene_st:698268- LOC645313
HuGene_st:64902-HuGene_st:749928-
HuGene_st:713000-HuGene_st:562893- HuGene_st MYL9
206106-HuGene_st:608837- MYL9 0.013 11.1754 1.37 72.2 59.6-
HuGene_st:706186-HuGene_st:874422- 82.4
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- HuGene_st:900552-HuGene_st:662901- 82.3
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-
HuGene_st:473960-HuGene_st:98947- 81.3
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-
HuGene_st:385534-HuGene_st:924057- 81.3
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 58- 81.1 G0S2 888942-HuGene_st:346957- G0S2 0.0383 0.9923 1.53
69 56.3- HuGene_st:62728-HuGene_st:334340- 79.9
HuGene_st:897401-HuGene_st CDH11 60296-HuGene_st:609892- CDH11
0.0384 1.01 1.98 69.3 56.7- HuGene_st:167614-HuGene_st:184349- 80
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-
HuGene_st:1010566-HuGene_st:895693- 80.1
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 56- 79.4 SMOC2 NA SMOC2 0.2175 0.6581 2.06 62.9 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-00070 TABLE 9 SEQ ID Probe NO: Set ID Target Sequence 1
200660_at
caaggctgggccgggaagggcgtgggttgaggagaggctccagacccgcacgccgcgc
gcacagagctctcagcgccgctcccagccacagcctcccgcgcctcgctcagctccaa
catggcaaaaatctccagccctacagagactgagcggtgcatcgagtccctgattgct
gtcttccagaagtatgctggaaaggatggttataactacactctctccaagacagagt
tcctaagcttcatgaatacagaactagctgccttcacaaagaaccagaaggaccctgg
tgtccttgaccgcatgatgaagaaactggacaccaacagtgatggtcagctagatttc
tcagaatttcttaatctgattggtggcctagctatggcttgccatgactccttcctca
aggctgtcccttcccagaagcggacctgaggaccc 2 200665_s_at
gttggttcaaacttttgggagcacggactgtcagttctctgggaagtggtcagcgcat
cctgcagggcttctcctcctctgtcttttggagaaccagggctcttctcaggggctct
agggactgccaggctgtttcagccaggaaggccaaaatcaagagtgagatgtagaaag
ttgtaaaatagaaaaagtggagttggtgaatcggttgttctttcctcacatttggatg
attgtcataaggtttttagcatgttcctccttttcttcaccctcccctttgttcttct
attaatcaagagaaacttcaaagttaatgggatggtcggatctcacaggctgagaact
cgttcacctccaagcatttcatgaaaaagctgcttcttattaatcatacaaactctca
ccatgatgtg 3 200832_s_at
aaaagcgaggtggccatgttatgctggtggttgccagggcctccaaccactgtgccac
tgacttgctgtgtgaccctgggcaagtcacttaactataaggtgcctcagttttcctt
ctgttaaaatggggataataatactgacctacctcaaagggcagttttgaggcatgac
taatgctttttagaaagcattttgggatccttcagcacaggaattctcaagacctgag
tattttttataataggaatgtccaccatgaacttgatacgtccgtgtgtcccagatgc
tgtcattagtctatatggttctccaagaaactgaatgaatccattggagaagcggtgg
ataactagccagacaaaatttgagaatacataaacaacgcattgccacggaaacatac
agaggatgccttttctgtgattgggtgggattttttccctttttatgtgggatatagt
agttacttgtgacaagaataattttggaataatttctattaatatcaactctgaagct
aattgtactaatctgagat 4 200903_s_at
gcagcgggaacagagtaccctcttcaagccccggtcatgatggaggtcccagccacag
ggaaccatgagctcagtggtcttggaacagctcactaagtcagtccttccttagcctg
gaagccagtagtggagtcacaaagcccatgtgttttgccatctaggccttcacctggt
ctgtggacttatacctgtgtgcttggtttacaggtccagtggttcttcagcccatgac
agatgagaaggggctatattgaagggcaaagaggaactgttgtttgaattttcctgag
agcctggcttagtgctgggccttctcttaaacctcattacaatgaggttagtactttt
agtccctgt 5 201014_s_at
agtgttgatgggctctacttctgatcttggtcactgtgaaaaaatcaagaaggcctgt
ggaaattttggcattccatgtgaacttcgagtaacatctgcgcataaaggaccagatg
aaactctgaggattaaagctgagtatgaaggggatggcattcctactgtatttgtggc
agtggcaggcagaagtaatggtttgggaccagtgatgtctgggaacactgcatatcca
gttatcagc 6 201112_s_at
agatctgtgcggttggcataaccaacttactaacagaatgtcccccaatgatggacac
tgagtataccaaactgtggactccattattacagtctttgattggtctttttgagtta
cccgaagatgataccattcctgatgaggaacattttattgacatagaagatacaccag
gatatcagactgccttctcacagttggcatttgctgggaaaaaagagcatgatcctgt
aggtcaaatggtgaataaccccaaaattcacctggcacagtcacttcacatgttgtct
accgcctgtccaggaagggttc 7 201195_s_at
tcagaaggtaggggccgtgtcccgcggtgctgactgaggcctgcttccccctccccct
cctgctgtgctggaattccacagggaccagggccaccgcaggggactgtctcagaaga
cttgatttttccgtccctttttctccacactccactgacaaacgtccccagcggtttc
cacttgtgggcttcaggtgttttcaagcacaacccaccacaacaagcaagtgcatttt
cagtcgttgtgcttttttgttttgtgctaacgtcttactaatttaaagatgctgtcgg
caccatgtttatttatttccagtggtcatgctcagccttgctgctctgcgtggcgcag
gtgccatgcctgctccctgtctgtgtcccagccacgcagggccatccactgtgacgtc
ggccgaccaggctggacaccctctgccgagtaatgacgtgtgtggctgggaccttctt
tattctgtgttaatggctaacctgttacactgggctgggttgggtagggtgttctggc 8
201261_x_at
tctctctttctgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtcttgtgctt
cctcagacctttctcgcttctgagcttggtggcctgttccttccatctctccgaacct
ggcttcgcctgtccctttcactccacaccctctggccttctgccttgagctgggactg
ctttctgtctgtccggcctgcacccagcccctgcccacaaaaccccagggacagcggt
ctccccagcctgccctgctcaggccttgcccccaaacctgtactgtcccggaggaggt
tgggaggtggaggcccagcatcccgcgcagatgacaccatcaaccgccagagtcccag
acaccggttttcctagaagcccctcacccccactggcccactggtggctaggtctccc
cttatccactggtccagcgcaaggaggggctgatctgaggtcggtggctgtattccat
taaagaaacacc 9 201292_at
tacagatactctactacactcagcctcttatgtgccaagtattattaagcaatgagaa
attgctcatgacttcatcactcaaatcatcagaggccgaagaaaaacactaggctgtg
tctataacttgacacagtcaatagaatgaagaaaattagagtagttatgtgattattt
cagctcttgacctgtcccctctggctgcctctgagtctgaatctcccaaagagagaaa
ccaatactaagaggactggattgcagaagactcggggacaacatttgatccaagatct
taaatgttatattgataaccatgctcagcaatgagctattagattcattagggaaatc
tccataatttcaatagtaaactagttaagacctgtctacattgttatatg 10 201328_at
agcatcggagccattcattcggagaaaacgattgatcaaaatggagacttagtagtcg
atcaaaagagcacctgagtcatgtgtattcccggcnnnattataaatgacccggtcaa
gaggatcaaagtncgacaggcagtctgatactagctgcgtggccaggacgggtggctg
acatctgtaaagaatcctcctgtgatgaaactgaggaatcgggtggccgggcaagctg
ggaagagcaaagccagnagctgcgctgcctcaatacccacaaaagaccattcccagta
tacataagcacaggatgatactcaagagggatgtatttatcacttggacatctgatat
aatataaacagacatgtgactgggaacatcagctgccaaaagaatcctaggcagtggc
tcattgtatgtgaggagaaccacgtgaaattgccaatattaggctggcattatctaca
aagaaggagtacatggggacagcctaacagttatggaaactacagtccttataaacca ttggcatg
11 201338_x_at
gatgtatgtcgctgtccaagagaaggctgtggaagaacctatacaactgtgataatct
ccaaagccatatcctctccaccatgaggaaagccgccatagtgtgtgaacatgctggc
tgtggcaaaacatttgcaatgaaacaaagtctcactaggcatgctgagtacatgatcc
tgacaagaagaaaatgaagctcaaagtcaaaaaatctcgtgaaaaacgggagtaggcc
tctcatctcagtggatatatcctcccaaaaggaaacaagggcaaggcttatctagtgt
caaaacggagagtcacccaactgtgtggaagacaagatgctctcgacagagcagtact
tacccaggctaagaactgcactgattgataaaggactgcagaccaaggagtcgagctt tctctca
12 201341_at
ggtctgacttgaatcctctattaattactgtgtgtgagccagagggagctgtggtaag
ggagggcccccagcctgtagggaactactggactcccactattgaatcgatataggca
taggtctcactacttgaccattctcaccctgtgaaacgtcccacactagaagcaaata
caattcacagcacagtacacacaaaaaccaggcataagacagagaaggacttcttatt
agtgggctggagctgtagaaacatataacaaagggcagccctccacactggtataatt
gtgtagcccatttctagggcttgacacctgtcttgaataagagtgattagagctgcat
aatgtccctctctt 13 201416_at
gaggtcagataggagatctcattgcacgcggagattattattgcatcgggaccaagcc
aatgggaagcccgggggaggggtaggcatgaggaagcgaggttacagcagctgattgg
ctgcagccaagactgtgaaaggataaagaggcgcgaggcggaattggggtctgctcta
agctgcagcaagagaaactgtgtgtgaggggaagaggcctgatcgctgtcgggtctct
agacttgcacgctattaagagtctgcactggaggaactcctgccattaccagctccat
cttgcagaagggagggggaaacatacatttattcatgccagtctgagcatgcaggcta
nnggatcctaccagcaacaaaataattgcaccaactccttagtgccgattccgcccac
agagagtcctggagccacagtcttttttgctttgcattgtaggagagggactaagtgc
tagagactatgtcgctttcctgagctaccgagagcgctcgtgaactggaatcaact 14
201417_at
gtaaaccacatatattgcacttatttataagcaaaaacgtgccgataaaccactggat
ctatctaaatgccgatttgagttcgcgacactatgtactgcgtattcattcagtattt
gactatttaatcattctacttgtcgctaaatataattgattagtcttatggcatgatg
atagcatatgtgacaggatatagctgagtgataaaaattgaaaaaagtggaaaacatc
tagtacatttaagtctgtattataataagcaaaaagattgtgtgtatgtatgataata
taacatgacaggcactaggacgtctgccatttaaggcagttccgttaagggtttttgt
ttttaaacttttttttgccatccatcctgtgcaatatgccgtgta 15 201468_s_at
gatgacttaccatgggatggggtccagtcccatgaccaggggtacaattgtaaaccta
gagattatcaactaggtgaacagattggcataatagtcaatactacactggaagtcat
ctcattccactgaggtattatataattcaaggagaatatgataaaacactgccctcag
tggtgcattgaaagaagagatgagaaatgatgaaaaggagcctgaaaaatgggagaca
gcctcttacttgccaagaaaatgaagggattggaccgagctggaaaacctcattacca
gatgctgactggcactggtggtattgctctcgacatatccacaatagctgacggctgg
gtgatcagtagcaaaatattagagcatcatatcactgcaattagtgta 16 201479_at
ttcagacccagtaactgtccgcagctgtctgctagtggagtcttaacatcgtagtcct
agtagcattattaaatcccctctgtttaaaaggtagtaaaacaaaaacaaaaaactaa
gtctgctcagtgaaatgctgtagaaccctaaataagtggtagaagagtgtcactgaat
tttgtctctgaattcagtataactgagttttgtccatgctggtgtctgggttataggc
ctgatgggcctggtagattccatcttgactggcctagaggtcagtcattgcacttcct
caaagatgtgtacagtgctcacctaaatccatctgactacttgacctgtgccctcttg
attaggcctcgatactataaaaaatgaaattgacattgctgggagaagaatgagtaat
tatacttattaaagtcaacttgttaagttttttatgtattcctgttgggttttcttgt tg 17
201506_at
acaggaggaatgcaccacggcagctctccgccaatactctcagataccacagagactg
atgaatgattcaaaaccaagtatcacactttaatgtacatgggccgcaccataatgag
atgtgagccagtgcatgtgggggaggagggagagagatgtactattaaatcatgaccc
cctaaacatggctgttaacccactgcatgcagaaacttggatgtcactgcctgacatt
cacttccagagaggacctatcccaaatgtggaattgactgcctatgccaagtccctgg
aaaaggagcttcagtattgtggggctcataaaacatgaatcaagcaatccagcctcat
gggaagtcctggcacagtattgtaaagccatgcacagctggagaaatggcatcattat
aagctatgagttgaaatgactgtcaaatgtgtctcacatctacacgtggcttggaggc
attatggggccctgtccaggtagaaaagaaatggtatgtagagcttagatttccctat
tgtgacagagcc 18 201563_at
aggaaactgctacttgtggacctcaccagagaccaggagggtttggttagctcacagg
acttcccccaccccagaagattagcatcccatactagactcatactcaactcaactag
gctcatactcaattgatggttattagacaattccatactactggttattataaacaga
aaatctacctcactcattaccagtaaaggctatggtatattctgaggaatgatttcta
tgaacttgtcttatataatggtgggattattctggtaagatttagacctaaatcgcat
catgccaacttgtgactagagactattcatcaagaatgaggatatagtagccatgaca
tagcttgagctatagcattaattccttactaggctatgggtggagggtgagatgaaga
ggttctgattttcttgtaacctggga 19 201577_at
gattccgccttgaggtctgaaattcatgcaagatccgaagatcactcaaggaacacta
cgttgacctgaaggaccgtccattattgccggcctggtgaaatacatgcactcagggc
cggtagagccatggtctgggaggggctgaatgtggtgaagacgggccgagtcatgctc
ggggagaccaaccctgcagactccaagcctgggaccatccgtggagacactgcataca
agaggcaggaacattatacatggcagtgattctgtggagagtgcagagaaggagatcg
gcagtggatcaccctgaggaactggtagattacacgagctgtgctcagaactggatct
atgaatgacaggagggcagaccacattgatttcacatccatttcccctccacccatgg
gcagaggaccaggctgtaggaaatctagttatttacaggaacttcatcataataggag
ggaagctcttggagctgtgagttctccctgtacagtgttaccatc 20 201601_x_at
agaaaaccacacactcataccacactcaacacttcatccccaaagccagaagatgcac
aaggaggaacatgaggtggctgtgctgggggcaccccccagcaccatccttccaaggt
ccaccgtgattaacatccacagcgagacctccgtgcccgaccatgtcgtctggtccct
gacaacaccctcacttgaactggtgctgtctgggcttcatagcattcgcctactccgt
aaagtctagggacaggaagatggaggcgacgtgaccggggcccaggcctatgcctcca
ccgccaagtgcctgaacatctgggccctgattctgggcatcctcatgaccattggatt
catcctgttactggtattcggctctgtaacagtctaccatattatgaacagataatac
aggaaaaacggggttactagtagccgcccatagcctgcaaccatgcactccactgtgc
aatgctggcc 21 201656_at
gtagtgccactgagattggggggggctattactattccggaaaatccttaaaccttaa
gatactaaggacgttgattggttgtacttggaattcttagtcacaaaatatattagat
acaaaaatactgtaaaacaggttataacagtgataaagtctcagatcttgatggggaa
cttgtgtccctaatgtgttagattgctagattgctaaggagctgatacttgacagtta
ttagacctgtgaactaaaaaaaagatgaatgtcggaaaagggtgagggagggtggtca
acaaagaaacaaagatgttatggtgatagacttatggagttaaaaatgtcatctcaag
tcaagtcactggtctgatgcatttgatacatttagtactaactagcattgtaaaatta
tttcatgattagaaattacctgtggatatagtataaaagtgtgaaataaattattata
aaagtgacattgatcgtaacacagcatt 22 201666_at
tcagggccaagttcgtggggacaccagaagtcaaccagaccaccttataccagcgtta
tgagatcaagatgaccaagatgtataaagggaccaagccttaggggatgccgctgaca
tccggacgtctacacccccgccatggagagtgtctgcggatacttccacaggtcccac
aaccgcagcgaggagtactcattgctggaaaactgcaggatggactatgcacatcact
acctgcagatcgtggctccctggaacagcctgagcttagctcagcgccggggcttcac
caagacctacactgaggctgtgaggaatgcacagtgatccctgatatccatcccctgc
aaactgcagagtggcactcattgatgtggacggacc 23 201925_s_at
gtgattataccacaagatctgtaatgttatttccacttataaaggaaataaaaaatga
aaaacattatttggatatcaaaagcaaataaaaacccaattcagtctcactaagcaaa
attgctaaagagagatgaaccacattataaagtaatctaggctgtaaggcattacata
ttcatcgggaggcaaaatatataaaggtaaaacatgctggtgaaccaggggtgagatg
gtgataagggaggaatatagaatgaaagactgaatatcattgagcacaaatagagtag
gaaaaagcctgtgaaaggtgtatattgacttaatgtattaaaagtatccagagatact
acaatattaacataagaaaagattatatattatactgaatcgagatgtccatagtcaa atttgtaa
24 201926_s_at
gagagcactctatttattgtactgtgaataatgatgaaggagagtggagtggcccacc
acctgaatgcagaggaaaatctctaacttccaaggtcccaccaacagttcagaaacct
accacagtaaatgaccaactacagaagtctcaccaacttctcagaaaaccaccacaaa
aaccaccacaccaaatgctcaagcaacacggagtacacctgatccaggacaaccaagc
attacatgaaacaaccccaaataaaggaagtggaaccacttcaggtactacccgtcac
tatctgggcacacgtgatcacgttgacaggatgcagggacgctagtaaccatgggctt
gctgacttagccaaagaagagttaagaagaaaatacacacaagtatacagactgttcc
tagtttcttagactta 25 202286_s_at
gtatgacaacccgggatcgtagcaagtaactgaatccattgcgacattgtgaaggctt
aaatgagatagatgggaaatagcgagttatcgccagggataaattatttgatgagacc
acttgtatcatggcctacccgaggagaagaggagtagttaactgggcctatgtagtag
cctcatttaccatcgtagtattactgaccacatatgatgtcactgggaaagaagcctg
atcagctgcctgaacgcagtaggatgtattgaggacagacattgcccggaaactcagt
ctatttattatcagcttgccc 26 202310_s_at
tggcctacatggaccagcagactggcaacctcaagaaggccctgctcctccagggctc
caacgagatcgagatccgcgccgagggcaacagccgcttcacctacagcgtcactgtc
gatggctgcacgagtcacaccggagcctggggcaagacagtgattgaatacaaaacca
ccaagacctcccgcctgcccatcatcgatgtggcccccaggacgaggtgccccagacc
aggaattcggcttcgacgaggccctgtctgatcctgtaaactccctccatcccaacct
ggctccctcccacccaaccaactttccccccaacccggaaacagacaagcaacccaaa
ctgaaccccctcaaaagccaaaaaatgggagacaatttcacatggactaggaaaatat
tatttcattgcattcatctctcaaacttagatttatattgaccaaccgaacatgacca 27
202311_s_at
gctccccattatataccaaaggtgctacatctatgtgatgggtggggtggggagggaa
tcactggtgctatagaaattgagatgcccccccaggccagcaaatgaccatttgacaa
agtctattatattccagatattattntantattattattagtggatggggacttgtga
atttactaaaggtgctatttaacatgggaggagagcgtgtgcggctccagcccagccc
gctgctcacatccaccctctctccacctgcctctggatctcaggcctctgctctccga
cctctctcctctgaaaccctcctccacagctgcagcccatcctcccggctccctccta
gtctgtcctgcgtcctctgtccccgggtttcagagacaacttcccaaagcacaaagca
gtttttncccctaggggtgggaggaagcaaaagactctgtacctattttgt
28 202403_s_at
aacctgaaaacatcccagccaagaactggtataggagctccaaggacaagaaacacgt
ctggctaggagaaactatcaatgctggcagccagatgaatataatgtagaaggagtga
cttccaaggaaatggctacccaacttgcatcatgcgcctgctggccaactatgcctct
cagaacatcacctaccactgcaagaacagcattgcatacatggatgaggagactggca
acctgaaaaaggctgtcattctacagggctctaatgatgagaacttgagctgagggca
acagcaggttcacttacactgacttgtagatggctgctctaaaaagacaaatgaatgg
ggaaagacaatcattgaatacaaaacaaataagccatcacgcctgcccaccttgatat
tgcacctaggacatcggtggtgctgaccaggaattctagtggacattggcccagtctg a 29
202404_s_at
actacccatgagtgtgatccacattgttaggtgctgacctagacagagatgaactgag
gtccttgattgattgacataatacaaaggtgctaattaatagtatttcagatacttga
agaatgagatggtgctagaagaatttgagaagaaatactcctgtattgagagtatcgt
gtggtgtattattaaaaaatttgatttagcattcatattaccatcttattcccaatta
aaagtatgcagattatttgcccaaagagtcctatatcagattcagcatttgactagcc
agtctcattacatatatccatggaccacagaagctagtttcttgggca 30 202431_s_at
gcaacaaccgaaaatgcaccagccccaggtcctcggacaccgaggagaatgtcaagag
gcgaacacacaacgtcttggagcgccagaggaggaacgagctaaaacggagcttattg
ccctgcgtgaccagatcccggagaggaaaacaatgaaaaggcccccaaggtagttatc
cttaaaaaagccacagcatacatcctgtccgtccaagcagaggagcaaaagctcatac
tgaagaggacttgagcggaaacgacgagaacagttgaaacacaaacttgaacagctac
ggaactcagtgcgtaaggaaaagtaaggaaaacgattccactaacagaaatgtcctga
gcaatcacctatgaacttgatcaaatgcatgatcaaatgcaacctcacaaccttggct gagtc 31
202504_at
ggaaacctctcagtgtcttgacatcaccctacccaggcggtgggtctccaccacagcc
actttgagtctgtggtccctggagggtggcactcctgactggcaggatgaccttagcc
aagatattcctctgaccctctgctgagataaagaattcccttaacatgatataatcca
cccatgcaaatagctactggcccagctaccatttaccatttgcctacagaatttcatt
cagtctacactttggcattctctctggcgatggagtgtggctgggctgaccgcaaaag
gtgccttacacactgcccccaccctcagccgagccccatcagaggctgcctcctccac
tgattaccccccatgagcatatcaggg 32 202718_at
atccccaactgtgacaagcatggcctgtacaacctcaaacagtgcaagatgtctctga
acgggcagcgtggggagtgctggtgtgtgaaccccaacaccgggaagctgatccaggg
agcccccaccatccggggggaccccgagtgtcatctcttctacaatgagcagcaggag
gcttgcggggtgcacacccagcggatgcagtagaccgcagccagccggtgcctggcgc
ccctgccccccgcccctctccaaacaccggcagaaaacggagagtgcttgggtggtg 33
202779_s_at
ccgaacgtgggcgccaatggcgagatctgcgtcaacgtgctcaagagggactggacgg
ctgagctgggcatccgacacgtactgctgaccatcaagtgcctgctgatccaccctaa
ccccgagtctgcactcaacgaggaggcgggccgcctgctcaggagaactacgaggagt
atgcggctcgggcccgtctgctcacagagatccacgg 34 202831_at
ctacccttatgatgacccattaccctcatgaccgatcccaagctcatcataggagccc
tgtgcgccgctcagatgtggcctggaactagagaagacctcatagggccggagggaga
gccatccgacgctacagccgcaccacccaaccatcaacattgagcctgacatcaagcg
cctccttaaagttgccatatagatgtgaactgctcaacacacagatctcctactccat
ccagtcctgaggagccttaggatgcagcatgccttcaggagacactgctggacctcag
cattcccttgatatcagtccccttcactgcagagccttgcctttcccctctgcctgtt
tccttttcctctcccaaccctctggttggtgattcaacttgggctccaagacttgggt
aagctctgggccttcacagaatgatggcaccttcctaaaccctcatgggtgg 35 202833_s_at
gaagcgataggcatgataacatccagcactgtaagaagctgtccagctgggtactgct
aatgaaatacctgggcaatgccaccgccatatcacctacctgatgaggggaaactaca
gcacctggaaaatgaactcacccacgatatcatcaccaagttcctggaaaatgaagac
agaaggtctgccagcttacatttacccaaactgtccattactggaa 36 202859_x_at
gtacccagttaaattacatttcagataaacaacaaataattattagtataagtacatt
attgatatctgaaagattaattgaactaacaatcctagatgatactcccagtcagtca
ttgccagctgtgaggtagtgctgtgagaattacggaataatgagttagaactattaaa
acagccaaaactccacagtcaatattagtaatacttgctggagaaacttgatattatg
tacaaatagattcttataatattatttaaatgactgcattataaatacaaggattata
ttataacataagatgatttatgtgctctccaaattatatactgtttctgattgtat 37
202935_s_at
gagaggaccaaccagaattccctaggacatagtgatattgattatattagattgatta
cttatatatatccttaaagacatttaagctaaaggcaactcgtacccaaatttccaag
acacaaacatgacctatccaagcgcattacccacttgtggccaatcagtggccaggcc
aaccaggctaaatggagcagcgaaatcaacgagaaactggactattaaaccctcacag
agcaagcgtggaggatgatggagaatcgtgtgatcagtgtgctaaatctctctgcctg
taggactagtaattattatttagcagtaattaaagaaaaaagtcctctgtgaggaata
ttctctatataaatattatagtatgtactgtgtatgattcattaccattagaggggat
ttatacatattatagataaaattaaatgctcttattatccaacagctaaactactctt
agttgaacagtgtgccctagcttttcttgcaaccagagta 38 202936_s_at
gtagtgtatcactgagtcatttgcagtgattctgccacagacctagggctgccttata
ttgtgtgtgtgtgtgggtgtgtgtgtgattgacacaaaaacaatgcaagcatgtgtca
tccatatactctacatcactcaggagtgagggaggctacctggaggggatcagcccac
tgacagaccttaatcttaattactgctgtggctagagagatgaggattgctattaaaa
aagacagcaaacttattattatttaaaaaaagatatattaacagattagaagtcagta
gaataaaatcttaaagcactcataatatggcatccttcaatactgtataaaagcagat
catttaaaaaagatacttctgtaacttaagaaacctggcatttaaatcatattagtat
taggtaaaagctaggtagtgacgtgattgatgatcacttgatccctcccagccccaaa
ccattgactctccgtgaaacttaccttt 39 202954_at
gccaccctgaatcagacaaccattcaaatgggtagggaccatccatggagcagctgga
acagtatatgaagacctgaggtataagctctcgctagagttccccagtggctaccctt
acaatgcgcccacagtgaagttcctcacgccctgctatcaccccaacgtggacaccca
gggtaacatatgcctggacatcctgaaggaaaagtggtctgccctgtatgatgtcagg
accattctgctctccatccagagccactaggagaacccaacattgatagtcccttgaa
cacacatgctgccgagctctggaaaaaccccacagatttaagaagtacctgcaagaaa
cctactcaaagcaggtcaccagccaggagccctgacccaggctgcccagcctgtcctt
gtgtcgtctttttaatttttccttagatggtctgtcctttttgtgattt 40 202998_s_at
gccagtcttgaccgggatgaggcccacagacaggagtcatcagatgtcccattcaagc
caccgagctcaccacagacacagtggagccgcgctcactccagtgacacgtggacaaa
tgcgggctcatcagcccccccagagagggtcaggccgaaccccatactcctcctctta
ggtcattacagcaaacttgaatatctagacctctatccaatgaaaccctccagtctat
tatagtcacatagataatggtgccacgtgattctgataggtgagctcagacttggtga
tccctctccacaacccccaccccttgtttttcaagatactattattatattacacaga
cattgaagcacaaatttattggcatttaatattggacatctgggcccaggaagtacaa
atctaaggaaaaaccaacccactgtgtaagtgactcatcacctgagaccaattctgtg
ggtattgattcaacggtgctataaccagggtcctgggtgacagggcgctcactgagca
ccatgtgtcatcacagaca 41 203083_at
caggaaatagtcactcatcccactccacataaggggatagtaagagaagtctgtctgt
ctgatgatggatagggggcaaatattacccctactgttaatagtcatcacatttctat
gccaaacaggaacgatccataactttagtcttaatgtacacattgcaattgataaaat
taattagttgatcattgaggagatcgagtgagattgctgcactattacttattgcgtg
tggagctgtattcccgagacaacgaagcgagggatacttcattaaatgtagcgactgt
caacagcgtgcaggattctgatctgtgagtggggtcaaccgtacaatggtgtgggaat
gacgatgatgtgaatatttagaatgtaccatattattgtaaattatttatgatactaa
acaaatttatcgtataggagatgaaacgtcatgtgattgccaaagactgtaaatattt
atttatgtgacacatggtcaaaatttcaccactgaaaccctgcacttagctagaacct 42
203124_s_at
atggtaacatgtatattgccctgggtctgggtgggtccagtcagtctcagatttacaa
gcatttaggagcctaggtaaaagctgctagtattcattaaaagttatatttatgactt
gcaatgatagaaaactccaccaattaaatggcatatataatattatgtgtgtacttca
cagtgttaaaaataccctcatacgttattgcatttgatatcacagaaagtgcatataa
ccagtactctgggtgcaataaataatatgtagaaatttaagtcctccaattccagcat
atccagtgagattgacagtgtgatatgtggaatgataaggatatacaattgtacttta
tataaattggacttgacacttaaatgtgacatgaaataattgtgctgctacattatac
tggaaattaacaggggaaaagggaagagctcaggctcccttgaggactgctagtggtg
ttaggagtggttacaactgagatttagtaaccatttaaccg 43 203213_at
tgctaagttcaagatcgtaatgattgaagtattatatgctctgaatgataaatgactc
atcagatcttgccatgagttaactatacaacctggctaaagatgaatatttactactg
gtatataatattgacctaaatgataagcattcggaatgagaaaactatacagatttga
gaaatgatgctaaatttataggagattcagtaacttaaaaagctaacatgagagcatg
ccaaaatttgctaagtcttacaaagatcaagggctgtccgcaacagggaagaacagat
tgaaaatttatgaactatcttattataggtaggattgaaagctattgtctaagtgaat
tcttatgccaggtcagagtaataactgaaggagntgcttatcaggattcgagtctgag
tttaaaactacacattttgacatagtgtttattagcagccatc 44 203256_at
gtggccgtagcaacttggcggagacaggctatgagtctgacgttagagtggagatcct
tagccatcaggatggaggaatgtgggcagatgacttcagcactgaaaacctctccacc
tgggccagggagcctcagaggccaagtaccagaagcctcttacctgccgtaaaatgct
caaccctgtgtcctgggcctgggcctgctgtgactgacctacagtggactactctctg
gaatggaaccttcttaggcctcctggtgcaacttaatttttttttttaatgctatctt
caaaacgttagagaaagttcttcaaaagtgcagcccagagctgctgggcccactggcc
gtcctgcatactggtaccagaccccaatgcctcccattcggatggatctctgcgtatt
atactgagtgtgcctaggagccccttattattattaccctgagcgttgctatagatg 45
203313_s_at
agagtggtcattcaacactcctccccctactccaccggacctcaaccaggacttcagt
ggatttcagatctagtggatgagcactcaaacgggctgcagagatggagcttcaggca
aaacttacagcttaacccattacaagcaaaacagactcagaaatgtcatgattgccgg
ggtgaaggcaagagatgaattgcattatatatatattattattaatatttgcacatgg
gattgctaaaacagatcctgttactgagatgtatcaatggaatacagtcattccaaga
actataaacttaaagctactgtagaaacaaagggattcttattaaatgatcaggtaga
ttattcataatgtgagatggacccaatatcatgtgattatttattcctcccatccctt
tattgttattattcagactgtgcaatacttagagaacctatagcatcactcattccca
tgtggaacaggatgcccacatactgtctaatta 46 203510_at
gaagccaagggttaacccagcaagctacaaagagggtgtgtcacactgaaactcaata
gttgagtaggctgagagcaggaaaatgattataactaaaagctctctgatagtgcaga
gacttaccagaagacacaaggaattgtactgaagagctattacaatccaaatattgcc
gatcataaatgtaataagtaatactaattcacagagtattgtaaatggtggatgacaa
aagaaaatctgctctgtggaaagaaagaactgtctctaccagggtcaagagcatgaac
gcatcaatagaaagaactcggggaaacatcccatcaacaggactacacacttgtatat
acattcttgagaacactgcaatgtgaaaatcacgtagctatttataaacttgtcctta
gattaatgtgtctggacagattgtgggagtaagtgattcactaagaattagatacttg
tcactgcctatacctgcagctgaactgaatggtacttcgtatg 47 203860_at
gaagcaggtggaaacatgagcattcagatcaggtacagtgtacaaggtgaatatctta
accagacttgccgcagaattgaacaaatttatgctggaaaaagtgactgaggacacaa
gcagtgactgcgaccccgatgcccggagtggtggtggccgtctctgtcaagcctggag
acgcggtagcagaaggtcaagaaatagtgtgattgaagccatgaaaatgcagaatagt
atgacagctgggaaaactggcacggtgaaatctgtgcactgtcaagctggagacacag
aggagaaggggatctgctcgtggagctggaatgaaggatttataaccatcagtcatca
cccaatttaattagccatttgcatgatgattcacacacaattgattcaagcattatac
aggaacacccctgtgcagctacgtttacgtcgtcatttattccacagagtcaagacca
atattctgccaaaaaatcaccaatggaaattttcatgatataaatacttgtactatag
atgtacttctgctgtg 48 203878_s_at
tgccagcgactgtctcagactgggcagggaggctaggcatgacttaagaggaagggca
gtcagggacccgctatgcaggtcctggcaaacctggctgccctgtctcatccctgtcc
ctcagggtagcaccatggcaggactgggggaactggagtgtccttgctgtatccctgt
tgtgaggttccttccaggggctggcactgaagcaagggtgctggggccccatggcctt
cagccctggctgagcaactgggctgtagggcagggccacttcctgaggtcaggtcttg
gtaggtgcctgcatctgtctgccttctggctgacaatcctggaaatctgactccagaa
tccaggccaaaaagttcacagtcaaatggggaggggtattatcatgcaggagacccca
ggccctggaggctgcaacatacctcaatcctgtcccaggccggatcctcctgaagccc
attcgcagcactgctatcctccaaagccattgtaaatgtgtgtacagtgtgtataaac
cttcttcttctt 49 203895_at
gactaatccatacacagttaacctaatgccaaataaatactggttaaataaatgtatg
gcacagaatataatttgactatcaagacattagcataatgaaaaaccctctctctata
tatatatgtgtatatgaattatgtgggcattcttgatacttcaagactagatgaaaaa
aatacataactaatttaatatacacaaaaatatttatgcagattacagaatttcatat
caggaaatgaccatttatgtctgttaaatatcaaaacaatttgctacagtgttaatct
gcatggtattaagcctgctgtagttgagagcagacagtgcatgaaaaagtattccgct
gggaattgagccatgccaccaaagccaagaggagcgcatggaaacccggtagtctaga
actaatcagattactgatatagggcacagcaccagatgaattgagtatatgatgtaaa
aattgattctgtgtgacctctgaacaaagcgg 50 203896_s_at
gtccagcttgaacatctagaattcctagagaaacagaatgagcaggcgaaggagatgc
agcagatggtgaaattggaagccgagatggaccgcagaccagcaacagtagtatgaaa
ctccaaaatgcaaactgaagcagcaaacccacaaagcatcaaaagactcactcacaaa
acactgaacacaaactccatggatgaaagctgatattagatcattatgtgtaaacaag
atgatatctgaaaccagagagacttggaatgtctgactgacactatttaacagcttga
gtattgcatttccaggccaaacaaaaatagctacaaatccacaaaaatttactattcc
agtaaggcagagtccaaccattgataatacaacttaaacatgatgctataaaatacca
tcacaagtaaatgagcttggtgtgaacaactcttcctttgtgatgccttagg 51 203961_at
ggactagagcaacatcgtgctgcccaaaggactaacctatgcaaactagttcacatat
agtggatgtcgcagttaatgtgtaataagacattatacccctgcataatgtacaacag
cattgaaatgacacattaagcctagcatcacattgtatagtacagtcactcacaaacc
atcaaggctaccctaatcattaacattaatatttgataaaagcaaatcaccgatttat
ctattgaaactacttaaatgacggcaaaccaggaatgacagatggctgtgtcagcaat
ggattaatgtgaccctgcaagtggtctcctatgantagaactgcgactcaaatgcact
ctatcagggtcttaatattctgtgattctctctgtatagtaaaacattataacacatt
aatacctatctctacacatagg 52 203962_s_at
gtcaaggcattgtatgagatctgtggttattattctgtgatgcttagactacttgaac
ccataaacttggaagaatattgagcaaattactcagagtctgtatgacttcagtatat
tcctgggaatgccataggattattgtgcttgatacatggtatccagtagcatagtatc
acactagtaatccagagctgttaagaatgatgtactttaaaggaaaagagaaaactgc
atcacagtcccattctccagtgtccatgcaatgaattgctgagcatttaggaagcagc
accaagtctattacaggcatggtgtgaaacttgatgatgacctgtgatcaaaattgaa
ccattgtacagtaggcactgatgcttcaaaatatgtagaattgtggagatgattaatt
tgcgagactaactagagagtgtaacagattgaagaaaacattgaatgattacaaatga
aggggcttcacggaatgttacaa 53 204051_s_at
aaccagccagtcccaagaagaacattaaaactaggagtgcccagaagagaacaaaccc
gaaaagagtgtgagctaactagtaccaaagcggagacttccgacttccttacaggatg
aggctgggcattgcctgggacagcctatgtaaggccatgtgcccatgccctaacaact
cactgcagtgctatcatagacacatcttgcagcattatcttaaggctatgcttcagat
ttattgtaagccatcacaagccatagtggtaggtttgccctttggtacagaag 54 204127_at
agtgattgtcattagctctgccatataattaaatattaggacatggaccaaagggata
cttgacaaatttgtgtgacagactccgaacaattcattactacgaagtataatttata
aaataaaatatacccatataagggtacagatgatattgaccagtgaaactatgatccc
aatcaaggtatagatgccgtcaccccaaaaagaccctccatatccattgcagtcagtt
catccctaccctggcccagatgatcactgatcagtcattatagatgagattgccagtt
caagaatttaatggaatcagatattgtaagcattcagtgtaatacttcattctctctc
attattgagattcatccatattgagaatgatcactagttaatgatattgacaatattt
agtatatacttttaaagcctattcacttgctgatggatctt 55 204170_s_at
cgctctcgatcattactgcagcgcgccacgaggatggcccacaagcagatctactact
cggacaagtacttcgacgaacactacgagtaccggcatgttatgttacccagagaact
accaaacaagtacctaaaactcatctgatgtctgaagaggagtggaggagacttggtg
tccaacagagtctaggctgggacattacatgattcatgagccagaaccacatattatc
tattagacgacctcaccaaaagatcaacaaaaatgaagatatctggggatcgtcaaat
attacaaatttaatgtatatgtgtatataaggtagtattcagtgaatacttgagaaat
gtacaaatattcatccatacctgtgcatgagctgtattatcacagcaacagagctcag
ttaaatgcaactgcaagtaggttactgtaagatgataagataaaagttcaccagtcag
atttctcttaagtgcct 56 204259_at
ctcatggggactcctacccatttgatgggccaggaaacacgctggctcatgcattgcg
cctgggacaggtctcggaggagatgctcacttcgatgaggatgaacgctggacggatg
gtagcagtctagggattaacttcctgtatgctgcaactcatgaacttggccattctag
ggtatgggacattcctctgatcctaatgcagtgatgtatccaacctatggaaatggag
atccccaaaatataaactacccaggatgatattaaaggcattcagaaactatatggaa
agagaagtaattcaagaaagaaatagaaacacaggcagaacatccattcattcattca
ttggattgtatatcattgagcacaatcagaattgataagcactgacctccactccatt
tagcaattatgtcacccttattattgcagaggtattgaatgtattcactcatttattg
gttaaactcattatggtgtgactgtgtcttattccatctatgagctttgtcagtgcgc gtagatgt
57 204320_at
gaaaatgtaccaggtgccaccaacccattagtgccacatgcaagattgaataaggatg
tatggaaaacaacgctgcatatacaggtaccatttaggaaataccgatgcctagtggg
ggcagaatcacagacaaaagctagaaaatcataaagatataagttggtgtggctaaga
tggaaacagggctgattcttgattcccaattctcaactctccttttcctatttgaatt
tctttggtgctgtagaaaacaaaaaaagaaaaatatatattcataaaaaatatggtgc
tcattctcatccatccaggatgtactaaaacagtgtgataataaattgtaattattag
tgtacagactatactgttatctgtgtccataccaaaacttgcacgtgtccctgaattc
cgctgactctaatttatgaggatgccgaactctgatggcaataatatatgtattatga
aaatgaagttatgataccgatgaccctaagtcc 58 204351_at
gggtctgaatctagcaccatgacggaactagagacagccatgggcatgatcatagacg
tatacccgatattcgggcagcgagggcagcacgcagaccctgaccaagggggagctca
aggtgctgatggagaaggagctaccaggcacctgcagagtggaaaagacaaggatgcc
gtggataaattgctcaaggacctggacgccaatggagatgcccaggtggacttcagtg
agttcatcgtgacgtggctgcaatcacgtctgcctgtcacaagtactagagaaggcag
gactcaaatgatgccctggagatgtcacagattcctgcagagccatggtcccaggcac
ccaaaagtgatgaggcaattattcccctaggctgagcctgctcatgtacc 59 204401_at
gtagctggacccacgaggaggaaccaggctactaccccagtactgaggtggtggacat
cgtctctgccactcctgacccagccctgaacaaagcacctcaagtgcaaggaccaaag
ggggccctggcaggagtgggaggcttgctgatggctgctggaggggacgctggctaaa
gtgggtaggccttggcccacctgaggccccaggtgggaacatggtcacccccactctg
cataccctcatcaaaaacactctcactatgctgctatggacgacctccagctctcagt
tacaagtgcaggcgactggaggcaggactcctgggtccctgggaaagagggtactagg
ggcccggatccaggattctgggaggcttcagttaccgctggccgagctgaagaactgg
gtatgaggctggggcggggctggaggtggcgccccctggtgggacaacaaagaggaca
ccatttttccagagctgc 60 204404_at
agaccaagacataccggcagatcaggttaaatgagttattaaaggaacattcaagcac
agctaatattattgtcatgagtctcccagagcacgaaaaggtgctgtgtctagtgctc
tctacatggcatggttagaagctctatctaaggacctaccaccaatcctcctagttcg
tgggaatcatcagagtgtccttaccactattcataaatgactatacagtggacagccc
tccagaatggtacttcagtgcctagtgtagtaacctgaaatatcaatgacacattaac
atcacaatggcgaatggtgacattattcacgatttcattaatttgaaagcacacagga
aagcttgctccattgataacgtgtatggagacttcggattagtcaattccatatc 61
204470_at
tatgattaactctacctgcacactgtcctattatattcattctattgaaatgtcaacc
ccaagttagttcaatctggattcatatttaatttgaaggtagaatgattcaaatgact
ccagtcattatgttaatatactgaggagcctgcaacatgccagccactgtgatagagg
ctggcggatccaagcaaatggccaatgagatcattgtgaaggcaggggaatgtatgtg
cacatctgattgtaactgatagatgaatgtcagagttatttattgaaatgatttcaca
gtgtgtggtcaacatactcatgagaaactttaagaactaaaatgactaaatatcccag
gacatatatgtattcagtaaggcatactgccttgataatggtagattacagtgatctg
gcttagaaca 62 204475_at
gaagaactgtctattactcagtcattataacctctagagtcactgatacacagaatat
aatcttatttatacctcagtagcataattatactatttagaatgtagccattagtact
gatataatttagaccacaaatggtgggtacaaaaagtcaagtagtggcttatggattc
atataggccagagagcaaagatcattccagagtatgcaactctgacgttgatcccaga
gagcagcttcagtgacaaacatatcattcaagacagaaagagacaggagacatgagta
ttgccggaggaaaagcagctcaagaacacatgtgcagtcactggtgtcaccctggata
ggcaagggataactcactaacaca 63 204580_at
agatgatggaccctggttatcccaaactgattaccaagaacttccaaggaatcgggcc
taaaattgatgcagtcactattctaaaaacaaatactactatttcaccaaggatctaa
ccaatttgaatatgacttcctactccaacgtatcaccaaaacactgaaaagcaatagc
tggtaggagttagaaatggtgtaattaatggtattgttagttcacttcagcttaataa
gtatttattgcatatttgctatgtcctcagtgtaccactacttagagatatgtatcat
aaaaataaaatctgtaaaccataggtaatgattatataaaatacataatattatcaat
tagaaaactctaattgtccattatgcttgactctactattaagatgaaaatagttacc
acaaagcaagataattctatttgaagcatgctctgtaagttgatcctaacatccagga
ctgagaaattatacttacactggcataactaaa 64 204620_s_at
tgccgtgctcccaaaacatataaatgaaagtattggcattcaaaaagacagcagacaa
aatgaaagaaaatgagagcagaaagtaagcataccagcctatctaatttattagattc
tatttgcctccagtgcagtccatacctaatgtataccagcctactgtactatttaaaa
tgctcaatttcagcaccgatggccatgtaaataagatgatttaatgagatataatcct
gtatataaaataaaaagtcacaatgagtagggcatatttaatgatgattatggagcct
tagaggtattaatcattggacggctgatttatgtagataggctggaaatggatcactt
gctattgactgtcagcaagactgaagatggcattcctggacagctagaaaacacaaaa
tcagtaggtcattgcacctatctcagccataggtgcagatgatctacatgatgctaaa
ggctgcgaatgggatcctgatggaactaaggactccaatgtcgaactcttctttgctg c 65
204702_s_at
tgctctccagtgtacccatgatggaagtatcttgatagtacccaaagaactggtggcc
tcaggccacaaaaaggaaacccaaaagggaaagagaaagtgagaagaaactgaagatg
gactctattatgtgaagtagtaatgacagaaactgattatttggatcagaaaccattg
aaactgcttcaagaattgtatattaagtactgctacttgaataactcagttaacgctg
attgaagcttacatggacaaatgataggacttcaagatcacacttgtgggcaatctgg
gggagccacaactatcatgaagtgcattgtatacaaaattcatagttatgtccaaaga
ataggttaacatgaaaacccagtaagactaccatcaggcagccatccatttaagagta
agaggttacttcaaaaagagcaaacactggggatcaaattatataagaggtatttcag
attaaatgcaaaatagccttattttcatttagtttgttagcactatagtgagcttttc
aaacactattttaatc 66 204855_at
cacgttcgcagagatttcagattgtggaatgaggataaggaattatagacctctagta
gctgaaatgcaagaccccaagaggaagttcagatcttaatataaattcactacatatt
gatagctgtcccatctggtcatgtggaggcactagactggtggcaggggcactagctg
actcgcacagggattctcacaatagccgatatcagaatagtgagaaggaacttgtcta
tcatctaatatgatagcgggaaaaggagaggaaactactgcattagaaaatataagta
aagtgattaaagtgctcacgttaccttgacacatagtattcagtctatgggatagtta
ctttagatggcaagcatgtaacttatattaatagtaatagtaaagagggtggataagc
tatccctgagccggacatggattacttctctataaaaaatatatatttaccaaaaaat
tagtgacattccactcccatctcttccttgacatgcattgtaaataggttcttcttgt tctgag
67 204885_s_at
taccagaacatgaacgggtccgaatacttcgtgaagatccagtccacctgggtggggc
ccccacggaggatttgaaggcgctcagtcagcagaatgtgagcatggacttggccacg
ttcatgaagctgcggacggatgcggtgctgccgttgactgtggctgaggt 68 205174_s_at
gtctggcacaccatggatgacaatgaagaaaataggatgaatcaaccattgacaatct
aaacaaaatcctacaagtattgtgaggaatatatcatagtaatactctgatttagata
ggataattggactagaattgaattcaaaagtcaaggcatcatttaaaataatctgatt
tcagacaaatgctgtgtggaaacatctatcctatagatcatcctattcttatgtgtct
aggttatcagatcaattacagaataattgtgagtgatattgtgtcctaaattgctcat
taatattatttacagattgaaaaagaggcaccgtgtaaagaaaatggcaaaataaata
tctaccaaggatcatcatcacgatagctaaacagtacttaaatagcggaggaactagg
tagcattcgaatatatgattattcatatgtggaaatctattacatgtaatacaaaaca
aacatgtagatgaaggcggtcagatttctttgag 69 205361_s_at
aaggcggctgcagaagatgtcaatgttactacgaagatcaacaaaagataaacaaatt
tgcacggaatacaagtagaatcacagagctgaaggaagaaatagaagtaaaaaagaaa
caactccaaaacctagaagatgatgtgatgacatcatgcttgcagatgatgattgctt
aatgataccttatcaaattggtgatgtaatcattagccattctcaagaagaaacgcaa
gaaatgagaagaagcaaagaaaaatttgcaagaagaaattgacgccttagaatccaga
gtggaatcaattcagcgagtgttagcagatttgaaagttcagttgtatgcaaaattcg
ggagcaacataaaccttgaagctg 70 205366_s_at
cctcagcctgatcaggcacctggtgagaactgaggagcggactcacttgatgatcctg
gaagcagagcaaaagactcttgtccctgtcgcgtctcattagtccatgtcccccgtgc
acggttcaatggtagattcgctgtcctcagcgggggccttgaagactccctgatccca
gacctggtcgtctctcccaccccctccccaaagccactggaaggagcacatactacct
agaagtaagaagaggagcctcagaagaaaacaaagactatatattaattactatgtga
gtgatgtagtatgtcttagctctggacg 71 205470_s_at
gccaacatcaccatcattgagcaccagaagtgtgagaacgcctaccccggcaacatca
cagacaccatggtgtgtgccagcgtgcaggaagggggcaaggactcctgccagggtga
ctccgggggccctctggtctgtaaccagtctcttcaaggcattatctcctggggccag
gatccgtgtgcgatcacccgaaagcctggtgtctacacgaaagtctgcaaatatgtgg
actggatccaggagacgatgaagaacaattagactggacccacccaccacagcccatc
accctccataccacttggtgatggacctgacactctgttaataagaaaccctaagcca
agaccctctacgaacattctagggcctcctggactacaggagatgctgtcacttaata
atcaacctggggacgaaatcagtgagacctggattcaaattctgccttgaaatattgt
gactctgggaatgacaacacctggatgactctgagtatccccagccccaaagacagct
cctggccatatatca 72 205476_at
ttcacacggcagctggccaatgaaggctgtgacatcaatgctatcatattcacacaaa
gaaaaagagtctgtgtgcgcaaatccaaaacagacttgggtgaaatatattgtgcgtc
tcctcagtaaaaaagtcaagaacatgtaaaaactgtggcttttctggaatggaattgg
acatagcccaagaacagaaagaaccagctggggaggaggatcacttgcacatcatgga
gggatagtgcttatctaatagtgcctcactggacttgtccaattaatgaagttgattc
atattgcatcatagtagctagataagcatcacattaaagttaaactgtatatatgtta
tttatagctgtaggattctgtgatagctatttaatactaattaccataagctattagg
atagtgcaaagtataaaattatatagggggggaataagattatatggactacttgcaa gcaacaa
73 205479_s_at
cccgaccggtgggcatagtgaggcccatggagagaaatgaataatttcccaattagga
agtgtaagcagctgaggtctcttgagggagcttagccaatgtgggagcagcggtaggg
gagcagagacactaacgacttcagggcagggctctgataaccatgaatgtatcaggaa
atatatatgtgtgtgtatgatgcacacttgagtgtgggctgtgagtgtaagtgtgagt
aagagctggtgtctgattgttaagtctaaatataccttaaactgtgtggactgtgatg
ccacacagagtggtattctggagaggttataggtcactcctggggcctcagggtcccc
cacgtgacagtgcctgggaatgtacttattctgcagcatgacctgtgaccagcactgt
ctcagatcactacacatagatgtccattcaggccagttatccatccattagcctagtt
catccaatcctcactgggtgggg 74 205513_at
aacaaagactcacttgcgtctctgcttcaggtaacttcaacatctccgctgatgagcc
tataactgtgacacctcctgactcacaatcatatatctccgtcaattactctgtgaga
atcaatgaaacatatttcaccaatgtcactgtgctaaatggactgtcttcctcagtgt
gatggagaaagcccagaaaatgaatgatactatataggatcacaatggaggagcgctc
atgggggccctatatcacctgtattcagggcctatgtgccaacaataatgacagaacc
tactgggaacttctgagtggaggcgaaccactgagccaaggagctggtagttacgagt
ccgcaatggagaaaacttggaggacgctggagcaaatactaataagcccaaactttcc
tcagctgcataaaatccatttgcagtggagttccatgtttattgtccttatgccttct 75
205713_s_at
caaacgtattggcaggcgaacccatccgtgctgtggccgagcctggcatccaactcaa
ggctgtgaagtatccacaggccccggggaacagctgcggaacgctctgtggcatacag
gagacacagagtcccaggtgcggctgctgtggaaggacccgcgaaacgtgggaggaag
gacaagaagtcctatcgaggacctgcagcaccggccccaagtgggctacatcagggtg
cgattctatgagggccctgagctggtggccgacagcaacgtggtcaggacacaaccat
gcggggtggccgcctgggggtcactgatctcccaggagaacatcatctgggccaacct
gcgttaccgctgcaatgacaccatcccagaggactatgagacccatcagctgcggcaa
gcctagggacc 76 205765_at
caccacctacctatgatgccgtggtacagatggagtaccttgacatggtggtgaatga
aacactcagattattcccagagctattagacttgagaggacttgcaagaaagatgaga
aatcaatggggtattcattcccaaagggtcaatggtggtgattccaacttatgctatc
accatgacccaaagtactggacagagcctgaggagaccgccctgaaaggacagtaaga
agaaggacagcatagatccttacatatacacaccctaggaactggacccagaaactgc
attggcatgaggatgctctcatgaacatgaaacttgctctaatcagagtcatcagaac
actcatcaaaccagtaaagaaacacagatccccttgaaattagacacgcaaggactta
tcaaccagaaaaacccattgactaaaggtggattcaagagatggaaccctaagtggag
aatgagttaactaaggacactactaggtatcaagaaagctgtgccccagaacaccaga
gatttcaacttagtca 77 205815_at
tgctatgccagtattgtcaccaaaatcctggacagatgcagatctggcctgccagaag
cggccctctggaaacctggtgtctgtgctcagtggggctgagggatcatcgtgtcctc
cctggtgaagagcattggtaacagctactcatacgtctggattgggctccatgacccc
acacagggcaccgagcccaatggagaaggagggagtggagtagcagtgatgtgatgaa
ttactttgcatgggagagaaatccctccaccatctcaagccccggccactgtgcgagc
ctgtcgagaagcacagcatttctgaggtggaaagattataactgtaatgtgaggttac
cctatgtctgcaagttcactgactagtgcaggagggaagtcagcagcctgtgtaggtg
tgcaactcatcatgggcatgagaccagtgtgaggactcaccctggaagagaatattcg
cttaattcccccaacctgaccacctcattcttatattcactgatcacctccccgctgt
catttcagtctatcattagtc 78 205825_at
taccattcccaatctagtgctagatgtataaatattcattgattcacctaacaaaata
ttactgggttaaaaccccagccaactcattgggagtagccaaaggacactctcaagaa
gattaatatttaaataaaatcatattgaatgatccaacctggagtataatattcagat
ataaaacagttttgtcagtctttcttagtgcctgtgtggatttttgtgaaaatgtcaa
agagaaaacttatatactatacccttgaaatataaactatattactttacaggtattt
ataatataccaatgatttatcaaacagaatataaagagcataataaattatattaaag
aaccaaaagattcctgagaataagaaagatcacccaataaaatatattgaaaggcatg
acctctgtcaatgaaaaaaagtacatgtatgtgagtgatattaaaagtgacatagtct
aatagcctaatacaacatgtagctgagataacatgtgtggtcttg 79 205828_at
gaaaatcgatgcagccatttctgataaggaaaagaacaaaacatatttctttgtagag
gacaaatactggagatttgatgagaagagaaattccatggagccaggctacccaagca
aatagctgaagactaccagggattgactcaaagattgatgctgtattgaagaataggg
actatatttattactggatatcacagaggagatgacccaaatgcaaagaaagtgacac
acactttgaagagtaacagctggcttaattgagaaagagatatgtagaaggcacaata
tgggcactttaaatgaagctaataattcttcacctaagtctctgtgaattgaaatgac
gattctcctgcctgtgctgtgactcgagtcacactcaagggaacttgagcgtgaatct
gtatcttgccggtcattatatgttattacagggcattcaaatgggctgctgcttagct
tgcaccagtcacatagagtgatctttcccaagagaaggggaagcactcgtgtgcaaca gac 80
205886_at
cacccaggcggagggtgccacgtggcctcactgattaaggagagtagcactgatgaca
gcaatgtctggattggcctccatgacccaaaaaagaaccgccgctggcactggagtag
tgggtccctggtctcctacaagtcctgggacactggatccccgagcagtgctaatgct
ggctactgtgcaagcctgacttcatgctcaggattcaagaaatggaaggatgaatcag
tgagaagaagactcattgatgcaagttcaaaaactagaggaagctgaaaaatggatgt
ctagaactggtcctgcaattactatgaagtcaaaaattaaactagactatgtctccaa
ctcagttcagaccatctcctccctaatgagtagcatcgctgatatcagtaccttc 81
205890_s_at
gatcttaaagccacggagaagcctctcatcttatggcattgacaaagagaagaccatc
caccttaccctgaaagtggtgaagcccagtgatgaggagctgcccttgatcagtggag
tcaggtgatgaggcaaagaggcacctcctccaggtgcgaaggtccagctcagtggcac
aagtgaaagcaatgatcgagactaagacgggtataatccctgagacccagattgtgac
ttgcaatggaaagagactggaagatgggaagatgatggcagattacggcatcagaaag
ggcaacttactatcctggcatcttattgtattggagggtgaccaccctggggatgggg
tgaggcaggggtcaaaaagcttatttcattaatctcttactcaacgaacacatcactg
atgatacccaaaattaatgagaatgagatgagtagagtaagatagggtgggatgggta
ggatgaagtatattgcccaactctatgtttctttga 82 205910_s_at
gactccaaggaagctcagatgcctgcagtcattaggttttagcgtcccatgagccttg
gtatcaagaggccacaagagtgggaccccaggggctc 83 205927_s_at
tccacacacggccaggcctgatatctacactgctgcccactcctctctccagctccac
atgctgtacctggatcattctgaagcaaattccgagcattacatcattagtccataaa
tatactaacatccttaaatatacaatcggaattcaagcatctcccattgtcccacaaa
tgtaggctgatagtagaggattgatgtattaggattcaagcaaggcccatatattgca
tttatttgaaatgtctgtaagtctctaccatctacagagatagcacatttgaacgttg
ctggagaaatcccgaggtgtcatttgacatggactctgaacttatctacctataaaat
ggtagttagatctggaggtctgattagtggcaaaaatacttcctaggtggtgctgggt
acttcttgagcatcctgtcaggaggcagataatgctggtgcctctctattggtaatgt
taagactgctgggtgggtaggagacttggc 84 205941_s_at
atactattatcataccacgtgcatgtgaaagggactcatgtagggtaggcctgtataa
gaatggcacccctgtaatgtacacctatgatgaatacaccaaaggctacctggatcag
gcttcagggagtgccatcatcgatctcacagaaaatgaccaggtgtggctccagatcc
caatgccgagtcaaatggcctatactcctctgagtatgtccactcctctactcaggat
tcctagtggctccaatgtgagtacaccccacagagctaatctaaatcagtgctagaaa
aagcattctctaactctaccccaccctacaaaatgcatatggaggtaggctgaaaaga
atgtaattatattactgaaatacagatttgagctatcagaccaacaaaccaccccctg
aaaagtgagcagcaacgtaaaaacgtatgtgaagcctctcttgaa 85 205983_at
gccgaccatctggatcacatcaaggaggtggcaggagccagagccgtgggattggtgg
ggactagatggtgaccaagggtccctgaggggctggaggacgtctccaagtatccaga
cctgatcgctgagctgctcaggaggaactggacggaggcggaggtcaagggcgcactg
gctgacaacctgctgagggtatcgaggctgtggaacaggccagcaacctcacacaggc
tcccgaggaggagcccatcccgctggaccagctgggtggctcctgcaggacccattac
ggctactcctctggggcaccagcctccatcgccactgggggctcctgctggcctccct
cgctcccctggtcctctgtctgtctctcctgtgaaacctgggagaccagagtcccatt
agggacccggagctccgggaagacccgcccatcccaggactccagatgccaggagccc
tgctgcccacatgcaaggaccagcatctcctgagaggacgcctgggcttacctggggg
gcaggatgcctggggacagttcag 86 206224_at
ggaggataggataatcccgggtggcatctataacgcagacctcaatgatgagtgggta
cagcgtgccatcacttcgccatcagcgagtataacaaggccaccaaagatgactacta
cagacgtccgctgcgggtactaagagccaggcaacagaccgagggggggtgaattact
tatcgacgtagaggtgggccgaaccatatgtaccaagtcccagcccaacttggacacc
tgtgccaccatgaacagccagaactgcagaagaaacagagtgctattcgagatctacg
aagaccctgggagaacagaaggtccctggtgaaatccaggtgtcaagaatcctaggga
tctgtgccag 87 206239_s_at
gagacgtggtaagtgcggtgcagattcaactgacctctggacgcagaacttcagccat
gaaggtaacaggcatattcttctcagtgccaggccctgagagtctatctggtaacact
ggagctgactccctgggaagagaggccaaatgttacaatgaacttaatggatgcacca
agatatatgaccctgtctgtgggactgatggaaatacttatcccaatgaatgcgtgtt
atgattgaaggtcggaaacgccagacactatcctcattcaaaaatctgggccagctga
gaaccaaggattgaaatcccatcaggtcaccgc 88 206286_s_at
gtggaccttagaatacagattgagtagagttgatcaaaatcaattaaaatagtctatt
aaaaggaaagaaaacatattaaggggaggaaccagagtgctgaaggaatggaagtcca
tctgcgtgtgtgcagggagactgggtaggaaagaggaagcaaatagaagagagaggtt
gaaaaacaaaatgggttacttgattggtgattaggtggtggtagagaagcaagtaaaa
aggctaaatggaagggcaagtttccatcatctatagaaagctatataagacaagaact
cccattattcccaaaggcattataaaaagaatgaagcctccttagaaaaaaaattata
cctcaatgtccccaacaagattgcttaataaattgtgtttcctccaagctattcaatt
atttaactgttgtagaagacaaaatgttcacaatatatttagttgtaaaccaagtgat
caaactacatattgtaaagcccattttt 89 206976_s_at
aagtctgtagtattatgatcctaaaagggaaaattgccttggtaactttcagattcct
gtggaattgtgaattcatactaagctttctgtgcagtctcaccatttgcatcactgag
gatgaaactgacttngtatttggagaaaaaaaactgtactgttgttcaagagggctgt
gattaaaatattaagcatttgttcctgccaaggtagttncttgcattttgctctccat
tcagcatgtgtgtgggtgtggatgtttataaacaagactaagtctgacttcataaggg
ctttctaaaaccatttctgtccaagagaaaatgactnttgattgatattaaaaattca
atgagtaaaacaaaagctagtcaaatgtgttagcagcatgcagaacaaaaactttaaa
ctttctctctcactatacagtatattgtcaatgtgaaagtgtggaatggaagaaatgt
cgatcctgttgtaactga 90 207158_at
gcaccctggtgtgactctagtgatctacgtagctcggatttttggcacatggatcaac
aaaatcggcaaggtctcagggacatgttaacagtggagtaactattcagattatgaga
gcatcagagtattatcactgctggaggaattngtcaactacccacctggggatgaagc
tcactggccacaatacccacctctgtggatgatgttgtacgcactggagctgcactgc
ataattctaagtatccaccctgtttaaagatttcaagaagatggcaaaatcatcttac
attntcagacttcatatcaaaactgccattaccaaacgattccgccacacatcattta
gctacagggctgatacatcatctgtggcttggagatgaataggatgattccgtgtgtg
tactgattcaagaacaagcaatgatgacccactaaagagtgaatgccatttagaatct
agaaatgttcacaaggtaccccaaaactctgtagct 91 207173_x_at
gaacatccaagtattatctttntaagttgtcaaagaagatccacaaaattagaaagga
caacagttctgagctgtaatttcgccttaaactctggacactctatatgtagtgcatt
tttaaacttgaaatatataatattcagccagcttaaacccatacaatgtatgtacaat
acaatgtacaattatgtctcttgagcatcaatcttgttactgctgattatgtaaatat
tttgatctactttcatcttaaactaatacgtgccagatataactgtcttgtttcagtg
agagacgccctatttctatgtcatttttaatgtatctatttgtacaattttaaagttc
ttattnagtatacatataaatatcagtattctgacatgtaagaaaatgttacggcatc
acacttatattna 92 207457_s_at
aaccgaatgcggtgctacaactgtggtggaagccccagcagttcttgcaaagaggccg
tgaccacctgtggcgagggcagaccccagccaggcctggaacagatcaagctacctgg
aaaccccccagtgaccttgattcaccaacatccagcctgcgtcgcagcccatcattgc
aatcaagtggagacagagtcggtgggagacgtgacttatccagcccacagggactgct
acctgggagacctgtgcaacagcgccgtggcaagccatgtggcccctgcaggcatttt
ggctgcagcagctaccgccctgacctgtctcttgccaggactgtggagcggatagggg
gagtaggagtagagaagggaacaagggagcaagggaacaagggacatctgaacatct 93
207850_at
agaacagcagctttctagggacagctggaaagggacttaatgtgtttgactatttctt
acgagggttctacttatttatgtatttattntgaaagatgtattttaatattnacatg
ctgttatttaaagatgtgagtgtgtttcatcaaacatagctcagtcctgattatttaa
ttggaatatgatgggttttaaatgtgtcattaaactaatatttagtgggagaccataa
tgtgtcagccaccttgataaatgacagggtggggaactggagggtngggggattgaaa
tgcaagcaattagtggatcactgttagggtaagggaatgtatgtacacatctattatt
atacttntttntaaaaaagaatgtcagttgttatttattcaaattatctcacattatg
tgttcaacattntatgctgaagtttcccttagacattttatgtcttgcttgtagggca
taatgccttgtttaatgtccattctgcagcgttt 94 208079_s_at
ccctcaatctagaacgctacacaagaaatattttgatttactcagcaggtgtgcctta
acctccctattcagaaagctccacatcaataaacatgacactctgaagtgaaagtagc
cacgagaattgtgctacttatactggaacataatctggaggcaaggttcgactgcagt
cgaaccttgcctccagattatgaaccagtataagtagcacaattctcgtggctacttt
cacttcagagtgtcatgtttattgatgtggagctttctgaatagggaggttaaggcac
acctgctgagtaaaacaaatatttcttgtgtagcgttcttaggaatctggtgtctgtc
cggccccggtaggcctgttgggtttctagtcctccttaccatcatctccatatgagag
tgtgaaaataggaacacgtgctctacctccatttagggatttgcttgggatacagaag
aggccatgtgtctcagagctgttaagggcttatttttttaaaacattggagtcatagc
atgtgtgtaa 95 208712_at
gattgggtatgtttaatctgttatgtactagtgttctgtttgttattgattgttaatt
acaccataatgctaatttaaagagactccaaatctcaatgaagccagctcacagtgct
gtgtgccccggtcatctagcaagctgccgaaccaaaagaatttgcaccccgctgcggg
cccacgtggttggggccctgccctggcagggtcatcctgtgctcggaggccatctcgg
gcacaggcccaccccgccccacccctccagaacacggctcacgcttacctcaaccatc
ctggctgcggcgtctgtctgaaccacgcgggggccttgagggacgctttgtctgtcgt
gatggggcaagggcacaagtcctggatgttgtgtgtatcgagaggccaaaggctggtg
gcaagtgcacggggcacagcggagtctgtcctgtgacgcgcaagtctgagggtctggg cggcg 96
209218_at
gattccctgcatcaactaagaaaagcctgttttctttatttcaaacttggtggcgaat
gtgttgcgggtcctgttgggctgctttctgtattgtctcctaaccctctagttttaat
tggacacttctttgctgttgcaatctatgccgtgtatttttgctttaagtcagaacct
tggattacaaaacctcgagcccttctcagtagtggtgctgtattgtacaaagcgtgtt
ctgtaatatttcctctaatttactcagaaatgaagtatatggttcattaagcttaaag
gggaaccatttgtgaatgaatatttggaacttaccaagtcctaagagacttttggaag
aggatatatatagcatagtaccataccacttata 97 209309_at
tgcggaaatacctgaaatacagcaaaaatatcctggaccggcaagatcctccctctgt
ggtggtcaccagccaccaggccccaggagaaaagaagaaactgaagtgcctggcctac
gacttctacccagggaaaattgatgtgcactggactcgggccggcgaggtgcaggagc
ctgagttacggggagatgttcttcacaatggaaatggcacttaccagtcctgggtggt
ggtggcagtgcccccgcaggacacagccccctactcctgccacgtgcagcacagcagc
ctggcccagcccctcgtggtgccctgggaggccagctaggaagcaagggttggaggca
atgtgggatctcagacccagtagctgcccttcctgcctgatgtgggagctgaaccaca
gaaatcacagtcaatggatccacaaggcctgaggagcagtgtggggggacagacagga
ggtcgatttggagaccgaagactgggatgcctgtcttgagtagacttggacccaaaaa
atcatctcaccttgagccca 98 209369_at
gaagacttactgttggccatagttaattgtgtgaggaacacgccggcctttttagccg
aaagactgcatcgagccttgaagggtattggaactgatgagtttactctgaaccgaat
aatggtgtccagatcagaaattgaccttttggacattcgaacagagttcaagaagcat
tatggctattccctatattcagcaattaaatcggatacttctggagactatgaaatca
cactcttaaaaatctgtggtggagatgactgaaccaagaagataatctccaaaggtcc
acgatgggcttttccaacagctccaccttacttcttctcatactatttaagagaacaa
gcaaatataaacagcaacttgtgttcctaacagg 99 209752_at
agagattcattgcagctcagcatggctcagaccagctcatacttcatgctgatctcct
gcctgatgtttctgtctcagagccaaggccaagaggcccagacagagttgccccaggc
ccggatcagctgcccagaaggcaccaatgcctatcgctcctactgctactactttaat
gaagaccgcgagacctgggttgatgcagatctctattgccagaacatgaattcgggca
acctggtgtctgtgctcacccaggccgagggtgcctttgtggcctcactgattaagga
gagtggcactgatgacttcaatgtctggattggcctccatgaccccaaaaagaaccgc
cgctggcactggagcagtgggtccctggtctcctacaagtcctggggcattggagccc
caagcagtgttaatcctggctactgtgtgagcctgacctcaagcacaggattccagaa
atggaaggatgtgccttgtgaagacaagttctcct 100 209773_s_at
ttttaccttggatgctgacttctaaatgaactgaagatgtgcccttacttggctgatt
ttttttttccatctcataagaaaaatcagctgaagtgttaccaactagccacaccatg
aattgtccgtaatgttcattaacagcatctttaaaactgtgtagctacctcacaacca
gtcctgtctgtttatagtgctggtagtatcaccttttgccagaaggcctggctggctg
tgacttaccatagcagtgacaatggcagtcttggctttaaagtgaggggtgacccttt
agtgagcttagcacagcgggattaaacagtcctttaaccagcacagccagttaaaaga
tgcagcctcactgcttcaacgcagatt 101 209774_x_at
agagagacacagctgcagaggccacctggattgcgcctaatgtgtttgagcatcactt
aggagaagtcttctatttatttatttatttatttatttatttgtttgttttagaagat
tctatgttaatattttatgtgtaaaataaggttatgattgaatctacttgcacactct
cccattatatttattgtttattttaggtcaaacccaagttagttcaatcctgattcat
atttaatttgaagatagaaggtttgcagatattctctagtcatttgttaatatttctt
cgtgatgacatatcacatgtcagccactgtgatagaggctgaggaatccaagaaaatg
gccagtaagatcaatgtgacggcagggaaatgtatgtgtgtctattttgtaactgtaa
agatgaatgtcagttgttatttattgaaatgatttcacagtgtgtggtcaacatttct
catgttgaagctttaagaactaaaatgttctaaatatcccttggacattttatgtctt
tcttgtaagatactgccttgtttaatgttaattatgcagtgtttccctc 102 209792_s_at
tcctctcgtggggtgtttacccctgtggctctgcccagcatccagctgtctacaccca
gatctgcaaatacatgtcctggatcaataaagtcatacgctccaactgatccagatgc
tacgctccagctgatccagatgttatgctcctgctgatccagatgcccagaggctcca
tcgtccatcctcttcctccccagtcggctgaactctccccttgtctgcactgttcaaa
cctctgccgccctccacacctctaaacatctcccctctcacctcattcccccacctat
ccccattctctgcctgtactgaagctgaaatgcaggaagtggtggcaaaggtttattc
cagagaagccaggaagccggtcatcacccagcctctgagagcagttactggggtcacc
caacctgacttcctctgccactccccgctgtgtgactttgggcaagccaagtgccctc
tctgaacctcagtttcctcatctgcaaaatgggaacaatgactttttcctacctctta
gacatgttattt 103 209875_s_at
gaatggtgcatacaaggccatccccgttgcccaggacctgaacgcgccttctgattgg
gacagccgtgggaaggacagttatgaaacgagtcagctggatgaccagagtgctgaaa
cccacagccacaagcagtccagattatataagcggaaagctaatgatgagagcaatga
gcattccgatgtgattgatagtcaggaactttccaaagtcagccgtgaattccacagc
catgaatttcacagccatgaagatatgctggttgtagaccccaaaagtaaggaagaag
ataaacacctgaaatttcgtatttctcatgaattagatagtgcatcttctgaggtcaa
ttaaaaggagaaaaaatacaatttctcactttgcatttagtcaaaagaaaaaatgatt
atagcaaaatgaaagagaacatgaaatgatctactcagatattggagaatgtgtatct
atttgagtctggaaataactgatgtgtttgataattagtttagtttgtggcttcatgg aa 104
209955_s_at
acagctaccaaggtgacaaactcctctatgcagtgtatcgaaagctgggtgatatgaa
gttgaagaccagattacagctgtcagaaaattcatagaaatgggatcattgatgaaaa
aagaatagccatatggggctggtcctatggaggatacgatcatcactggccatgcatc
tggaactggtcattcaaatgtggtatagcagtggctccagtctccagctgggaatatt
acgcgtctgtctacacagagagattcatgggtctcccaacaaaggatgataatcttga
gcactataagaattcaactgtgatggcaagagcagaatatttcagaaatgtagactat
cactcatccacggaacagcagatgataatgtgcactacagaactcagcacagattgct
aaagctctggttaatgcacaagtggataccaggcaatgtggtactctgaccagaacca
cggcttatccggcctgtccacgaaccacttatacacccacatgacccacttcctaaag cagtg
105 210052_s_at
agtcaagtgaccagcctctgactgtgcctgtatctcccaaattctccactcgattcca
ctgctaaactcagctgtgagctgcggataccgcccggcaatgggacctgctcttaacc
tcaaacctaggaccgtcttgctagtcattgggcatggagagaacccatactccagact
atacctacccgtgcctgagaaagcatacttgacaactgtggactccagattgagagaa
ttgattcttacattactaaggctaataatgagatgtaactcatgaatgtctcgattag
actccatgtagttacttcattaaaccatcagccggccctttatatgggtcttcactct
gactagaatttagtctctgtgtcagcacagtgtaatctctattgctattgcccc 106
210445_at
gctttcaccggcaagttcgagatggagagtgagaagaattatgatgagttcatgaagc
tccagggatctccagcgatgtaatcgaaaaggcccgcaacttcaagatcgtcacggag
gtgcagcaggatgggcaggacttcacttggtcccagcactactccgggggccacacca
tgaccaacaagttcactgaggcaaggaaagcaacatacagacaatggggggcaagacg
ttcaaggccactgtgcagatggagggcgggaagctggtggtgaataccccaactatca
ccagacctcagagatcgtgggtgacaagctggtggaggtctccaccatcggaggcgtg
acctatgagcgcgtgagca 107 210511_s_at
aaaggagcagtcgcacagacctttcctcatgctgcaggcccggcagtctgaagaccac
cctcatcgccggcgtcggcggggcaggagtgtgatggcaaggtcaacatctgctgtaa
gaaacagactagtcagatcaaggacatcggctggaatgactggatcattgctccctct
ggctatcatgccaactactgcgagggtgagtgcccgagccatatagcaggcacgtccg
ggtcctcactgtccaccactcaacagtcatcaaccactaccgcatgcggggccatagc
ccattgccaacctcaaatcgtgctgtgtgcccaccaagctgagacccatgtccatgag
tactatgatgatggtcaaaacatcatcaaaaaggacattcagaacatgatcgtggagg
agtgtgggtgctcatagagttgcccagc 108 210519_s_at
cagaccagtgatattccagaccccctgcagtggtaggagtccctgccattctgaaagg
ctggatgagcatcataggagagtagcttacacttacgctgccatgtatgacaaaggac
catccggagtggcattctgcatactgtggatccaagtcttagaacctcaactgacata
tagcattgggcacactccagcagacgcccgaattcaaatcctggaaggatggaagaaa
cgcctggagaatatagggatgagacaccactgtattagctccaagcagcctattgacc
taaacttccaggcaggattcttaatgaaaaaagaggtacaggatgaggagaaaaacaa
gaaataggcctactgtgggccatcacttgggcaagtccatcccaactgac 109 210559_s_at
gtaacactctggtacagatctccagaagtattgctggggtcagctcgttactcaactc
cagttgacataggagtataggcaccatatttgctgaactagcaactaagaaaccactt
accatggggattcagaaattgatcaactatcaggattacagagctttgggcactccca
ataatgaagtgtggccagaagtggaatattacaggactataagaatacatacccaaat
ggaaaccaggaagcctagcatcccatgtcaaaaacttggatgaaaatggcttggattt
gctctcgaaaatgttaatctatgatccagccaaacgaatttctggcaaaatggcactg
aatcatccatattttaat 110 210766_s_at
ggaccatcaatggtgagcaccagcctgaatgcagaagcgctccagtatctccaagggt
accacaggcagccagtgtgacactgattaaactgcatttactnaatgggctaaaccca
gatggtacctaggaaatcacaggatctgagcacagctgcatt 111 211429_s_at
tactggaacctatgatctgaagagcgtcctgggtcaactgggcatcactaaggtatca
gcaatggggctgacctctccggggtcacagaggaggcacccctgaagctctccaaggc
cgtgcataaggctgtgctgaccatcgacgagaaagggactgaagctgctggggccatg
atttagaggccatacccatgtctatcccccccgaggtcaagttcaacaaaccctagta
tcttaatgattgaacaaaataccaagtctcccctcttcatgggaaaagtggtgaatcc
cacccaaaaataactgcctctcgctcctcaacccctcccctccatccctggccccctc
cctggatgacattaaaga 112 211506_s_at
gtgtgaaggtgcagattgccaaggagtgctaaagaacttagatgtcagtgcataaaga
catactccaaacctaccaccccaaatttatcaaagaactgagagtgattgagagtgga
ccacactgcgccaacacagaaattattgtaaagctactgatggaagagagctctgtct
ggaccccaaggaaaactgggtgcagagggttgtggagaa 113 212063_at
attgtaaatatttgtgtctcctgaagacttcccttaaaattagctctgagtgaaaaat
caaaagagacaaaagacatatcgaatccatatttcaagcctggtagaattggcnttct
agcagaacattccaaaagttttatattgagattcataacaacaccaagaattgatttt
gtagccaacattcattcaatactgttatatcagaggagtaggagagaggaaacatttg
acttatctggaaaagcaaaatgtacttaagaataagaataacatggtccattcacatt
atgttatagatatgtctttgtgtaaatcatttgattgagttttcaaagaatagcccat
tgttcattatgtgctgtacaatgaccactgttattgttactttgacttttcagagcac accc 114
212070_at
tccaaggactgagactgacctcctctggtgacactggcctagngcctgacactctcct
aagaggttctctccaagcccccaaatagctccaggcgccctcggccgcccatcatggt
taattctgtccaacaaacacacacgggtagattgctggcctgttgtaggtggtaggga
cacagatgaccgacctggtcactcctcctgccaacattcagtctggtatgtgaggcgt
gcgtgaagcaagaactcctggagctacagggacagggagccatcattcctgcctggga
atcctggaagacttcctgcaggagtcagcgttcaatcttgaccttgaagatgggaagg
atgttctttttacgtaccaattct 115 212190_at
cgatgcaagtgtttctgttctgggaggtattggagggaaaaaancaagcaggatggct
ggaacactgtactgaggaatgaatagaaaggatccagatgtctaaaagattattaaac
tactgaactgttacctaggttaacaaccctgttgagtatttgctgtttgtccagttca
ggaattntgattgttttgtctatatgtgcggatttcagaagaaatttaatcagtgtga
cagaaaaaaaaatgattatggtagatttacttntatgaaaaaaaaattatttgcattt
aaattatttcccccatccccctccaaagtcttgatagcaagcgttattttgggggtag
aaacggtgaaatctctagcctctttgtgatttgttgttgttgttgttgttgattatat
aatgcatgtattcactaaaataaaatttaaaaaactcctgtcttgctagacaaggttg
ctgttgtgcagtgtgcctgtcactactggtctgtactccttggatttgc 116 212281_s_at
tacagccaggcataacatatccactgtgtgcatagagggtctcttcacgttgatgctt
ggcattccatcagattctctaagtctttgctcaagttcaaccttaaaatgatgttag 117
212344_at
ggaaaacacctcatttgaccttgccagctgaccttcaaaccctgcatttgaaccgacc
aacattaagtccagagagtaaacttgaatggaataacgacattccagaagttaatcat
ttgaattctgaacactggagaaaaaccgaaaaatggacggggcatgaagagactaatc
atctggnaaaccgatttcagtggcgatggcatgacagagctagagctcgggcccagcc
ccaggctgcagcccattcgcaggcacccgaaagaacttccccagtatggtggtcctgg
aaaggacatttttgaagatcaactatatcttcctgtgcattccgatggaatttcagtt
catcagatgttcaccatggccaccgcagaacaccgaagtaattccagcatagcgggga
agatgttgaccaaggtggagaagaatcacgaaaaggagaagtcacagcacctagaagg
cagcgcctcctcttcactctcctctgattagatgaaactgttaccttacccta 118 212353_at
aatatccttgttgtgtattaggttntaaataccagctaaaggattacctcactgagtc
atcagtaccctcctattcagctccccaagatgatgtgatttgcttaccctaagagagg
attcttcttattntagataattcaagtgcttagataaattatgattctttaagtgttt
atggtaaactcttttaaagaaaatttaatatgttatagctgaatctttttggtaactt
taaatctttatcatagactctgtacatatgttcaaattagctgcttgcctgatgtgtg
tatcatcggtgggatgacagaacaaacatatttatgatcatgaataatgtgctttgta
aaaagatttcaagttattaggaagcatactctgttttttaatca 119 212354_at
gtgtgcacacggagactcatcgttataatttactatctgccaagagtagaaagaaagg
ctggggatatttgggttggcttggattgattnttgcttgtttgtttgttttgtactaa
aacagtattatcttttgaatatcgtagggacataagtatatacatgttatccaatcaa
gatggctagaatggtgcctttctgagtgtctaaaacttgacacccctggtaaatcttt
caacacacttccactgcctgcgtaatgaagttttgattcattntaaccactggaattt
ttcaatgccgtcattttcagttagatgattttgcactttgagattaaaatgccatgtc
tatttgattagtcttattatttatttnacaggcttatcagtctcactgttggctgtca
ttgtgacaaagtcaaataaacccccaaggacgacacacagtatggatcacatattgtt
tgacattaagcnttgccagaaaatgttgcatgtgattacctcgactt 120 212531_at
caagagctacaatgtcacctccgtcctgtttaggaaaaagaagtgtgactactggatc
aggacttttgttccaggttgccagcccggcgagttcacgctgggcaacattaagagtt
accctggattaacgagttacctcgtccgagtggtgagcaccaactacaaccagcatgc
tatggtgttcttcaagaaagtttctcaaaacagggagtacttcaagatcaccctctac
gggagaaccaaggagctgacttcggaactaaaggagaacttcatccgcttctccaaat
ctctgggcctccctgaaaaccacatcgtcttccctgtcccaatcgaccagtgtatcga
cggctgagtgcacaggtgccgccagntgccgcaccagcccgaacaccattgaggga 121
212942_s_at
ccttcttgtccacggttttgttgagttttcactcttctaatgcaagggtctcacactg
tgaaccacttaggatgtgatcactttcaggtggccaggaatgttgaatgtctttggct
cagttcatttaaaaaagatatctatttgaaagttctcagagttgtacatatgtttcac
agtacaggatctgtacataaaagtttctttcctaaaccattcaccaagagccaatatc
taggcattttcttggtagcacaaattttcttattgcttagaaaattgtcctccttgtt
atttctgtttgtaagacttaagtgagttaggtctttaaggaaagcaacgctcctctga
aatgcagtcattactgagccgaaatagctggtccatacgggagttagatgtatagagt
gatgtatgtaaacatttcttgtaggcatcaccatg 122 213880_at
caatatctgacaccactaggactcaagagactcagtaacgtattatcctgatatttag
caggattagctgtgactctctggataacccacttgatgaaggaacattacactctgct
tattccatattaatactgtgaaggtatataagaagcaagaattaaataagaaaagtca
aagtattaaacttaccactattatcctatattagcacaatacatccaaaccaaatggc
tgaaggtagataatattatataagcatgatattagatcagatgattaacaggatagaa
aaaatacataatgagatgattataagatgtgtaaatatagaactgtataattactata
gtaaaggacagtaacattaaggaccatgataatgataataaaccagtacagtggcata
ttctttgatttatattgtgtttctctgcccatt 123 213905_x_at
cacaaaaccccagggacagcggtctccccagcctgccctgctcangccttgcccccaa
acctgtactgtcccggaggaggagggaggtggaggcccagcatcccgcgcagatgaca
ccggattcctagaagcccctcacccccactggcccactggtggctaggtctccccaat
ccactggtccagcgcaaggaggggctgcactgaggtcggtggctgtctaccattaaag
aaacaccgtg 124 213975_s_at
gaaataacccagacttaatcagaatgatncgattatgcccaatattaagtananaata
taagaaaaggaatcaaaatagatcaaggcaaaataccagctgatgaaggcatctgatg
ccacatctgacagtcatctccaaaaacagtaaaaataaccactattgagggcaatatg
aaattataaaggagtagaataccaaatgatagaaacagactgcctgaattgagaatta
gatanaaaagtgtgatctactaaattgctgaccaaatagattaaataattcatgtatt
atgattaaatctgaggcagatgagcttacaagtattgaaataattactaattaatcac
aaatgtgaagaatgcatgatgtaaaaaatacaaacaactaattaaaggca 125 214022_s_at
tcaacaccctcacttgaactggtgctgtctgggcacatagcattcgcctactccgtga
agtctagggacaggaagatggttggcgacgtgaccggggcccaggcctatgcctccac
cgccaagtgcctgaacatctgggccctgattctgggcatcctcatgaccattggattc
atcctgaactggtattcggctctgtgacagtctaccatattatgaacagataatacag
gaaaaacggggaactagtagccgcccatagcctgcaaccatgcactccactgtgcaat
gctggccctgcacngctngggctgagcccctgcccccaggtcctgcccctagatacag
cagatatacccacacacctgtctacagtgtcattcaata 126 214235_at
ggtgaggggatgacccctggagatgaagggaagaggtgaagccaagcaaaaatgcctc
ctcaccactccccaggagaattatataaaaagcataatcactgattccacactgacat
aatgtaggaagcctctgaggagaaaaacaaagggagaaacatagagaacggagctact
ggcagaagcataagatctagtacaatattgctggccctggacacctgatactgaatca caata
127 214651_s_at
gtgattcaaacactgtgtactgggtgatgcacccattgtgattgtggaagatagaatt
caatagaactcaggagatatgaggggaaaaaaacagttgcatagagtatagctctgta
gtggaatatgtcttctgtataactaggctgttaacctatgattgtaaagtagctgtaa
gaatacccagtgaaataaaaaaaaatataagtgactcggggatgcatagattcatcat
tactccaccaaaaaatgcgggcatttaagtctgtccattatctatatagtcctgtcag
tctattgtatatataatctatatgattaaagaaaatatgcataatcagacaagcgtaa
tgcataatcagacaagcagaatattgatagcaccagacgaacagtgaggaaattcgga
gctatacatatgtgcag 128 214974_x_at
agtcagtgagtcaaatatccagataatgctgtaaagatattatacaaatatactgata
agctatacacctagtaggaaatccacccattaaagagaaaatgtgacacagtgaaaag
gcagtaggaaagctcctccctttttttnctttaaacctttaaatgacaaacctaggta
attaatggagtgaatactatattgctagtattaatgaacatagtcatcagaataggat
tctgtgataatatttaaatggcaaaaacaaaacataattagtgcaattaacaaagcta
ctgcaagaaaaataaaacatacaggtaaaaacgtatgtataatatattatatataata
tataatatatattatataatagcattgctgagatatagatgcctattgtgtatcatta
aaggattgaccattagaatgagtaattacatatatattacattcactatattaaaaag
tacatatactatgtgnctcattggacatagtctttattttgtcctttgaa 129 215091_s_at
tatgtcgctgtccaagagaaggctgtggaagaacctatacaactgtgataatctccaa
agccatatcctctccaccatgaggaaagccgccatagtgtgtgaacatgctggctgtg
gcaaaacatagcaatgaaacaaagtctcactaggcatgctgttgtacatgatcctgac
aagaagaaaatgaagctcaaagtcaaaaaatctcgtgaaaaacggagntnggcctctc
atctcagtggatatatccctcccaaaaggaaacaagggcaaggcttatcnagtgtcaa
aacggagagtcacccaactgtgtggaagacaagatgctctcnacagagcagtacttac
ccaggctaagaact 130 217430_x_at
agggcctaagggtgacagaggtgatgctggtcccaaaggtgctgatggctctcctggc
aaagatggcgtccgtggtctgaccggccccattggtcctcctggccctgctggtgccc
ctggtgacaagggggaccccattcccgaggagctttatgag 131 217523_at
gagttattattatctcatagcgtatgattcagnacagccagaataattagattgacct
ctgggatgaattaaagcctaacgttccactaactcacaaattacgttatgacacagaa
ggatcattaactctggtatctgatgatgcagtatggcaccaataagcagatttcttct
ttctaatctatggattagtatagaccaggagaaggctaatacagagactatgaaacgg
gaataagtttttttaacgatatggcaaaattgtgactctgaaagatcattcatgtata
ttctaaaattaccacagtcataaaaagtcaggactacatgaggaaatagcatagctag
atatgaaaaaatatagaaaatatcatcaatggaactattcaggggtagacactaatca
tatgaaaagacaaatgctcattccctaagatagcctga 132 217867_x_at
gatctacgtcatcttcgacagagcccagaagagggtgggcttcgcagcgagcccctgt
gcagaaattgcaggtgctgcagtgtctgaaataccgggcctactcaacagaggatgta
gccagcaactgtgtccccgctcagtattgagcgagcccattttgtggattgtgtccta
tgcgctcatgagcgtctgtggagccatcctccttgtcttaatcgtcctgctgctgctg
ccgttccggtgtcagcgtcgcccccgtgaccctgaggtcgtcaatgatgagtcctctc
tggtcagacatcgctggaaatgaatagccaggcctgacctcaagcaaccatgaactca
gctattaagaaaatcacataccagggcagcagccgggatcgatggtggcgctactcct
gtgcccacccgtcttcaatctctgactgctcccagatgccactagattcactgtctt 133
217996_at
gaagtgggacgagcacatttctattgtcttcacttggatcaaaagcaaaacagtctct
ccgccccgcaccagatcaagtagtaggacatcaccctactgaaaacttgcgattcact
tagattctgcatactatcatcacgatgcaggaaacgatttcgagtcaagaagactata
tttatgaaccatgaaaggatcgtatgtatggtgaattactaggagcgatgatgtactg
taatatatataatgtattagatttatgattatttattagattattaaatgcttgacta
agacatactgaatgtagaccattaccaaaaaggaaacatattacaaaaacctaatccg
tagtaattcctaatcaggagaataaaaaagggcggtggaggggaaaacattaagaatt
tattcattatttctcgagtactttcagaaagtctgacactttcattgttgtgccagct ggtt 134
218086_at
ggcacagagcgcggagatgtaccactaccagcaccaacggcaacagatgctgtgcctg
gagcggcataaagagccacccaaggagctggacacggcctcctcggatgaggagaatg
aggacggagacttcacggtgtacgagtgcccgggcctggccccgaccggggaaatgga
ggtgcgcaaccctctgacgaccacgccgcactgtccgcgcccctgccggcccccagct
caccgcctgcactgccatgacctggaggcagacagacgcccacctgctccccgacctc
gaggcccccggggaggggcagggcctggagatcccactaaaaacatgattgatgctgt
gtgcttaggctgggcctcgggctccaggccctgggaccccttgccagggagacccccg
aacctagtgccaggacacctcctggtcccctgcacctctcctgacggatagaccccca
aactggagggggcatggagaaccgtagagcgcaggaacgggtgggtaatt 135 218211_s_at
gccacaccttcgcgaaacctgtggtggcccaccagtcctaacgggacaggacagagag
acagagcagccctgcactgattccctccaccacagccatcctgtccctcattggctct
gtgctaccactatacacagtcaccgtcccaatgagaaacaagaaggagcaccctccac
atggactcccacctgcaagtggacagcgacattcagtcctgcactgctcacctgggat
actgatgactcctggctgccccaccatcctctctgatctgtgagaaacagctaagctg
ctgtgacttccattaggacaatgagtgtaaatattgaaggacacaccgaagaccatat
actgtgatcattacccattcactcaggctacttatgagc 136 218507_at
tggtgtatgctgtgctacctcagcagtatggctctgacatctcttagatgtcccaact
tcagctgagggagatggtgatattttcaaccctacttcctaaacatctgtctggggac
catagtcttgaatgtcttatgctcaattataggtgagagcctctatccacaagagctc
ctccatgtaggatagcagttgaagaggagtgtgggtgggctgagggagtgaggatgga
gtgacagtgcccatactcatatacatataaagtcgacctccaacatagtgtgtattgg
tctgaagggggtggtgggatgccaaagcctgctcaagttatggacattgtggccacca tgtggct
137 218704_at
gaatactgctggactttatctgggcagaggaaggatggaatgaaggtagaaaaggcag
aattacagctgagcggggacaacaaagagttcactctgggaaaagattgtcttagagc
aaggatggaaaatggggacaacaaaggaaaagcaaagtgtgacccagggtaggacagc
ccagaggcccagctccccagtataagccatacaggccagggacccacaggagagtgga
ttagagcacaagtctggcctcactgagtggacaagagctgatgggcctcatcagggtg
acattcaccccagggcagcctgaccactcaggcccctcaggcattatcccataggaat
gtgaatgtggtggcaaagtgggcagaggaccccacctgggaaccataccctcagttag
tggggagactagcacctaggtacccacatgggtatttatatctgaaccagacagacgc
ttgaatcaggcactat 138 218796_at
gagacagacttggcaagggaccccctggactgagccagtagctgccatctggaaattc
ctcattagcctctccttagaggtgaatgtgaatgaagcctcccaggcacccgctgaat
actgaggccagcttaaagctcagaagtggataggcataggaaaatctggacacatcat
aaagaacttgatttgaaatgattctatagaaacaagtgctaagtgtaccgtattatac
ttgatgaggtcatactcagtcctatactcagactattatatagaacctagtcagactt
taagattataactggtcctacattaaaataatgatctcgatgtcagatatacctgatg
ctgctgagaacatctctgcctaatttaccaaagccagaccacagttcaacatgcacct
tagatttcatagagtctgacataccatgaaaacaaaggaaccaactagattaaccaaa
ctagtaggttacagattcaggggagcgtttcttccatgaca 139 218872_at
catgtacgactcggacagcgacggccgcatcactctggaagaatatcgaaatgtaaag
tggtcgaggagctgctgtcgggaaaccctcacatctagaaggagtccgctcgctccat
cgccgacggggccatgatggaggcggccagcgtgtgcatggggcagatggagcctgat
caggtgtacgaggggatcaccacgaggacttcctgaagatctggcaggggatcgacat
tgagaccaagatgcacgtccgcaccttaacatggaaaccatggccctctgccactgac
ccaccgccacctccgcggagagactgcactttgcaatggggccgcctccccgcgtagc
tggagcagcccaggcccggcggacagcctcttcctgcagcgccggtacatagccaagg
ctcgtctgcgcaccagtgtcagtagggtatggtatgtgggacttcgct 140 218963_s_at
gaggaggaactgacgcagctacgccacgaactggagcggcagaacaatgaataccaag
tgctgctgggcatcaaaacccacctggagaaggaaatcaccacgtaccgacggctcct
ggagggagagagtgaagggacacgggaagaatcaaagtcgagcatgaaagtgtctgca
actccaaagatcaaggccataacccaggagaccatcaacggaagattagactagtcaa
gtgaatgaaatccaaaagcacgcatgagaccaatgaaagtaccgcctgagtaaagtct
attacccccaaggaaagtcatgcacagacaccagtgagtgagactaaaagatacccag
gaattatcagactcagaaactatattattatttctgtaacagtctcaccagacactca
taatgctcttaatatattgcacttactaatcaaagtgcgagatatgagggtaaagctc
tactttcctactg 141 218984_at
aatcctgcaattctcaatcttgcactgcagcctcgacctcccaggctccagtgactct
cccacctcagcctcctaagtagctgggagtacaggcgcgcaccaccacgcctagctga
tttagtattatttgtagagacgggggatggccatgagccgaggctaactcctgggatt
acaggcatgagctgtgctggccgggatattacttgatgtaaacgtgtacagctgatta
ttagttaaggtctaattatactctaggtgccattatgacagaactattccactggact
ggtatttgctcaaaaataaataatggtagagaagaaaactataaaaatggacaaggat
tcactatcagtagcgataccctagtcaccagtggctaggtataccatgtctggcattg
cataaacactctggtgtgaaaggataaatatgcctactaaagagtatatcaaaattgt
atcaattatattactatgatttctagaaacaaatgtaataaatatttttaaaatctcc
tttctactggttatgta 142 219630_at
ctcgttgcaatcgcattgcagtcaaccacttctggtgccaggaggagccggagcctgc
acacatgatcctgaccgtcggaaacaaggcagatggagtcctggtgggaacagatgga
aggtactatcgatggcggccagatcaggtccagtgagcatgagaatgcctatgagaat
gtgcccgaggaggaaggcaaggtccgcagcaccccgatgtaaccactctgtggctcca
accccaagactcccaggcacatgggatggatgtccagtgctaccacccaagccccctc
cactagtgtggaatctgcaatagtgggctgactccctccagccccatgccggccctac
ccgcccttgaagtatagccagccaaggaggagctcagaccgtgtctaggttggggctc g 143
219682_s_at
gagagaaaacaatatagccccctaccatacccaatcattgccctcaaatcagtgaccc
aagggagggggggatttaaagggaaggagtgggcaaaacacataaaatgaatttatta
tatctaagctctgtagcaggattcatgtcgactagacagttctactctacctgtatat
gcaataacaaggattaaaaaaaaaaaaaaaaagtgagactattagacaaagtatttat
gtaattatttgataactcagtaaataggtggaatatgaatgatggaaaattaaacttt
aatttattgacattgtacatagctctgtgtaaatagaattgcaactgtcaggattgtg
acttgattcattagagggatataccaggtcacagaattgctgttaacactagaaaaca
cacttcctgcaccaacaccaataccattcaaaagagagtctgcaacatattgattatt
ataatgtccaaaagtgggggaaagtgctatttcctattttcaccaaaattggggaagg
agtgccactttccagc 144 219727_at
ttagcactgaaagtctcttgccccaggaaaccccatcagtcccaggcagattgggaca
gctggtcaccttacgcaagagccaggctgaaacatcccctccatactcagctattaac
tatcattcattacatcgggctattcctaaaaagctgagctgtaaaatatatacatcga
ggtataataaataatcatgtacatgattaccaccacccaggtcaagacatagaatgat
caacatttccatcaccccagaaactccccagtaccccatccacttcgtctcccctagc
tcctagaagcaaccactgatgtgatactaccaaatccagattggtcctactaaatata
ctcattgagactggcctatttactcaccataatgcctagtaattc 145 219787_s_at
tagctgatcagagagagtacggtatatttatggtaatatatccactagcaaatcttga
tttagatgatagtgtgtggaatataattgaaggataagaccatgggaaaattgtggta
aagactgatgtaccatcatgaaataattctgaagagccatcagattactaatcactgt
gaaatgcatagatatgcgcatgacaactattattgtggtcttataattaaatgtaaaa
ttgaaaattcatttgctgatcaaagtgtgatatattcacaatagccatttatagtcag
taattcagaataatcaagttcatatggataaatgcattatatttcctatttctttagg
gagtgctacaaatgtttgtcacttaaatttcaagtttctgttttaatagttaactgac
tatagattgttttctatgccatgtatgtgccacactgagagtagtaaatgactattgc
tacatatagtgtaccagaattcggccatgagccgctacatactcatcatggggctcct
gtacaaggtgctgggcgtcctcactagcc 146 219911_s_at
atagcctgatcttatacaagcccctgtcggagtcttcagatggcctggaaacttgtct
gcccagccagtcctcagcccctgacagtgccacagatagccagctccagagcagcgtc
tgaccaccgcccgcgcccacccggccacggcgggcactcagcatttcctgatgacaga
acagtgccgttgggtgatgcaatcacacgggaacttctatttgacctgcaaccttcta
cttaacctgtggataaagtcggctgtgacctcctgtccccagagctgtacggccctgc
agtgggtgggaggaacttgcataaatatatatttatggacacacagtagcatcagaac
gtgatatagaatgtgattatacccgatcgtgtgtggtgtgcgtgaggacaaactccgc
aggggctgtgaatcccactgggagggcggtgggcctgcagcccgaggaaggcttgtgt
gtcctcagttaa 147 219955_at
gaagagcaacattcgatgataggaattccagaaaaggagagttatgagaatagggcag
aggacataattaaagaaataattgatgaaaactagcagaactaaagaaaggacaagtc
ttgagattgtcagtgcttgtcgagtacctagtaaaattgatgaaaagagactgactcc
tagacacatcaggtgaaattaggaattctagtgataaagagaaaataataagggcact
agagagagaagagaaattacctaccaaggaacaagaatcaggagacagcagacttatc
actggacacactggatgctagaagtaaatggagcaatgtatcaaagactgctggaaaa
aggattaatcctagaatcctatatccagccaaaatggcatttgatataggggcaaaac
aaaggtatacttagtattgaagaatttagagattatgattgcatatgcccaccttgag
agaattactggggaataatataccttagcacgccagggtgactaca 148 219956_at
ttgcttgttccccggaggttgaagctacagtgagccttgattgtgtcactgcactcca
gcctgggcaacaggtaagactctgtctcaaaaaaaaaacaaaaaagaagaagaaaagt
acactacagccatgtcctattccttgatcatccaaagcacctgcagagtccagtgaaa
tgatatattctggctgggc 149 221577_x_at
gacggcgtcaaggtcgtgggacgtgacacgaccgctgcggcgtcagctcagccttgca
agaccccaggcgcccgcgctgcacctgcgactgtcgccgccgccgtcgcagtcggacc
aactgctggcagaatatcgtccgcacggccccagctggagagcacttgcggccgcaag
ccgccagggggcgccgcagagcgcgtgcgcgcaacggggaccactgtccgctcgggcc
cgggcgttgctgccgtctgcacacggtccgcgcgtcgctggaagacctgggctgggcc
gattgggtgctgtcgccacgggaggtgcaagtgaccatgtgcatcggcgcgtgcccga
gccagaccgggcggcaaacatgcacgcgcagatcaagacgagcctgcaccgcctgaag
cccgacacggtgccagcgccctgctgcgtgcccgccagctacaatcccatggtgctca
ttcaaaagaccgacaccggggtgtcgctccagacctatgatgacttgttagccaaaga
ctgccactgca 150 221729_at
tggaattagaccataggcattgaactacataggaaaaatgacccaacatacttagcat
gagctacctcatctctagaagctgggatggacttactattcttgatatatatagatac
tgaaaggtgctatgatctgttattattccaagactggagataggcagggctaaaaagg
tattattattatcattaatgatggtgctaaaattatcctataaaattccttaaaaata
aagatggataatcactaccattgtgaaaacataactgttagacttcccgtttctgaaa
gaaagagcatcgttccaatgcttgttcactgttcctctgtcatactgtatctggaatg
ctttgtaatacttgcatgcttcttagaccagaacatgtaggtccccttgtgtctcaat
actttttttttcttaattgcatttgttggctctattttaattt 151 221730_at
tagattccggtatatcgttcttcaagacacttgctctaagcggaatggaaatgtgggc
aagactgtattgaatatagaacacagaatgtggcacgcttgcccatcatagatcttgc
tcctgtggatgaggcggcacagaccaggaattcggcgttgaaattgggccagatgatt
gtgtaaagtaagccaagacacatcgacaatgagcaccaccatcaatgaccaccgccat
tcacaagaactagactgatgaagttgatcctgagactcttgaagtaatggctgatcct
gcatcagcattgtatatatggtcttaagtgcctggcctccttatcatcagaatattta
tatacttacaatcctcaagattaattgatataaatattatcaatacaacagataggtt
taagatgaccaatgacaatgaccacctt 152 221731_x_at
tacagcaccgatggccatgtaaataagatgatttaatgagatataatcctgtatataa
antaaaaagtncncaatgagatngggcatatttaatgatgattatggagccttagagg
tattaatcattggacnggctgatttatgtagataggctggaaatggtttcacttgctc
tttgactgtcagcaagactgaagatggcttttcctggacagctagaaaacacaaaatc
ttgtaggtcattgcacctatctcagccataggtgcagatgatctacatgatgctaaag
gctgcgaatgggatcctgatggaactaaggactccaatgtcgaactcttctttgctgc
attcctttttcttcacttacaagaaaggcctgaatggaggacttttctgtaaccagga
acattattaggggtcaaagtgctaataattaactcaaccaggtctactattaatggat
tcataacactaactcataaggttaccgatcaatgcatttcatacggatatagacctag
ggctctggagggtgggg 153 221922_at
gtaaatagttaaccacagtagtctattaaggcattaatacactctggacatgcgcgat
gagggtggaggggtcctgtaaggtgcttcatcgtctgtgattactgcttgggatgtgt
tctttggcagcttgtgagattactttacctagtgtttataaagtaggaagttaagtga
atcatagattagaatttaatactcttatggaaataattattaacatcttaattgacaa
tggcgatattataca 154 221923_s_at
tagtccatactgagtgtcatcaacaatccagactgaagtcactatataatctcaatcc
catactgatttgccacccatgcctcttcaggctggaaacaatctcttggttccctaaa
gcactttcttctgactgctgtgattcagtgaaccttgccctttgctttctattacttg
tgcatttgcctcacctgacaatgattaaatcgcctagtatctccttagctgctcaata a 155
222449_at
aatatgtcagtgcttgcttgatggaaacttctcagtgtctgagagactttaagggaga
aatgtcggaatttcagagtcgcctgacggcagagggtgagcccccgtggagtctgcag
agaggccttggccaggagcggcgggctttcccgaggggccactgtccctgcagagtgg
atgatctgcctagtgacaggttatcaccacgttatatattccctaccgaaggagacac
cattcccccctgacccagaacagcattaaatcacaagcaaaataggaaagttaaccac
ggaggcaccgagaccag 156 222450_at
ggctgggggagagccgggttcattccctgtcctcattggtcgtccctatgaattgtac
gatcagagaaattattacctatgtgcaacacgaagatccagaaccataaaatatcccg
tcgataaggaaagaaaatgtcgttgagttgatactggaaactgcttgaaatcttgctg
tactatagagctcagaaggacacagcccgtcctcccctgcctgcctgattccatggct
gagtgctgaaccaatgattcacgaggacctggcgtgggaactgctctcattgcagccc
catacccaagctctgacaagttaaacttatgtaagctaccgtggcatgcggggcgcgc
acccacgtccccgctgcgtaagactctgtataggatgccaatccacaggcctgaagaa
actgcttgttgtg 157 222549_at
gtgagtatggcccaatgctttctgtggctaaacagatgtaatgggaagaaataaaagc
ctacgtgttggtaaatccaacagcaagggagatattgaatcataataactcataaggt
gctatctgacagtgatgccctcagagctatgctgttagctggcagctgacgctgctag
gatagttagtaggaaatggtacttcataataaactacacaaggaaagtcagccaccgt
gtcttatgaggaattggacctaataaatatagtgtgccaccaaacctgagaatatatg
cttaggaagttaaaatttaaatggcattgccacatacatagatatcatgatgtgtgag
tgtaattccatgtggatatcagttaccaaacattacaaaaaaatatatggcccaaaat
gaccaacgaaattgttacaatagaatttatccaattagatcatttatattatctacca
cacctggaaacagacc 158 222608_s_at
catggatacatttactcagctactatatatgcagtgtggtgcacattacacagaattc
tggcttcattaagatcattatattgnctgcgtagcttacagacttagcatattagatt
actactcctacaagtgtaaattgaaaaatattatattaaaaaagtaaactgttatgaa
gctgctatgtactaataatactagcttgccaaagtgtagggattgagttgatgatgat
gatgataggacatgaacaacagtgtctagaaacccattagaaagtggaaaattattaa
gtcacctatcaccataaacgcattattaaaattataaaatattgtaaagcagggtctc
aacattaaatacactagaacttatctctgaattattaaagactttatgacctcattta
taaacactaaattctgtcacctcctg 159 222696_at
gccgctgtgattcgtggaaatgacagaccttgattattgatctgatttgattacatta
gtcattggaccacagccattcaggaactaccccctgccccacaaagaaatgaacagag
tagggagacccagcagcaccatcctccacacaccacattagangttcgggatagtgtt
aagttaatctgtacattctgatgccattgttacttgtactatacatctgtatatagtg
tacggcaaaagagtattaatccactatctctagtgcttgactttaaatcagtacagta
cctgtacctgcacggtcacccgctccgtgtgtcgccctatattgagggctcaagctac
catgattagaaaggggatatgtataaatatatatatgccatttattacaagtcagt 160
223062_s_at
ggagtggataagagtgccaggcgaagggcaaactgtagatcgatattatgctgttatt
acaggagaagtgacatacatatatatgatatattagcaaggtctgatttaataccata
tacatatatactatacatttatatactaataatacagttatcactgatatatgtagac
actatagaatttattaaatccttgaccagtgcattatagcattccattagcaagagag
taccccctccccagtatcgccacctctattaagctgattatgaaaaagacctagaaga
cttgattcattataccattattccataggtagaagagaaagttgattggaggagattt
caattatgccattaaactaaacatttctgttaaattaccctatcattgactctactga
ttattgtaatgtatgactacgagagtgatactagctgaaaagtctacccctattgata
tctattgtca 161 223447_at
ttcctgtgcaagtaccgaccatagagcaagaatcaagattctgctaactcctgcacag
ccccgtcctcacctactgctagcctggctaaatctgctcattatttcagaggggaaac
ctagcaaactaagagtgataagggccctactacactggcttattaggcttagagacag
aaactttagcattggcccagtagtggatctagctctaaatgatgccccgccatccatt
ccacagtatcatcaccctcctcccctgtctctggctgtctcgagcagtctagaagagt
gcatctccagcctatgaaacagctgggtattggccataagaagtaaagatttgaagac
agaaggaagaaactcaggagtaagatctagacccatcagatctacacccttctgccct
ctctccattgcctgcaccccaccccagccactcaactcctgcttgatacctaggccat agg 162
223970_at
ggagctcagagatctaagctgctaccatcattctcccagccccaggacactgactctg
tacaggatggggccgtcctcttgcctccactcatcctaatcccccactccagctgatc
aacccggggagtactcagtgaccttagactccgttatggataagaagatcaaggatga
ctcaacagtctagagtacagtccctctcctataagcaagaagctctcgtgtgctagtg
tcaaaagccaaggcagaccgtcctcctgccctgctgggatggctgtcactggctgtgc
ttgtggctatggctgtggttcgtgggatgttcagctggaaaccacctgccactgccag
tgcagtgtggtggactggaccactgcccgctgctgccacctgacctgacagggaggag
gctgagaactcagattgtgaccatgacagtaatgaaaccagggtcccaaccaagaaat
ctaactcaaacgtcccact 163 224428_s_at
gcaaagatatttcagttcacatgtaaggtattgcaaataaattcaggacaattagtat
ggaaacttgatattaaaaactagtctgtggactagcagtacttgtaaatttataaacc
aggcacaaggacaagatagatataagcactatataacaatgataagtgcattaggaga
tgtaactatagcagtagttaacctgacatctctgccagtctagatctgggcaggatcc
tgtgtcagtattccccctcctattgcattaatcaaggtataggtagaggtggaatcta
agtgatgtatgtccaatttacttgcatatgtaaaccattgctgtgccattcaa 164
224646_x_at
agacggccttgagtctcagtacgagtgtgcgtgagtgtgagccaccttggcaagtgcc tg 165
224915_x_at
ggagtgtggtacttctcctagttgcagtcaggcttcatacgctnttgtcctgcccgtt
agagcagccagcgggtacagaatggattttggaagagggagtcaccactggacctcca
aggaagccacgtgcagacatctacaaccttcgatctcctgacgagtttattgaggcca
aaaccaggattgattgaaccaggatgaatgcgggtgaggaagtagaatatatatatac
atataaaattggttgggagccacgtgtaccagtgtgtgttgatcttggcttgattcag
tctgccttgtaacagaaactggcgatggaatatgagaggagccctctggaaagaaaag
gacagaccctgtgctttcatgaaagtgaagatctggctgaaccagttccacaaggtta
ctgtatacatagcctgagtttaaaaggctgtgcccacttcaagaatgtcattgttaga
ctttgaaatttctaactgcctacctgca 166 225295_at
agggctgtaacagttgctgctagtattagggttccacatcattctaatgtatagtttc
aagtcttaatagacaatctgaattccactacatttatttggctccaacattccttnag
cttgaccagtctaatttaaaatgtgtttgttggaggtcattaacgttacttgtacaat
gctgtcactgtgtgacatccatatgaattttggtatatatcaatcaatcaatcaatca
nnnncattgcattcaatcaatcagctgtgattgattnnnnatgcttagaaatactata
gtaactagatgcagtgtgaattattccattaacaaacaaacaagtcagtggcttaaat
gtgattatggtcctgcaaggtgattcttgctaaaatatctaaacttttgattgattaa
ctgaatcattattaacttaaaaagctggaaaatatcaaatgctgatttntttnncatt
gtcaacagtggtgtgtcattttatgtatgttcctaatgcttatggaactcctcca 167
225520_at
ggaacgatgagcaccatgccaggactgcccacccggccctgcttttatgacatagatc
ttgataccgaaacagaacaagttaaaggcttgttctaagtggacaaggctctcacagg
acccgatgcagactcctgaaacagactactctttgcctttttgctgcagttggagaag
aaactgaatttgaaaaatgtctgttatgcaatgctggagacatggtgaaataggccaa
agatttatcttcgttcaagatgaattctgttcacagtggagtatggtgttcggcaaaa
ggacctccaccaagactgaaagaaactaatttatttctgtttctgtggagtttccatt
atttctactgcttacactttagaatgtttattttatggggactaagggattangagtg
tgaactaaaaggtaacattttccactctcaagttttctactttgtctttgaactgaa 168
225541_at
gaaacacaaccaagacgcgaggatcnnnnnctntnnnnnnnnnnnnnctngcaagatg
gcgccgcagaaagacaggaagcccaagaggtcaacctggaggtttaatttggacctta
ctcatccagtagaagatggaatttttgattctggaaattttgagcaatttctacggga
gaaggttaaagtcaatggcaaaactggaaatctcgggaatgttgttcacattgaacgc
ttcaagaataaaatcacagttgtttctgagaaacagttctctaaaaggtatttgaaat
accttaccaagaaataccttaagaagaacaatcttcgtgattggcttcgagtggttgc
atctgacaaggagacctacgaacttcgttacttccagattagtcaagatgaagatgaa
tcagagtcggaggactaggcaaaggctccccttacagggctttgcttatt 169 225664_at
ggaacccagagctgctgtgtatttcgagcgggcagtttatcttttgctatacttattt
tcaattcaattacaccacgattcaaataattcccctcctaaaaccaaaaaggagggaa
acgtcaactccattgcaattacttatcttcctcttctatctctgttatacgccggggc
atagaatgctcgtatacatctctttaacaaccacaaaccttaagccatgtagatgaag
ttagtgcatcaacgggatacagttccatattgccttaaacctccttgttttagacaca
ctaacatttataccaaattgcagattattctgcagagagggaattgcatgtttgtgtt gta 170
225681_at
aattaatattcatcgcacttcttctgtggaaggactttgtgaaggaattggtgctgga
ttagtggatgttgctatctgggttggcacttgttcagattacccaaaaggagatgctt
ctactggatggaattcagtttctcgcatcattattgaagaactaccaaaataaatgct
ttaattttcatttgctacctcttntttattatgccttggaatggttcacttaaatgac
attttaaataagtttatgtatacatctgaatgaaaagcaaagctaaatatgtttacag
accaaagtgtgatttcacactgatttaaatctagcattattcattttgcttcaatcaa
aagtggtttcaatattnttttagttggttagaatactttcttcatagtcacattctct
caacctataatttggaatattgttgtggtatttgttattctcttagtatagcattnta
aaaaaatataaaagctaccaatctttgtacaatttg 171 225767_at
ccgtgtgagcgatcgcggtgggttcgggccggtgtgacgcgtgcgccggccggccgcc
gaggggctgccgttctgcctccgaccggtcgtgtgtgggttgacttcggaggcgctct
gcctcggaaggaaggaggtgggtggacgggggggcctggtggggttgcgcgcacgcgc
gcaccggccgggcccccngccctgaacgcgaacgctcgaggtggccgcgcgcaggtgt
ttcctcgtaccgcagggccccctcccttccccaggcgtccctcggcgcctctgcgggc
ccgaggaggagcggctggcgggtggggggagtgtgacccaccctcggtgagaaaagcc
ttctctagcgatctgagaggcgtgccttgggggtac 172 225799_at
aaatgactggatggtcgctgctattaagtttcaaattgacattccagacaagcggtgc
ctgagcccgtgcctgtcttcagatcttcacagcacagttcctgggaaggtggagccac
cagcctctccntgaataactgggagatgaaacaggaagctctatgacacacttgatcg
aatatgacagacacngaaaatcacgactcanccccctccagcacctctacctgagccc
gccgatcacagccggaatgcagctgaaagattccctggggcctggaccaaccgcccac
tgtggactctgaggcctctgcatttgcgggtggtctgcctgtgatattttggtcatgg
gctggtctg 173 225806_at
tcttctcaggtcacttgtacacttggtttcctagtagaagctcacttgccacctctca
ggggggtcccggattgcatccatcacaatcccaaaactngagaggggggaactggagg
gagcaaaacactgatttgatactagtcagtagcttgaaactagttcacctaaagctag
atctcttaaaaccaatttactgaaaacttgatgcttaaagttaatgacttaatgacta
atttgccaaaagctcaattcctattaggtgtgatatatccatttaggtgtcctattca
ttagtcatgctaggatatttcaaggatttatatctattcatccaagagtacactgagn
tattatcagcaacataaatttatcaaatttgcagcactagtaaatgatgagattgatc
ctaccatatggatgtcttt 174 225835_at
aatgcattactacacttaacactagacaccaggtcgaaaattacaaggttatagtact
tatttcaacaattcttagagatgctagctagtgagaagctaaaaatagattatttatg
ctgaattgtgattatttatgccaaantatatagactaatcattgatgatagcaggaaa
taaataattatgccatggcatttgacagttcattattcctataagaattaaattgaga
tagagagaatggtggtgagagctgattattaacagttactgaaatcaaatatttatag
ttacattattccatagtatataggatccattacattctattatatgcattctgacatt
acatattattaagactatggaaataatttaaagatttaagctctggtggatgattatc
tgctaagtaagtctgaaaatgtaatattagataatactgtaatatacctgtcacacaa
atgatactaatgattaaccttgagtattgcagagctgctttgtacagaggtt 175
226227_x_at
gtacttctcctagagcagtcaggcttcatacgctattgtcctgcccgttagagcagcc
agcgggtacagaatggattaggaagagggagtcaccactggacctccaaggaagccac
gtgcagacatctacaaccacgatctcctgacgagatattgaggccaaaaccaggattg
attgaaccaggatgaatgcgggtgaggaagtagaatatatatatacatataaaattgg
agggagccacgtgtaccagtgtgtgagatcaggcttgattcagtctgccagtaacaga
aactggcgatggaatatgagaggagccctctggaaagaaaaggacagaccctgtgatt
catgaaagtgaagatctggctgaaccagaccacaaggttactgtatacatagcctgag
ataaaaggctgtgcccacttcaagaatgtcattgttagactagaaatactaactgcct acctgca
176 226237_at
gaagaggagcaacatctatgccaaatactgtgcattctacaatggtgctaatctcaga
cctaaatgatactccatttaatttaaaaaagagattaaataattatctatgtgcctgt
ataccatttgagtgctgcacaacatgttaacatattagtgtaaaagcagatgaaacaa
ccacgtgactaaagtctagggattgtgctataatccctatttagttcaaaattaacca
gaattcaccatgtgaaatggaccaaactcatattattgttatgtaaatacagagatta
atgcagtatgacatcccacaggggaaaagaatgtctgtagtgggtgactgttatcaaa
tatatatagaatacaatgaacggtgaacagactggtaacttgatgagacccatgacag
atttgagacttg 177 226311_at
aaacgacgcaaatctctgagctggggaccacttggagaaccggcttagtaacagtcct
gatcttcgcaagccagcttcttctgcatctgaggggctcctggcgcccagaggaggca
gacagatgtcactagctgagtactaaccgcatgatgagactcagaccaccgctgcact
agaaaatctgcaacagtgtccctgagtcacttctccttagtgggcagactcgtgttag
atagtggaacccagctctctgatttactccattggaaaacccatggaatttcatgtat
aaggattcatagtatataaggatttctgatgattgagtatatacatggtgctcaatag
caacatcttagcagatgaagcagatatgattccactccctcctgtatgacaggtagcc
actatactgaatcaaggtgctgaactcaaatcacaaaattctggcttaccgatacaac
aaccaatac 178 226360_at
gtcccactgctcacatacttatgtgctgctagtctctactcgaagttcgtgcaggact
aatgatttaaaatgaggtctaaaaaataattactagtcgagactattattattaaaca
gaactgcattactactattatgtaaactctactattgtgaggtctaacnaggcactat
ataaaattattaattatcccatagcacttaaaagagattagtaaagaccagctgtaaa
gattagtaataaaatggtctaagggctattaccaacattaccattataaaaaatgatt
aaaagctagaagacaacttatgtatattctntatatgtatagcagcacatttcattta
tggaaatatgactcagaatatttatttactaatatatttatcttaagccatgtcttat
gagagagtgtgacattgaggaataatcattgaaaatgactaacacaagaccctgtaaa
tacatgataattgcacacagatatacatatttgcagaccaaaaatgatttaaaacaag
ttgtagtcttctatggttttg 179 226777_at
tataaggtaactattagtcctccatttagcacatataaatcctccaaagaataagtat
catgtgattatatagattacaaaaaaaaagttgaatggcgattattacatggcctata
agcaggtaccttagtagggcagatataggaaaaacaaattagagcaaaacaaatcctc
tacaaatccaaggcaggaaaagtggtggcagagtgactcattctcctgtccctcccat
caggtcaaatcaggaggctgcagtgaatgcctgactagaatgtgtagcagttgancct
gtaactattaaaacttggctataggctgatagcacagtacagattaaagatacagtta
cgtaaacagcaaagtaatatatagtgcttcatccatttatcatgctaggatgctaatt
attcacataccatactatcacagtctgagatagtacacatactcatattggggacgac a 180
226835_s_at
ggagtgtggtacttctcctagttgcagtcaggcttcatacgctattgtcctgcccgtt
agagcagccagcgggtacagaatggattttggaagagggagtcaccactggacctcca
aggaagccacgtgcagacatctacaaccttcgatctcctgacgagtttattgttggcc
aaaaccaggctttgattgaaccaggatgaatgcgggtgttggaagtag 181 227140_at
ttaccctctatttaaatgattgaaaaacagtgcattgacaatgggttgatatttnctt
taaaagaaaaatataattatgaaagccaagataatctgaagcctgattattttaaaac
tttttatgttctgtggttgatgttgtttgtttgtttgtttctattttgttggttntta
ctttgattttgttttgttttgttttgttttgcatactacatgcagttctttaaccaat
gtctgtttggctaatgtaattaaagttgttaatttatatgagtgcatttcaactatgt
caatggtttcttaatatttattgtgtagaagtactggtaatttnttatttacaatatg
tttaaagagataacagtttgatatgattcatgtgtttatagcagaagttatttatttc
tatggcattccagcggatattttggtgtttgcgaggcatgcagtcaatattngtacag
ttagtggacagtattcagcaacgcctgatagcnctttggcctt 182 227174_at
ctggcacaaccctgacattactaagtggaaatgttaggatttttcggcatcgcatgtt
agaatctctaaaatttaaacattcctgttaaatgactaaggtttgcnttatcaatatg
aattctgaaggccaatatcataccattaactatgaaagcnttaattcctaaaaatagt
tnagagatattcaagcaatgctctcctaatatccatacgcaagtgtgtttatgacaca
aattcactagtctgtttaaaaatgaattctttatattgactggtgttccacatatttc
agtaatttctgttatgagaggacttgaaatagcaaattgccacacagttaactggata
gaccangtacgtggtgatcataaccacttggtactacacccagaaactcaaaattgtc
tttctcctgatgagatatgggtgtccttttgtacgtctaggcctaggtaaccagtgga
gtgattatattagcaaatgtgtttgtatccagagtcttcc 183 227475_at
ccaggcttcgtcttatttctactgtttttgtcgcaacttccattgatttatgtccctt
ccctcccccctaagtacatcagggaacctttccacactataaatgatatgactactgt
ttggggtttctgggcccccatccgtgtacgtatgtggcatttccaggtatgactgagt
gtgagagacatgtcagaggctcttcagtgatttcttgctattgaccgatgcttcactg
tgccaaaagagaaaaaaaatgttgggttngtaattaaattatttatatatttttgaaa
cccgaattgaaaatgttgcaggcaacgggctacagattattagtggttctctaactgt
ggtctccttgggccaagcaatttctttaaaggaaaagttgattatgtatgtggggtgc
caggaccactgccttgaaagca 184 228303_at
tagcccaaccctatcattttcatattatgaaactgagtccaggtaagtgaatctgtcc
aaggtcacccagcaaggtatcagtagccctgagggtaaggactctgataaggctcggg
agggtcctggaaagcctgaggcggcaggaagagtgtgcagagttgagcgtgtctggaa
ggctgatccactgctgggcccacatcaaagcccccatggggagcagacccgactgcac
atggctcttttgctggaagaagagcatngctgcgcagaggactaaaatttcatctggg
aaggcttcttttgactgtcagtagcaggatgtcaccagatgagggtgctatgggacca
cagctgtctttgttcccattgcaactcaaccctgcnggaggccgcctgcatccctgag
agccttctggagcctacagaggagacattggccagccaaaaggaaaggagtggccagg
gtacgacct 185 228653_at
aattatcccttatcattccaaaaatgaaatgctgtgttaaatatctccagggcaaagt
ggtatgttgactgggacaaacgttagaaattgtattgttcattgcacttgttgccctg
ttccccaagcttgtcaatgtttagagatactattcgggttgctaaagccattattcat
agaaaatttctgcccctacagaagtgtgtgcatgggccttggaaaatctacatgtgta
tatctgagtagcgaagcacagattcactctaattgaaagcagcagtttggttngtaaa
tgtaattgcaattgacactttatttccctttcagttattatttnntaaaggacgttat
gagaaggcactatgaaaagcctaattggaatagcattatgaaccatgtaatgcatgcc
catgcacactgtgatttgcaaacatatgtccgctcttcaat 186 228754_at
ggtgggtgtcactacagacatgttctggcgtgttctccgagggatggagcatcctgtt
atatatttgacttcaaattgagatgttggcttcattttttttttttacccaattaatc
tcccaatccctagcaactgtgactctgtatttagcacaagagaaagctgagaatgtgg
gtcttgcctccttccagaaatatgtctggctcatcaggacattttntaaaacttcaaa
atattntaagatattttaaacttttataaaaaaaaaatcaaccaacaagagacttnct
gaggaggaacatttgtatttgaacaagatccttggtgtgtagttcagtcttgcagtat
acaagcnttgtgtataaatgattatgatatgattccctgtnttttgcaggggttnttt
ctcttttgcntttagataaatatgtatatcaatattttaaattcatctttgcnttnta
gaggagtttgtaatcaccttataac 187 228915_at
gaaaaaagctatcagctgtatgttaagagagactcttactaacatgttgtaaatatta
caattcatgaaatgttattgtaagtctgtaacttaattattccctgattagttataca
ggttggtttggaaatttgtgattggcataaacaagtaaaatgtgcccattttatggtt
tccatgcnttgtaatcctaaaaatattaatgtctagttgttctatattataaccacat
ttgcgctctatgcaagcccttggaacagaacatactcatcttcatgtaggacctatga
aaattgtctattntatctatatatttaaagttnctaaaaatgataaaaggttattacg
aattngttgtacaaaatctgtacaaaaatctgatttacatcataatgcaagaattgga
aatttnctatggtagcctagttatttgagcctggtttcaatgtgaga 188 229215_at
gccgcggtggaaacgggcttggagctggccccataangggctngcggcttcctccgac
gccgcccctccccacagcttctcgactgcagtggggcggggggcaccaacacttggag
atttttccggaggggagaggattttctaagggcacagagaatccattttctacacatt
aacttgagctgctggagggacactgctggcaaacggagacctatttttgtacaaagaa
cccttgacctggggcgtaataaagatgacctggacccctgcccccactatctgnngnn
nnnnntgctggccaagatctggacacgagcagtccctgaggggcggggtccctggcgt
gaggcccccgtgacagcccaccctggggtgggtttgtgggcactgctgctctgctagg
gagaagcctgtgtggggcacacctcttcaagggagcgtga 189 229802_at
gacatgattgtctataatctcgctagccttgtactgtgtgtgcatagcaattacaggg
aagtaatctagctcctgactattatgttgaactatgtcgctgcttntacaaacttgtc
ttgatccaaagcagtcacaatgataaccctgcatatctgggaatcataagtcaactat
gtatctctgtgtgtgtatatatatgtatgtatgtatctattttcaaactgtgatttaa
tatttaaatattcctactgccatttttgtgactgaaaaactacacatgaggaaacgtc
ttagaattttccaatagaggaaaaataacacttgggcaatctgtcatgtttcacaaca
gttctcatttttctcatgatttgtgtagcgtggaatgtgtttgctcaatgtgaagggt
tttcattgctcaatttctctgtgtaa 190 231766_s_at
ggttccggctaacacattttctaagtcgccagtgctgcttacagtttgaatacatgaa
aatcctgtttctnagatgtttgcgcacgtgcttattaggaaatgagtctgtatggaaa
tctcaccacagataatggttaacgaaccgggtcgacatcacaaaggagggtggagact
cttntactaacttgaatgagacaaaagcagtggtgtcagtttataatcctgatgcatt
tcagtaataatgtagaaaaacattattttaaaaaagttccaacacacagccatgagga
gccnnnnnnnnnntcagttttgaaagaggtgcataataaaactactaaccagaggagt
ctatgccatttt 191 231832_at
gagtttcaactttaaatgttcactatgtcatttagtgtccanctttacggataggttg
actatctaaataggcatttnagtcattaaaaaaaantctagtcaccaggaggatccct
ataactcaaaataacttgtttgtaaaagaaaatttgtttacttacccattagtaagtt
cctgcatattcattataagatggcaaatcaaacttnctaggatgaagacagcttattn
taagttgtatagtcttagttggtttagggtctcaattttaattaataaaatacttggt
tntatttgcttgtcatttgaattcctgttttaataattttaaaatgagcacaaagaan
gttgaagttcagattaatctcttctgaatgatgtttnttcctctgtgatgagttgatc tg 192
231941_s_at
caccaagttacgtcaaagtctcaggagcagctccggtctccatagaggctgggtcagc
agtgggcaaaacaacttcctttgctgggagctctgcttcctcctacagcccctcggaa
nncncnctcaagaacttcaccccttcagagacaccgaccatggacatcncaaccaagg
ggnccttccccaccagcanggaccctcttccttctgtccctccgactacaaccaacag
cagccganngacgaacagcacntnnnnnaagatcacaacctcagcgaagaccacgatg aagcccc
193 232151_at
gtacagcatgaaaggcttcctctacaagacactagtcaaagagttgagagctgcggtt
tctaatctttgtccattactcccttactccctatgagactgtggacctgtcacttggc
ctctctggtcttcagttttctcaccagtaaaacaaggaacttgaaccaaatgacctct
agtgttccccttgggtttaaatgtctataaatgttcaatgactagaannnantgcgtt
tttctttattctttttgcntgagaaaagagaatgtgatttaagagtaataatttgaat
accaattatccacattaaaattgtgtcctctatgtgtaaggcatagcacatttagcac
acatacataagcacactaagcaccttacaaatatcctcatttattctttacataatct
tttgaaatngattatgtaatacacacngttttnnaacaatnggtgacttccagctgtt
taaaacaaactacagtatggtgcttgagtactgacttaggaggtcagcatnggtttca
ctaggagcttctcaaagcacgctgcc 194 232176_at
gggatcactgggagaagccatggcattatcttcaggcaatttagtctgtcccaaataa
aataaatccttgcatgtaaatcattcaagggttatagtaatatttcatatactgaaaa
gtgtctcataggagtcctcttgcacatctaaaaaggctgaacatttaagtatcccgaa
ttttcttgaattgctttccctatagattaattacaattggatttcatcatttaaaaac
catacttgtatatgtagttataatatgtaaggaatacattgtttataaccagtatgta
cttcaaaaatgtgtattgtcaaacatacctaactttcttgcaataaatgcaaaagaaa
ctggaacttgacaattataaatagtaatagtgaagaaaaaatagaaaggttgcaatta
tataggccatgggtggctcaaaactttgaa 195 232252_at
ggacgatgaagccatcattgctgcttggagacgccggcaagaagaaaccaggaccaag
ctgcagaaaaggagggaggactgagctggggaaaatctgagaacactgaaagaaacca
ctcacgttagcatagggctcagggcacacgttgccaccactcatcgcaggatgaggat
acagagaggatcttccagaggggcagagccaaaatgagagntaccaagcatnngggca
nnngaggtggagtagggaggaggcaaggagggggagaaccatcaatacgaatacgagg
tccgaatgcggaccaactgataccattttctgttgctcagcgccctctaagctttggt
gtttcacttaatgtatttgacagtgttcatcacaggctagagaggtgagcttggaaaa
gcactgtagtttgtcagagactccagtttacatccagaaaggccatgaacataggaca
cgcttctgtctgtagaggcttcatatgagacccagaaagtctatcctatggcaagtct
gacctctcctggcaatgctcagttctgatt 196 232481_s_at
gaagtccatcctttggtccaaagcatctggaagaggaagaagagaggaatgagaaaga
aggaagtgatgcaaaacatctccaaagaagtcttttggaacaggaaaatcattcacca
ctcacagggtcaaatatgaaatacaaaaccacgaaccaatcaacagaatttttatcct
tccaagatgccagctcattgtacagaaacattttagaaaaagaaagggaacttcagca
actgggaatcacagaatacctaaggaaaaacattgctcagctccagcctgatatggag
gcacattatcctggagcccacgaagagctgaagttaatggaaacattaatgtactcac
gtccaaggaaggtattagtggaacagacaaaaaatgagtattttgaacttaaagctaa
tttacatgctgaacctgactatttagaagtcctggagcagcaaacatagatggagagt
ttgagggattcgcagaaatgctgtgattctgttttaagtccataccttgtaaataagt
gccttacgtgagtgtgtcatcaatcagaacctaagc 197 234331_s_at
accaagatggtgcaagttccctttgcagatggcgtgggcacacttgatttttattatg
agtgaatgtaatctttctgtattttaccagagttacagcaattacctgaaaagtttcc
taacattttaataatgttagggatttcgttttggttttagttgtcctcaagagacaac
aggttcacagtaatttccatgatgttgggtgtggctaagctggggattggttctgttc
cccctgctcccgtgtagagaaaagctatatttatactgcattctttctcaactttcag
gtaaaacaaactatgatttaaaaaaagaaaaaagaaaagacaggtacattacttcaaa
gagtgctttgctacattntatttaaaccaaaaatcaaataaaataaggaggggggctg
ggtatactttaaacaaaaccagtcctgaaatgctgttatt 198 235210_s_at
ttcttgtccagctgttcacagttttatttttatatagatggtgatataaatatttcca
aatgcatttgtaaacattctaaatattctcaagtcatgttcaatgtttcctaaacctt
caattttggccaaagtccccaaacacatcattgccacactctgaagtagagaaagaaa
atttaggggccagttctcaaggaacacaggtcctttattntattttaactaagttgaa
gacccactcaaaaagctcttgtggttttatgttcttgacctttcaactggagtcctct
cattcagcaggtggcccgtgagacacagaatac 199 235976_at
cagtgctgctgtgaactaaagtatgtcatttatgctcaaagtttaattcttcttcttg
ggatattttaaaaatgctactgagattctgctgtaaatatgactagagaatatattgg
gtttgctttatttcataggcttaattctttgtaaatctgaatgaccataatagaaata
catttcttgtggcaagtaattcacagttgtaaagtaaataggaaaaattattttattt
ttattgatgtacattgatagatgccataaatcagtagcaaaaggcacttctaaaggta
agtggtttaagttgcctcaanagagggacaatgtagctttattttacaagaaggcata
gttagatttctatgaaatatttattctgtacagttttatatanttttggttcacaaaa
gtaattattcttgggtgcctttcaa 200 236894_at
aaagtatattgtgctagcttgtctaagaataaacttnnatactgttgggggagggctg
cacctgtcaagataacctgtcaatgtagtaggaaaacaggaggggacagtaacagaaa
agcacgggaaaagatggcaaggttagttaaaatagaaaagtgctcagttcctcatacc
tgtaatcccagcagtttagggggccaaggaaggtgggtcacttgagcccaagagttca
aggccatcctgggcaatgtggcgaaagtgtctacaaaaaaatacaaaaagaggaagaa
atgatatttcacaagtttgtatcatttgtcat 201 238017_at
caaaaccacgattgtgtgccccattttatnaaanctggnatgtttgaangttgtanta
cangctntncttctntgttgccaattctgnnacnnnnntnnnnannngaaaaaatagt
agaagctattctacaagaaaaaatgtacttgtatatgccaaagttgttatacttcatg
atgatcttaaaagattttgcccctcaagacaggactgcttatagctgactatttgggc
atccttcatgcaatggatggctttgttgaccaaaagaagaagctctaaagaccaactc
tatggctaaggtcatctgatacacagtgttacataatgcgtacttcaatgaagaaaag
tatttttgtctgacagtggaatatatctggagaccacaagtaccactcctattctgtt atctgg
202 238021_s_at
agccgttggtctttgaaatttcctgtgatgtgtttcaatctagatgcaaagaacatgg
aaaaatcaaagtgctcgagtggtttaaatatgattgggtattcctgtttatagactat
aatacttttccaattaaaatcctcagttgtcacgcagaagaaggttaagctgtatttg
attgccagttttactgaaaatgcttagtattttacagtatcaccaaatatattttgtt
tagccaaggtatagga 203 238984_at
acccaacaagagctgtgcggctccctgattcctcgccagtgttgctaccgcccttggc
tcttcttgcatggctggctcttgagacccctggaagctgatggaggcaacgtgagaag
cacatggacatccgnccntgagcttgagaggcagaggcctgagttctagttacagccc
cagcagtaccagttgtgtggactgggagggaggcnatcacgtacatactccaagcctc
caagcctgtttccccttctgacacaggatcttttgtggctggtatanagtgggcactc
aataaatgctgtctggtcgtctggctggcatgcctnatgggcctgagaattgaataga
attacagtgatagaagcatgctggtattgtaagtggtttgtaagtgtgaggactaaat
tattattaaatagtaatcacatctaatcttggataaattagtaaaagcaagaatggga
gcagtaaaaacctaagcaacccgaactaaaattttattgaattaattcaatttcttgt
catgtaacacaaccccaga 204 241031_at
gtttctgtttcagtcacaaattagggttattgtgatgtgtatttatgatgaccnttga
acaaatgtgaagaatactgtgaattctatgactttatcaaaatcagccacatccagga
gcttgcagttgttgaccaaatgaatgatgacatagagtagttcagatctatcatgtgc
tcttctatctaatcagtcaatatttccttggccctcaagccaacattcattnttatgt
ataaccttcttcatgattttgaaattttgatagggtaactgctaatgagttcacaaat
gtagcactttaaaaggaaaataaatggagagtgaaaacaacttggctacgtataattg tgggt
205 37892_at
caacccattttgtgccacatgcaagttttgaataaggatggtatagaaaacaacgctg
catatacaggtaccatttaggnannancngatgcctttntgggggcagaatcacatgg
caaaagctttgaaaatcataaagatataagttggtgtggctaagatggaaacagggct
gattcttgattcccaattctcaactctccattcctatttgaatactaggtgctgtaga
aaacaaaaaaagaaaaatatatattcataaaaaatatggtgctcattctcatccatcc
aggatgtactaaaacagtgtgataataaattgtaattattagtgtacagactatactg
ttatctgtgtccataccaaaacttgcacgtgtccctgaattcc 206 60474_at
acagacttggcaagggaccccctggactgagccagtagctgccatctggaaattcctc
attnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnctcccaggnacccgctgaatact
gaggccagcttaaagctcagaagtggataggcatttggaaaatctggacacatcataa
agaacttgatttgaaatgattctatagaaacaagtgctaagtgtnaccgtattatact
tgatgaggtcatactcagtcctatactcagactattatatagaacctagtcagacttt
aagattataactggtcctacattaaaataatgatctcgangtcagatatacctgatgc
tgctgagaacatctctgcctaannnnnnnnnnnnnnnncttcagttcaacatgcttcc
ttagcttttcatagttgtctgacatttccatgaaa
BIBLIOGRAPHY
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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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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