U.S. patent application number 14/810081 was filed with the patent office on 2016-06-09 for methods for determining cancer resistance to histone deacetylase inhibitors.
The applicant listed for this patent is Pharmacyclics LLC. Invention is credited to Sriram BALASUBRAMANIAN, Joseph J. BUGGY.
Application Number | 20160160286 14/810081 |
Document ID | / |
Family ID | 39674490 |
Filed Date | 2016-06-09 |
United States Patent
Application |
20160160286 |
Kind Code |
A1 |
BUGGY; Joseph J. ; et
al. |
June 9, 2016 |
METHODS FOR DETERMINING CANCER RESISTANCE TO HISTONE DEACETYLASE
INHIBITORS
Abstract
Described herein are methods and compositions for determining
whether a particular cancer is resistant to or susceptible to a
histone deacetylase inhibitor or to histone deacetylase inhibitors.
The methods include analysis of the expression levels of at least
four biomarker genes associated with response to a histone
deacetylase inhibitor. Also described herein are methods and
compositions for increasing the likelihood of a therapeutically
effective treatment in a patient, comprising an analysis of the
expression levels of at least four biomarker genes associated with
response to a histone deacetylase inhibitor. Also described herein
are isolated populations of nucleic acids derived from a cancer
sensitive to or resistant to a histone deacetylase inhibitor.
Further described are kits and indications that are optionally used
in conjunction with the aforementioned methods and
compositions.
Inventors: |
BUGGY; Joseph J.; (Mountain
View, CA) ; BALASUBRAMANIAN; Sriram; (San Carlos,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Pharmacyclics LLC |
Sunnyvale |
CA |
US |
|
|
Family ID: |
39674490 |
Appl. No.: |
14/810081 |
Filed: |
July 27, 2015 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12898314 |
Oct 5, 2010 |
9128096 |
|
|
14810081 |
|
|
|
|
12022977 |
Jan 30, 2008 |
7838234 |
|
|
12898314 |
|
|
|
|
60911855 |
Apr 13, 2007 |
|
|
|
60887318 |
Jan 30, 2007 |
|
|
|
Current U.S.
Class: |
506/16 |
Current CPC
Class: |
C12Q 2600/158 20130101;
C12Q 2600/112 20130101; G01N 33/57492 20130101; C07H 21/04
20130101; C12Q 1/6886 20130101; C12Q 2600/16 20130101; C12N 15/11
20130101; G01N 2800/52 20130101; A61P 35/00 20180101; C12Q 2600/136
20130101; C12N 5/0693 20130101; C12N 2503/02 20130101; C12Q
2600/106 20130101; G01N 33/57419 20130101 |
International
Class: |
C12Q 1/68 20060101
C12Q001/68 |
Claims
1.-19. (canceled)
20. A kit comprising an isolated population of nucleic acids,
wherein the isolated population of nucleic acids comprises a
plurality of nucleic acids derived from a cancer cell, wherein the
cancer cell is a type of cancer cell that is sensitive to an HDAC
inhibitor compound.
21. A kit comprising an isolated population of nucleic acids,
wherein the isolated population of nucleic acids comprises a
plurality of nucleic acids derived from a cancer cell, wherein the
cancer cell is the type of cancer cell that is resistant to an HDAC
inhibitor compound.
22. The kit of claim 20 or 21, wherein the nucleic acid sequences
of at least four of DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH,
NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, or DPEP1
are represented in the isolated population of nucleic acids.
23. The kit of claim 21, wherein the isolated population of nucleic
acids is
24. The kit of claim 20 or 21, wherein the isolated population
contains RNAs.
25. The kit of claim 20 or 21, wherein the isolated population
contains cDNAs.
26. The kit of claim 20 or 21 further comprising an insert
indicating the ratio of a biomarker gene nucleic acid level in the
population to an internal expression control gene acid nucleic
level in the population.
27. The kit of claim 20 or 21, wherein the HDAC inhibitor compound
is PCI-24781.
28. The kit of claim 20 or 21, wherein the cancer cell is a colon
carcinoma cell.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 12/898,314, filed Oct. 5, 2010, which is a continuation of U.S.
application Ser. No. 12/022,977, filed Jan. 30, 2008, issued as
U.S. Pat. No. 7,838,234 on Nov. 23, 2010, which claims the benefit
of U.S. Provisional Patent Application No. 60/887,318, filed Jan.
30, 2007, and U.S. Provisional Patent Application No. 60/911,855,
filed Apr. 13, 2007, all of which are incorporated herein by
reference in their entireties.
INCORPORATION BY REFERENCE OF SEQUENCE LISTING
[0002] The present application contains a Sequence Listing which
has been submitted in ASCII format via EFS-Web and is hereby
incorporated by reference in its entirety. Said ASCII copy, created
Jul. 27, 2015, is named "25922753302.txt" and is 171,930 bytes in
size.
BACKGROUND OF THE INVENTION
[0003] The highly heterogeneous response of the same type of cancer
(e.g., colon cancer) to a given anti-cancer compound in different
patients is one of the most vexing and tragic problems of modern
medicine. It is widely thought that human genetic and epigenetic
diversity underlies much of the variation in response to
chemotherapy. Thus, there is an ongoing effort to identify in the
human population the molecular genetic correlates (i.e., molecular
signatures) of cancer resistance and sensitivity to specific
therapeutic agents. It is hoped that such efforts will ultimately
enable physicians to predetermine the likelihood that a patient's
cancer can be effectively treated with a particular anti-cancer
compound.
SUMMARY OF THE INVENTION
[0004] Described herein are methods and compositions for
classifying a cancer in a patient as resistant or sensitive to a
histone deacetylase inhibitor (HDACi) compound by (i) comparing the
expression levels of at least four biomarker genes to a first set
of biomarker gene expression level values, which was determined in
cancer cells known to be resistant to the HDACi compound, or by
comparing the expression levels to a second set of biomarker gene
expression level values, which was determined in cancer cells known
to be sensitive to the HDACi compound, and (ii) indicating that the
cancer is sensitive to the HDACi compound if the biomarker gene
expression levels are significantly lower than the first set of
expression level values, or indicating that the cancer is resistant
to the HDACi compound if the biomarker gene expression levels are
greater than the second set of expression level values. The
referred-to biomarker genes include PTPN3, ABCC3, SARG, PPAP2C,
NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4, GALNT12,
TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C, TM4SF4,
TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18,
BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15, DPEP1,
NOXO1, IF127, CYP3A43, and PKP2.
[0005] Accordingly, in one aspect provided herein is a method for
classifying a cancer in a patient, comprising comparing the
expression levels of at least four biomarker genes in the cancer to
expression level to a first or second set of expression level
threshold values for the biomarker genes, and indicating that the
cancer is sensitive to a HDAC inhibitor if the expression levels of
the biomarker genes are lower than the first set of expression
level threshold values, or indicating that the cancer is resistant
to a HDAC inhibitor if the expression levels are greater than the
second set of expression level threshold values, wherein the at
least four biomarker genes are selected from PTPN3, ABCC3, SARG,
PPAP2C, NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4,
GALNT12, TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C,
TM4SF4, TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3,
IL18, BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15,
DPEP1, NOXO1, IF127, CYP3A43, and PKP2. In some embodiments, the at
least four marker genes are selected from DEFA6, ITGB4, TM4SF4,
SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1,
ABCC3, TPMT, IL18, and DPEP1. In some embodiments, the at least
four biomarker genes include at least one of DEFA6, RAB25, TM4SF4,
or IL18. In some embodiments, the at least four biomarker genes
include DEFA6, ITGB4, TM4SF3, SYK, PPAP2C, and RAB25. In some
embodiments, the at least four biomarker genes include DEFA6,
ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3,
EPHA2, FGFBP1, ABCC3, TPMT, IL18, and DPEP1. In some embodiments,
one or more of the above-mentioned expression levels is an mRNA
expression level. In some embodiments, one or more of the
expression levels is a polypeptide expression level. In some
embodiments, the patient's cancer is a colon cancer. In some
embodiments, the method for classifying the cancer further
comprises determining the level of expression of the at least four
biomarker genes in the cancer prior to the step of comparing. In
some embodiments, the referred-to HDAC inhibitor is PCI-24781. In
some embodiments, the expression levels of the at least four
biomarker genes are compared to the first set and the second set of
biomarker gene expression level threshold level values.
[0006] In another aspect provided herein is a method for
classifying a cancer in a patient, comprising determining the
expression levels of at least four biomarker genes in the cancer,
comparing the expression levels of the at least four biomarker
genes in the cancer to expression level to a first or second set of
expression level threshold values for the biomarker genes, and
indicating that the cancer is sensitive to a HDAC inhibitor if the
expression levels of the biomarker genes are lower than the first
set of expression level threshold values, or indicating that the
cancer is resistant to a HDAC inhibitor if the expression levels
are greater than the second set of expression level threshold
values, wherein the at least four biomarker genes are selected from
PTPN3, ABCC3, SARG, PPAP2C, NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3,
GALNT5, CALML4, GALNT12, TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK,
SLC12A2, GUCY2C, TM4SF4, TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6,
TNFRSF21, TM4SF3, IL18, BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4,
ANXA3, CCL15, DPEP1, NOXO1, IF127, CYP3A43, and PKP2.
[0007] In some embodiments, at least one of the at least four
marker genes are selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C,
RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT,
IL18, and DPEP1. In some embodiments, the at least four biomarker
genes include at least one of DEFA6, RAB25, TM4SF4, or IL18. In
some embodiments, the at least four biomarker genes include DEFA6,
ITGB4, TM4SF3, SYK, PPAP2C, and RAB25. In some embodiments, the at
least four biomarker genes include DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, and DPEP1. In some embodiments, wherein one or more of
the expression levels of the referred-to biomarker genes is an mRNA
expression level. In some embodiments, one or more of the
expression levels is a polypeptide expression level. In some
embodiments, the patient's cancer is a colon cancer. In some
embodiments, the HDAC inhibitor is PCI-24781. In some embodiments,
the method further comprises prescribing or administering an HDAC
inhibitor to the patient based on the comparison of the biomarker
gene expression levels. In some embodiments, the expression levels
of the at least four biomarker genes are compared to the first set
and the second set of biomarker gene expression level threshold
level values.
[0008] In a further aspect provided herein is an isolated
population of nucleic acids comprising a plurality of nucleic acids
derived from a cancer cell, wherein the cancer cell is a type of
cancer cell that is sensitive to an HDAC inhibitor compound. In
some embodiments, the isolated population contains RNAs. In some
embodiments, the isolated population contains cDNAs. In some
embodiments, the referred-to HDAC inhibitor is PCI-24781. In some
embodiments, the referred-to cancer cell was isolated from a
population of cells grown in vitro. In some embodiments, the cancer
cell is a colon carcinoma cell. In some embodiments, the colon
carcinoma cell is derived from colon carcinoma R1059261097,
R4498160614, R5456781761, R7424107588, or R0948311023. In some
embodiments, the nucleotide sequences of at least four of DEFA6,
ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3,
EPHA2, FGFBP1, ABCC3, TPMT, IL18, or DPEP1 are represented in the
isolated population of nucleic acids.
[0009] In a related aspect provided herein is an isolated
population of nucleic acids comprising a plurality of nucleic acids
derived from a cancer cell, wherein the cancer cell is a type of
cancer cell that is resistant to an HDAC inhibitor compound. In
some embodiments, the isolated population contains RNAs. In some
embodiments, the isolated population contains cDNAs. In some
embodiments, the referred-to HDAC inhibitor is PCI-24781. In some
embodiments, the referred-to cancer cell was isolated from a
population of cells grown in vitro. In some embodiments, the cancer
cell is a colon carcinoma cell. In some embodiments, the colon
carcinoma cell is derived from colon carcinoma R1059261097,
R4498160614, R5456781761, R7424107588, or R0948311023. In some
embodiments, the nucleotide sequences of at least four of DEFA6,
ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3,
EPHA2, FGFBP1, ABCC3, TPMT, IL18, or DPEP1 are represented in the
isolated population of nucleic acids.
[0010] In some embodiments provided herein is a kit comprising the
above referred-to isolated population of nucleic acids and an
insert indicating the ratio of a biomarker gene nucleic acid level
in the population to an internal expression control gene nucleic
acid level in the population.
[0011] In some embodiments provided herein is a kit comprising the
above referred-to isolated population of nucleic acids and an
insert indicating the ratio of a biomarker gene nucleic acid level
in the population to a nucleic acid level of the biomarker gene in
a population of nucleic acids derived from a cancer cell, wherein
the cancer cell is a type of cancer cell that is sensitive to the
HDAC inhibitor compound.
[0012] In another aspect provided herein is a method for generating
an expression level reference population of nucleic acids for
expression profiling, comprising deriving an isolated population of
nucleic acids from a cancer cell, wherein the cancer cell is a type
of cancer cell that is sensitive to an HDAC inhibitor compound. In
some embodiments, the isolated population contains RNAs. In some
embodiments, the isolated population contains cDNAs. In some
embodiments, the just-referred to HDAC inhibitor compound is
PCI-24781. In some embodiments, the cancer cell is present in a
biopsy sample. In some embodiments, the cancer cell is present in a
population of cells grown in vitro. In some embodiments, the cancer
cell is a colon carcinoma cell. In some embodiments, the carcinoma
cell is derived from colon carcinoma R1059261097, R4498160614,
R5456781761, R7424107588, or R0948311023. In some embodiments, the
nucleotide sequences of at least four of DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, or DPEP1 are represented in the above referred-to
isolated population of nucleic acids. In some embodiments, the
method further comprises determining, prior to the isolating step,
that the type of cancer cell is sensitive to an HDAC inhibitor
compound. In some embodiments, the type of cancer cell determined
to be sensitive to an HDAC inhibitor compound HDAC inhibitor
compound in vitro. In some embodiments, the HDAC inhibitor compound
is PCI-24781.
[0013] In a related aspect provided herein is a method for
generating an expression level reference sample for expression
profiling, comprising deriving an isolated population of nucleic
acids from a cancer cell, wherein the cancer cell is a type of
cancer cell that is resistant to an HDAC inhibitor compound. In
some embodiments, the isolated population contains RNAs. In some
embodiments, the isolated population contains cDNAs. In some
embodiments, the just-referred to HDAC inhibitor compound is
PCI-24781. In some embodiments, the cancer cell is present in a
biopsy sample. In some embodiments, the cancer cell is present in a
population of cells grown in vitro. In some embodiments, the cancer
cell is a colon carcinoma cell. In some embodiments, the carcinoma
cell is derived from colon carcinoma R1059261097, R4498160614,
R5456781761, R7424107588, or R0948311023. In some embodiments, the
nucleotide sequences of at least four of DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, or DPEP1 are represented in the above referred-to
isolated population of nucleic acids. In some embodiments, the
method further comprises determining, prior to the isolating step,
that the type of cancer cell is resistant to an HDAC inhibitor
compound. In some embodiments, the type of cancer cell determined
to be resistant to an HDAC inhibitor compound HDAC inhibitor
compound in vitro. In some embodiments, the HDAC inhibitor compound
is PCI-24781.
[0014] In another aspect provided herein is a human cancer cell
line that is resistant to an HDAC inhibitor compound in vitro. In
some embodiments, the human cell line expresses DEFA6, ITGB4,
TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2,
FGFBP1, ABCC3, TPMT, IL18, and DPEP1. In some embodiments, the HDAC
inhibitor compound to which the referred-to human cancer cell line
is resistant is PCI 24781. In some embodiments, the PCI
24781-resistant human cancer cell line is resistant to a PCI 24781
concentration of at least about 1 .mu.M. In some embodiments, the
human cancer cell line is a colon carcinoma cell line. In some
embodiments, the colon carcinoma cell line is R5247682266,
R9866135153, R1078103114, or R4712781606.
[0015] In a further aspect provided herein is a method for
increasing the likelihood of therapeutically effective treatment of
a cancer with an HDAC inhibitor, comprising providing an indication
that a cancer in a patient is sensitive to treatment with an HDAC
inhibitor if expression levels of at least four biomarker genes in
a sample from the patient's cancer are lower than expression level
threshold values for the four biomarker genes, or providing an
indication that the cancer is resistant to treatment with the HDAC
inhibitor if the expression levels of the biomarker genes are
higher than the expression level threshold values, wherein the at
least four biomarker genes are selected from PTPN3, ABCC3, SARG,
PPAP2C, NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4,
GALNT12, TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C,
TM4SF4, TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3,
IL18, BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15,
DPEP1, NOXO1, IF127, CYP3A43, and PKP2, whereby the likelihood of
therapeutically effective treatment of the cancer with the HDAC
inhibitor is increased. In some embodiments, the indication is
provided in a digital medium. In some embodiments, the indication
is provided in a hardcopy medium. In some embodiments, the
indication is a biomedical publication reference. In some
embodiments, the indication refers to expression levels of at least
two of the biomarker genes. In some embodiments, the at least four
biomarker genes include DEFA6, RAB25, TM4SF4, or IL18. In some
embodiments, the at least four biomarker genes include DEFA6,
ITGB4, TM4SF3, SYK, PPAP2C, and RAB25. In some embodiments, the at
least four biomarker genes include DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, and DPEP1. In some embodiments, the cancer is colon
cancer. In some embodiments, the HDAC inhibitor is PCI-24781.
[0016] In yet another aspect provided herein is a method for
optimizing selection of an anti-cancer agent for treating a cancer
in combination with an HDAC inhibitor compound, by: (i) comparing a
first set of biomarker genes the expression of which is correlated
to resistance or sensitivity of the cancer to the anti-cancer agent
to a second set of biomarker genes the expression of which is
correlated with resistance to the HDAC inhibitor compound; and (ii)
selecting the anti-cancer agent for treatment of the cancer in
combination with the HDAC inhibitor if the biomarker genes in the
first set are different from the biomarker genes in the second set,
where the biomarker genes in the second set are DEFA6, ITGB4,
TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2,
FGFBP1, ABCC3, TPMT, IL18, and DPEP1. In some embodiments, the
method further comprises comparing the expression level of the
second set of biomarker genes in a plurality of cancer cells
treated with the HDAC inhibitor together with a second anti-cancer
agent.
[0017] In a further aspect provided herein is an indication of the
likelihood of a therapeutically effective treatment of a cancer
with an HDAC inhibitor compound, comprising a means of
communicating an interpretation of expression levels of at least
four biomarker genes selected from DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, and DPEP. In some embodiments, the indication further
comprises the expression levels of the at least four biomarker
genes. In some embodiments, the means of communicating is a paper
document or an electronic document. In some embodiments, the
interpretation includes a biomedical publication reference. In some
embodiments, the interpretation includes a graph. In some
embodiments, the interpretation includes information that indicates
that a cancer in a patient is sensitive to treatment with an HDAC
inhibitor if expression levels of the biomarker genes in a sample
from the patient's cancer are lower than expression level threshold
values for the four biomarker genes, or information that indicates
that the cancer is resistant to treatment with the HDAC inhibitor
if the expression levels of the biomarker genes are higher than the
expression level threshold values.
[0018] In another aspect provided herein is a method for
determining the likelihood of effectively treating a cancer in a
patient with an HDAC inhibitor compound, comprising: (i)
determining in the cancer the expression levels of at least four
biomarker genes selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C,
RAB25, HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT,
IL18, and DPEP; and (ii) comparing the expression levels of that at
least four biomarker genes in the cancer to expression levels of
the at least four biomarker genes in an expression level reference
sample derived from cancer cells previously determined to be
resistant to the HDAC inhibitor compound, wherein the likelihood of
effectively treating the cancer is higher if the expression level
of the at least four biomarkers in the cancer from the patient is
lower than the expression levels of the biomarker genes in the
expression level reference sample. In some embodiments, the method
further comprises selecting an anti-cancer agent other than an HDAC
inhibitor compound for treating the cancer.
[0019] In yet another aspect provided herein is a method for
classifying a cancer in a patient, comprising comparing the
expression levels of at least four biomarker genes in the cancer to
a first or second set of expression level values for the biomarker
genes, and for each comparison assigning a probability to the
biomarker gene expression level that the cancer in the patient is
resistant to a histone deacetylase inhibitor compound, where: (i)
the first set of expression level values were measured in cancer
cells determined to be resistant to the histone deacetylase
inhibitor compound; (ii) the second set of expression level values
were measured in cancer cells determined to be sensitive to the
histone deacetylase inhibitor compound; (iii) the assigned
probability is inversely proportional to a negative deviation of
the biomarker gene expression level from the first set of
expression level values and directly proportional to a positive
deviation of the biomarker gene expression level from the second
set of expression level values; and (iv) the at least four
biomarker genes are selected from PTPN3, ABCC3, SARG, PPAP2C,
NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4, GALNT12,
TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C, TM4SF4,
TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18,
BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15, DPEP1,
NOXO1, IF127, CYP3A43, and PKP2.
[0020] In another aspect provided herein is a method for
classifying a population of cells, comprising comparing the
expression levels of at least four biomarker genes in the
population of cells to a first or second set of expression level
threshold values for the biomarker genes, and indicating that the
population of cells is sensitive to a HDAC inhibitor if the
expression levels of the biomarker genes are lower than the first
set of expression level threshold values, or indicating that the
population of cells is resistant to a HDAC inhibitor if the
expression levels are greater than the second set of expression
level threshold values, wherein the at least four biomarker genes
are selected from PTPN3, ABCC3, SARG, PPAP2C, NPDC1, CTEN, RAB25,
HEPH, TPMT, PKP3, GALNT5, CALML4, GALNT12, TPK1, DEFA6, EPLIN,
CLIC5, PERP, SYK, SLC12A2, GUCY2C, TM4SF4, TGFA, FGFBP1, PTK6,
EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18, BMP4, SMPDL3B, TMPRSS2,
GDA, MST1R, ITGB4, ANXA3, CCL15, DPEP1, NOXO1, IF127, CYP3A43, and
PKP2.
[0021] In another aspect provided herein is a method for
determining HDAC inhibition in vivo, comprising determining the
expression level of an HDAC inhibitor-responsive biomarker gene in
a biological sample obtained from a subject after the subject had
been administered an HDAC inhibitor compound, wherein the HDAC
inhibitor-responsive biomarker genes are any of the genes listed in
Table 5.
[0022] In another aspect provided herein is a method for
determining the most responsive tissues and the tumors derived
therefrom to an HDAC inhibitor, comprising: (i) providing a first
tissue of the tissue type (including blood) at a first time point
and administration of HDAC inhibitor compound to the first tissue
by any applicable route at a first time point, (ii) providing a
second tissue of the tissue type (including blood) at a second time
point and administration of HDAC inhibitor compound to the second
tissue by any applicable route at a second time point, and (iii)
determining expression profiles in the first and second tissues for
any of the genes listed in Table 5.
[0023] In a further aspect provided herein is a method for
classifying one or more cells, comprising determining the
expression levels of no more than four to fifty biomarker genes in
the one or more cells, wherein at least four of the biomarker genes
are selected from PTPN3, ABCC3, SARG, PPAP2C, NPDC1, CTEN, RAB25,
HEPH, TPMT, PKP3, GALNT5, CALML4, GALNT12, TPK1, DEFA6, EPLIN,
CLIC5, PERP, SYK, SLC12A2, GUCY2C, TM4SF4, TGFA, FGFBP1, PTK6,
EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18, BMP4, SMPDL3B, TMPRSS2,
GDA, MST1R, ITGB4, ANXA3, CCL15, DPEP1, NOXO1, IF127, CYP3A43, and
PKP2. In some embodiments, the method further comprises comparing
the expression levels of the four to fifty biomarker genes to a
first or second set of expression level threshold values for the
biomarker genes, and indicating that the cancer is sensitive to a
HDAC inhibitor if the expression levels of the biomarker genes are
lower than the first set of expression level threshold values, or
indicating that the cancer is resistant to a HDAC inhibitor if the
expression levels are greater than the second set of expression
level threshold values. In some embodiments, the one or more cells
are cancer cells. In some embodiments, the at least four biomarker
genes are selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25,
HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, and
DPEP. In some embodiments, the method further comprises determining
the expression levels of no more than four to twenty biomarker
genes. In some embodiments, the method comprises determining the
expression levels of no more than four biomarker genes. In some
embodiments, the four biomarker genes consist of DEFA6, RAB25,
TM4SF4, and IL18.
[0024] In yet another aspect provided herein is a nucleic acid
hybridization array comprising nucleic acid probes that hybridize
under high stringency hybridization conditions to nucleic acids of
no more than four to fifty biomarker genes, wherein at least four
of the biomarker genes are selected from PTPN3, ABCC3, SARG,
PPAP2C, NPDC1, CTEN, RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4,
GALNT12, TPK1, DEFA6, EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C,
TM4SF4, TGFA, FGFBP1, PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3,
IL18, BMP4, SMPDL3B, TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15,
DPEP1, NOXO1, IF127, CYP3A43, and PKP2. In some embodiments, the
nucleic acid hybridization array comprises at least four biomarker
genes selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH,
NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, and DPEP.
In some embodiments, the at least four biomarker genes consist of
DEFA6, RAB25, TM4SF4, and IL18.
[0025] It is to be understood that the methods and compositions
described herein are not limited to the particular methodology,
protocols, cell lines, constructs, and reagents described herein
and as such may vary. It is also to be understood that the
terminology used herein is for the purpose of describing particular
embodiments only, and is not intended to limit the scope of the
methods and compositions described herein, which will be limited
only by the appended claims.
[0026] As used herein and in the appended claims, the singular
forms "a," "an," and "the" include plural reference unless the
context clearly indicates otherwise.
[0027] The term "biomarker gene" refers to a gene whose expression
or activity yields at least one expression product the level of
which is quantitatively correlated to a phenotypic state of
interest (e.g., drug resistance, pathology).
[0028] The term "detectable label" refers to a label which is
observable using analytical techniques including, but not limited
to, fluorescence, chemiluminescence, electron-spin resonance,
ultraviolet/visible absorbance spectroscopy, mass spectrometry,
nuclear magnetic resonance, magnetic resonance, and electrochemical
methods.
[0029] The terms "differentially expressed gene," "differential
gene expression," and their synonyms, which are used
interchangeably, refer to a gene whose expression is upregulated or
downregulated in a first cell population relative to the expression
of the same gene in a second population of cells. Such differences
are evidenced by, e.g., a change in mRNA levels, surface
expression, secretion or other partitioning of a polypeptide.
Differential gene expression includes, in some embodiments, a
comparison of expression between two or more genes or their gene
products, or a comparison of the ratios of the expression between
two or more genes or their gene products, or even a comparison of
two differently processed products of the same gene, which differ
between two populations of cells. Differential expression includes
both quantitative, as well as qualitative, differences in the
temporal or cellular expression pattern in a gene or its expression
products among, for example, normal and diseased cells, or among
cells which have undergone different disease events or disease
stages, or cells that are significantly sensitive or resistant to
certain therapeutic drugs.
[0030] The term "fluorophore" refers to a molecule which upon
excitation emits photons and is thereby fluorescent.
[0031] The phrase "gene amplification" refers to a process by which
multiple copies of a gene or gene fragment are formed in a
particular cell or cell line. The duplicated region (a stretch of
amplified DNA) is often referred to as "amplicon." Frequently, the
amount of the messenger RNA (mRNA) produced, i.e., the level of
gene expression, also increases in proportion to the number of
copies made of the particular gene.
[0032] The term "gene expression profiling," unless otherwise
specified, is used in the broadest sense, and includes methods of
quantification of a gene's mRNA or nucleic acids derived therefrom,
and/or protein levels or peptides derived therefrom and/or protein
functions in a biological sample.
[0033] The term "high stringency hybridization" refers to
hybridization conditions of incubating at 68 .degree. C. for an
hour, followed by washing 3 times for 20 minutes each at room
temperature in 2.times.SSC and 0.1% SDS and twice at 50 .degree. C.
in 0.1.times.SSC and 0.1% SDS, or any art-recognized equivalent
hybridization conditions.
[0034] The term "internal expression control gene" refers to a gene
the expression level of which is known to or expected to be very
similar in cells that differ in one or more phenotypes, or which
have been subjected to differing experimental treatments. For
example, the expression of the gene HDAC3 is shown to be to very
similar in colon cancer cells that are resistant or sensitive to
treatment with an HDACi compound.
[0035] The term "isolated" refers to separating and removing a
component of interest from components not of interest. Isolated
substances are optionally in either a dry or semi-dry state, or in
solution, including but not limited to an aqueous solution. The
isolated component is optionally in a homogeneous state or the
isolated component is optionally a part of a pharmaceutical
composition that comprises additional pharmaceutically acceptable
carriers and/or excipients. Purity and homogeneity are determined,
for example, using analytical chemistry techniques including, but
not limited to, polyacrylamide gel electrophoresis or high
performance liquid chromatography. In addition, when a component of
interest is isolated and is the predominant species present in a
preparation, the component is described herein as substantially
purified. The term "purified," as used herein, refers to a
component of interest which is at least 85% pure, at least 90%
pure, at least 95% pure, at least 99% or greater pure. By way of
example only, nucleic acids or proteins are "isolated" when such
nucleic acids or proteins are free of at least some of the cellular
components with which it is associated in the natural state, or
that the nucleic acid or protein has been concentrated to a level
greater than the concentration of its in vivo or in vitro
production.
[0036] The term "label" refers to a substance which is incorporated
into a compound and is readily detected, whereby its physical
distribution is detected and/or monitored.
[0037] The term "microarray" refers to an ordered arrangement of
hybridizable array elements, preferably polynucleotide probes, on a
substrate.
[0038] The term "nucleic acid" or "nucleic acid probe," when used
in singular or plural, generally refers to any polyribonucleotide
or polydeoxribonucleotide, which includes unmodified RNA or DNA or
modified RNA or DNA. Thus, for instance, nucleic acids as defined
herein include, without limitation, single- and double-stranded
DNA, DNA including single- and double-stranded regions, single- and
double-stranded RNA, and RNA including single- and double-stranded
regions, hybrid molecules comprising DNA and RNA that are
optionally single-stranded or, more typically, double-stranded or
include single- and double-stranded regions. In addition, the term
"nucleic acid" as used herein refers to triple-stranded regions
comprising RNA or DNA or both RNA and DNA. The strands in such
regions are optionally from the same molecule or from different
molecules. The regions optionally include all of one or more of the
molecules, but more typically involve only a region of some of the
molecules. One of the molecules of a triple-helical region often is
an oligonucleotide. The term "nucleic acid" specifically includes
cDNAs. The term includes DNAs (including cDNAs) and RNAs that
contain one or more modified bases. Thus, DNAs or RNAs with
backbones modified for stability or for other reasons are "nucleic
acids" as referred to herein. DNAs or RNAs comprising unusual
bases, such as inosine, or modified bases, such as tritiated bases,
are included within the term "nucleic acid" as defined herein. In
general, the term "nucleic acid" embraces all chemically,
enzymatically and/or metabolically modified forms of unmodified
polynucleotides, as well as the chemical forms of DNA and RNA
characteristic of viruses and cells, including simple and complex
cells.
[0039] The term "oligonucleotide" refers to a relatively short
polynucleotide, including, without limitation, single-stranded
deoxyribonucleotides, single- or double-stranded ribonucleotides,
RNA:DNA hybrids and double-stranded DNAs. Oligonucleotides, such as
single-stranded DNA probe oligonucleotides, are often synthesized
by chemical methods, for example using automated oligonucleotide
synthesizers that are commercially available. However,
oligonucleotides are optionally made by a variety of other methods,
including in vitro recombinant DNA-mediated techniques and by
expression of DNAs in cells and organisms.
[0040] The terms "prediction," "predicting," "prognostic," or
"prognosis" are used herein to refer to the likelihood that a
patient will respond either favorably or unfavorably to a drug
(e.g., an anti-cancer compound) or set of drugs, and also the
extent of those responses. The predictive methods of described
herein are valuable tools in predicting if a patient suffering from
a cancer is likely to respond favorably to an HDAC inhibitor
compound treatment regimen alone or in combination with another
therapeutic agent (e.g., a second anti-cancer compound).
[0041] The term "subject" or "patient" refers to an animal which is
the object of treatment, observation or experiment. By way of
example only, a subject includes, but is not limited to, a mammal
including, but not limited to, a human.
[0042] The term "substantially purified" refers to a component of
interest that is substantially or essentially free of other
components which normally accompany or interact with the component
of interest prior to purification. By way of example only, a
component of interest is "substantially purified" when the
preparation of the component of interest contains less than about
30%, less than about 25%, less than about 20%, less than about 15%,
less than about 10%, less than about 5%, less than about 4%, less
than about 3%, less than about 2%, or less than about 1% (by dry
weight) of contaminating components. Thus, a "substantially
purified" component of interest optionally has a purity level of
about 70%, about 75%, about 80%, about 85%, about 90%, about 95%,
about 96%, about 97%, about 98%, about 99% or greater.
[0043] The term "therapeutically effective amount" refers to the
amount of a composition administered to a patient already suffering
from a disease, condition or disorder, sufficient to cure or at
least partially arrest, or relieve to some extent one or more of
the symptoms of the disease, disorder or condition being treated.
The effectiveness of such compositions depend conditions including,
but not limited to, the severity and course of the disease,
disorder or condition, previous therapy, the patient's health
status and response to the drugs, and the judgment of the treating
physician. By way of example only, therapeutically effective
amounts are determined by methods, including but not limited to a
dose escalation clinical trial.
[0044] The terms "treat," "treating" or "treatment," include
alleviating, abating or ameliorating a disease or condition
symptoms, preventing additional symptoms, ameliorating or
preventing the underlying metabolic causes of symptoms, inhibiting
the disease or condition, e.g., arresting the development of the
disease or condition, relieving the disease or condition, causing
regression of the disease or condition, relieving a condition
caused by the disease or condition, or stopping the symptoms of the
disease or condition. The terms "treat," "treating" or "treatment",
include, but are not limited to, prophylactic and/or therapeutic
treatments.
[0045] The term "tumor" or "cancer" refers to all neoplastic cell
growth and proliferation, whether malignant or benign, and all
pre-cancerous and cancerous cells and tissues.
[0046] Unless otherwise indicated, conventional methods of cell
culture, protein chemistry, biochemistry, recombinant DNA
techniques including gene amplification and hybridization
techiques, mass spectroscopy, and pharmacology, are employed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] FIG. 1 is an illustrative schematic flow diagram of a method
for identifying biomarker genes for HDACi compound resistance in
cancer cells based on gene expression profiling, and the clinical
application of expression profiling of the identified biomarker
genes.
[0048] FIG. 2 is an illustrative graph showing in vitro inhibition
of cell proliferation versus concentration of the HDACi compound
PCI-24781 for a series of colon carcinoma cell lines.
[0049] FIG. 3 is an illustrative flow diagram illustrating the
statistical approach used to analyze microarray data to identify
differentially expressed genes in populations of cancer cells
resistant to a HDACi compound versus cancer cells that are
sensitive to the compound.
[0050] FIG. 4 is an illustrative scatter plot illustrating
principal component analysis of gene expression microarray data in
HDACi compound-treated and untreated cancer cells, and sensitive
and resistant cancer cells.
[0051] FIG. 5 is an illustrative bar graph comparing the results of
a microarray method versus TaqMan.RTM. quantitative RT-PCR method
for determining the ratio of mRNA expression levels for a series of
identified HDACi compound resistance biomarker genes in
PCI-24781-resistant versus PCI-24781 colon carcinoma cells.
[0052] FIG. 6 is an illustrative bar graph comparing relative
expression levels of four HDACi compound resistance biomarker genes
in cancer cells that are resistant to the HDAC inhibitor compound
(PCI-24781) versus expression of the biomarker genes in cancer
cells that are sensitive to the compound.
[0053] FIG. 7(A) is an illustrative bar graph showing the time
course of tubulin acetylation in peripheral blood mononuclear cells
from mice treated with the HDAC inhibitor compound PCI-24781; (B)
is a time course of the expression profile of genes whose mRNA
levels are correlated with changes in tubulin acetylation.
[0054] FIG. 8 is an illustrative set of two line graphs
illustrating the expression profiles of two HDAC
inhibitor-responsive biomarker genes as determined by microarray
analysis, quantitative RT-PCR, and immunoblotting.
[0055] FIG. 9 is an illustrative bar graph showing average in vivo
mRNA levels in various tissues of five of the HDAC
inhibitor-responsive biomarker genes at 3 and 8 hours post-HDAC
inhibitor treatment.
[0056] FIG. 10 is an illustrative series of dose response curves
for the effect of the HDAC inhibitor PCI-24781 on tumors derived
from the indicated tumors
[0057] FIG. 11(A) is a series of line graphs illustrating the
amount of in vitro growth inhibition by the HDAC inhibitor
PCI-24781 of primary colon tumor cells derived from newly
diagnosed, naive colon cancer patients; (B) is a series of line
graphs illustrating the amount of in vitro growth inhibition by the
HDAC inhibitor PCI-24781 of colon cancer cells derived from
patients having advanced, metastatic colon tumors; (C) is a bar
graph illustrating the correlation between metastatic tumor cell
resistance to an HDAC inhibitor in vitro and the mRNA expression
level of the HDAC resistance biomarker gene DEFA6.
DETAILED DESCRIPTION OF THE INVENTION
[0058] The methods described herein include classifying a cancer in
a patient as resistant or sensitive to a histone deacetylase
inhibitor (HDACi) compound by comparing the expression levels of at
least four biomarker genes expressed in the cancer to biomarker
gene expression level threshold values, as described herein. Where
the expression levels of at least four biomarker genes are greater
than the expression level threshold values, the cancer is indicated
as being resistant to the HDACi compound. Conversely, if the
expression levels of the at least four biomarker genes are lower
than the expression level threshold values, the cancer is indicated
to be sensitive to the HDACi compound.
[0059] Also described herein is a population of nucleic acids
derived from a cancer cell, where the cancer cell is a type of
cancer cell that is resistant to an HDACi compound. Further
described herein is a population of nucleic acids derived from a
cancer cell, where the cancer cell is a type of cancer cell that is
sensitive to an HDACi compound. Also described herein are methods
for generating these populations of nucleic acids. Such populations
of nucleic acids are optionally used as expression level reference
standards for setting biomarker gene expression threshold levels as
described herein. Further described herein are cell lines
determined to be resistant to an HDACi compound. Also described
herein are cell lines determined to be sensitive to an HDACi
compound.
[0060] Also described herein is a method for increasing the
likelihood of therapeutically effective treatment of a cancer with
an HDACi compound by providing an indication that a cancer is
sensitive to treatment with an HDACi compound if the expression
levels of at least four of the biomarker genes described herein are
lower than the expression level threshold values for those
biomarker genes, or providing an indication that a cancer is
resistant to treatment with an HDACi compound if the expression
levels of at least four of the biomarker genes described herein are
higher than the expression level threshold values for those
biomarker genes.
[0061] Further described herein are methods for optimizing
selection of an anti-cancer agent for treating cancer in
combination with an HDACi compound by comparing a first set of
biomarker genes the expression of which is correlated to resistance
or sensitivity of the cancer to the anti-cancer agent to a second
set of biomarker genes the expression of which is correlated with
resistance to the HDACi compound, and then selecting the
anti-cancer agent for treatment of the cancer in combination with
the HDAC inhibitor only if all of the biomarker genes in the first
set are different from the biomarker genes in the second set.
Identification of HDACi Compound Resistance Biomarker Genes
(HDACiR-BGs)
[0062] Described herein are methods for identifying genes whose
expression levels in cancer cells are significantly and
consistently correlated with resistance of the cells to an HDACi
compound. Such genes are termed HDACi compound resistance biomarker
genes (HDACiR-BGs). In an exemplary embodiment, HDACiR-BGs are
identified as follows.
[0063] The ex-vivo response of primary tumor cells (e.g., colon
cancer cells) from various patients to an HDAC inhibitor is
determined by culturing the cells in the presence of varying
concentrations of the HDACi compound.
[0064] After determining the HDACi compound sensitivity the cancer
cells from each patient, mRNA expression profiles are determined
for HDACi-resistant and sensitive tumors. Total RNA is isolated and
fluorescent probes are prepared and hybridized to a whole genome
cDNA microarray (e.g., Codelink Human Whole Genome oligonucleotide
microarrays containing .about.55,000 unique probes; GE Healthcare
Bio-Sciences Corp., Piscataway, N.J.) according to the
manufacturer's instructions. Following hybridization, the
microarrays are scanned (e.g., in a GenePix 4000B scanner;
Molecular Devices Corporation, Sunnyvale Calif.). The images are
then processed with Codelink software and the data are normalized
to the median.
[0065] The median-normalized microarray data are imported into a
microarray data analysis program for principal component analysis
(PCA) and hierarchical clustering analysis (e.g., Genespring
software from Agilent). Multiple analysis methods are employed to
provide additional confidence in the mRNA expression analysis. For
multiple hypothesis correction, the q-values approach for false
discovery rates (FDR) are optionally used as described in Storey et
al. (2003), Proc. Nat. Acad. Sci. USA, 100:9440-9445. As a second
analytical approach the Bayesian ANOVA approach described in
Ishwaran et al. (2003), J. Amer. Stat. Assoc., 98:438-455 is
optionally used.
[0066] In the Bayesian ANOVA method, the contributions of
irrelevant genes to the ANOVA model are selectively shrunk to
balance total false detections against total false non-detections.
The output is a Zcut score which identifies genes whose
contribution to the ANOVA model is larger than the standard
z-score. See Ishwaran et al., ibid., and the website at
bamarray.com.
[0067] The just-described method and variants thereof is optionally
used to identify biomarker genes for other specific phenotypic
states, e.g., resistance to anti-cancer agents other than HDACi
compounds.
[0068] HDACiR-BGs identified by the just-described methods include
those listed in Table 1. The sequence for the mRNA of each of the
listed genes is included herein in an appendix.
TABLE-US-00001 TABLE 1 HDACi Compound Resistance Biomarker Genes
(HDACiR-BGs) Gene GenBank SEQ Gene Name Symbol Accession # ID NO
PTPN3 PTPN3 AK096975 1 ATP-binding cassette, sub- ABCC3 NM_020037 2
family C (CFTR/MRP), member 3 specifically androgen-regulated SARG
NM_023938 3 protein phosphatidic acid phosphatase PPAP2C NM_177526
4 type 2C neural proliferation, NPDC1 NM_015392 5 differentiation
and control, 1 C-terminal tensin-like CTEN NM_032865 6 RAB25,
member RAS oncogene RAB25 NM_020387 7 family Hephaestin HEPH
NM_138737 8 thiopurine S-methyltransferase TPMT NM_000367 9
plakophilin 3 PKP3 NM_007183 10 UDP-N-acetyl-alpha-D- GALNT5
NM_014568 11 galactosamine:polypeptide N-
acetylgalactosaminyltransferase 5 (GalNAc-T5) calmodulin-like 4
CALML4 NM_033429 12 UDP-N-acetyl-alpha-D- GALNT12 AK024865 13
galactosamine:polypeptide N- acetylgalactosaminyltransferase 12
(GalNAc-T12) thiamin pyrophosphokinase 1 TPK1 NM_022445 14
defensin, alpha 6, Paneth cell- DEFA6 NM_001926 15 specific
epithelial protein lost in EPLIN NM_016357 16 neoplasm beta
chloride intracellular channel 5 CLIC5 NM_016929 17 PERP, TP53
apoptosis effector PERP NM_022121 18 spleen tyrosine kinase SYK
NM_003177 19 solute carrier family 12 SLC12A2 NM_001046 20
(sodium/potassium/chloride transporters), member 2 guanylate
cyclase 2C (heat GUCY2C NM_004963 21 stable enterotoxin receptor)
transmembrane 4 superfamily TM4SF4 NM_004617 22 member 4
transforming growth factor, TGFA NM_003236 23 alpha fibroblast
growth factor binding FGFBP1 NM_005130 24 protein 1 PTK6 protein
tyrosine kinase 6 PTK6 NM_005975 25 epithelial V-like antigen 1
EVA1 NM_005797 26 EPH receptor A2 EPHA2 NM_004431 27 integrin,
alpha 6 ITGA6 NM_000210 28 tumor necrosis factor receptor TNFRSF21
NM_014452 29 superfamily, member 21 transmembrane 4 superfamily
TM4SF3 NM_004616 30 member 3 interleukin 18 (interferon- IL18
NM_001562 31 gamma-inducing factor) bone morphogenetic protein 4
BMP4 NM_130850 32 sphingomyelin SMPDL3B NM_014474 33
phosphodiesterase, acid-like 3B transmembrane protease, serine 2
TMPRSS2 NM_005656 34 guanine deaminase GDA NM_004293 35 macrophage
stimulating 1 MST1R NM_002447 36 receptor (c-met-related tyrosine
kinase) integrin, beta 4 ITGB4 NM_000213 37 annexin A3 ANXA3
NM_005139 38 chemokine (C-C motif) ligand 15 CCL15 NM_032965 39
dipeptidase 1 (renal) DPEP1 NM_004413 40 NADPH oxidase organizer 1
NOXO1 NM_172167 41 interferon, alpha-inducible IFI27 NM_005532 42
protein 27 cytochrome P450, family 3, CYP3A43 NM_057095 43
subfamily A, polypeptide 43 plakophilin 2 PKP2 NM_004572 44
Classification of Individual Patient Cancers as Resistant or
Sensitive to an HDACi Compound
[0069] In some embodiments, gene expression profiling is performed
on a biological sample obtained from an individual patient
suffering from a cancer (e.g., a colon cancer tumor) to classify
the cancer in the patient as resistant or sensitive to an HDACi
compound. The gene expression profiling includes profiling the
expression of at least one of the HDACi compound resistance
biomarker genes (HDACiR-BGs) listed in Table 1, which were
identified as described herein.
[0070] In some embodiments the HDACiR-BG is selected from among
DEFA6, TM4SF4, TGFA, FGFBP1, EPHA2, TNFRSF2, TM4SF3, IL18, TMPRSS2,
and CCL15.
[0071] In some embodiments, at least four of the HDACiR-BGs are
expression profiled. In some embodiments, at least one of the four
HDACiR-BGs are selected from among DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF3, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, or DPEP1. In some embodiments, all of the at least four
HDACiR-BGs are selected from among DEFA6, ITGB4, TM4SF4, SYK,
PPAP2C, RAB25, HEPH, NOXO1, TM4SF3, PTPN3, EPHA2, FGFBP1, ABCC3,
TPMT, IL18, or DPEP1.
[0072] In some embodiments, the expression of at least sixteen of
the HDACiR-BGs is profiled. In some embodiments, the at least
sixteen HDACiR-BGs include one or more of DEFA6, ITGB4, TM4SF4,
SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF3, PTPN3, EPHA2, FGFBP1,
ABCC3, TPMT, IL18, or DPEP1. In some embodiments, the at least 16
HDACiR-BGs include DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH,
NOXO1, TM4SF3, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, or
DPEP1.
[0073] In various embodiments, the types of cancers and tumors that
are optionally classified (from individual patients) for resistance
or sensitivity to an HDACi compound include, but are not limited
to, colorectal cancer, ovarian cancer, pancreatic cancer biliary
tract cancer; bladder cancer; bone cancer; brain and CNS cancer;
breast cancer; cervical cancer; choriocarcinoma; connective tissue
cancer; cancer of the digestive system; endometrial cancer;
esophageal cancer; eye cancer; cancer of the head and neck; gastric
cancer; intra-epithelial neoplasm; kidney cancer; larynx cancer;
leukemia; liver cancer; lung cancer (e.g., small cell and non-small
cell); lymphoma including Hodgkin's and non-Hodgkin's lymphoma;
melanoma; myeloma; neuroblastoma; oral cavity cancer (e.g., lip,
tongue, mouth, and pharynx); prostate cancer; retinoblastoma;
rhabdomyosarcoma; rectal cancer; renal cancer; cancer of the
respiratory system; sarcoma; skin cancer; stomach cancer;
testicular cancer; thyroid cancer; uterine cancer; cancer of the
urinary system, as well as other carcinomas and sarcomas.
[0074] Types of cancer cells that are optionally classified in
various embodiments include, but are not limited to, squamous cell
papilloma, squamous cell carcinoma, basal cell tumor, basal cell
carcinoma, transitional cell papilloma, transitional cell
carcinoma, glandular epithelium adenoma, melanocytes glomus tumor,
melanocytic nevus, malignant melanoma, fibroma, fibrosacroma, an
adenocarcinoma, gastrinoma, malignant gastrinoma, an oncocytoma,
cholangiocellular adenoma, cholangiocellular carcinoma,
hepatocellular adenoma, hepatocellular carcinoma, renal tubular
adenoma, renal cell carcinom(Grawitz tumor), myxoma, myxosarcoma,
lipoma, liposarcoma, leiomyoma, leiomyosarcoma, rhabdomyoma,
rhabdomyosarcoma, benign teratoma, malignant teratoma, hemangioma,
hemangiosarcoma, Kaposi sarcoma, lymphangioma, lymphangiosarcoma,
an osteoma, an osteosarcoma, an osteogenic sarcoma, cartilage
chondroma, chondrosarcoma, meninges meningioma, malignant
meningioma, oligoastrocytoma, an ependymoma, an astrocytoma,
pilocytic astrocytoma, glioblastommultiforme, an oligodendroglioma,
neuroblastoma, schwanoma, retinoblastoma, or neurofibroma. Other
types of cancers and tumors include those described in reference
sources, e.g., the "International Classification of Diseases for
Oncology," 3rd Edition, International Association of Cancer
Registries.
[0075] A biological sample is any biological sample that includes
cellular material from which DNA, RNA or protein are optionally
isolated, e.g., solid tissue samples, such as a biopsy specimen or
tissue cultures or cells derived therefrom and the progeny thereof,
blood and other liquid samples of biological origin, e.g., sputum
(including saliva, buccal wash, or bronchial brush), stool, semen,
urine, ascitic fluid, cerebral spinal fluid, bladder wash, or
pleural fluid. The term "biological sample" also encompasses
samples that have been manipulated in any way after their
procurement, such as by treatment with reagents, solubilization, or
enrichment for certain components. The term encompasses a clinical
sample, and also includes cells in cell culture, cell supernatants,
cell lysates, serum, plasma, biological fluids, and tissue samples,
e.g., freshly collected tissue, frozen tissue, archived tissue,
orbiological fluids
[0076] In some embodiments, the biological sample is a tumor biopsy
(e.g., a core biopsy, a needle biopsy, or an excisional biopsy)
containing one or more cancer cells. In one embodiment the
biological sample is a population of cancer cells obtained by laser
capture dissection from a tumor tissue section as described in,
e.g., U.S. Pat. No. 6,040,139. Methods for optimizing tissue sample
preparation and processing for expression profiling include, e.g.,
Bova et al. (2005), Methods Mol. Med., 103:15-66.
[0077] In some embodiments, one or more cells (e.g., from a
cultured cancer cell line), are classified by determining the
expression levels of no more than four to fifty biomarker genes
described herein., e.g., 5, 6, 7, 8, 9, 10, 12, 16, 18, 20, 24, 30,
32, 35, 40, 44, 45, 47, or any other number of biomarker genes from
four to fifty. In some embodiments, four to fourty four of the
biomarker genes are selected from Table 3, e.g., 5, 6, 7, 8, 9, 10,
12, 16, 18, 20, 24, 30, 32, 35, 40, or any other number of
biomarker genes from four to fourty four is selected from Table 3.
In some embodiments, at least four of the biomarker genes are
selected from PTPN3, ABCC3, SARG, PPAP2C, NPDC1, CTEN, RAB25, HEPH,
TPMT, PKP3, GALNT5, CALML4, GALNT12, TPK1, DEFA6, EPLIN, CLIC5,
PERP, SYK, SLC12A2, GUCY2C, TM4SF4, TGFA, FGFBP1, PTK6, EVA1,
EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18, BMP4, SMPDL3B, TMPRSS2, GDA,
MST1R, ITGB4, ANXA3, CCL15, DPEP1, NOXO1, IF127, CYP3A43, and PKP2.
In some embodiments, the four to fifty biomarker comprises one or
more genes selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25,
HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, and
DPEP In some embodiments, classification of the cells comprises
comparing the determined expression levels to a first or second set
of expression level threshold values for the biomarker genes, and
indicating that the one or more cells are sensitive to a HDAC
inhibitor if the expression levels of the biomarker genes are lower
than the first set of expression level threshold values, or
indicating that the one or more cells are resistant to a HDAC
inhibitor if the expression levels are greater than the second set
of expression level threshold values. In some embodiments, the
expression of no more than four to twenty biomarker genes is
determined. In some embodiments, the expression levels of no more
than four biomarker genes is determined. In some embodiments, the
four biomarker genes the expression level of which is determined
are: DEFA6, RAB25, TM4SF4, and IL18.
Methods for HDACiR-BG Expression Profiling
[0078] HDACiR-BG expression profiles are optionally generated by
any convenient means for determining differential gene expression
between two samples, e.g. quantitative hybridization of mRNA,
labeled mRNA, amplified mRNA, cRNA, etc., quantitative PCR, ELISA
for protein quantitation, and the like.
[0079] In some embodiments, HDACiR-BG mRNA levels (including cDNA
copy or aRNA copies) are quantified. The expression profile is
optionally generated from the initial nucleic acid sample using any
convenient protocol. While a variety of different manners of
generating expression profiles are known, such as those employed in
the field of differential gene expression analysis, one
representative and convenient type of protocol for generating
expression profiles is array based gene expression profile
generation protocols. Such applications are hybridization assays in
which a nucleic acid that displays "probe" nucleic acids for each
of the genes to be assayed/profiled in the profile to be generated
is employed. In these assays, a sample of target nucleic acids is
first prepared from the initial nucleic acid sample being assayed,
where preparation optionally includes labeling of the target
nucleic acids with a label, e.g., a member of signal producing
system. Following target nucleic acid sample preparation, the
sample is contacted with the array under hybridization conditions,
whereby complexes are formed between target nucleic acids that are
complementary to probe sequences attached to the array surface.
HDACiR-BG hybridization complexes are then detected and
quantified.
[0080] Specific hybridization technologies which are optionally
practiced to generate the HDACiR-BG expression profiles employed in
the methods described herein includes the technology described in
U.S. Pat. Nos. 5,143,854; 5,288,644; 5,324,633; 5,432,049;
5,470,710; 5,492,806; 5,503,980; 5,510,270; 5,525,464; 5,547,839;
5,580,732; 5,661,028; 5,800,992; as well as WO 95/21265; WO
96/31622; WO 97/10365; WO 97/27317; EP 373 203; and EP 785 280. In
these methods, an array of "probe" nucleic acids that includes a
probe for each of the phenotype determinative genes whose
expression is being assayed is contacted with target nucleic acids
as described above. Contact is carried out under hybridization
conditions, e.g., stringent hybridization conditions as those
conditions are practiced in the art, and unbound nucleic acid is
then removed. The resultant pattern of hybridized nucleic acid
provides quantitative information regarding expression for each of
the HDACiR-BGs that have been probed.
[0081] Evaluation of differences in expression values is optionally
performed using any convenient methodology, e.g., by comparing
digital images of the expression profiles, by comparing databases
of expression data, etc. Patents describing ways of comparing
expression profiles include, but are not limited to, U.S. Pat. Nos.
6,308,170 and 6,228,575 and U.S. patent application Ser. No.
10/858,867.
[0082] In some embodiments, the methods described herein are
performed on nucleic acid hybridization arrays comprising nucleic
acid probes that hybridize under high stringency hybridization
conditions to nucleic acids of no more than four to fifty biomarker
genes, e.g., 5, 6, 7, 8, 9, 10, 12, 16, 18, 20, 24, 30, 32, 35, 40,
44, 45, 47, or any other number of biomarker genes from four to
fifty. In some embodiments, four to fourty four of the biomarker
genes are selected from Table 3, e.g., 5, 6, 7, 8, 9, 10, 12, 16,
18, 20, 24, 30, 32, 35, 40, or any other number of biomarker genes
from four to fourty four is selected from Table 3. In some
embodiments, at least four of the biomarker genes for the array
probes are selected from PTPN3, ABCC3, SARG, PPAP2C, NPDC1, CTEN,
RAB25, HEPH, TPMT, PKP3, GALNT5, CALML4, GALNT12, TPK1, DEFA6,
EPLIN, CLIC5, PERP, SYK, SLC12A2, GUCY2C, TM4SF4, TGFA, FGFBP1,
PTK6, EVA1, EPHA2, ITGA6, TNFRSF21, TM4SF3, IL18, BMP4, SMPDL3B,
TMPRSS2, GDA, MST1R, ITGB4, ANXA3, CCL15, DPEP1, NOXO1, IF127,
CYP3A43, and PKP2. In some embodiments, the at least four biomarker
genes are selected from DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25,
HEPH, NOXO1, TM4SF4, PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, and
DPEP. In some embodiments, the at least four biomarker genes are
DEFA6, RAB25, TM4SF4, and IL18.
[0083] Alternatively, non-array based methods for quantitating the
levels of one or more nucleic acids in a sample are employed,
including quantitative PCR, and the like.
[0084] In some embodiments, expression profiling of HDACiR-BGs
expressed in a biological sample (e.g., a tumor biopsy) is done by
a quantitative reverse transcription PCR assay (qRT-PCR). In this
method, RNA from a biological sample is reverse transcribed to
generate segments of cDNA which are then be amplified by
gene-specific quantitative PCR. The rate of accumulation of
specific PCR products is optionally correlated to the abundance of
the corresponding RNA species in the original sample and thereby
provide an indication of gene expression levels.
[0085] In one embodiment, the qPCR assay is a TaqMan.TM. assay. In
brief, PCR typically utilizes the 5' exonuclease activity of Taq or
Tth polymerase to hydrolyze a fluorescently-labelled hybridization
probe bound to its target amplicon, but any enzyme with equivalent
5' exonuclease activity is optionally used. Two oligonucleotide
primers are used to generate an amplicon typical of a PCR reaction.
A third oligonucleotide, or probe, is designed to hybridize to a
nucleotide sequence located between the two PCR primers. The probe
is non-extendible by Taq DNA polymerase enzyme, and is 5' labeled
with a reporter fluorescent dye and a 3' labeled with a quencher
fluorescent dye. Any laser-induced emission from the reporter dye
is quenched by the quenching dye when the two dyes are located
close together as they are on the probe. During the amplification
reaction, the Taq DNA polymerase enzyme cleaves the probe in a
template-dependent manner. The resultant probe fragments
disassociate in solution, and signal from the released reporter dye
is free from the quenching effect of the second chromophore. One
molecule of reporter dye is liberated for each new molecule
synthesized, and detection of the unquenched reporter dye provides
the basis for quantitative interpretation of the data.
[0086] qRT-PCR is optionally performed using commercially available
equipment, such as, for example, the ABI PRISM 7900.TM. Sequence
Detection System.TM. (Perkin-Elmer-Applied Biosystems, Foster City,
Calif.), or LightCycler.TM.. (Roche Molecular Biochemicals,
Mannheim, Germany). In one embodiment, the 5' exonuclease procedure
is run on a real-time quantitative PCR device such as the ABI PRISM
7900.TM. Sequence Detection System.TM. or one of the similar
systems in this family of instruments. The system consists of a
thermocycler, laser, charge-coupled device (CCD), camera and
computer. The system amplifies samples in 96-well or 384 well
formats on a thermocycler. During amplification, laser-induced
fluorescent signal is collected in real-time through fiber optic
cables for all reaction wells, and detected at the CCD. The system
includes software for running the instrument and for analyzing the
data.
[0087] Exonuclease assay data are initially expressed as a C.sub.T
value, i.e., the PCR cycle at which the fluorescent signal is first
recorded as statistically significant.
[0088] In order to minimize errors and the effects of
sample-to-sample variation and process variability mRNA level
measurements are generally normalized to the expression level of an
internal expression control gene. Methods for normalizing qPCR
assays include, see, e.g., the website at
normalisation.gene-quantification.info. The ideal internal
expression control gene is one that is expressed at a relatively
constant level among different patients or subjects, and is
unaffected by the experimental treatment.
[0089] In some embodiments, the internal expression control gene is
RNA polymerase II (GenBank Accession No. X74870).
[0090] In other embodiments, the internal expression control gene
is HDAC3 (NM_003883).
[0091] In further embodiments, the internal expression control gene
is ZNF217 (NM_006526).
[0092] In some embodiments, HDAiR-BG mRNA expression levels for
each sample are normalized by the total amount of RNA in each
sample. The amount of RNA in a sample is optionally determined,
e.g., by UV-spectrophotometry or by using an RNA detection reagent,
e.g., RiboGreen.RTM. from Invitrogen (Carlsbad, Calif.).
[0093] Where the HDACiR-BG expression profile to be determined is a
protein expression profile, any convenient protein quantitation
protocol is optionally employed, where the levels of one or more
proteins in the assayed sample are determined. Representative
methods include, but are not limited to; proteomic arrays, mass
spectrometry, or standard immunoassays (e.g., RIA or ELISA). See,
e.g., the methods set forth in R. Scopes, Protein Purification,
Springer-Verlag, N.Y. (1982); Sandana (1997) Bioseparation of
Proteins, Academic Press, Inc.; Bollag et al. (1996) Protein
Methods. 2nd Edition Wiley-Liss, NY; Walker (1996) The Protein
Protocols Handbook Humana Press, NJ, Harris and Angal (1990)
Protein Purification: Principles and Practice 3rd Edition Springer
Verlag, NY; Janson and Ryden (1998) Protein Purification:
Principles, High Resolution Methods and Applications, Second
Edition Wiley-VCH, NY; and Satinder Ahuja ed., Handbook of
Bioseparations, Academic Press (2000); Harlow et al., Antibodies: A
Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring
Harbor, N.Y., 353-355 (1988).
[0094] Proteomic expression profiling methods detection methods
include various multidimensional electrophoresis methods (e.g., 2-D
gel electrophoresis), mass spectrometry based methods e.g., SELDI,
MALDI, electrospray, etc.), or surface plasmon reasonance methods.
For example, in MALDI, a sample is usually mixed with an
appropriate matrix, placed on the surface of a probe and examined
by laser desorption/ionization. See, e.g., U.S. Pat. Nos.
5,045,694, 5,202,561, and 6,111,251. Similarly, for SELDI, a first
aliquot is contacted with a solid support-bound (e.g.,
substrate-bound) adsorbent. A substrate is typically a probe (e.g.,
a biochip) that is optionally positioned in an interrogatable
relationship with a gas phase ion spectrometer. SELDI has been
applied to diagnostic proteomics. See, e.g. Issaq et al. (2003),
Anal. Chem. 75: 149A-155A.
[0095] In one embodiment, any of the just-described protein
detection methods are used to determine the expression level of one
or more HDACiR-BG proteins that are known to be secreted proteins,
e.g., DEFA6, TM4SF4, TM4SF3,TGFA, FGFBP1, EPHA2, TNFRSF2, IL18,
CCL15, or TMPRSS2.
Expression Level Reference Samples
[0096] In some embodiments, expression profiles of HDACiR-BGs in a
biological sample of interest (e.g., a colon cancer biopsy) are
compared to HDACiR-BG expression profiles in an expression level
reference sample. The expression level reference sample is a
biological sample derived from one or more cancer patients
determined to be suffering from a particular cancer or tumor for
which sensitivity or resistance to treatment with an HDACi compound
(e.g., PCI-24781) has been determined. In other words, the
expression level reference sample serves as a standard with which
to compare expression level values for each HDACiR-BG in a test
sample. The deviation of HDACiR-BG expression levels from the
expression level values in a reference sample indicates whether the
cancer in the patient from the biological sample was derived is
sensitive or resistant to treatment with an HDACi compound. In some
embodiments, HDACiR-BG threshold expression level values are
optionally set based on one or more statistical criteria for
deviation from HDACiR-BG expression level values in an expression
level reference sample, e.g., two or more SDs away from the value
for a reference sample HDACiR-BG expression level.
[0097] In some embodiments, the expression level reference sample
is a "negative" reference sample, i.e., a sample derived from a
patient having a cancer or tumor determined to be sensitive to an
HDACi compound. Thus, where expression levels of multiple
HDACiR-BGs (e.g. at least 4, 5, 6, 8, 10, 12, or 16) are
significantly greater than the threshold expression level values
based on the negative reference sample, the patient's cancer is
indicated as resistant to the HDACi compound.
[0098] In some embodiments, the expression level reference sample
is a "positive" reference sample, i.e., a sample derived from a
patient having a cancer or tumor determined to be resistant to an
HDACi compound.
[0099] Thus, where expression levels of multiple HDACiR-BGs (e.g.
at least 4, 5, 6, 8, 10, 12, or 16) are significantly lower than
the threshold expression level values based on the negative
reference sample, the patient's cancer is indicated as sensitive to
the HDACi compound.
[0100] In some embodiments, HDACiR-BG expression profiles are
compared to those in both positive and negative reference
samples.
[0101] In some embodiments, HDACiR-BGs expression level
measurements are performed in parallel for the biological sample of
interest and the (positive or negative) expression level reference.
For example, where an array hybridization method is used, HDACiR-BG
mRNA levels in the biological sample of interest and in an
expression level reference sample are optionally measured
simultaneously by separately labeling nucleic acid populations
(e.g., mRNA, cDNA, aRNA populations) from each with a detectably
distinct fluorophore, and then hybridizing the fluorescently
labeled nucleic acids to the same array.
[0102] In some embodiments an expression level reference sample is
a population of nucleic acids (e.g., mRNAs, aRNAs, cDNAs, or aRNAs)
derived from a cancer biopsy sample within which the sequences of
at least four HDACiR-BGs are represented, and for which sensitivity
to an HDACi compound has been determined. In some embodiments, the
population of nucleic acids is derived from patient tumor cells
cultivated in culture. In other embodiments, the population is
derived directly from a biopsy without a cell culture step.
[0103] In some embodiments, the population of nucleic acids serving
as an expression level reference sample is generated as follows. A
cancer biopsy is obtained from a patient as described above, and
afterwards viable tumors cells are then isolated and grown in
culture as described in, e.g., Kern et al. (1990), J. Natl. Cancer
Inst., 82:582-588. In order to determine if cancer cells are
sensitive to an HDACi compound, they are then grown in the presence
of the HDACi compound at a range of concentrations, e.g., (0-10
.mu.M), and cell proliferation is measured by any number of
methods, e.g., tritiated thymidine incorporation. Inhibition of
tumor cell proliferation by the HDACi compound is measured relative
to tumor cell proliferation in the absence of the compound (i.e.,
no inhibition). Assignment of the cancer as sensitive or resistant
is optionally determined based on a number of cell proliferation
criteria. For example, if the IC.sub.50 of the HDACi compound in
the tested cancer cells is significantly lower (e.g., by 2 SDs)
than that observed for cells known to be sensitive to the compound,
the cancer is characterized as resistant. Thus, cells derived from
the resistant cancer (e.g., directly or after passage in culture)
are optionally used to generate a population of nucleic acids
serving as an expression level (positive) reference sample used for
setting HDACiR-BG expression level threshold values as described
above. Conversely, tumor cells found to be sensitive to an HDACi
compound are used generate a population of nucleic acids serving as
an expression level (negative) reference sample.
[0104] Methods for obtaining RNA from biological samples (e.g.,
tissues or cells) including linear aRNA amplification from single
cells include, e.g., Luzzi et al. (2005), Methods Mol Biol.,
293:187-207. Further, diverse kits for high quality RNA
purification are available commercially, e.g., from Qiagen
(Valencia, Calif.), Invitrogen (Carlsbad, Calif.), Clontech (Palo
Alto, Calif.), and Stratagene (La Jolla, Calif.).
[0105] In some embodiments, the expression level reference sample
is an RNA sample isolated from one or more HDACi compound-resistant
colon cancer cells. In one embodiment, the cells were derived from
colon carcinoma biopsy R5247682266, R9866135153, R1078103114, or
R4712781606 described herein.
HDACi Inhibitor Compounds
[0106] In another embodiment, HDACi inhibitor tumor compounds for
which cancer resistance or sensitivity include, but are not limited
to carboxylates, short-chain fatty acids, hydroxamic acids,
electrophilic ketones, epoxides, cyclic peptides, and benzamides.
In a further embodiment, HDACi inhibitor tumor compounds for which
cancer resistance or sensitivity include, but are not limited to
hydroxamic acids having the structure of Formula (A):
##STR00001##
wherein [0107] Q is an optionally substituted C.sub.5-12 aryl or an
optionally substituted C.sub.5-12 heteroaryl; [0108] L is a linker
having at least 4 atoms; [0109] R.sup.1 is H or alkyl; and a
pharmaceutically acceptable salt, pharmaceutically acceptable
N-oxide, pharmaceutically active metabolite, pharmaceutically
acceptable prodrug, pharmaceutically acceptable solvate
thereof.
[0110] HDACi inhibitor tumor compounds for which cancer resistance
or sensitivity include, but are not limited to compounds having the
structure of Formula (I):
##STR00002##
wherein: [0111] R.sup.1 is hydrogen or alkyl; [0112] X is --O--,
--NR.sup.2--, or --S(O).sub.n where n is 0-2 and R.sup.2 is
hydrogen or alkyl; [0113] Y is alkylene optionally substituted with
cycloalkyl, optionally substituted phenyl, alkylthio,
alkylsulfinyl, alkysulfonyl, optionally substituted
phenylalkylthio, optionally substituted phenylalkylsulfonyl,
hydroxy, or optionally substituted phenoxy; [0114] Ar.sup.1 is
phenylene or heteroarylene wherein said Ar.sup.1 is optionally
substituted with one or two groups independently selected from
alkyl, halo, hydroxy, alkoxy, haloalkoxy, or haloalkyl; [0115]
R.sup.3 is hydrogen, alkyl, hydroxyalkyl, or optionally substituted
phenyl; and [0116] Ar.sup.2 is aryl, aralkyl, aralkenyl,
heteroaryl, heteroaralkyl, heteroaralkenyl, cycloalkyl,
cycloalkylalkyl, heterocycloalkyl, or heterocycloalkylalkyl; and
individual stereoisomers, individual geometric isomers, or mixtures
thereof; or a pharmaceutically acceptable salt thereof.
[0117] In another embodiment, HDACi inhibitor tumor compounds for
which cancer resistance or sensitivity include, but are not limited
to, PCI-24781.
[0118] In some embodiments, a patient is prescribed or administered
an HDAC inhibitor to the patient based on a classification of the
patient's cancer as being sensitive or resistant to an HDAC
inhibitor according to the methods described herein.
[0119] In some embodiments, the methods described herein are used
to optimize the selection of an anti-cancer agent for use in
combination with an HDACi compound. In some embodiments, optimized
selection of the second anti-cancer agent is performed by first
comparing the set of known biomarker genes for resistance to the
HDACi compound to sets of biomarker genes identified for other
anti-cancer agents. The second anti-cancer agent is then selected
for use in combination with the HDACi compound based on minimal
overlap of the respective sets of resistance biomarker genes.
[0120] Examples of anti-cancer agents that are optionally used in
combination with an HDACi compound include, but are not limited to,
any of the following: gossyphol, genasense, polyphenol E,
Chlorofusin, all trans-retinoic acid (ATRA), bryostatin, tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL),
5-aza-2'-deoxycytidine, all trans retinoic acid, doxorubicin,
vincristine, etoposide, gemcitabine, imatinib (Gleevec.RTM.),
geldanamycin, 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG),
flavopiridol, LY294002, bortezomib, trastuzumab, BAY 11-7082,
PKC412, or PD184352, Taxol.TM., also referred to as "paclitaxel",
is an anti-cancer drug which acts by enhancing and stabilizing
microtubule formation, and analogs of Taxol.TM., such as
Taxotere.TM.. Compounds that have the basic taxane skeleton as a
common structure feature, have also been shown to have the ability
to arrest cells in the G2-M phases due to stabilized microtubules
and are optionally useful for treating cancer in combination with
the compounds described herein.
[0121] Further examples of anti-cancer agents for use in
combination with an HDACi compound include inhibitors of
mitogen-activated protein kinase signaling, e.g., U0126, PD98059,
PD184352, PD0325901, ARRY-142886, SB239063, SP600125, BAY 43-9006,
wortmannin, or LY294002.
[0122] Other anti-cancer agents that are optionally employed in
combination with an HDACi compound include Adriamycin,
Dactinomycin, Bleomycin, Vinblastine, Cisplatin, acivicin;
aclarubicin; acodazole hydrochloride; acronine; adozelesin;
aldesleukin; altretamine; ambomycin; ametantrone acetate;
aminoglutethimide; amsacrine; anastrozole; anthramycin;
asparaginase; asperlin; azacitidine; azetepa; azotomycin;
batimastat; benzodepa; bicalutamide; bisantrene hydrochloride;
bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar
sodium; bropirimine; busulfan; cactinomycin; calusterone;
caracemide; carbetimer; carboplatin; carmustine; carubicin
hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin;
cladribine; crisnatol mesylate; cyclophosphamide; cytarabine;
dacarbazine; daunorubicin hydrochloride; decitabine; dexormaplatin;
dezaguanine; dezaguanine mesylate; diaziquone; doxorubicin;
doxorubicin hydrochloride; droloxifene; droloxifene citrate;
dromostanolone propionate; duazomycin; edatrexate; eflornithine
hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidine;
epirubicin hydrochloride; erbulozole; esorubicin hydrochloride;
estramustine; estramustine phosphate sodium; etanidazole;
etoposide; etoposide phosphate; etoprine; fadrozole hydrochloride;
fazarabine; fenretinide; floxuridine; fludarabine phosphate;
fluorouracil; flurocitabine; fosquidone; fostriecin sodium;
gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin
hydrochloride; ifosfamide; iimofosine; interleukin I1 (including
recombinant interleukin II, or r1L2), interferon alfa-2a;
interferon alfa-2b; interferon alfa-n1; interferon alfa-n3;
interferon beta-1a; interferon gamma-1b; iproplatin; irinotecan
hydrochloride; lanreotide acetate; letrozole; leuprolide acetate;
liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone
hydrochloride; masoprocol; maytansine; mechlorethamine
hydrochloride; megestrol acetate; melengestrol acetate; melphalan;
menogaril; mercaptopurine; methotrexate; methotrexate sodium;
metoprine; meturedepa; mitindomide; mitocarcin; mitocromin;
mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone
hydrochloride; mycophenolic acid; nocodazoie; nogalamycin;
ormaplatin; oxisuran; pegaspargase; peliomycin; pentamustine;
peplomycin sulfate; perfosfamide; pipobroman; piposulfan;
piroxantrone hydrochloride; plicamycin; plomestane; porfimer
sodium; porfiromycin; prednimustine; procarbazine hydrochloride;
puromycin; puromycin hydrochloride; pyrazofurin; riboprine;
rogletimide; safingol; safingol hydrochloride; semustine;
simtrazene; sparfosate sodium; sparsomycin; spirogermanium
hydrochloride; spiromustine; spiroplatin; streptonigrin;
streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur;
teloxantrone hydrochloride; temoporfin; teniposide; teroxirone;
testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin;
tirapazamine; toremifene citrate; trestolone acetate; triciribine
phosphate; trimetrexate; trimetrexate glucuronate; triptorelin;
tubulozole hydrochloride; uracil mustard; uredepa; vapreotide;
verteporfin; vinblastine sulfate; vincristine sulfate; vindesine;
vindesine sulfate; vinepidine sulfate; vinglycinate sulfate;
vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate;
vinzolidine sulfate; vorozole; zeniplatin; zinostatin; zorubicin
hydrochloride.
[0123] Other anti-cancer agents that are optionally employed in
combination with an HDACi compound include: 20-epi-1,25
dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin;
acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK
antagonists; altretamine; ambamustine; amidox; amifostine;
aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole;
andrographolide; angiogenesis inhibitors; antagonist D; antagonist
G; antarelix; anti-dorsalizing morphogenetic protein-1;
antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston;
antisense oligonucleotides; aphidicolin glycinate; apoptosis gene
modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA;
arginine deaminase; asulacrine; atamestane; atrimustine;
axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin;
azatyrosine; baccatin III derivatives; balanol; batimastat; BCR/ABL
antagonists; benzochlorins; benzoylstaurosporine; beta lactam
derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF
inhibitor; bicalutamide; bisantrene; bisaziridinylspermine;
bisnafide; bistratene A; bizelesin; breflate; bropirimine;
budotitane; buthionine sulfoximine; calcipotriol; calphostin C;
camptothecin derivatives; canarypox IL-2; capecitabine;
carboxamide-amino-triazole; carboxyamidotriazole; CaRest M3; CARN
700; cartilage derived inhibitor; carzelesin; casein kinase
inhibitors (ICOS); castanospermine; cecropin B; cetrorelix;
chlorins; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin;
cladribine; clomifene analogues; clotrimazole; collismycin A;
collismycin B; combretastatin A4; combretastatin analogue;
conagenin; crambescidin 816; crisnatol; cryptophycin 8;
cryptophycin A derivatives; curacin A; cyclopentanthraquinones;
cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor;
cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin;
dexamethasone; dexifosfamide; dexrazoxane; dexverapamil;
diaziquone; didemnin B; didox; diethylnorspermine;
dihydro-5-azacytidine; 9-dioxamycin; diphenyl spiromustine;
docosanol; dolasetron; doxifluridine; droloxifene; dronabinol;
duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab;
eflornithine; elemene; emitefur; epirubicin; epristeride;
estramustine analogue; estrogen agonists; estrogen antagonists;
etanidazole; etoposide phosphate; exemestane; fadrozole;
fazarabine; fenretinide; filgrastim; finasteride; flavopiridol;
flezelastine; fluasterone; fludarabine; fluorodaunorunicin
hydrochloride; forfenimex; formestane; fostriecin; fotemustine;
gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix;
gelatinase inhibitors; gemcitabine; glutathione inhibitors;
hepsulfam; heregulin; hexamethylene bisacetamide; hypericin;
ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine;
ilomastat; imidazoacridones; imiquimod; immunostimulant peptides;
insulin-like growth factor-1 receptor inhibitor; interferon
agonists; interferons; interleukins; iobenguane; iododoxorubicin;
ipomeanol, 4-; iroplact; irsogladine; isobengazole;
isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F;
lamellarin-N triacetate; lanreotide; leinamycin; lenograstim;
lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting
factor; leukocyte alpha interferon;
leuprolide+estrogen+progesterone; leuprorelin; levamisole;
liarozole; linear polyamine analogue; lipophilic disaccharide
peptide; lipophilic platinum compounds; lissoclinamide 7;
lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone;
lovastatin; loxoribine; lurtotecan; lutetium texaphyrin;
lysofylline; lytic peptides; maitansine; mannostatin A; marimastat;
masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase
inhibitors; menogaril; merbarone; meterelin; methioninase;
metoclopramide; MIF inhibitor; mifepristone; miltefosine;
mirimostim; mismatched double stranded RNA; mitoguazone;
mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast
growth factor-saporin; mitoxantrone; mofarotene; molgramostim;
monoclonal antibody, human chorionic gonadotrophin; monophosphoryl
lipid A+myobacterium cell wall sk; mopidamol; multiple drug
resistance gene inhibitor; multiple tumor suppressor 1-based
therapy; mustard anticancer agent; mycaperoxide B; mycobacterial
cell wall extract; myriaporone; N-acetyldinaline; N-substituted
benzamides; nafarelin; nagrestip; naloxone+pentazocine; napavin;
naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid;
neutral endopeptidase; nilutamide; nisamycin; nitric oxide
modulators; nitroxide antioxidant; nitrullyn; O6-benzylguanine;
octreotide; okicenone; oligonucleotides; onapristone; ondansetron;
ondansetron; oracin; oral cytokine inducer; ormaplatin; osaterone;
oxaliplatin; oxaunomycin; palauamine; palmitoylrhizoxin; pamidronic
acid; panaxytriol; panomifene; parabactin; pazelliptine;
pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin;
pentrozole; perflubron; perfosfamide; perillyl alcohol;
phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil;
pilocarpine hydrochloride; pirarubicin; piritrexim; placetin A;
placetin B; plasminogen activator inhibitor; platinum complex;
platinum compounds; platinum-triamine complex; porfimer sodium;
porfiromycin; prednisone; propyl bis-acridone; prostaglandin J2;
proteasome inhibitors; protein A-based immune modulator; protein
kinase C inhibitor; protein kinase C inhibitors, microalgal;
protein tyrosine phosphatase inhibitors; purine nucleoside
phosphorylase inhibitors; purpurins; pyrazoloacridine;
pyridoxylated hemoglobin polyoxyethylerie conjugate; raf
antagonists; raltitrexed; ramosetron; ras farnesyl protein
transferase inhibitors; ras inhibitors; ras-GAP inhibitor;
retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin;
ribozymes; RII retinamide; rogletimide; rohitukine; romurtide;
roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU;
sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence
derived inhibitor 1; sense oligonucleotides; signal transduction
inhibitors; signal transduction modulators; single chain
antigen-binding protein; sizofiran; sobuzoxane; sodium borocaptate;
sodium phenylacetate; solverol; somatomedin binding protein;
sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin;
spongistatin 1; squalamine; stem cell inhibitor; stem-cell division
inhibitors; stipiamide; stromelysin inhibitors; sulfinosine;
superactive vasoactive intestinal peptide antagonist; suradista;
suramin; swainsonine; synthetic glycosaminoglycans; tallimustine;
tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium;
tegafur; tellurapyrylium; telomerase inhibitors; temoporfin;
temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine;
thaliblastine; thiocoraline; thrombopoietin; thrombopoietin
mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan;
thyroid stimulating hormone; tin ethyl etiopurpurin; tirapazamine;
titanocene bichloride; topsentin; toremifene; totipotent stem cell
factor; translation inhibitors; tretinoin; triacetyluridine;
triciribine; trimetrexate; triptorelin; tropisetron; turosteride;
tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubenimex;
urogenital sinus-derived growth inhibitory factor; urokinase
receptor antagonists; vapreotide; variolin B; vector system,
erythrocyte gene therapy; velaresol; veramine; verdins;
verteporfin; vinorelbine; vinxaltine; vitaxin; vorozole;
zanoterone; zeniplatin; zilascorb; and zinostatin stimalamer.
[0124] Yet other anticancer agents that are optionally employed in
combination with an HDACi compound include alkylating agents,
antimetabolites, natural products, or hormones, e.g., nitrogen
mustards (e.g., mechloroethamine, cyclophosphamide, chlorambucil,
etc.), alkyl sulfonates (e.g., busulfan), nitrosoureas (e.g.,
carmustine, lomusitne, ete.), or triazenes (decarbazine, etc.).
Examples of antimetabolites include but are not limited to folic
acid analog (e.g., methotrexate), or pyrimidine analogs (e.g.,
Cytarabine), purine analogs (e.g., mercaptopurine, thioguanine,
pentostatin).
[0125] Examples of natural products useful in combination with an
HDACi compound include but are not limited to vinca alkaloids
(e.g., vinblastin, vincristine), epipodophyllotoxins (e.g.,
etoposide), antibiotics (e.g., daunorubicin, doxorubicin,
bleomycin), enzymes (e.g., L-asparaginase), or biological response
modifiers (e.g., interferon alpha).
[0126] Examples of alkylating agents that are optionally employed
in combination an HDACi compound include, but are not limited to,
nitrogen mustards (e.g., mechloroethamine, cyclophosphamide,
chlorambucil, meiphalan, etc.), ethylenimine and methylmelamines
(e.g., hexamethlymelamine, thiotepa), alkyl sulfonates (e.g.,
busulfan), nitrosoureas (e.g., carmustine, lomusitne, semustine,
streptozocin, etc.), or triazenes (decarbazine, ete.). Examples of
antimetabolites include, but are not limited to folic acid analog
(e.g., methotrexate), or pyrimidine analogs (e.g., fluorouracil,
floxouridine, Cytarabine), purine analogs (e.g., mercaptopurine,
thioguanine, pentostatin.
[0127] Examples of hormones and antagonists useful in combination
with an HDACi compound include, but are not limited to,
adrenocorticosteroids (e.g., prednisone), progestins (e.g.,
hydroxyprogesterone caproate, megestrol acetate,
medroxyprogesterone acetate), estrogens (e.g., diethlystilbestrol,
ethinyl estradiol), antiestrogen (e.g., tamoxifen), androgens
(e.g., testosterone propionate, fluoxymesterone), antiandrogen
(e.g., flutamide), gonadotropin releasing hormone analog (e.g.,
leuprolide). Other agents that are optionally used in the methods
and compositions described herein for the treatment or prevention
of cancer include platinum coordination complexes (e.g., cisplatin,
carboblatin), anthracenedione (e.g., mitoxantrone), substituted
urea (e.g., hydroxyurea), methyl hydrazine derivative (e.g.,
procarbazine), adrenocortical suppressant (e.g., mitotane,
aminoglutethimide).
[0128] Examples of anti-cancer agents which act by arresting cells
in the G2-M phases due to stabilized microtubules and which are
optionally used in combination with an HDACi compound include
without limitation the following marketed drugs and drugs in
development: Erbulozole (also known as R-55104), Dolastatin 10
(also known as DLS-10 and NSC-376128), Mivobulin isethionate (also
known as CI-980), Vincristine, NSC-639829, Discodermolide (also
known as NVP-XX-A-296), ABT-751 (Abbott, also known as E-7010),
Altorhyrtins (such as Altorhyrtin A and Altorhyrtin C),
Spongistatins (such as Spongistatin 1, Spongistatin 2, Spongistatin
3, Spongistatin 4, Spongistatin 5, Spongistatin 6, Spongistatin 7,
Spongistatin 8, and Spongistatin 9), Cemadotin hydrochloride (also
known as LU-103793 and NSC-D-669356), Epothilones (such as
Epothilone A, Epothilone B, Epothilone C (also known as
desoxyepothilone A or dEpoA), Epothilone D (also referred to as
KOS-862, dEpoB, and desoxyepothilone B), Epothilone E, Epothilone
F, Epothilone B N-oxide, Epothilone A N-oxide, 16-aza-epothilone B,
21-aminoepothilone B (also known as BMS-310705),
21-hydroxyepothilone D (also known as Desoxyepothilone F and
dEpoF), 26-fluoroepothilone), Auristatin PE (also known as
NSC-654663), Soblidotin (also known as TZT-1027), LS-4559-P
(Pharmacia, also known as LS-4577), LS-4578 (Pharmacia, also known
as LS-477-P), LS-4477 (Pharmacia), LS-4559 (Pharmacia), RPR-112378
(Aventis), Vincristine sulfate, DZ-3358 (Daiichi), FR-182877
(Fujisawa, also known as WS-9885B), GS-164 (Takeda), GS-198
(Takeda), KAR-2 (Hungarian Academy of Sciences), BSF-223651 (BASF,
also known as ILX-651 and LU-223651), SAH-49960 (Lilly/Novartis),
SDZ-268970 (Lilly/Novartis), AM-97 (Armad/Kyowa Hakko), AM-132
(Armad), AM-138 (Armad/Kyowa Hakko), IDN-5005 (Indena),
Cryptophycin 52 (also known as LY-355703), AC-7739 (Ajinomoto, also
known as AVE-8063A and CS-39.HCI), AC-7700 (Ajinomoto, also known
as AVE-8062, AVE-8062A, CS-39-L-Ser.HCI, and RPR-258062A),
Vitilevuamide, Tubulysin A, Canadensol, Centaureidin (also known as
NSC-106969), T-138067 (Tularik, also known as T-67, TL-138067 and
TI-138067), COBRA-1 (Parker Hughes Institute, also known as DDE-261
and WHI-261), H10 (Kansas State University), H16 (Kansas State
University), Oncocidin A1 (also known as BTO-956 and DIME), DDE-313
(Parker Hughes Institute), Fijianolide B, Laulimalide, SPA-2
(Parker Hughes Institute), SPA-1 (Parker Hughes Institute, also
known as SPIKET-P), 3-IAABU (Cytoskeleton/Mt. Sinai School of
Medicine, also known as MF-569), Narcosine (also known as
NSC-5366), Nascapine, D-24851 (Asta Medica), A-105972 (Abbott),
Hemiasterlin, 3-BAABU (Cytoskeleton/Mt. Sinai School of Medicine,
also known as MF-191), TMPN (Arizona State University), Vanadocene
acetylacetonate, T-138026 (Tularik), Monsatrol, Inanocine (also
known as NSC-698666), 3-1AABE (Cytoskeleton/Mt. Sinai School of
Medicine), A-204197 (Abbott), T-607 (Tuiarik, also known as
T-900607), RPR-115781 (Aventis), Eleutherobins (such as
Desmethyleleutherobin, Desaetyleleutherobin, Isoeleutherobin A, and
Z-Eleutherobin), Caribaeoside, Caribaeolin, Halichondrin B, D-64131
(Asta Medica), D-68144 (Asta Medica), Diazonamide A, A-293620
(Abbott), NPI-2350 (Nereus), Taccalonolide A, TUB-245 (Aventis),
A-259754 (Abbott), Diozostatin, (-)-Phenylahistin (also known as
NSCL-96F037), D-68838 (Asta Medica), D-68836 (Asta Medica),
Myoseverin B, D-43411 (Zentaris, also known as D-81862), A-289099
(Abbott), A-318315 (Abbott), HTI-286 (also known as SPA-110,
trifluoroacetate salt) (Wyeth), D-82317 (Zentaris), D-82318
(Zentaris), SC-12983 (NCI), Resverastatin phosphate sodium,
BPR-OY-007 (National Health Research Institutes), and SSR-250411
(Sanofi).
Applications of HDACiR-BGs
[0129] The methods and compositions described herein are optionally
used to increase the likelihood of a therapeutically effective
treatment of a patient's cancer with an HDACi compound by providing
an indication (e.g. by oral or written communication in any analog
or digital medium) of which genes are HDACiR-BGs, as well as
HDACiR-BG expression level reference values (e.g., expression level
threshold values) above which HDACi compound resistance is likely
(i.e., greater than the probability by chance) or below which HDACi
compound sensitivity is likely.
[0130] In some embodiments, the indication includes a document with
an interpretation of expression levels of at least four biomarker
genes selected from Table 1 as to the likelihood that a patient's
cancer is resistant or sensitive to treatment with an HDACi
compound.
[0131] In some embodiments, the document includes an interpretation
of the expression levels of at least one HDACiR-BG selected from
DEFA6, ITGB4, TM4SF4, SYK, PPAP2C, RAB25, HEPH, NOXO1, TM4SF4,
PTPN3, EPHA2, FGFBP1, ABCC3, TPMT, IL18, and DPEP1.
[0132] In some embodiments an indication is provided in one or more
databases containing information concerning one or more HDACiR-BGs,
including one or more expression level threshold values that permit
the interpretation of the effect of HDACiR-BG expression levels on
the resistance or sensitivity of a cancer to an HDACi compound
according to any of the methods described herein. Such expression
level threshold values include those set based on, e.g., deviation
of HDACiR-BG expression levels in a test sample from the
corresponding HDACiR-BG expression levels in an expression level
(positive or negative) reference sample as described herein.
Alternatively, or in addition, expression level threshold values
are optionally set based on deviation of the expression ratios of
HDACiR-BGs to one or more internal expression control genes (e.g.,
RNA polymerase II, HDAC3, or ZNF217). For example, as described
herein, the mean expression ratio (based on TaqMan fluorescence
intensity) of the HDACiR-BG DEFA6 to the internal expression
control gene ZNF217 is 5.83 in HDACi-resistant colon cancer cells
and 0.24 in HDACi-sensitive colon cancer cells.
[0133] In some embodiments, the databases include HDACiR-BG
expression level profiles or thresholds associated with resistance
to one or more HDACi compounds for one or more types of cancer.
[0134] Other information that is optionally included in the
databases or in other types of indication include, but are not
limited to, HDACiR-BG sequence information, frequency distributions
of HDACiR-BG expression levels in a particular cancer population,
descriptive information concerning the clinical status of a
biological sample analyzed for HDACiR-BG expression profiles, or
the clinical status of the patient from which the sample was
derived. The database is optionally be designed to include
different parts, for instance an HDACiR-BG list database, and an
informative HDACiR-BG expression profile database, e.g., a database
associating with each HDACiR-BG expression profile record the
probability that the expressin profile is associated with
resistance to an HDACi compound. Methods for the configuration and
construction of databases are widely available, for instance, see
U.S. Pat. No. 5,953,727.
[0135] The databases described herein are optionally linked to an
outside or external database. In some embodiments, the database
optionally communicates with outside data sources, such as database
of the developmental therapeutics program of the national cancer
institute or the National Center for Biotechnology Information
through the internet.
[0136] Any appropriate computer platform is used to perform the
methods for interpreting one or more HDACiR-BG expression profiles
by the methods described herein. In some embodiments, the computer
platform receive direct input from a database, e.g., one of the
databases described herein. For example, a large number of computer
workstations are available from a variety of manufacturers, such
has those available from Silicon Graphics. Client-server
environments, database servers and networks are also widely
available and are appropriate platforms for the databases described
herein.
[0137] The databases described herein are optionally used to
present information identifying a set of HDACiR-BG expression
profiles in an individual and such a presentation is optionally
used to predict or diagnose the likelihood of a effective
therapeutic treatment of the individual's cancer with a particular
HDACi compound based on a statistical comparison of the
individual's expression profile to HDACiR-BG expression level
thresholds as described herein. Accordingly, one chooses to
partition cancer patients into subgroups at any threshold value of
the measured HDACiR-BG expression, where all patients with
expression values above the threshold have higher risk, and all
patients with expression values below the threshold have lower
risk, of and HDACi compound-resistant cancer resistance or vice
versa, depending on whether the expression level threshold is based
on an expression level in a cancer determined to be resistant to an
HDACi compound treatment (i.e., a positive reference sample) or
sensitive to the HDACi compound treatment (i.e., a negative
reference sample). Alternatively, HDACiR-BG expression profiles
ranked on a probability continuum, where the more an HDACiR-BG
expression level deviates negatively from (i.e., is less than) an
expression level positive reference value, the higher the
probability that the cancer is sensitive to treatment with an HDACi
compound. Conversely, the more an HDACiR-BG expression level
deviates positively from (i.e., is greater than) an expression
level negative reference value, the higher the probability that the
cancer is resistant to treatment with an HDACi compound.
EXAMPLES
[0138] The following specific examples are to be construed as
merely illustrative, and not limitative of the remainder of the
disclosure in any way whatsoever. Without further elaboration, it
is believed that one skilled in the art can, based on the
description herein, utilize the present invention to its fullest
extent.
Example 1
mRNA Expression Profiling of HDACi Sensitive Versus Resistant
Colorectal Tumor Cells Ex Vivo
[0139] We and others previously developed several pharmacodynamic
markers for HDACi compounds (such as tubulin or histone
acetylation, p21 expression etc). However, there is currently no
clinically predictive biomarker for response to these agents
available. In this work, we developed a strategy to identify such
biomarkers for the HDACi compound PCI-24781 in primary human
colorectal tumors.
[0140] The method used soft agar chemosensitivity assays in which
primary human tumors were exposed in culture to PCI-24781. Either a
trititated thymidine or alamar blue assay was then used to estimate
the percentage of resistance to PCI-24781. For example in the
trititated thymidine assay, sensitive tumor cells affected by the
drug divided less and therefore incorporated less thymidine,
whereas resistant tumor cells continued to grow and divide and
therefore incorporated more thymidine into their DNA. It has been
shown historically that under the optimized conditions of this
assay, a patient whose tumor is classified as resistant to a given
drug has <1% probability of response to that drug in the clinic
(in published correlations to clinical outcome, these assays
predicted resistance with an accuracy of 99% in solid cancers and
92% in blood cancers). For example, a recent paper correlated in
vitro sensitivity or resistance to fludarabine in the DiSC assay in
B-cell CLL patients with clinical outcome (median survival 7.9
months in resistant vs 41.7 months in sensitive patients). Similar
data has also been published for solid tumors : e.g., for
sensitivity or resistance to Pt in ovarian tumors, and to CPX and
DOX in breast tumors.
[0141] After determining ex vivo sensitivity or resistance to
PCI-24781 for each tumor, RNA isolated from tumor cells was then
profiled on microarrays and a marker set was identified by
statistical analysis of the data. This marker set was validated by
RT-PCR (TaqMan.TM.) analysis. Such pharmacogenomic biomarkers that
are used for patient stratification in the clinic provide a
competitive advantage in the development of PCI-24781. A graphic
summary of the method and its clinical applications is illustrated
in FIG. 1.
[0142] We examined the ex-vivo response of primary colorectal
tumors from various patients to an HDAC inhibitor, PCI-24781, and
subsequently determined whether there were robust differences in
the mRNA expression profiles of sensitive versus resistant tumor
cells prior to HDACi treatment.
[0143] Primary colorectal cancer (CRC) samples were obtained from
patient biopsies (Table 2). Viable tumor cells were plated and
cultured in soft agar as described in Kern et al. (1990), J. Natl.
Cancer Inst., 82:582-588, and were treated with a range of
PCI-24781 concentrations (0.01-2 .mu.M). Tritiated thymidine was
added to the culture after 3 days of exposure to the drug, and the
amount of radioactivity incorporated into the cells after a further
2 days was quantified. The percentage of cell growth inhibition (%
GI) was calculated by comparing the treated cells to the control
cells, and from these growth profiles the tumors were classified as
either sensitive or resistant based on deviation from the median
profile. As shown in FIG. 2, primary tumors displayed a spectrum of
growth inhibition phenotypes from 100% to 0% relative to control at
the PCI-24781concentrations tested (up to 2 .mu.M).
TABLE-US-00002 TABLE 2 Clinical data for colorectal cancer biopsies
Clinical Research ID Cancer Name Age Sex Site Diagnosis Histology
Specimen Type R1078103114 Colon Carcinoma 54 F R Ovary Colon
Carcinoma ADENOCARCINOMA Solid Tumor Biopsy R1105698572 Colon
Carcinoma 72 F Portion of Terminal Ileum Colon Carcinoma NA Solid
Tumor Biopsy R2163560366 Colon Carcinoma 58 F Uterus Rectal Cancer
NA Solid Tumor Biopsy R4712781606 Colon Carcinoma 59 M Colon
Resection Colon Carcinoma NA Solid Tumor Biopsy R5247682266 Colon
Carcinoma 51 F Upper Lobe Lung Colon Carcinoma ADENOCARCINOMA Solid
Tumor Biopsy R5891015174 Colon Carcinoma 43 F Colon Cecal Carcinoma
NA Solid Tumor Biopsy R6173297194 Colon Carcinoma 65 M Omentum
Colon Carcinoma ADENOCARCINOMA, Solid Tumor Biopsy R7103644976
Colon Carcinoma 52 F R Tube & Ovary Colon Cancer NA Solid Tumor
Biopsy R9866135153 Colon Carcinoma 55 F R Hepatic Lobe Colon
Carcinoma ADENOCARCINOMA Solid Tumor Biopsy R2881036089 Colon
Carcinoma 79 F Colon Colon Carcinoma CARCINOMA, PD Solid Tumor
Biopsy R5492724373 Colon Carcinoma 55 F Cecum Colon Carcinoma COLON
CARCINOMA Solid Tumor Biopsy R8624442989 Colon Carcinoma 47 F Brain
Colon Carcinoma NA Solid Tumor Biopsy R0948311023 Colon Carcinoma
33 F L Lower Lung Lobe Nodule Colon Carcinoma ADENOCARCINOMA, Solid
Tumor Biopsy R1059261097 Colon Carcinoma 50 M Liver Colon Cancer
ADENOCARCINOMA Solid Tumor Biopsy R2191729233 Colon Carcinoma 62 F
Ovary Colon Cancer ADENOCARCINOMA Solid Tumor Biopsy R4498160614
Colon Carcinoma 40 F L Ovary Colon Carcinoma ADENOCARCINOMA Solid
Tumor Biopsy R4891777011 Colon Carcinoma 53 F R Abdominal Sidewall
Colon Carcinoma ADENOCARCINOMA Solid Tumor Biopsy R5456781761 Colon
Carcinoma 65 F Liver Lobes 5&6 Met. Colon CA to L NA Solid
Tumor Biopsy R5978110794 Colon Carcinoma 63 F Sigmoid Rectum Colon
Carcinoma NA Solid Tumor Biopsy R6289195776 Colon Carcinoma 56 M
Liver Colon Carcinoma ADENOCARCINOMA Solid Tumor Biopsy R6324805249
Colon Carcinoma 55 F Ovary Colon Carcinoma ADENOCARCINOMA Solid
Tumor Biopsy R7424107588 Colon Carcinoma 48 M Lumbar/Spine Biopsy
Colon Carcinoma NA Solid Tumor Biopsy R8701041232 Colon Carcinoma
65 M Sigmoid Colon Colon Carcinoma ADENOCARCINOMA Solid Tumor
Biopsy R9418488310 Colon Carcinoma 55 F Cecum Colon Carcinoma
ADENOCARCINOMA Solid Tumor Biopsy
resistant and sensitive tumors that were treated with PCI-24781 (2
.mu.M) or untreated. Total RNA was isolated using Qiagen procedures
(Qiagen, Inc., Valencia, Calif.) and fluorescent probes were
prepared and hybridized to Codelink Human Whole Genome
oligonucleotide microarrays containing .about.55,000 unique probes
(GE Healthcare Bio-Sciences Corp., Piscataway, N.J.) according to
the manufacturer's instructions. The microarrays were scanned in a
GenePix 4000B scanner (Molecular Devices Corporation, Sunnyvale
Calif.). The images were processed with Codelink software and the
exported data was analyzed as follows.
[0144] The median-normalized microarray data were imported into
Genespring software (Agilent), and principal component analysis
(PCA) and hierarchical clustering analysis were performed. We
looked for consistent results from multiple analysis methods to
provide additional confidence in our results. For multiple
hypothesis correction, we used the q-values approach for false
discovery rates (FDR) as described in Storey et al. (2003), Proc.
Nat. Acad. Sci. USA, 100:9440-9445. As a second analytical approach
we adopted the Bayesian ANOVA approach described in Ishwaran et al.
(2003), J. Amer. Stat. Assoc., 98:438-455.
[0145] In the Bayesian ANOVA method, the contribution of irrelevant
genes to the ANOVA model are selectively shrunk to balance total
false detections against total false non-detections. The output is
a Zcut score which identifies genes whose contribution to the ANOVA
model is larger than the standard z-score. See Ishwaran et al.,
ibid., and the website at bamarray.com. For the identification of
biomarkers predictive of PCI-24781 resistance, we used only the
untreated control samples divided into pools based on the
sensitivity or resistance classification in the assay described
above. This analytical approach is summarized in FIG. 3.
[0146] As shown in FIG. 4, principal components analysis clearly
distinguished untreated cell expression profiles from treated cell
expression profiles. Controls (arrowhead) are more similar to each
other and well separated from the treated samples. The major
component PCA1 clearly resolves treated from control samples.
Interestingly, the resistant cell expression profiles (circled in
both the treated and untreated samples) clustered together before
and after treatment, whereas the sensitive samples varied widely in
their profiles after treatment with PCI-24781. This suggested that
it is easier to identify patients with the most resistant tumors
and exclude them from a clinical trial rather than to identifying
patients with sensitive tumors.
[0147] Based on the microarray analysis, we identified a total of
44 genes (see table 3) whose level of expression was significantly
higher (z-score greater than 3.5) in PCI-24781 resistant cells than
in PCI-24781 sensitive cells (data not shown). Of note, the
expression of the identified biomarker genes was not altered by
treatment with PCI-24781.
TABLE-US-00003 TABLE 3 Microarray Analysis: Upregulated Genes in
PCI-24781-resistant Colorectal Tumor Cells Res./Sens. GenBank Fold
Expression Gene Name Gene Symbol Accession # z-score Difference
PTPN3 PTPN3 AK096975 14.19 2.58 ATP-binding cassette, sub- ABCC3
NM_020037 13.24 2.37 family C (CFTR/MRP), member 3 specifically
androgen-regulated SARG NM_023938 13.04 4.00 protein phosphatidic
acid phosphatase PPAP2C NM_177526 12.95 4.75 type 2C neural
proliferation, NPDC1 NM_015392 11.88 2.45 differentiation and
control, 1 C-terminal tensin-like CTEN NM_032865 11.32 3.83 RAB25,
member RAS RAB25 NM_020387 10.96 3.51 oncogene family hephaestin
HEPH NM_138737 10.49 3.38 Thiopurine S-methyltransferase TPMT
NM_000367 9.97 2.56 plakophilin 3 PKP3 NM_007183 9.31 3.13
UDP-N-acetyl-alpha-D- GALNT5 NM_014568 9.31 2.54
galactosamine:polypeptide N- acetylgalactosaminyltransferase 5
(GalNAc-T5) calmodulin-like 4 CALML4 NM_033429 9.14 3.51
UDP-N-acetyl-alpha-D- GALNT12 AK024865 8.86 2.51
galactosamine:polypeptide N- acetylgalactosaminyltransferase 12
(GalNAc-T12) thiamin pyrophosphokinase 1 TPK1 NM_022445 8.81 3.55
defensin, alpha 6, Paneth cell- DEFA6 NM_001926 8.58 12.92 specific
epithelial protein lost in EPLIN NM_016357 8.49 2.33 neoplasm beta
chloride intracellular channel 5 CLIC5 NM_016929 7.20 3.60 PERP,
TP53 apoptosis effector PERP NM_022121 6.94 2.60 spleen tyrosine
kinase SYK NM_003177 6.90 3.59 solute carrier family 12 SLC12A2
NM_001046 6.75 4.85 (sodium/potassium/chloride transporters),
member 2 guanylate cyclase 2C (heat GUCY2C NM_004963 6.72 3.53
stable enterotoxin receptor) transmembrane 4 superfamily TM4SF4
NM_004617 6.54 12.09 member 4 transforming growth factor, TGFA
NM_003236 6.44 3.11 alpha fibroblast growth factor binding FGFBP1
NM_005130 6.27 5.35 protein 1 PTK6 protein tyrosine kinase 6 PTK6
NM_005975 6.24 3.10 epithelial V-like antigen 1 EVA1 NM_005797 5.96
4.55 EPH receptor A2 EPHA2 NM_004431 5.90 2.18 integrin, alpha 6
ITGA6 NM_000210 5.53 4.09 tumor necrosis factor receptor TNFRSF21
NM_014452 5.47 2.16 superfamily, member 21 transmembrane 4
superfamily TM4SF3 NM_004616 5.32 3.75 member 3 interleukin 18
(interferon- IL18 NM_001562 5.24 5.22 gamma-inducing factor) bone
morphogenetic protein 4 BMP4 NM_130850 4.82 3.91 sphingomyelin
SMPDL3B NM_014474 4.62 5.49 phosphodiesterase, acid-like 3B
transmembrane protease, TMPRSS2 NM_005656 4.62 3.51 serine 2
guanine deaminase GDA NM_004293 4.56 6.52 macrophage stimulating 1
MST1R NM_002447 4.49 4.52 receptor (c-met-related tyrosine kinase)
integrin, beta 4 ITGB4 NM_000213 4.41 3.98 annexin A3 ANXA3
NM_005139 4.11 3.34 chemokine (C-C motif) ligand CCL15 NM_032965
3.87 3.74 15 dipeptidase 1 (renal) DPEP1 NM_004413 3.72 5.53 NADPH
oxidase organizer 1 NOXO1 NM_172167 3.71 8.92 interferon,
alpha-inducible IFI27 NM_005532 3.69 3.65 protein 27 cytochrome
P450, family 3, CYP3A43 NM_057095 3.65 3.40 subfamily A,
polypeptide 43 plakophilin 2 PKP2 NM_004572 3.54 3.45
[0148] Analysis of the biological pathways associated with these
genes showed that homologous recombination, nucleotide excision
repair, cell cycle, and apoptosis were among those that affect
sensitivity to PCI-24781.
[0149] In order to validate the higher expression of each
resistance biomarker gene identified by microarray analysis, we
analyzed the expression of each biomarker gene by the TaqMan.RTM.
quantitave RT-PCR method as described below.
[0150] TaqMan.RTM. Gene Expression Assays for selected genes were
obtained from Applied Biosystems (Foster City, Calif.). One-step
RT-PCR was carried out in triplicate on 25 ng of total RNA from
each sample on an ABI PRISM.RTM. 7900HT sequence detection system.
The mRNA levels for each gene were normalized to the amount of RNA
in the well as measured in parallel using Ribogreen (Invitrogen,
Inc., Carlsbad, Calif.). We then calculated the ratios of
expression levels of the biomarker genes in the resistant &
sensitive samples (RIS) and compared them to the corresponding
ratios obtained from the microarray analysis. The comparative
analysis for 16 of the biomarker genes listed in Table 3 is shown
in Table 4. As a further validation of our microarray analysis, we
performed TaqMan assays for three genes whose expression, as
measured by microarray hybridization, was not found to correlate
with PCI-24781 resistance (see last three genes in Table 3).
TABLE-US-00004 TABLE 4 Microarray vs TaqMan Analysis of Genes
Upregulated in PCI-24781-Resistant vs Sensitive Colorectal Tumor
Cells Microarrays Taqman Resist Sens Ratio Sens GeneName GeneCards
Zcut mean mean ArR/S Ct ResistAvg SensAvg Ratio TaqR/S Taq/Arr
defensin, alpha 6, Paneth DEFA6 8.58 8.57 0.65 12.92 37.20 1.34
0.06 23.94 1.85 cell-specific integrin, beta 4 ITGB4 4.41 0.67 0.17
3.98 28.99 66.16 16.59 5.20 1.31 transmembrane 4 superfamily TM4SF3
5.32 239.99 65.01 3.75 29.21 108.96 14.30 7.62 2.03 member 3 spleen
tyrosine kinase SYK 6.90 5.16 1.48 3.59 35.45 1.50 0.19 7.90 2.20
phosphatidic acid phosphatase PPAP2C 12.95 5.35 1.14 4.75 36.45
1.26 0.09 13.31 2.80 type 2C RAB25, member RAS oncogene RAB25 10.96
55.31 15.92 3.51 32.56 16.97 1.40 12.10 3.45 family hephaestin HEPH
10.49 8.11 2.46 3.38 32.90 4.34 1.11 3.93 1.16 NADPH oxidase
organizer 1 NOXO1 3.71 0.98 0.11 8.92 35.41 4.60 0.19 23.76 2.66
transmembrane 4 superfamily TM4SF4 6.54 2.06 0.18 12.09 40.00 0.22
0.01 27.22 2.25 member 4 PTPN3 PTPN3 14.19 5.45 2.16 2.58 30.71
6.60 5.04 1.31 0.51 EPH receptor A2 EPHA2 5.90 29.27 13.49 2.18
31.91 25.80 2.20 11.73 5.37 fibroblast growth factor FGFBP1 6.27
27.93 5.30 5.35 37.76 0.84 0.04 22.08 4.13 binding protein 1
ATP-binding cassette, ABCC3 13.24 4.14 1.82 2.37 40.00 0.01 0.01
0.96 0.41 sub-family C, member 3 thiopurine S-methyltransferase
TPMT 9.97 26.21 10.11 2.56 40.00 0.01 0.01 0.96 0.38 interleukin 18
(interferon- IL18 5.24 26.57 5.04 5.22 40.00 0.62 0.01 77.06 14.77
gamma-inducing factor) dipeptidase 1 (renal) DPEP1 3.72 2.93 0.54
5.53 40.00 0.01 0.01 0.96 0.17 HDAC3 HDAC3 Not significant 25.66
141.70 167.11 0.85 Zinc Finger Protein znf217 ZNF217 Not
significant 35.07 0.23 0.25 0.93 TSG101 TSG101 Not significant
40.00 0.01 0.01 0.96
[0151] The comparison of microarray versus results is graphically
summarized in FIG. 2. As shown in Table 4 and FIG. 2, genes found
to be significantly upregulated by the microarray method were also
found to be upregulated by the TaqMan method, though the latter
generally yielded higher R/S ratios. Likewise, three genes whose
expression did not differ significantly in the microarray analysis
also showed no significant difference in the TaqMan assay.
[0152] Interestingly, several of the identified biomarker genes
have previously been studied in relation to cancer, e.g., DEFA6,
RAB25 small GTPase, MRP3 (ABCC3), and TM4SF4. Further, a number of
the identified genes encode secreted proteins or transmembrane
proteins that shed their extracellular domains. Genes encoding
secretable proteins include, e.g., DEFA6 (NM_001926), TM4SF4
(NM_004617), TGFA (NM_003236), FGFBP1 (NM_005130), EPHA2
(NM_004431), TNFRSF21 (NM_014452), TMF4SF3 (NM_004616), IL18
(NM_001562), TMPRSS2 (NM_005656), and CCL15 (NM_032965).
[0153] Based on these data, we concluded that the expression
pattern of subsets (e.g., four or more) of the identified biomarker
genes provide "resistance signatures" that are optionally used to
reliably identify colorectal tumors that are resistant or
susceptible to the HDAC inhibitor PCI-24781.
[0154] In a validation experiment, we found that ex vivo cultured
primary colon tumor cells from twelve newly diagnosed, naive
patients were all sensitive to growth inhibition by the HDAC
inhibitor PCI-24781 (FIG. 11A). In contrast, we found that in a
number of cases, advanced metastatic colon tumor cells were
resistant to growth inhibition by the HDAC inhibitor PCI-24781
(FIG. 11B), and the DEFA6 mRNA expression levels were higher in
HDAC-resistant cells than in HDAC-sensitive cells (FIG. 11C).
Example 2
Identification and Cross-Validation of Functional Biomarkers for
HDAC Inhibitor Compounds and Selection of Clinical Indications
[0155] In order to determine relevant tumor types and to identify
pharmacodynamic (PD) markers that are useful in the clinic, we
first identified biomarkers of HDAC inhibition in mice and used
these to identify HDACi-"sensitive" tissues. This was done by
identifying, in HDACi-treated mice, genes in peripheral blood
mononuclear cells (PBMC) whose mRNA levels showed the same
timecourse as acetylated tubulin levels, an index of HDAC
inhibition. These biomarker genes were then used to identify HDACi
responsive mouse tissues. Primary human tumors corresponding to
sensitive tissues were then tested ex-vivo with PCI-24781, and it
was found that tumors from tissues that showed higher levels of
activity were sensitive to inhibition by PCI-24781, thus validating
that this technique does indeed predict sensitive tumor types.
[0156] In brief, female BALB/c mice were injected IV with 50 mg/kg
PCI-24781 or vehicle. Blood and various tissues were collected at
0.25, 0.5, 1, 2, 3 & 8 hours after dosing. For acetylated
histone and tubulin detection, organs/tissues were pooled for each
vehicle and drug-treated organ group. RNA and protein were
extracted from the samples with the PARIS Protein and RNA Isolation
System (Ambion). Levels of acetylated and total a-tubulin &
histones were evaluated by immunoblotting.
[0157] RNA expression profiles were determined using on a
GE-Codelink Mouse Uniset1 10K oligonucleotide arrays in duplicate.
Each treated sample was normalized to the corresponding vehicle
control. In order to validate the expression profile of
HDADi-responsive genes identified by the gene expression array
assays, Taqman gene expression assays were performed using Applied
Biosystems Inc. assays. One-step RT-PCR was carried out in
triplicate on 25 ng of total RNA from each sample on a ABI PRISM
7700 instrument. The mRNA levels for each gene were normalized to
the amount of RNA in the well as measured in parallel using
Ribogreen (Molecular Probes). The treated samples were then
normalized to the vehicle control at that time point.
[0158] A set of 16 genes (Table 5) whose expression profile in PBMC
(FIG. 7A) closely tracked increases in tubulin acetylation levels
(FIG. 7B) following treatment with the HDAC inhibitor
PCI-24781.
TABLE-US-00005 TABLE 5 HDAC Inhibitor (HDACi)-Responsive Biomarker
Genes Common Description Function Slc9a3r1 solute carrier family 9
isoform 3 regulator 1 ION TRANSPORT Ing1l inhibitor of growth
family, member 1-like CELL PROLIFERATION AND DIFFERENTIATION
Gadd45g growth arrest and DNA-damage-inducible 45 gamma CELL
PROLIFERATION AND DIFFERENTIATION; APOPTOSIS Plaur urokinase
plasminogen activator receptor MULTIPLE EST RIKEN cDNA 2810405O22
gene UNKNOWN Insl6 insulin-like 6 BIOLOGICAL PROCESS UNKNOWN Luc7l
Luc7 homolog (S. cerevisiae)-like RNA PROCESSING Taf9 TAF9 RNA
polymerase II MRNA TRANSCRIPTION Gadd45b growth arrest and
DNA-damage-inducible 45 beta CELL PROLIFERATION AND DIFFERENTIATION
Syngr2 synaptogyrin 2 UNKNOWN Polr2e polymerase (RNA) II (DNA
directed) polypeptide E MRNA TRANSCRIPTION Kras2 Mouse c-Ki-ras
oncogene ONCOGENE Hspa5 heat shock 70 kD protein 5 STRESS RESPONSE
Fgf15 fibroblast growth factor 15 CELL PROLIFERATION AND
DIFFERENTIATION Tuba4 tubulin, alpha 4 CELL STRUCTURE H2afz H2A
histone family, member Z CHROMATIN PACKAGING
[0159] Subsequently, we validated the expression profile of two of
HDACi-responsive genes, Fgf15 and Syngr2, by quantitative RT-PCR
and immunoblotting. As shown in FIG. 8, the expression profiles
obtained the three different methods closely matched one another,
suggesting that the microarray analysis identified HDACi-responsive
genes reliably.
[0160] We then determined the in vivo expression levels for five of
the HDACi-responsive biomarker genes in various tissues following 3
hours or 8 hours following administration of PCI-24781 (50 mg/kg).
A Taqman assay was performed to determine mRNA expression levels in
brain, colon, kidney, liver, stomach, ovary, uterus, mammary,
muscle, heart, lung, spleen, and pancreas. The mean and SD for mRNA
expression levels of all 5 genes in each tissue at each time point
are shown in FIG. 9. The issue distribution pattern was very
reproducible across the biomarker set. Ovary showed the highest
level of induction, followed by uterus.
[0161] Subsequently, primary human tumor samples were obtained and
viable tumor cells were plated in soft agar and treated with the
HDAC inhibitor PCI-24781. Tritiated thymidine was added after 3
days, and 2 days later the radioactivity incorporated into the DNA
was quantified. The tumors were then classified as either resistant
(EDR: Extreme Drug Resistance), sensitive (LDR) or intermediate
(IDR) based on deviation from the median profile (Oncotech, Inc.
Tustin, Calif.). As predicted based on the HDACi responsive
biomarker gene profiles hematopoietic tumors had the lowest
proportion of resistant (EDR) tumors, and colon the most (38%). See
FIG. 10 and Table 6. Among the solid tumors, ovarian had the lowest
proportion of resistant tumors, consistent with the high
HDACi-biomarker responsiveness of this tissue.
TABLE-US-00006 TABLE 6 Tumor Resistance to HDAC Inhibitor PCI-24781
Tumor Resistant Intermediate Sensitive Type EDR IDR LDR Total %
Resistance AML 1 4 5 10 10 Multiple 2 0 4 6 33 Myeloma Ovarian 3 4
5 12 25 Glioblastoma 2 1 4 7 29 Colon 9 3 12 24 38 Note: EDR/LDR
status as determined by Oncotech's algorithm from their assay
data
[0162] Based on the above results, we concluded that expression
profiles of the orthologous human biomarkers will reflect PCI-24781
activity in human blood, and serve as PD markers in the clinic.
Further, the identified set of HDACi-responsiveness biomarker genes
accurately predicts tumor sensitivity to treatment with HDAC
inhibitors.
TABLE-US-00007 APPENDIX Nucleotide Sequences for HDACi Compound
Resistance Biomarker Genes GenBank Gene Name Gene Symbol Accession
# SEQ ID NO PTPN3 PTPN3 AK096975 1 1 tgaatagttt gctggtagca
agacggatga agacctatat gggagattct ttatctctag 61 agctagcata
tttacttgca tactttgttt cttttccaca tggatatttt actgctaaat 121
ggcagaggtg ggagggagat gtcacacagt accataaccc catattgaaa acaagaaacc
181 accagaaagt ttgcagctaa ggggcagggg attcagttcc tacgcccact
cagcactaac 241 tacttgcggg cctggttgct tagaagctct acctctcttt
cattatctgt aaaatagaaa 301 caatacttag gactttagtt ggaacatgag
gattgaataa gatcacgcta ttcatgtgac 361 tttttatcgg ctagaacagc
aacagacact gctgtgggtg agttacttag aaaagtttag 421 ttatcagtga
ttagcccaaa aacacatcag tcaaaaatag aatccactgg atttttgtct 481
ctctttttag agacagggtc tcactgtcgc ccaggctgga gtacagtggc atgatcattg
541 ttcactgcag cctcaaattc ctgggctcaa gcaatcctcg cacctcagcc
tcctgagtag 601 ccgggactat aggcacatgc cacctcacct ggcttgtgtg
tgtgtgtgtg tgtgtgtgtg 661 tgtgtgtgtg tgtgtgtgta gagacaggat
cttgatgtgt cgcctaggct ggtctcaaac 721 tcctggcctc aagtgatctt
cccacctcag cctccaaaac tgttgggatt ataggcgtga 781 gccactgtgc
ccagcctaac tgggttttta tgagaggaaa atagaaaatg ctcttctaga 841
agagagagaa caagagcaca aaataatctg gactcacaaa aattcagcaa gctccaagaa
901 agggggatgg agggaacgct ggcaaaaatt taaatgccat taggatattt
agcaagttat 961 tactgtttgg taaaaatgca tcatcaccct gtgtgcaaaa
tgcttgcaaa gtagtctaaa 1021 tgtctttgga gatgggtgtt ttactgcttt
tttccaaaaa caaattgttt attatggttg 1081 cagaaatgca gccattacgg
tcacataaat ttctaaaaag cctaccaaag gttgcaagca 1141 gtcttctgcc
actgggcagg ccagcagttc agacccagcg aggttgccag gaacaaatcc 1201
aggaaatact gggaagaaca agacaagaga attacctaaa agagcaaaca attcaagtaa
1261 atcctgtagc tattaccact taaaatccgt agctcaagat tcctgtttca
ccaccttata 1321 cacttaagca attatactta agcctttttt tagtcctaag
tgaagaacta catcagaatc 1381 aggataagta ttttgcctgg gaaatttggc
tgcatatgaa tggagaagac atttacatcc 1441 tatgttctgg cactttctga
aagatctaat taaacatgtt gatgtgccaa tttaatcaag 1501 atgagagatc
cctgctggtg tcaccctcta gaacctgcac ttggtgtttt gactttccag 1561
aagaaaaaaa tgcaactttg gttagggggc agtggttgga tcacacagtt gtctttcgtt
1621 tcctaccaca gtaattcata tttaaatatg cttttagatt agtgtggata
ctattgctgc 1681 tgtgttgcta cctgaccttt ttctgggggg ggtacctcag
aaatgagcat ttgagggcaa 1741 gcgaaaaagc cctcttcatc ctccagaggc
aacaaagagg cagcagaaat ggggaaagat 1801 tgtgagaggc agggcttggg
tctagacctg gacttaggca agatatgttg ccctcaaccc 1861 tgagttttct
tatatgtaaa aagggaaggt tgggctggac tagatgaggt caagatttgc 1921
cattctggga ggctgatatt ccagagaatc aaaattaatc ctaaaccaaa gctttatggc
1981 tgctacagag acatgtcaca tttctgagac ttgtcaccaa gagtttgtcc
ctcagacttt 2041 ggcgctgttg aatgcaaaga caaggatggc caccttctgg
ttcttgcctg ttgtcctcag 2101 ctgagagcag tctcggtaaa ggtggcaaag
attctgtgac ctcagaccgg ggaccaaatg 2161 cttgggagtc tgatggccgg
gctgggccac cattctcata gctctcattc tgtttggagc 2221 aaccaaagga
tttgtgtgaa gttatttgga aaaggacctt aactgagcag taatcttttt 2281
tctgtatatt tggaatgttt ttcattctga cctgttctgt cagtgattct actgaaaaac
2341 aatttaatca atataaaaat gttcaagcta tgcaac GenBank Gene Name Gene
Symbol Accession # SEQ ID NO ATP-binding cassette, ABCC3 NM_020037
2 sub-family C (CFTR/MRP), member 3 1 ctccggcgcc cgctctgccc
gccgctgggt ccgaccgcgc tcgccttcct tgcagccgcg 61 cctcggcccc
atggacgccc tgtgcggttc cggggagctc ggctccaagt tctgggactc 121
caacctgtct gtgcacacag aaaacccgga cctcactccc tgcttccaga actccctgct
181 ggcctgggtg ccctgcatct acctgtgggt cgccctgccc tgctacttgc
tctacctgcg 241 gcaccattgt cgtggctaca tcatcctctc ccacctgtcc
aagctcaaga tggtcctggg 301 tgtcctgctg tggtgcgtct cctgggcgga
ccttttttac tccttccatg gcctggtcca 361 tggccgggcc cctgcccctg
ttttctttgt cacccccttg gtggtggggg tcaccatgct 421 gctggccacc
ctgctgatac agtatgagcg gctgcagggc gtacagtctt cgggggtcct 481
cattatcttc tggttcctgt gtgtggtctg cgccatcgtc ccattccgct ccaagatcct
541 tttagccaag gcagagggtg agatctcaga ccccttccgc ttcaccacct
tctacatcca 601 ctttgccctg gtactctcta ccctcatctt ggcctgcttc
agggagaaac ctccattttt 661 ctccgcaaag aatgtcgacc ctaaccccta
ccctgagacc agcgctggct ttctctcccg 721 cctgtttttc tggtggttca
caaagatggc catctatggc taccggcatc ccctggagga 781 gaaggacctc
tggtccctaa aggaagagga cagatcccag atggtggtgc agcagctgct 841
ggaggcatgg aggaagcagg aaaagcagac ggcacgacac aaggcttcag cagcacctgg
901 gaaaaatgcc tccggcgagg acgaggtgct gctgggtgcc cggcccaggc
cccggaagcc 961 ctccttcctg aaggccctgc tggccacctt cggctccagc
ttcctcatca gtgcctgctt 1021 caagcttatc caggacctgc tctccttcat
caatccacag ctgctcagca tcctgatcag 1081 gtttatctcc aaccccatgg
ccccctcctg gtggggcttc ctggtggctg ggctgatgtt 1141 cctgtgctcc
atgatgcagt cgctgatctt acaacactat taccactaca tctttgtgac 1201
tggggtgaag tttcgtactg ggatcatggg tgtcatctac aggaaggctc tggttatcac
1261 caactcagtc aaacgtgcgt ccactgtggg ggaaattgtc aacctcatgt
cagtggatgc 1321 ccagcgcttc atggaccttg cccccttcct caatctgctg
tggtcagcac ccctgcagat 1381 catcctggcg atctacttcc tctggcagaa
cctaggtccc tctgtcctgg ctggagtcgc 1441 tttcatggtc ttgctgattc
cactcaacgg agctgtggcc gtgaagatgc gcgccttcca 1501 ggtaaagcaa
atgaaattga aggactcgcg catcaagctg atgagtgaga tcctgaacgg 1561
catcaaggtg ctgaagctgt acgcctggga gcccagcttc ctgaagcagg tggagggcat
1621 caggcagggt gagctccagc tgctgcgcac ggcggcctac ctccacacca
caaccacctt 1681 cacctggatg tgcagcccct tcctggtgac cctgatcacc
ctctgggtgt acgtgtacgt 1741 ggacccaaac aatgtgctgg acgccgagaa
ggcctttgtg tctgtgtcct tgtttaatat 1801 cttaagactt cccctcaaca
tgctgcccca gttaatcagc aacctgactc aggccagtgt 1861 gtctctgaaa
cggatccagc aattcctgag ccaagaggaa cttgaccccc agagtgtgga 1921
aagaaagacc atctccccag gctatgccat caccatacac agtggcacct tcacctgggc
1981 ccaggacctg ccccccactc tgcacagcct agacatccag gtcccgaaag
gggcactggt 2041 ggccgtggtg gggcctgtgg gctgtgggaa gtcctccctg
gtgtctgccc tgctgggaga 2101 gatggagaag ctagaaggca aagtgcacat
gaagggctcc gtggcctatg tgccccagca 2161 ggcatggatc cagaactgca
ctcttcagga aaacgtgctt ttcggcaaag ccctgaaccc 2221 caagcgctac
cagcagactc tggaggcctg tgccttgcta gctgacctgg agatgctgcc 2281
tggtggggat cagacagaga ttggagagaa gggcattaac ctgtctgggg gccagcggca
2341 gcgggtcagt ctggctcgag ctgtttacag tgatgccgat attttcttgc
tggatgaccc 2401 actgtccgcg gtggactctc atgtggccaa gcacatcttt
gaccacgtca tcgggccaga 2461 aggcgtgctg gcaggcaaga cgcgagtgct
ggtgacgcac ggcattagct tcctgcccca 2521 gacagacttc atcattgtgc
tagctgatgg acaggtgtct gagatgggcc cgtacccagc 2581 cctgctgcag
cgcaacggct cctttgccaa ctttctctgc aactatgccc ccgatgagga 2641
ccaagggcac ctggaggaca gctggaccgc gttggaaggt gcagaggata aggaggcact
2701 gctgattgaa gacacactca gcaaccacac ggatctgaca gacaatgatc
cagtcaccta 2761 tgtggtccag aagcagttta tgagacagct gagtgccctg
tcctcagatg gggagggaca 2821 gggtcggcct gtaccccgga ggcacctggg
tccatcagag aaggtgcagg tgacagaggc 2881 gaaggcagat ggggcactga
cccaggagga gaaagcagcc attggcactg tggagctcag 2941 tgtgttctgg
gattatgcca aggccgtggg gctctgtacc acgctggcca tctgtctcct 3001
gtatgtgggt caaagtgcgg ctgccattgg agccaatgtg tggctcagtg cctggacaaa
3061 tgatgccatg gcagacagta gacagaacaa cacttccctg aggctgggcg
tctatgctgc 3121 tttaggaatt ctgcaagggt tcttggtgat gctggcagcc
atggccatgg cagcgggtgg 3181 catccaggct gcccgtgtgt tgcaccaggc
actgctgcac aacaagatac gctcgccaca 3241 gtccttcttt gacaccacac
catcaggccg catcctgaac tgcttctcca aggacatcta 3301 tgtcgttgat
gaggttctgg cccctgtcat cctcatgctg ctcaattcct tcttcaacgc 3361
catctccact cttgtggtca tcatggccag cacgccgctc ttcactgtgg tcatcctgcc
3421 cctggctgtg ctctacacct tagtgcagcg cttctatgca gccacatcac
ggcaactgaa 3481 gcggctggaa tcagtcagcc gctcacctat ctactcccac
ttttcggaga cagtgactgg 3541 tgccagtgtc atccgggcct acaaccgcag
ccgggatttt gagatcatca gtgatactaa 3601 ggtggatgcc aaccagagaa
gctgctaccc ctacatcatc tccaaccggt cagaagccgc 3661 ctccctcgct
ccctgctcct ccaggaattc ccagcaggct ctctggtgtt cagggtcctt 3721
gtccctcctt tcccctaagc agaaaactgg ccctgccctg cccctgcccc atttcctcct
3781 catctgatcc cccataggcg gctgagcatc ggagtggagt tcgtggggaa
ctgcgtggtg 3841 ctctttgctg cactatttgc cgtcatcggg aggagcagcc
tgaacccggg gctggtgggc 3901 ctttctgtgt cctactcctt gcaggtgaca
tttgctctga actggatgat acgaatgatg 3961 tcagatttgg aatctaacat
cgtggctgtg gagagggtca aggagtactc caagacagag 4021 acagaggcgc
cctgggtggt ggaaggcagc cgccctcccg aaggttggcc cccacgtggg 4081
gaggtggagt tccggaatta ttctgtgcgc taccggccgg gcctagacct ggtgctgaga
4141 gacctgagtc tgcatgtgca cggtggcgag aaggtgggga tcgtgggccg
cactggggct 4201 ggcaagtctt ccatgaccct ttgcctgttc cgcatcctgg
aggcggcaaa gggtgaaatc 4261 cgcattgatg gcctcaatgt ggcagacatc
ggcctccatg acctgcgctc tcagctgacc 4321 atcatcccgc aggaccccat
cctgttctcg gggaccctgc gcatgaacct ggaccccttc 4381 ggcagctact
cagaggagga catttggtgg gctttggagc tgtcccacct gcacacgttt 4441
gtgagctccc agccggcagg cctggacttc cagtgctcag agggcgggga gaatctcagc
4501 gtgggccaga ggcagctcgt gtgcctggcc cgagccctgc tccgcaagag
ccgcatcctg 4561 gttttagacg aggccacagc tgccatcgac ctggagactg
acaacctcat ccaggctacc
4621 atccgcaccc agtttgatac ctgcactgtc ctgaccatcg cacaccggct
taacactatc 4681 atggactaca ccagggtcct ggtcctggac aaaggagtag
tagctgaatt tgattctcca 4741 gccaacctca ttgcagctag aggcatcttc
tacgggatgg ccagagatgc tggacttgcc 4801 taaaatatat tcctgagatt
tcctcctggc ctttcctggt tttcatcagg aaggaaatga 4861 caccaaatat
gtccgcagaa tggacttgat agcaaacact gggggcacct taagattttg 4921
cacctgtaaa gtgccttaca gggtaactgt gctgaatgct ttagatgagg aaatgatccc
4981 caagtggtga atgacacgcc taaggtcaca gctagtttga gccagttaga
ctagtccccc 5041 ggtctcccga ttcccaactg agtgttattt gcacactgca
ctgttttcaa ataacgattt 5101 tatgaaatga cctctgtcct ccctctgatt
tttcatattt tcctaaagtt tcgtttctgt 5161 tttttaataa aaagcttttt
cctcctggaa cagaagacag ctgctgggtc aggccacccc 5221 taggaactca
gtcctgtact ctggggtgct gcctgaatcc attaaaaatg ggagtactga 5281
tgaaataaaa ctacatggtc aacagtaaaa GenBank Gene Name Gene Symbol
Accession # SEQ ID NO specifically androgen- SARG NM_023938 3
regulated protein 1 gtgggggcca ggcagcacag atgaagcatt tacctatcta
ggtaagtcag gaggagctca 61 aaaggagaag aaaacagtag gaggcagggg
aagcagcctc tgtctccatc tctgcccttt 121 gaaacaaaag ggtatttctt
ttctctcttc agcccccaac ccagtggagg cccggcttgg 181 gacattgttc
acttcccctc gcttcccctc tagaagcccc ctttgccatc cctgcacctt 241
gtttcgggtg atgcccgaga gggagctgtg gccagcgggg actggctcag aacccgtgac
301 ccgtgtcggc agctgtgaca gcatgatgag cagcacctcc acccgctctg
gatctagtga 361 tagcagctac gacttcctgt ccactgaaga gaaggagtgt
ctgctcttcc tggaggagac 421 cattggctca ctggacacgg aggctgacag
cggactgtcc actgacgagt ctgagccagc 481 cacaactccc agaggtttcc
gagcactgcc cataacccaa cccactcccc ggggaggtcc 541 agaggagacc
atcactcagc aaggacgaac gccaaggaca gtaactgagt ccagctcatc 601
ccaccctcct gagccccagg gcctaggcct caggtctggc tcctacagcc tccctaggaa
661 tatccacatt gccagaagcc agaacttcag gaaaagcacc acccaggcta
gcagtcacaa 721 ccctggagaa ccggggaggc ttgcgccaga gcctgagaaa
gaacaggtca gccagagcag 781 ccaacccagg caggcacctg ccagccccca
ggaggctgcc cttgacttgg acgtggtgct 841 catccctccg ccagaagctt
tccgggacac ccagccagag cagtgtaggg aagccagcct 901 gcccgagggg
ccaggacagc agggccacac accccagctc cacacaccat ccagctccca 961
ggaaagagag cagactcctt cagaagccat gtcccaaaaa gccaaggaaa cagtctcaac
1021 caggtacaca caaccccagc ctcctcctgc agggttgcct cagaatgcaa
gagctgaaga 1081 tgctcccctc tcatcagggg aggacccaaa cagccgacta
gctcccctca caacccctaa 1141 gccccggaag ctgccaccta atattgttct
gaagagcagc cgaagcagtt tccacagtga 1201 cccccagcac tggctgtccc
gccacactga ggctgcccct ggagattctg gcctgatctc 1261 ctgttcactg
caagagcaga gaaaagcacg taaagaagct ctagagaagc tggggctacc 1321
ccaggatcaa gatgagcctg gactccactt aagtaagccc accagctcca tcagacccaa
1381 ggagacacgg gcccagcatc tgtccccagc tccaggtctg gctcagcctg
cagctccagc 1441 ccaggcctca gcagctattc ctgctgctgg gaaggctctg
gctcaagctc cggctccagc 1501 tccaggtcca gctcagggac ctttgccaat
gaagtctcca gctccaggca atgttgcagc 1561 tagcaaatct atgccaattc
ctatccctaa ggccccaagg gcaaacagtg ccctgactcc 1621 accgaagcca
gagtcagggc tgactctcca ggagagcaac acccctggcc tgagacagat 1681
gaacttcaag tccaacactc tggagcgctc aggcgtggga ctgagcagct acctttcaac
1741 tgagaaagat gccagcccca aaaccagcac ttctctggga aagggctcct
tcttggacaa 1801 gatctcgccc agtgtcttac gtaattctcg gccccgcccg
gcctccctgg gcacggggaa 1861 agattttgca ggtatccagg taggcaagct
ggctgacctg gagcaggagc agagctccaa 1921 gcgcctgtcc taccaaggac
agagccgtga caagcttcct cgccccccct gtgtcagtgt 1981 caagatctcc
ccaaagggtg tccccaatga acacagaagg gaggccctga agaagctggg 2041
actgttgaag gagtagactc tgcgaccagt acagaccctg tcctggctga acaagaagag
2101 acacatgctc cacttgggag cctttgccac cacgcaactc agggctcaag
atgaatggga 2161 gggagagatt tgagtccaag catacattta tattcagtgt
tgtgccattg agttcccatg 2221 tggatcattc tgaaggtgat ctccacaaga
gggtgtgtgt gtgtgtgttt ggtgtgtgtg 2281 tggagggggg gccgctggat
acatcactga agctattgat ataacacaat gagtcactgt 2341 tcagaatttt
gctcttgtta gatgttttct tacattgggt agagtccagc ctagtgagag 2401
ctgagtgaag gggctggcca tgcctgagac aaaaagtcaa atgagacaat ggacgtgtca
2461 atgacttgaa aaaaagtcac atccagcaaa tgcagggtca catgaaatat
gggcctcctg 2521 gaatccctac agtggatgga gactggctca taccttgcca
gatccctctc tcagttccag 2581 ccttctggac aaggcctggg ctaagaggag
ctgattcgtt atctcttcac ccactgccct 2641 ctcagtatca ccagtcccaa
agacaggata cgtccctgta acccaatctc tcggttgatt 2701 gatagcagaa
cagctcttgt tggtctgaga aggcaggata agtgaccaca tatttatgcc 2761
actacctcca ccagggagag tccttctcca caggcttgat aaattcaatc accaactgtg
2821 ctgtcgtccc tgactctgct actcccgttc ttcctgcttt cctgctccgt
atctcagtct 2881 gcactgaccc cagggctggg ctgacatcaa gatgggagcc
cagcccacgg gctttataaa 2941 cacccaagaa ccgtttcaga tcttctctgt
gctgatgcag gtagttttaa atttttctca 3001 gttccagtga tagaaaaccc
acacaataca tcctctgcca gtcttaatag aatatcagag 3061 gtaagagggg
cctcagagaa gctctgacgc agtgctgctg gggaagggaa gtgactaacc 3121
ccgggtcagc ctgccattta gggaaagagc tgaggttctt acccttgttg catgctgcca
3181 cctctcctta gccagtgctc ttgtacatcc acacagcacc ctaaggagcc
atagtcacca 3241 tcaaagactc aaccctaagg cccttcaaga tctcaaagtg
ccttctgaag catcagagat 3301 taaatattgt tcaaactaat agttattgct
gtggctttta attttatctt tggaagatag 3361 ctatatggta actcatcatt
aaccagaaca cctctcccct caaattccgt gaccaagttg 3421 tgcagcttga
gcaaatgccg aaagagggta ttatgggtgg gtggtgtggg cttgcaaata 3481
caagcttgga ggtgagacat ggccagacat gactcctgct tccccttagg aagtaaatct
3541 tacttatggt tgtgaactgc ttggagtcca ggatgcccag atgtgagggg
cagatgaagg 3601 gaatgttgct ggaaaggtgc cttttaaggc tgctgagaat
ttctggactg tgtcctgatg 3661 gacgcagcac catcaaagcc cagaatttct
gaaaacggtg acaaggttaa cataaggaca 3721 acaaatactc caccctgtca
tggtatgtga ggtgtgggtg tggcggtttc tgtgtacgtt 3781 tgctcataca
cgcacatcca aaagcctgtg cctcattcct ggccatgggt gaggacttgg 3841
tctgtcacgg ctgatgagga ctcccacaac cggccaagtt atgtcttatt atacaccccc
3901 agaaagagag aaagctgcct tctggaggac tgattccaca tgctatattc
agctgagttg 3961 atttctgtgt ctatttcaac ccataacctg aagaatgatc
accttattcc ttattcatta 4021 attttcttga ttaataggga aacttgggaa
tagctataaa gtaaaacttg ggtggaacct 4081 ggggccctgg catcacacaa
gtgtgattag gatggtcaag gtcatcagga gtacagccta 4141 ttatattccc
acatcctgag aaaggtcatt tctcccacac acgacaaagt cacagacatc 4201
ctgcacctgc cactaggcat cctcatccta ctgacatgcc catttctcca gttttcttaa
4261 tctgagactc ccttcccttg ttttttaaag ataccgtgct tctccacatc
ctcatccttc 4321 aaggagcata ttttgctctt aggatggtct ttgggattca
agaatagaat aataaatcca 4381 aacttggtca ttcccatttt gaagagatgc
aagagggccc agtgaggaca tccgcctccc 4441 tgaaagtggt gctagacaga
gctgaggtca ttgtatctgt gtatccacat aggatttctc 4501 ttaattcagc
ttgaattgat ggggagggag gtaagagtag ggtcagagtt actcatccct 4561
tttcaaagaa ttgtgggtgg aagtttgtaa aggccattca tttgattttc aaaatcaaag
4621 cgacagctct acttccactt ggccttagat ctctgctata ccctgccata
gccttgatgc 4681 cactgggcac aagccacctg ccaaatacag gagtggcctc
tcccagcctg gcatgatagg 4741 ggggtctgtg ccctcagatg tgttgacagc
tgctcttctg aattgccaca cctgtgctac 4801 acttggaatt ctgtgctctg
actctgcagg gtaggaccac gtgccatctc acacagaggt 4861 caaccgatga
gcccactcac tcgtacatgc cttcttccac agtgggaagc atgatctggc 4921
aggggccgcc ctgtaggctg gggatgggct gctgtgtgaa tgttgacgtt cgtttcatgg
4981 agaaagggga ggtgaaagat tgaagagcag gttcctgtca atgttctgag
ttcgagctgg 5041 aggtgtagat tgaatagtct acatggtctg tgagtgtgtg
agatgaaccc ttccatcctt 5101 tgacacctgg ttgtatgtgt aggctaagaa
ggaaggaccc tcctgtcagt gtgcaaagct 5161 gtaatctcat ggactagagg
agagggggcc aaggggatgg acaggagaag tcatgcagaa 5221 tctaagcagg
aatgcagata gaacacatct aggctctttt ccccaggaga gtgatgatgg 5281
agcatataga tctggctcaa attcagcctc catcacttac cagtcaggaa ccctggcgat
5341 atcactttaa ctttctgaac ctcagagtct tcacctataa gacggggaaa
ataataccac 5401 cctttcaaga ttgttgagat aaataagtga tataaaacat
gtaaagctta gttctggcca 5461 cagtgtagct actcaataaa tgataatact GenBank
Gene Name Gene Symbol Accession # SEQ ID NO phosphatidic acid
PPAP2C NM_177526 4 phosphatase type 2C 1 ctcctctccg cgcggggcgg
gctccgcgcc acgtgactcc gcggccgggc cgggacgcga 61 cgggacgcgc
tgggaccggc gtcgggggtc gcggggacca tgcagcggag cctccctgcc 121
cttcgctatc ctgacgctgg tgaacgcccc gtacaagcga ggattttact gcggggatga
181 ctccatccgg tacccctacc gtccagatac catcacccac gggctcatgg
ctggggtcac 241 catcacggcc accgtcatcc ttgtctcggc cggggaagcc
tacctggtgt acacagaccg 301 gctctattct cgctcggact tcaacaacta
cgtggctgct gtatacaagg tgctggggac 361 cttcctgttt ggggctgccg
tgagccagtc tctgacagac ctggccaagt acatgattgg 421 gcgtctgagg
cccaacttcc tagccgtctg cgaccccgac tggagccggg tcaactgctc 481
ggtctatgtg cagctggaga aggtgtgcag gggaaaccct gctgatgtca ccgaggccag
541 gttgtctttc tactcgggac actcttcctt tgggatgtac tgcatggtgt
tcttggcgct 601 gtatgtgcag gcacgactct gttggaagtg ggcacggctg
ctgcgaccca cagtccagtt 661 cttcctggtg gcctttgccc tctacgtggg
ctacacccgc gtgtctgatt acaaacacca 721 ctggagcgat gtccttgttg
gcctcctgca gggggcactg gtggctgccc tcactgtctg 781 ctacatctca
gacttcttca aagcccgacc cccacagcac tgtctgaagg aggaggagct 841
ggaacggaag cccagcctgt cactgacgtt gaccctgggc gaggctgacc
acaaccacta
901 tggatacccg cactcctcct cctgaggccg gaccccgccc aggcagggag
ctgctgtgag 961 tccagctgag gcccacccag gtggtccctc cagccctggt
taggcactga gggctctgga 1021 cgggctccag gaaccctggg ctgatgggag
cagtgagcgg gctccgctgc cccctgccct 1081 gcactggacc aggagtctgg
agatgcctgg gtagccctca gcatttggag gggaacctgt 1141 tcccgtcggt
ccccaaatat ccccttcttt ttatggggtt aaggaaggga ccgagagatc 1201
agatagttgc tgttttgtaa aatgtaatgt atatgtggtt tttagtaaaa tagggcacct
1261 gtttcacaaa GenBank Gene Name Gene Symbol Accession # SEQ ID NO
neural proliferation, NPDC1 NM_015392 5 differentiation and
control, 1 1 gcgcgcctcg ccggcgcctc catcccggat ccttgctgca gcgtcagcgc
cgccgcccgt 61 gcctttcctc ttcctcctcc tcctccttgg catccgcctc
ttcttcctcc tgcgtcctcc 121 cccgctgcct ccgctgctcc cgacgcggag
cccggagccc gcgccgagcc cctggcctcg 181 cggtgccatg ctgccccggc
ggcggcgctg aaggatggcg acgccgctgc ctccgccctc 241 cccgcggcac
ctgcggctgc tgcggctgct gctctccggc ctcgtcctcg gcgccgccct 301
gcgtggagcc gccgccggcc acccggatgt agccgcctgt cccgggagcc tggactgtgc
361 cctgaagagg cgggcaaggt gtcctcctgg tgcacatgcc tgtgggccct
gccttcagcc 421 cttccaggag gaccagcaag ggctctgtgt gcccaggatg
cgccggcctc caggcggggg 481 ccggccccag cccagactgg aagatgagat
tgacttcctg gcccaggagc ttgcccggaa 541 ggagtctgga cactcaactc
cgcccctacc caaggaccga cagcggctcc cggagcctgc 601 caccctgggc
ttctcggcac gggggcaggg gctggagctg ggcctcccct ccactccagg 661
aacccccacg cccacgcccc acacctccat gggctcccct gtgtcatccg acccggtgca
721 catgtcgccc ctggagcccc ggggagggca aggcgacggc ctcgcccttg
tgctgatcct 781 ggcgttctgt gtggccggtg cagccgccct ctccgtagcc
tccctctgct ggtgcaggct 841 gcatcgtgag atccgcctga ctcagaaggc
cgactacgcc actgcgaagg cccctggctc 901 acctgcagct ccccggatct
cgcctgggga ccaacggctg gcacagagcg cggagatgta 961 ccactaccag
caccaacggc aacagatgct gtgcctggag cggcataaag agccacccaa 1021
ggagctggac acggcctcct cggatgagga gaatgaggac ggagacttca cggtgtacga
1081 gtgcccgggc ctggccccga ccggggaaat ggaggtgcgc aaccctctgt
tcgaccacgc 1141 cgcactgtcc gcgcccctgc cggcccccag ctcaccgcct
gcactgccat gacctggagg 1201 cagacagacg cccacctgct ccccgacctc
gaggcccccg gggaggggca gggcctggag 1261 cttcccacta aaaacatgtt
ttgatgctgt gtgcttttgg ctgggcctcg ggctccaggc 1321 cctgggaccc
cttgccaggg agacccccga acctttgtgc caggacacct cctggtcccc 1381
tgcacctctc ctgttcggtt tagaccccca aactggaggg ggcatggaga accgtagagc
1441 gcaggaacgg gtgggtaatt ctagagacaa aagccaatta aagtccattt
cagaaaaaaa GenBank Gene Name Gene Symbol Accession # SEQ ID NO
C-terminal tension- CTEN NM_032865 6 like 1 gggcaacagt ctgcccacct
gtggacacca gatcctggga gctcctggtt agcaagtgag 61 atctctggga
tgtcagtgag gctggttgaa gaccagaggt aaactgcaga ggtcaccacc 121
cccaccatgt cccaggtgat gtccagccca ctgctggcag gaggccatgc tgtcagcttg
181 gcgccttgtg atgagcccag gaggaccctg cacccagcac ccagccccag
cctgccaccc 241 cagtgttctt actacaccac ggaaggctgg ggagcccagg
ccctgatggc ccccgtgccc 301 tgcatggggc cccctggccg actccagcaa
gccccacagg tggaggccaa agccacctgc 361 ttcctgccgt cccctggtga
gaaggccttg gggaccccag aggaccttga ctcctacatt 421 gacttctcac
tggagagcct caatcagatg atcctggaac tggaccccac cttccagctg 481
cttcccccag ggactggggg ctcccaggct gagctggccc agagcaccat gtcaatgaga
541 aagaaggagg aatctgaagc cttggacata aagtacatcg aggtgacctc
cgccagatca 601 aggtgccacg attggcccca gcactgctcc agcccctctg
tcaccccgcc cttcggctcc 661 cctcgcagtg gtggcctcct cctttccaga
gacgtccccc gagagacacg aagcagcagt 721 gagagcctca tcttctctgg
gaaccagggc agggggcacc agcgccctct gcccccctca 781 gagggtctct
cccctcgacc cccaaattcc cccagcatct caatcccttg catggggagc 841
aaggcctcga gcccccatgg tttgggctcc ccgctggtgg cttctccaag actggagaag
901 cggctgggag gcctggcccc acagcggggc agcaggatct ctgtgctgtc
agccagccca 961 gtgtctgatg tcagctatat gtttggaagc agccagtccc
tcctgcactc cagcaactcc 1021 agccatcagt catcttccag atccttggaa
agtccagcca actcttcctc cagcctccac 1081 agccttggct cagtgtccct
gtgtacaaga cccagtgact tccaggctcc cagaaacccc 1141 accctaacca
tgggccaacc cagaacaccc cactctccac cactggccaa agaacatgcc 1201
agcatctgcc ccccatccat caccaactcc atggtggaca tacccattgt gctgatcaac
1261 ggctgcccag aaccagggtc ttctccaccc cagcggaccc caggacacca
gaactccgtt 1321 caacctggag ctgcttctcc cagcaacccc tgtccagcca
ccaggagcaa cagccagacc 1381 ctgtcagatg ccccctttac cacatgccca
gagggtcccg ccagggacat gcagcccacc 1441 atgaagttcg tgatggacac
atctaaatac tggtttaagc caaacatcac ccgagagcaa 1501 gcaatcgagc
tgctgaggaa ggaggagcca ggggcttttg tcataaggga cagctcttca 1561
taccgaggct ccttcggcct ggccctgaag gtgcaggagg ttcccgcgtc tgctcagaat
1621 cgaccaggtg aggacagcaa tgacctcatc cgacacttcc tcatcgagtc
gtctgccaaa 1681 ggagtgcatc tcaaaggagc agatgaggag ccctactttg
ggagcctctc tgccttcgtg 1741 tgccagcatt ccatcatggc cctggccctg
ccctgcaaac tcaccatccc acagagagaa 1801 ctgggaggtg cagatggggc
ctcggactct acagacagcc cagcctcctg ccagaagaaa 1861 tctgcgggct
gccacaccct gtacctgagc tcagtgagcg tggagaccct gactggagcc 1921
ctggccgtgc agaaagccat ctccaccacc tttgagaggg acatcctccc cacgcccacc
1981 gtggtccact tcgaagtcac agagcagggc atcactctga ctgatgtcca
gaggaaggtg 2041 tttttccggc gccattaccc actcaccacc ctccgcttct
gtggtatgga ccctgagcaa 2101 cggaagtggc agaagtactg caaaccctcc
tggatctttg ggtttgtggc caagagccag 2161 acagagcctc aggagaacgt
atgccacctc tttgcggagt atgacatggt ccagccagcc 2221 tcgcaggtca
tcggcctggt gactgctctg ctgcaggacg cagaaaggat gtaggggaga 2281
gactgcctgt gcacctaacc aacacctcca ggggctcgct aaggagcccc cctccacccc
2341 ctgaatgggt gtggcttgtg gccatattga cagaccaatc tatgggacta
gggggattgg 2401 catcaagttg acacccttga acctgctatg gccttcagca
gtcaccatca tccagacccc 2461 ccgggcctca gtttcctcaa tcatagaaga
agaccaatag acaagatcag ctgttcttag 2521 atgctggtgg gcatttgaac
atgctcctcc atgattctga agcatgcaca cctctgaaga 2581 cccctgcatg
aaaataacct ccaaggaccc tctgacccca tcgacctggg ccctgcccac 2641
acaacagtct gagcaagaga cctgcagccc ctgtttcgtg gcagacagca ggtgcctggc
2701 ggtgacccac ggggctcctg gcttgcagct ggtgatggtc aagaactgac
tacaaaacag 2761 gaatggatag actctatttc cttccatatc tgttcctctg
ttccttttcc cactttctgg 2821 gtggcttttt gggtccaccc agccaggatg
ctgcaggcca agctgggtgt ggtatttagg 2881 gcagctcagc agggggaact
tgtccccatg gtcagaggag acccagctgt cctgcacccc 2941 cttgcagatg
agtatcaccc catcttttct ttccacttgg tttttatttt tatttttttt 3001
gagacagagt ctcactgtca cccaggctga actgcagtgg tgtgatctag gctcactgca
3061 acctccacct cccaggttca agcaattatc ctgcctcagg ctcccgagta
gctgggatta 3121 caggcatgtg caactcaccc agctaatttt gtatttttag
tagagacagg gtttcaccat 3181 gttggccagg ctggtcttga actcctgacc
gcaggtaatc cacctgcttc ggcctcccaa 3241 agtgctggga ttacaggcgc
aagccaccca gcccagcttc tttccattcc ttgataggcg 3301 agtattccaa
agctggtatc gtagctgccc taatgttgca tattaggcgg cgggggcaga 3361
gataagggcc atctctctgt gattctgcct cagctcctgt cttgctgagc cctcccccaa
3421 cccacgctcc aacacacaca cacacacaca cacacacaca cacacacaca
cacacacaca 3481 cacgcccctc tactgctatg tggcttcaac cagcctcaca
gccacacggg ggaagcagag 3541 agtcaagaat gcaaagaggc cgcttcccta
agaggcttgg aggagctggg ctctatccca 3601 cacccacccc caccccaccc
ccacccagcc tccagaagct ggaaccattt ctcccgcagg 3661 cctgagttcc
taaggaaacc accctaccgg ggtggaaggg agggtcaggg aagaaaccca 3721
ctcttgctct acgaggagca agtgcctgcc ccctcccagc agccagccct gccaaagttg
3781 cattatcttt ggccaaggct gggcctgacg gttatgattt cagccctggg
cctgcaggag 3841 aggctgagat cagcccaccc agccagtggt cgagcactgc
cccgccgcca aagtctgcag 3901 aatgtgagat gaggttctca aggtcacagg
ccccagtccc agcctggggg ctggcagagg 3961 cccccatata ctctgctaca
gctcctatca tgaaaaataa aatgt GenBank Gene Name Gene Symbol Accession
# SEQ ID NO RAB25, member RAS RAB25 NM_020387 7 oncogene family 1
ctctgcttcc ttacagcacc cccacctgcc agagctgatc ctccctaggc cctgcctaac
61 cttgagttgg cccccaatcc ctctggctgc agaagtcccc ttacccccaa
tgagaggagg 121 ggcaggacca gatcttttga gagctgaggg ttgagggcat
tgagccaaca cacagatttg 181 tcgcctctgt ccccgaagac acctgcaccc
tccatgcgga gccaagatgg ggaatggaac 241 tgaggaagat tataactttg
tcttcaaggt ggtgctgatc ggcgaatcag gtgtggggaa 301 gaccaatcta
ctctcccgat tcacgcgcaa tgagttcagc cacgacagcc gcaccaccat 361
cggggttgag ttctccaccc gcactgtgat gttgggcacc gctgctgtca aggctcagat
421 ctgggacaca gctggcctgg agcggtaccg agccatcacc tcggcgtact
atcgtggtgc 481 agtgggggcc ctcctggtgt ttgacctaac caagcaccag
acctatgctg tggtggagcg 541 atggctgaag gagctctatg accatgctga
agccacgatc gtcgtcatgc tcgtgggtaa 601 caaaagtgac ctcagccagg
cccgggaagt gcccactgag gaggcccgaa tgttcgctga 661 aaacaatgga
ctgctcttcc tggagacctc agccctggac tctaccaatg ttgagctagc 721
ctttgagact gtcctgaaag aaatctttgc gaaggtgtcc aagcagagac agaacagcat
781 ccggaccaat gccatcactc tgggcagtgc ccaggctgga caggagcctg
gccctgggga 841 gaagagggcc tgttgcatca gcctctgacc ttggccagca
ccacctgccc ccactggctt 901 tttggtgccc cttgtcccca cttcagcccc
aggacctttc cttgcccttt ggttccagat 961 atcagactgt tccctgttca
cagcaccctc agggtcttaa ggtcttcatg ccctatcaca
1021 aatacctctt ttatctgtcc acccctcaca gactaggacc ctcaaataaa
gctgttttat 1081 atcaaaaaaa GenBank Gene Name Gene Symbol Accession
# SEQ ID NO hephaestin HEPH NM_138737 8 1 gcccagcctg cctggagaaa
agtgtctgct cctagccaag atctcctcat cacaaaagta 61 atgtgggcca
tggagtcagg ccacctcctc tgggctctgc tgttcatgca gtccttgtgg 121
cctcaactga ctgatggagc cactcgagtc tactacctgg gcatccggga tgtgcagtgg
181 aactatgctc ccaagggaag aaatgtcatc acgaaccagc ctctggacag
tgacatagtg 241 gcttccagct tcttaaagtc tgacaagaac cggatagggg
gaacctacaa gaagaccatc 301 tataaagaat acaaggatga ctcatacaca
gatgaagtgg cccagcctgc ctggttgggc 361 ttcctggggc cagtgttgca
ggctgaagtg ggggatgtca ttcttattca cctgaagaat 421 tttgccactc
gtccctatac catccaccct catggtgtct tctacgagaa ggactctgaa 481
ggttccctat acccagatgg ctcctctggg ccactgaaag ctgatgactc tgttcccccg
541 gggggcagcc atatctacaa ctggaccatt ccagaaggcc atgcacccac
cgatgctgac 601 ccagcgtgcc tcacctggat ctaccattct catgtagatg
ctccacgaga cattgcaact 661 ggcctaattg ggcctctcat cacctgtaaa
agaggagccc tggatgggaa ctcccctcct 721 caacgccagg atgtagacca
tgatttcttc ctcctcttca gtgtggtaga tgagaacctc 781 agctggcatc
tcaatgagaa cattgccact tactgctcag atcctgcttc agtggacaaa 841
gaagatgaga catttcagga gagcaatagg atgcatgcaa tcaatggctt tgtttttggg
901 aatttacctg agctgaacat gtgtgcacag aaacgtgtgg cctggcactt
gtttggcatg 961 ggcaatgaaa ttgatgtcca cacagcattt ttccatggac
agatgctgac tacccgtgga 1021 caccacactg atgtggctaa catctttcca
gccacctttg tgactgctga gatggtgccc 1081 tgggaacctg gtacctggtt
aattagctgc caagtgaaca gtcactttcg agatggcatg 1141 caggcactct
acaaggtcaa gtcttgctcc atggcccctc ctgtggacct gctcacaggc 1201
aaagttcgac agtacttcat tgaggcccat gagattcaat gggactatgg cccgatgggg
1261 catgatggga gtactgggaa gaatttgaga gagccaggca gtatctcaga
taagtttttc 1321 cagaagagct ccagccgaat tgggggcact tactggaaag
tgcgatatga agcctttcaa 1381 gatgagacat tccaagagaa gatgcatttg
gaggaagata ggcatcttgg aatcctgggg 1441 ccagtgatcc gggctgaggt
gggtgacacc attcaggtgg tcttctacaa ccgtgcctcc 1501 cagccattca
gcatgcagcc ccatggggtc ttttatgaga aagactatga aggcactgtg 1561
tacaatgatg gctcatctta ccctggcttg gttgccaagc cctttgagaa agtaacatac
1621 cgctggacag tcccccctca tgccggtccc actgctcagg atcctgcttg
tctcacttgg 1681 atgtacttct ctgctgcaga tcccataaga gacacaaatt
ctggcctggt gggcccgctg 1741 ctggtgtgca gggctggtgc cttgggtgca
gatggcaagc agaaaggggt ggataaagaa 1801 ttctttcttc tcttcactgt
gttggatgag aacaagagct ggtacagcaa tgccaatcaa 1861 gcagctgcta
tgttggattt ccgactgctt tcagaggata ttgagggctt ccaagactcc 1921
aatcggatgc atgccattaa tgggtttctg ttctctaacc tgcccaggct ggacatgtgc
1981 aagggtgaca cagtggcctg gcacctgctc ggcctgggca cagagactga
tgtgcatgga 2041 gtcatgttcc agggcaacac tgtgcagctt cagggcatga
ggaagggtgc agctatgctc 2101 tttcctcata cctttgtcat ggccatcatg
cagcctgaca accttgggac atttgagatt 2161 tattgccagg caggcagcca
tcgagaagca gggatgaggg caatctataa tgtctcccag 2221 tgtcctggcc
accaagccac ccctcgccaa cgctaccaag ctgcaagaat ctactatatc 2281
atggcagaag aagtagagtg ggactattgc cctgaccgga gctgggaacg ggaatggcac
2341 aaccagtctg agaaggacag ttatggttac attttcctga gcaacaagga
tgggctcctg 2401 ggttccagat acaagaaagc tgtattcagg gaatacactg
atggtacatt caggatccct 2461 cggccaagga ctggaccaga agaacacttg
ggaatcttgg gtccacttat caaaggtgaa 2521 gttggtgata tcctgactgt
ggtattcaag aataatgcca gccgccccta ctctgtgcat 2581 gctcatggag
tgctagaatc tactactgtc tggccactgg ctgctgagcc tggtgaggtg 2641
gtcacttatc agtggaacat cccagagagg tctggccctg ggcccaatga ctctgcttgt
2701 gtttcctgga tctattattc tgcagtggat cccatcaagg acatgtatag
tggcctggtg 2761 gggcccttgg ctatctgcca aaagggcatc ctggagcccc
atggaggacg gagtgacatg 2821 gatcgggaat ttgcattgtt gttcttgatt
tttgatgaaa ataagtcttg gtatttggag 2881 gaaaatgtgg caacccatgg
gtcccaggat ccaggcagta ttaacctaca ggatgaaact 2941 ttcttggaga
gcaataaaat gcatgcaatc aatgggaaac tctatgccaa ccttaggggt 3001
cttaccatgt accaaggaga acgagtggcc tggtacatgc tggccatggg ccaagatgtg
3061 gatctacaca ccatccactt tcatgcagag agcttcctct atcggaatgg
cgagaactac 3121 cgggcagatg tggtggatct gttcccaggg acttttgagg
ttgtggagat ggtggccagc 3181 aaccctggga catggctgat gcactgccat
gtgactgacc atgtccatgc tggcatggag 3241 accctcttca ctgttttttc
tcgaacagaa cacttaagcc ctctcaccgt catcaccaaa 3301 gagactgaaa
aagcagtgcc ccccagagac attgaagaag gcaatgtgaa gatgctgggc 3361
atgcagatcc ccataaagaa tgttgagatg ctggcctctg ttttggttgc cattagtgtc
3421 acccttctgc tcgttgttct ggctcttggt ggagtggttt ggtaccaaca
tcgacagaga 3481 aagctacgac gcaataggag gtccatcctg gatgacagct
tcaagcttct gtctttcaaa 3541 cagtaacatc tggagcctgg agatatcctc
aggaagcaca tctgtagtgc actcccagca 3601 ggccatggac tagtcactaa
ccccacactc aaaggggcat gggtggtgga gaagcagaag 3661 gagcaatcaa
gcttatctgg atatttcttt ctttatttat tttacatgga aataatatga 3721
tttcactttt tctttagttt ctttgctcta cgtgggcacc tggcactaag ggagtacctt
3781 attatcctac atcgcaaatt tcaacagcta cattatattt ccttctgaca
cttggaaggt 3841 attgaaattt ctagaaatgt atccttctca caaagtagag
accaagagaa aaactcattg 3901 attgggtttc tacttctttc aaggactcag
gaaatttcac tttgaactga ggccaagtga 3961 gctgttaaga taacccacac
ttaaactaaa ggctaagaat ataggcttga tgggaaattg 4021 aaggtaggct
gagtattggg aatccaaatt gaattttgat tctccttggc agtgaactac 4081
tttgaagaag tggtcaatgg gttgttgctg ccatgagcat gtacaacctc tggagctaga
4141 agctcctcag gaaagccagt tctccaagtt cttaacctgt ggcactgaaa
ggaatgttga 4201 gttacctctt catgttttag acagcaaacc ctatccatta
aagtacttgt tagaacactg GenBank Gene Name Gene Symbol Accession # SEQ
ID NO thiopurine S- TPMT NM_000367 9 methyltransferase 1 gcgggcggag
gcggggcgcg gagaagtggc ggaggtggaa gcggaggcgt acccgcccct 61
ggggacgtca ttggtggcgg aggcaatggc cggcaaccag ctgtaagcga ggcacggaag
121 acatatgctt gtgagacaaa ggtgtctctg aaactatgga tggtacaaga
acttcacttg 181 acattgaaga gtactcggat actgaggtac agaaaaacca
agtactaact ctggaagaat 241 ggcaagacaa gtgggtgaac ggcaagactg
cttttcatca ggaacaagga catcagctat 301 taaagaagca tttagatact
ttccttaaag gcaagagtgg actgagggta ttttttcctc 361 tttgcggaaa
agcggttgag atgaaatggt ttgcagaccg gggacacagt gtagttggtg 421
tggaaatcag tgaacttggg atacaagaat tttttacaga gcagaatctt tcttactcag
481 aagaaccaat caccgaaatt cctggaacca aagtatttaa gagttcttcg
gggaacattt 541 cattgtactg ttgcagtatt tttgatcttc ccaggacaaa
tattggcaaa tttgacatga 601 tttgggatag aggagcatta gttgccatca
atccaggtga tcgcaaatgc tatgcagata 661 caatgttttc cctcctggga
aagaagtttc agtatctcct gtgtgttctt tcttatgatc 721 caactaaaca
tccaggtcca ccattttatg ttccacatgc tgaaattgaa aggttgtttg 781
gtaaaatatg caatatacgt tgtcttgaga aggttgatgc ttttgaagaa cgacataaaa
841 gttggggaat tgactgtctt tttgaaaagt tatatctact tacagaaaag
taaatgagac 901 atagataaaa taaaatcaca ctgacatgtt tttgaggaat
tgaaaattat gctaaagcct 961 gaaaatgtaa tggatgaatt tttaaaattg
tttataaatc atatgataga tctttactaa 1021 aaatggcttt ttagtaaagc
catttacttt ttctaaaaaa gttttagaag aaaaagatgt 1081 aactaaactt
ttaaagtagc tcctttggag aggagattat gatgtgaaag attatgccta 1141
tgtgtcttgc agattgcaag atattttacc aatcagcatg tgttacctgt acaattaaaa
1201 aaatatttca aaatgcaatg catattaaat ataatacaca cagaaaaact
ggcatttatt 1261 ttgttttatt tttttgagat ggagtttcgt tcttgttgcc
caacctggag tgcaatggtg 1321 caatctcagc tcactgcaac ctctgcctcc
caggttcagg tgattctcct gcctcagcct 1381 cctgagtagc tgggattaca
ggtgtgcgcc accacgccca gctaattttt tgtattttta 1441 gtagagacag
ggtttcacca tgttggtcag gctgatctcg agctcctgac ctcaggtgat 1501
ctacccacct cggcctccca aagtgctggg attacaggcg tgagccactg cacctggcct
1561 gacattcttt atgaaattta gaattgttga agaactataa catttcagta
gggttcaagg 1621 tggtcccaaa agttatataa aagattagtt tttactataa
acccttgtct tttactcaga 1681 tcctagcatc ccttttcaca tggtttctcc
atgtatataa cagaatcaag aaacaaattt 1741 taattaaaca atctgtaaca
gaatcaagaa acaaatacat tttaattaaa caatctatat 1801 ggaacaaaca
ttcccaaatt ctaagaataa atttttcttt aagttttctc tgagtttggc 1861
aattgttgtt ttttataatt taatctgttt aaatcatcag gtcttataaa atataatgta
1921 cttagagctg gattcatggc tgtttattat gaaaggttag atttctcagt
tcttctttaa 1981 ccacattttg ttatatcaga cagtcctcta taactctgta
ctacccaaca actaaatggt 2041 ttagattgtt tagctcatgt taataggatg
gttgtgtatt ataaaaaacg agttacgtgt 2101 gtgtgtgcac gcatgcacgc
acatgtgctg gcttaaaggt tgttaatgca aggtttgggg 2161 tcccctttaa
cactggtgaa agctacggta ctctccccag agatatgtct tgtcagcctc 2221
tctagttccc cttggcctgc atgtacaaac ttctacccta gaagctctct gccatcgatg
2281 tattctaata gatttgtaag gctattaatt tgaagcaact ccttgctcac
agtgattctt 2341 gcttctctga gacctgctcc cagtcgatac tgtgggcttc
agaagccatg actccccaac 2401 tctgcctgta tcaccggttg aatggacaac
taacccgagc tggaccaaca caattctctc 2461 cagagacttt tgattttact
tttatgtaga gacagggtct cactttgttg cccacgctga 2521 tgttgaactt
gacgtgaggc ctcaagcagt cctcctgtct tggccaccca aagtgctagg 2581
attacaggta tgagccattg cgctggccct cttcataggc ttttggactt gggaatagaa
2641 aagcaacccc gtctctacta aaaatacaaa aaaattagcc aggcgtggtg
gcacgtgcct 2701 gtaatcccag ctacttggga ggctgaggca ggagaatcac
ttgaacctag gaggcggagg 2761 ttgcagtgag ctgagatcat gccactgcac
gcaagcctgg gcaacagagc aagactctgt
2821 ctcaaaagaa agaaaaagaa aagaaaaaaa agaaaggcaa gttgactgct
gaaaggggaa 2881 tctgtgtacg cctgggagct gtggggcagc cacattccag
cacatggatc tgagaaacag 2941 aacgctgatc tgcagaaaga gatgagaacc
aaagagaggc cacctgcgtc ctgggtccat 3001 tttcatcctc cctgaagccc
agctgcccag ggtggggaga aacaccctgt gtccatggga 3061 tagagtcctt
tccgcttgca gttgtgccca aagaatctta aatacaaatg agatatcctt 3121
aggtagttga tcatttatgt aatatgtgtc ttcactgggg aatactgact tcctaaaatc
3181 tcaagatgga agatatacca catgtaaatt attttagagc aattaaattg
ttttcaggat 3241 tttccaaaaa GenBank Gene Name Gene Symbol Accession
# SEQ ID NO plakophilin 3 PKP3 NM_007183 10 1 ggcctcgagg gacaggacgt
gaagatagtt gggtttggag gcggccgcca ggcccaggcc 61 cggtggacct
gccgccatgc aggacggtaa cttcctgctg tcggccctgc agcctgaggc 121
cggcgtgtgc tccctggcgc tgccctctga cctgcagctg gaccgccggg gcgccgaggg
181 gccggaggcc gagcggctgc gggcagcccg cgtccaggag caggtccgcg
cccgcctctt 241 gcagctggga cagcagccgc ggcacaacgg ggccgctgag
cccgagcctg aggccgagac 301 tgccagaggc acatccaggg ggcagtacca
caccctgcag gctggcttca gctctcgctc 361 tcagggcctg agtggggaca
agacctcggg cttccggccc atcgccaagc cggcctacag 421 cccagcctcc
tggtcctccc gctccgccgt ggatctgagc tgcagtcgga ggctgagttc 481
agcccacaac gggggcagcg cctttggggc cgctgggtac gggggtgccc agcccacccc
541 tcccatgccc accaggcccg tgtccttcca tgagcgcggt ggggttggga
gccgggccga 601 ctatgacaca ctctccctgc gctcgctgcg gctggggccc
gggggcctgg acgaccgcta 661 cagcctggtg tctgagcagc tggagcccgc
ggccacctcc acctacaggg cctttgcgta 721 cgagcgccag gccagctcca
gctccagccg ggcagggggg ctggactggc ccgaggccac 781 tgaggtttcc
ccgagccgga ccatccgtgc ccctgccgtg cggaccctgc agcgattcca 841
gagcagccac cggagccgcg gggtaggcgg ggcagtgccg ggggccgtcc tggagccagt
901 ggctcgagcg ccatctgtgc gcagcctcag cctcagcctg gctgactcgg
gccacctgcc 961 ggacgtgcat gggttcaaca gctacggtag ccaccgaacc
ctgcagagac tcagcagcgg 1021 ttttgatgac attgacctgc cctcagcagt
caagtacctc atggcttcag accccaacct 1081 gcaggtgctg ggagcggcct
acatccagca caagtgctac agcgatgcag ccgccaagaa 1141 gcaggcccgc
agccttcagg ccgtgcctag gctggtgaag ctcttcaacc acgccaacca 1201
ggaagtgcag cgccatgcca caggtgccat gcgcaacctc atctacgaca acgctgacaa
1261 caagctggcc ctggtggagg agaacgggat cttcgagctg ctgcggacac
tgcgggagca 1321 ggatgatgag cttcgcaaaa atgtcacagg gatcctgtgg
aacctttcat ccagcgacca 1381 cctgaaggac cgcctggcca gagacacgct
ggagcagctc acagacctgg tgttgagccc 1441 cctgtcgggg gctgggggtc
cccccctcat ccagcagaac gcctcggagg cggagatctt 1501 ctacaacgcc
accggcttcc tcaggaacct cagctcagcc tctcaggcca ctcgccagaa 1561
gatgcgggag tgccacgggc tggtggacgc cctggtcacc tctatcaacc acgccctgga
1621 cgcgggcaaa tgcgaggaca agagcgtgga gaacgcggtg tgcgtcctgc
ggaacctgtc 1681 ctaccgcctc tacgacgaga tgccgccgtc cgcgctgcag
cggctggagg gtcgcggccg 1741 cagggacctg gcgggggcgc cgccgggaga
ggtcgtgggc tgcttcacgc cgcagagccg 1801 gcggctgcgc gagctgcccc
tcgccgccga tgcgctcacc ttcgcggagg tgtccaagga 1861 ccccaagggc
ctcgagtggc tgtggagccc ccagatcgtg gggctgtaca accggctgct 1921
gcagcgctgc gagctcaacc ggcacacgac ggaggcggcc gccggggcgc tgcagaacat
1981 cacggcaggc gaccgcaggt gggcgggggt gctgagccgc ctggccctgg
agcaggagcg 2041 tattctgaac cccctgctag accgtgtcag gaccgccgac
caccaccagc tgcgctcact 2101 gactggcctc atccgaaacc tgtctcggaa
cgctaggaac aaggacgaga tgtccacgaa 2161 ggtggtgagc cacctgatcg
agaagctgcc gggcagcgtg ggtgagaagt cgcccccagc 2221 cgaggtgctg
gtcaacatca tagctgtgct caacaacctg gtggtggcca gccccatcgc 2281
tgcccgagac ctgctgtatt ttgacggact ccgaaagctc atcttcatca agaagaagcg
2341 ggacagcccc gacagtgaga agtcctcccg ggcagcatcc agcctcctgg
ccaacctgtg 2401 gcagtacaac aagctccacc gtgacttccg ggcgaagggc
tatcggaagg aggacttcct 2461 gggcccatag gtgaagcctt ctggaggaga
aggtgacgtg gcccagcgtc caagggacag 2521 actcagctcc aggctgcttg
gcagcccagc ctggaggaga aggctaatga cggaggggcc 2581 cctcgctggg
gcccctgtgt gcatctttga gggtcctggg ccaccaggag gggcagggtc 2641
ttatagctgg ggacttggct tccgcagggc agggggtggg gcagggctca aggctgctct
2701 ggtgtatggg gtggtgaccc agtcacattg gcagaggtgg gggttggctg
tggcctggca 2761 gtatcttggg atagccagca ctgggaataa agatggccat
gaacagtcaa GenBank Gene Name Gene Symbol Accession # SEQ ID NO
UDP-N-acetyl-alpha-D- GALNT5 NM_014568 11 galactosamine:polypeptide
N- acetylgalactosaminyltransferase 5 (GalNAc-T5) 1 agtgtttatc
agaacttagc cagggccagc caagcaggca cagatgctct gctatgaaat 61
gccacgcagg cagagactga caagcggtag gaactgagct ttccccttgg actgctgctt
121 cctgctgtgt tcaggggagg gggtcacttt ctggcaactc tgctgctgct
gctgctgctg 181 ctgctacttc agcttcctct ccactcaagg taagcaggct
aagggagggc aggctgctag 241 ggaaagcttt gtaccatgaa caggatccga
aagtttttcc gaggaagtgg gcgagtcttg 301 gcatttatct ttgtagcttc
tgtcatctgg ctcctctttg acatggcagc tctccgcctc 361 tcattcagtg
agatcaacac tcgggtcatc aaggaagaca ttgtgaggag ggagcggata 421
ggattcagag ttcagccaga ccaaggaaaa attttttaca gcagcataaa agagatgaaa
481 cctcccctaa ggggacatgg gaaaggggca tggggcaaag agaatgttag
aaaaactgag 541 gagagtgtgc tcaaggttga ggtggacttg gaccaaaccc
agagggaaag aaaaatgcag 601 aatgccctgg gaaggggcaa ggttgtgccg
ttgtggcat cctgcacatct gcagaccctc 661 cctgtgactc ctaacaagca
gaagacagac gggagaggc accaaacctga agcctcctct 721 caccagggga
caccaaagca aacgacagct cagggggct ccaaagacctc attcatagca 781
gcaaaaggaa ctcaggtagt caaaatatca gtacacatg ggacgtgtcag tttaaaacag
841 gagccccgga agagtcatag tcccagcagt gacacatca aaactagcagc
tgaaagggac 901 ttgaatgtga ccatcagtct tagtactgat agaccaaag
cagcgatcaca ggcagtagca 961 aacgagaggg cacaccctgc cagcacagca
gtgccgaag tctggggaagc catggcctta 1021 aacaaaacta agactcagag
caaagaagtc aatgcaaata aacacaaagc caatacgagt 1081 cttccttttc
ctaagttcac tgtcaattca aatcgcttaa ggaagcaatc tattaatgag 1141
acacctttgg gaagtttgtc aaaggatgat ggagctagag gggctcatgg gaagaaactc
1201 aatttctctg aaagccatct tgtgattata accaaagagg aagagcaaaa
ggcagacccc 1261 aaagaggtct ctaattctaa aaccaaaaca atatttccta
aagtattggg taaaagccaa 1321 agtaaacaca tttccaggaa tagaagtgag
atgtcttcct cttcacttgc tccacataga 1381 gtgccactgt cccaaactaa
ccatgcttta actggagggc tagagccagc aaaaatcaac 1441 ataactgcca
aagccccctc tacagaatac aaccagagtc atataaaagc ccttttacct 1501
gaagacagtg gaacgcacca ggtgttaaga attgatgtga cactttctcc aagggacccc
1561 aaagctccag ggcagtttgg gcgtcctgta gttgtccccc atggaaagga
gaaggaggca 1621 gaaagaagat ggaaagaagg aaacttcaat gtctacctta
gcgatttgat cccagtggat 1681 agagccattg aagacaccag acctgctgga
tgtgcagagc agctagttca caataacctc 1741 ccaaccacca gtgtcatcat
gtgctttgtg gatgaagtgt ggtccactct cctgagatct 1801 gttcacagtg
tcatcaatcg ctctcctcca cacctcatca aggagattct gctggtagat 1861
gacttcagca ccaaagacta tctaaaagat aatttggata aatacatgtc ccagtttcca
1921 aaagttcgga ttcttcgcct caaagagaga catggcttaa taagggccag
gctggcagga 1981 gcacagaatg caacaggtga tgtgttgaca tttttagatt
ctcatgtgga atgtaacgtt 2041 ggttggttgg aacctcttct ggaaagagtt
tatttaagta gaaagaaagt ggcctgtcca 2101 gtaatcgaag tcatcaatga
taaggatatg agttacatga cagtggataa ctttcaaaga 2161 ggcatctttg
tgtggcccat gaactttggt tggagaacaa ttcctccaga tgtcattgca 2221
aaaaacagaa ttaaagaaac tgatacaata aggtgccctg tcatggctgg tggattgttt
2281 tctattgaca aaagttactt ttttgaactt ggaacatacg accctggcct
tgatgtttgg 2341 ggtggggaaa atatggagct ctcattcaag gtgtggatgt
gtggtggtga aattgagatc 2401 attccctgct cccgagtggg ccatatattc
agaaatgaca atccatattc cttccccaaa 2461 gaccggatga agacagtgga
gcggaacttg gtgcgggttg ccgaggtctg gctggatgag 2521 tataaggagc
tgttctatgg ccacggagac cacctcatcg accaagggct agatgttggc 2581
aacctcaccc agcaaaggga gctgcgaaag aaactgaagt gcaaaagttt caaatggtac
2641 ttggagaatg tctttcctga cttaagggct cccattgtga gagctagtgg
tgtgcttatt 2701 aatgtggctt tgggtaaatg catttccatt gaaaacacta
cagtcattct ggaagactgc 2761 gatgggagca aagagcttca acaatttaat
tacacctggt taagacttat taaatgtgga 2821 gaatggtgta tagcccccat
ccctgataaa ggagccgtaa ggctgcaccc ttgtgataac 2881 agaaacaaag
ggctaaaatg gctgcataaa tcaacatcag tctttcatcc agaactggtg 2941
aatcacattg tttttgaaaa caatcagcaa ttattatgct tggaaggaaa tttttctcaa
3001 aagatcctga aagtagctgc ctgtgaccca gtgaagccat atcaaaagtg
gaaatttgaa 3061 aaatattatg aagcctgaag tgtaactgat gtttttatat
agtaaaccca ttaaatactg 3121 tgaaaataac a GenBank Gene Name Gene
Symbol Accession # SEQ ID NO calmodulin-like 4 CALML4 NM_033429 12
1 ggggctgagg gtggagagag gaagggaagg aagaaaaggg gagccttcct ggccagggta
61 accggcacta agaggcctca ctccaagccc ccgaggagcc tgtggtgggg
ctggagaccc 121 ggctcaggcc cctccaccac ccttaaagtc ctcagaaggt
gggaactgaa ctggcacagg 181 atgggaaccg gctgtgcgct ggccacttga
ttttgccagc tgccctgtaa ttcagctggt 241 gaggaaactg aggcacagac
tgaggtagaa tgattcgcca gtcactcagc aagtcagcag 301 acggggagga
ctgaatccca gcctgagagc accgaagctt gtatccctgc aataccgagc 361
cccaagcctg cgagccccgg tgcccatctc tgagttaggc cgtcttggaa gggttccctt
421 cctcctacaa gatggtgtgt gaggagcctt caatacgacc cggggtgtaa
agtgtccaac 481 tctagtaggg gcctgatggc atccccgccg agtcccagga
gagagagaga agaccccttc
541 ctggagtcca gggctcccgg gaagaaacac tggcatttgt ccctttgctt
cggcttctgg 601 aggcagagac tctgagccca gggagagcct tctgcagccc
catttcctca aaaatccaac 661 ctgcccaggt ggcgggtcat gagctgtgct
caggaagctg gaatctgacc ctggtggcgt 721 cgggcccagt ctccatggca
gccgagcatt tattacccgg gcctccaccc agcttggcag 781 actttagact
tgaggctgga ggaaagggaa ctgaacgcgg ttctgggagc agcaagccca 841
cgggtagcag ccgaggcccc agaatggcca agtttctttc ccaagaccaa attaatgagt
901 acaaggaatg cttctccctg tatgacaagc agcagagggg gaagataaaa
gccaccgacc 961 tcatggtggc catgaggtgc ctgggggcca gcccgacgcc
aggggaggtg cagcggcacc 1021 tgcagaccca cgggatagac ggaaatggag
agctggattt ctccactttt ctgaccatta 1081 tgcacatgca aataaaacaa
gaagacccaa agaaagaaat tcttctagcc atgttgatgg 1141 tggacaagga
gaagaaaggt tacgtcatgg cgtccgacct gcggtcaaaa ctcacgagtc 1201
tgggggagaa gctcacccac aaggaagtgg atgatctctt cagggaagca gatatcgaac
1261 ccaatggcaa agtgaagtat gatgaattta tccacaagat cacccttcct
ggacgggact 1321 attgaaggag gagaatggga gagcctcccc tgggcctgaa
aacttggagc aattaatttt 1381 ttttaaaaag tgttcttttc acttgggaga
gatggcaaac acagtggcaa gacaacatta 1441 cccaactata gaagagaggc
taactagcaa caataataga tgatttcagc catggtatga 1501 gtagatcttt
aataaaagat ttgtattgat tttattaact accgtgagtc cggccctttc 1561
aagcatggaa ggagcctgcg gtttggagtc tggcctgggt tccagtcctg gctctgctgc
1621 ttcccactgt gactttgggc aaatcatttc actcctcaaa gcccccccac
acaagctgga 1681 ttcccacttc ttacctcatg gagcctgttg aggaaggatt
gagctgatga cttaagggca 1741 atctaccaag agacttattc tgtatttggg
ggctagaacc atcttccata tttccaagat 1801 tttccaagat gaagccagtg
ctagctgaga agcagcaatg aacagaaagc tgtaacactt 1861 atgacaacaa
ttcttgcagt gccagaggcc catttacaaa ttctcatttc catctcaaca 1921
gatatagtga catagctcag gctattcatt cataaacaca gagtgtagag tgaaaacact
1981 agagtgaaaa cacatgctac aatgaggcag catcagctga gagcaggaag
agcgatctac 2041 tttacacccc acaccaaagg aaaccagatg tgagctgcta
aattgactgg ccttgcagag 2101 ctcaagaagg gggcttccaa tgctgtgaga
attccgagct gttccctggg ctctgttaac 2161 aggcagagag gttccgggat
ggtctgctca agtggcccac actggtcatt gccttaagcc 2221 acctccccag
gacttacgga gagaaataag gggatgtaac cagcaatggc cagggtacaa 2281
cagccctgga aaacagtagt aggagcacta ggctttctgg gagtccatcc agctggagtg
2341 gctttgagtg agttacacag ctagaaggtg ccaggttggt gctgccagag
attcagaggt 2401 gccatacact tgtcaaatct ggatcattcg tagtgccagc
acagtcctaa aagggctgga 2461 gtaccacacc aacacaggta ggggtgcagg
gcttcaagta caaagatttg catccatgta 2521 tgtatcaaaa gtgggttctc
tgggctgtgg ctttgtctag tagtaccaca gtggctaaag 2581 tagaagaaaa
ccaaatcaaa tgggatgtgt cttttgggag gatgtacaag acacaaatct 2641
ttcactaggc accgggcaca gggaaaactg cagggaacaa gagttgtagt gttagtgcaa
2701 ctgtctcaac gatgctgtgt ggcttcagac ccaaacaagg ccctgaggaa
ggagactctc 2761 atttccccaa gcataactgc aaggagagga ggaattccta
ggagccaaag agttttgtgg 2821 ggtgagggta aataaatggc ccaaatgcca
actaggtgaa gttgtgacca tctggctggg 2881 aagcccaggt ccacacagtg
taggagcaga tgttttgtgg ggtctgaggt ttacgagatt 2941 tggctgcctt
aagaatacaa aaacagaaat gcagaatttc tggggctgct cctaggacca 3001
gaacaagtga agggtcctgg tgcttaaact tcattacctt catggtaaat ccaccagagg
3061 gccggttaga tgctggcccc gccgagagaa ctgctgtcac tttcaggcaa
agctcaaagg 3121 tcctaggccc acagttcttt tgagctccag tcatggacat
taggaagtaa atcctgcaca 3181 gccaacctgg aataccaaag attagatggg
agatagatac caatgattta gatggcacag 3241 gaagagcaag ttctggatat
aataaatgag ggtactttcc gtcaaagctt ttctatgtct 3301 atatttatca
ctgaatagtc ccagtatggt tttaaagcaa gttttatgaa tctcatttgc 3361
ctaacaggaa tctgaaatat aacttgccaa aaacacacag ttggtgtgga atggtcatta
3421 gaacctgggg ctcctcttca cggactccct gctcattaag ggattcagtg
gtccagagtc 3481 taagatccta ttaagtgttt gattcaaacc tctacccgag
gaagggctgt taccttactc 3541 ctggtcctgg tttcaagctc attcctgaaa
ttccagctgg tttctctagc acctagtgtt 3601 gtttacaaga aggccacggt
gctcttagca ttcaaactgc agatactaaa cagatgctgt 3661 gatttattaa
agagttagcc atatttcaac aagaaaggga aatgatggct atattcatta 3721
cttacctcaa agcatgctgc aagaaaatta gttagttact tgtcatgctt tgaaatctct
3781 ggatgaaagg tgctttggaa gcacaaacca ttatcacttg tctcataggg
attgtcccct 3841 tgaacatcca gcagtgttat tttacagaag acaaattaac
tgaaggcttt tcttttatta 3901 catctaaaga gctctacata aacaggtaac
attcaatagg taaacaattt ttttccaatg 3961 catgtaataa atattttcac
ttggtacttt tatacaaact gacattgtct actatacatt 4021 tttaaaagcc
attttactgg tttggcatgc ggtatggaaa ttctaagaga gaaagtttta 4081
aggcaatgaa tcacagattt aagttcatgg aatttatggt aactttatct gtttatgtac
4141 attttcccct ttgttaaaca attaacagca gcacactctg ggaccaccag
ctattttccc 4201 tctctttctg aaatctaagc tttgtattta attaaaaaac
agaattcaac atctattgat 4261 aaaacaaaat tcttactaaa ataatttcaa
atgtgcttta aaaagtcctg aagatcttga 4321 aagttttatg tgtttaaaat
tgaaattgtc taaaaaaatg ctctttccac attaatttag 4381 ttaggatata
ttttcactcc atttcagaca cttgactcaa aggaaaatct gccaaagaat 4441
ccgatttttc agagcttacg tgaatctttc ctcagtaaag atacagaatt gtgatcatgt
4501 ctaaataatt agtaaagcaa ttttaatgct caaaatagtc aaccaagtat
ggcatggttc 4561 tggttcagat tttttttttt taagatgtat ccaataacac
tcacgaagta attaaaagcc 4621 actttaaccc tgctaaaaaa GenBank Gene Name
Gene Symbol Accession # SEQ ID NO UDP-N-acetyl-alpha-D- GALNT12
AK024865 13 galactosamine:polypeptide N-
acetylgalactosaminyltransferase 12 (GalNAc-T12) 1 cattttataa
tgaagcctgg tcaactctcc ttcggacagt ttacagtgtc cttgagacat 61
ccccggatat cctgctagaa gaagtgatcc ttgtagatga ctacagtgat agagagcacc
121 tgaaggagcg cttggccaat gagctttcgg gactgcccaa ggtgcgcctg
atccgcgcca 181 acaagagaga gggcctggtg cgagcccggc tgctgggggc
gtctgcggcg aggggcgatg 241 ttctgacctt cctggactgt cactgtgagt
gccacgaagg gtggctggag ccgctgctgc 301 agaggatcca tgaagaggag
tcggcagtgg tgtgcccggt gattgatgtg atcgactgga 361 acaccttcga
atacctgggg aactccgggg agccccagat cggcggtttc gactggaggc 421
tggtgttcac gtggcacaca gttcctgaga gggagaggat acggatgcaa tcccccgtcg
481 atgtcatcag gtctccaaca atggctggtg ggctgtttgc tgtgagtaag
aaatattttg 541 aatatctggg gtcttatgat acaggaatgg aagtttgggg
aggagaaaac ctcgaatttt 601 cctttaggat ctggcagtgt ggtggggttc
tggaaacaca cccatgttcc catgttggcc 661 atgttttccc caagcaagct
ccctactccc gcaacaaggc tctggccaac agtgttcgtg 721 cagctgaagt
atggatggat gaatttaaag agctctacta ccatcgcaac ccccgtgccc 781
gcttggaacc ttttggggat gtgacagaga ggaagcagct ccgggacaag ctccagtgta
841 aagacttcaa gtggttcttg gagactgtgt atccagaact gcatgtgcct
gaggacaggc 901 ctggcttctt cgggatgctc cagaacaaag gactaacaga
ctactgcttt gactataacc 961 ctcccgatga aaaccagatt gtgggacacc
aggtcattct gtacctctgt catgggatgg 1021 gccagaatca gtttttcgag
tacacgtccc agaaagaaat acgctataac acccaccagc 1081 ctgagggctg
cattgctgtg gaagcaggaa tggataccct tatcatgcat ctctgcgaag 1141
aaactgcccc agagaatcag aagttcatct tgcaggagga tggatcttta tttcacgaac
1201 agtccaagaa atgtgtccag gctgcgagga aggagtcgag tgacagtttc
gttccactct 1261 tacgagactg caccaactcg gatcatcaga aatggttctt
caaagagcgc atgttatgaa 1321 gcctcgtgta tcaaggagcc catcgaagga
gactgtggag ccaggactct gcccaacaaa 1381 gacttagcta agcagtgacc
agaacccacc aaaaactagg ctgcattgct ttgaagaggc 1441 aatcattttg
ccatttgtga aagttgtgtt ggatttagta aaaatgtgaa taagctttgt 1501
acttattttg agaacttttt aaatgttcca aaatacccta ttttcaaagg gtaatcgtaa
1561 gatgttaacc cttggtattt agaaaattaa aaccttataa tatttttcta
tcaagatgta 1621 tattttacag tcgtgccttt tactctcatt agcaaaaaag
ataaagattt tattttggta 1681 tttacaagaa ttcccaggta cgaagatatc
tgcatgggtg gaaatcaggt tcaagcaacg 1741 tactttgcat taactgataa
tacctcagct gcggggttaa agttttccca gtatagagag 1801 actgtcacta
ggaacattgt attgatttat tcaggtcatt gagatcttct agatgtattt 1861
taaaaagaat gctttttggt tatgtgttgc taccacagtt aacactccat aatgttcatg
1921 tcagccaaag aggactaacc aaagctgaaa tctcagagaa caatttgctt
tactaagctg 1981 agtcaacttg agagcgaact tctaacaatg ccgcactgta
gtgtggctgg ttctaccact 2041 atgactttaa aacatgttta tatcattttt
aatttttatg atacggtagt gtcagggaga 2101 aatgtaatgt tctatatgaa
attccttttt caagtttgtt cattaataac agttattaat 2161 ttaaatcagc
gttagagttt gtgctgctgc aactgctgtg aaaatttctc tgagtaattc 2221
tgatttgtga atgatcccag accaaccctg agattttgtc aacctgatta agtcaatatg
2281 aatgattaaa aagatgtgag GenBank Gene Name Gene Symbol Accession
# SEQ ID NO thiamin TPK1 NM_022445 14 pyrophosphokinase 1 1
aaggctcctc agccgagcgc cgagcggtcg atcgccgtag ctcccgcagc ctgcgatctc
61 cagtctgtgg ctcctaccag ccattgtagg ccaataatcc gttatggagc
atgcctttac 121 cccgttggag cccctgcttt ccactgggaa tttgaagtac
tgccttgtaa ttcttaatca 181 gcctttggac aactattttc gtcatctttg
gaacaaagct cttttaagag cctgtgccga 241 tggaggtgcc aaccgcttat
atgatatcac cgaaggagag agagaaagct ttttgcctga 301 attcatcaat
ggagactttg attctattag gcctgaagtc agagaatact atgctactaa 361
gggatgtgag ctcatttcaa ctcctgatca agaccacact gactttacta agtgccttaa
421 aatgctccaa aagaagatag aagaaaaaga cttaaaggtt gatgtgatcg
tgacactggg 481 aggccttgct gggcgttttg accagattat ggcatctgtg
aataccttgt tccaagcgac 541 tcacatcact ccttttccaa ttataataat
ccaagaggaa tcgctgatct acctgctcca
601 accaggaaag cacaggttgc atgtagacac tggaatggag ggtgattggt
gtggccttat 661 tcctgttgga cagccttgta tgcaggttac aaccacaggc
ctcaagtgga acctcacaaa 721 tgatgtgctt gcttttggaa cattggtcag
tacttccaat acctacgacg ggtctggtgt 781 tgtgactgtg gaaactgacc
acccactcct ctggaccatg gccatcaaaa gctaacctgt 841 tgactggcat
ccataagtgt gcctctgcct tatctcattt ctcaacagtt cattgctcaa 901
caagaacgat tcacctgggt ttgcaagaat ctaaacctct ctaggggaag cccactgggt
961 ttaaagatgt tagtgtttag ataatacagg taacattata aatgacagat
ctcaatttta 1021 tagtagtggg aaagatacat gctaagaaag caaataagct
ctattatatt cggttggaac 1081 ctaatgggaa tcattccact atacaattca
gtactgatta ttcttcttac attattaatc 1141 attccattta tcctagaaaa
ttgtttttaa tttgaatcag agaaaactgt tgaggttcct 1201 cttggagtct
agaacatcct taaatgtcta acaacaaggg ctacctctga gtacctttta 1261
gtattagttt tctgtatatg atatatatta tcttatactg aaaaaaaatt cctttcagat
1321 tggggtgtta gaagtgcacc aggtcactct gaccttatta ctgtctttgg
tattgtctta 1381 aataaatcaa gaatcattga cctaattgtt aaatttaaaa
ataggtagtt agcaataggt 1441 ggaaagagaa atgatgtgaa agataaatga
tgattcgtgg agccctactc acacattaac 1501 ccccaaattc aaaagtaaga
atgcaaaagt ctagaggggg taacagtctg catcatcatc 1561 acaacctaaa
tggagaaagc tgtgcagagg aaacttaagc ataaaaattg aattcgtttc 1621
tgacatacct tagactgaaa aactgttggt tcatccagaa gtgtattcat attaccagaa
1681 aatgagtttg tctatgggga tacatgaact tcatatacta aggagcctaa
ctccaaagcc 1741 tgcgttctca tcccagtctg atattcacct aagtttccgg
acccttttcc ttagctgtaa 1801 aatggaagcg gttggactga tggtgtctga
ggttctttcc cacactgaaa ttctaaatat 1861 tgacacttag cagtcatagg
gctgataata cacacagtta ctgacttagc ctaaacaacc 1921 tggtgcatcg
aaatgtattc acctttcttt tgtaaagaga ccatcttcta tcttctttcc 1981
acctttctct gttttatgaa accaactgtt gacatacaaa ccatgattga aggagaacct
2041 gtccaacatg ttttatgtac acaaatccct atgttgctat aagaaaagtg
aaagtaactg 2101 ttttcttctt ggtgctatga cagtgtgaga ctcaggttgt
ctgtagagaa tgaaaggagc 2161 agtggcccgc gtgattgtgg catttaagga
gcagtggccc atgtgactgt ggcattttcg 2221 gcacttttca ttactttctg
cttgaccgga agttgaggct tagctatgtt tccatcttca 2281 gtttctgaag
actagttata tattccttac tagaaatata ttcataatat ataaaagaaa 2341
tatatctgtg attttaaaat tttgctacca aagaatgcat gttctgtgtg ccctgaaaat
2401 gttaccagtg ttaataaatg gatacttatc aaaaaagaaa GenBank Gene Name
Gene Symbol Accession # SEQ ID NO defensin, alpha 6, DEFA6
NM_001926 15 Paneth cell-specific 1 acacatctgc tcctgctctc
tctcctccag cgaccctagc catgagaacc ctcaccatcc 61 tcactgctgt
tctcctcgtg gccctccagg ccaaggctga gccactccaa gctgaggatg 121
atccactgca ggcaaaagct tatgaggctg atgcccagga gcagcgtggg gcaaatgacc
181 aggactttgc cgtctccttt gcagaggatg caagctcaag tcttagagct
ttgggctcaa 241 caagggcttt cacttgccat tgcagaaggt cctgttattc
aacagaatat tcctatggga 301 cctgcactgt catgggtatt aaccacagat
tctgctgcct ctgagggatg agaacagaga 361 gaaatatatt cataatttac
tttatgacct agaaggaaac tgtcgtgtgt cccatacatt 421 gccatcaact
ttgtttcctc atctcaaata aagtcctttc agcaaaaaaa aaaaa GenBank Gene Name
Gene Symbol Accession # SEQ ID NO epithelial protein lost in EPLIN
NM_016357 16 neoplasm beta 1 gcgctaggta gagcgccggg acctgtgaca
gggctggtag cagcgcagag gaaaggcggc 61 ttttagccag gtatttcagt
gtctgtagac aagatggaat catctccatt taatagacgg 121 caatggacct
cactatcatt gagggtaaca gccaaagaac tttctcttgt caacaagaac 181
aagtcatcgg ctattgtgga aatattctcc aagtaccaga aagcagctga agaaacaaac
241 atggagaaga agagaagtaa caccgaaaat ctctcccagc actttagaaa
ggggaccctg 301 actgtgttaa agaagaagtg ggagaaccca gggctgggag
cagagtctca cacagactct 361 ctacggaaca gcagcactga gattaggcac
agagcagacc atcctcctgc tgaagtgaca 421 agccacgctg cttctggagc
caaagctgac caagaagaac aaatccaccc cagatctaga 481 ctcaggtcac
ctcctgaagc cctcgttcag ggtcgatatc cccacatcaa ggacggtgag 541
gatcttaaag accactcaac agaaagtaaa aaaatggaaa attgtctagg agaatccagg
601 catgaagtag aaaaatcaga aatcagtgaa aacacagatg cttcgggcaa
aatagagaaa 661 tataatgttc cgctgaacag gcttaagatg atgtttgaga
aaggtgaacc aactcaaact 721 aagattctcc gggcccaaag ccgaagtgca
agtggaagga agatctctga aaacagctat 781 tctctagatg acctggaaat
aggcccaggt cagttgtcat cttctacatt tgactcggag 841 aaaaatgaga
gtagacgaaa tctggaactt ccacgcctct cagaaacctc tataaaggat 901
cgaatggcca agtaccaggc agctgtgtcc aaacaaagca gctcaaccaa ctatacaaat
961 gagctgaaag ccagtggtgg cgaaatcaaa attcataaaa tggagcaaaa
ggagaatgtg 1021 cccccaggtc ctgaggtctg catcacccat caggaagggg
aaaagatttc tgcaaatgag 1081 aatagcctgg cagtccgttc cacccctgcc
gaagatgact cccgtgactc ccaggttaag 1141 agtgaggttc aacagcctgt
ccatcccaag ccactaagtc cagattccag agcctccagt 1201 ctttctgaaa
gttctcctcc caaagcaatg aagaagtttc aggcacctgc aagagagacc 1261
tgcgtggaat gtcagaagac agtctatcca atggagcgtc tcttggccaa ccagcaggtg
1321 tttcacatca gctgcttccg ttgctcctat tgcaacaaca aactcagtct
aggaacatat 1381 gcatctttac atggaagaat ctattgtaag cctcacttca
atcaactctt taaatctaag 1441 ggcaactatg atgaaggctt tgggcacaga
ccacacaagg atctatgggc aagcaaaaat 1501 gaaaacgaag agattttgga
gagaccagcc cagcttgcaa atgcaaggga gacccctcac 1561 agcccagggg
tagaagatgc ccctattgct aaggtgggtg tcctggctgc aagtatggaa 1621
gccaaggcct cctctcagca ggagaaggaa gacaagccag ctgaaaccaa gaagctgagg
1681 atcgcctggc caccccccac tgaacttgga agttcaggaa gtgccttgga
ggaagggatc 1741 aaaatgtcaa agcccaaatg gcctcctgaa gacgaaatca
gcaagcccga agttcctgag 1801 gatgtcgatc tagatctgaa gaagctaaga
cgatcttctt cactgaagga aagaagccgc 1861 ccattcactg tagcagcttc
atttcaaagc acctctgtca agagcccaaa aactgtgtcc 1921 ccacctatca
ggaaaggctg gagcatgtca gagcagagtg aagagtctgt gggtggaaga 1981
gttgcagaaa ggaaacaagt ggaaaatgcc aaggcttcta agaagaatgg gaatgtggga
2041 aaaacaacct ggcaaaacaa agaatctaaa ggagagacag ggaagagaag
taaggaaggt 2101 catagtttgg agatggagaa tgagaatctt gtagaaaatg
gtgcagactc cgatgaagat 2161 gataacagct tcctcaaaca acaatctcca
caagaaccca agtctctgaa ttggtcgagt 2221 tttgtagaca acacctttgc
tgaagaattc actactcaga atcagaaatc ccaggatgtg 2281 gaactctggg
agggagaagt ggtcaaagag ctctctgtgg aagaacagat aaagagaaat 2341
cggtattatg atgaggatga ggatgaagag tgacaaattg caatgatgct gggccttaaa
2401 ttcatgttag tgttagcgag ccactgccct ttgtcaaaat gtgatgcaca
taagcaggta 2461 tcccagcatg aaatgtaatt tacttggaag taactttgga
aaagaattcc ttcttaaaat 2521 caaaaacaaa acaaaaaaac acaaaaaaca
cattctaaat actagagata actttactta 2581 aattcttcat tttagcagtg
atgatatgcg taagtgctgt aaggcttgta actggggaaa 2641 tattccacct
gataatagcc cagattctac tgtattccca aaaggcaata ttaaggtaga 2701
tagatgatta gtagtatatt gttacacact attttggaat tagagaacat acagaaggaa
2761 tttaggggct taaacattac gactgaatgc actttagtat aaagggcaca
gtttgtatat 2821 ttttaaatga ataccaattt aattttttag tatttacctg
ttaagagatt atttagtctt 2881 taaatttttt aggttaattt tcttgctgtg
atatatatga ggaatttact actttatgtc 2941 ctgctctcta aactacatcc
tgaactcgac gtcctgaggt ataatacaac agagcacttt 3001 ttgaggcaat
tgaaaaacca acctacactc ttcggtgctt agagagatct gctgtctccc 3061
aaataagctt ttgtatctgc cagtgaattt actgtactcc aaatgattgc tttcttttct
3121 ggtgatatct gtgcttctca taattactga aagctgcaat attttagtaa
taccttcggg 3181 atcactgtcc cccatcttcc gtgttagagc aaagtgaaga
gtttaaagga ggaagaagaa 3241 agaactgtct tacaccactt gagctcagac
ctctaaaccc tgtatttccc ttatgatgtc 3301 ccctttttga gacactaatt
tttaaatact tactagctct gaaatatatt gatttttatc 3361 acagtattct
cagggtgaaa ttaaaccaac tataggcctt tttcttggga tgattttcta 3421
gtcttaaggt ttggggacat tataaacttg agtacatttg ttgtacacag ttgatattcc
3481 aaattgtatg gatgggaggg agaggtgtct taagctgtag gcttttcttt
gtactgcatt 3541 tatagagatt tagctttaat attttttaga gatgtaaaac
attctgcttt cttagtctta 3601 cctagtctga aacattttta ttcaataaag
attttaatta aaatttgaaa GenBank Gene Name Gene Symbol Accession # SEQ
ID NO chloride intracellular CLIC5 NM_016929 17 channel 5 1
gacagtcgcg gatcctgtga cacctccggg cagcccggca cttgttgctc ccacgacctg
61 ttgtcattcc cttaacccgg ctttccccgt ggccccccgc ctcctcccgg
cttcgctcct 121 tttcatgtga gcatctggga cactgatctc tcagaccccg
ctgctcgggc tggagaatag 181 atggttttgt gaaaaattaa acaccgccct
gaagaggagc cccgctgggc agcggcagga 241 gcgcagagtg ctggcccagg
tgctgcagag gtggcgcctc cccggcccgg gacggtagcc 301 ccgggcgcca
acggcatgac agactcggcg acagctaacg gggacgacag ggaccccgag 361
atcgagctct ttgtgaaggc tggaatcgat ggagaaagca tcggcaactg tcctttctct
421 cagcgcctct tcatgatcct ctggctgaaa ggagtcgtgt tcaatgtcac
cactgtggat 481 ctgaaaagaa agccagctga cctgcacaac ctagcccccg
gcacgcaccc gcccttcctg 541 accttcaacg gggacgtgaa gacagacgtc
aataagatcg aggagttcct ggaggagacc 601 ttgacccctg aaaagtaccc
caaactggct gcaaaacacc gggaatccaa cacagcgggc 661 atcgacatct
tttccaagtt ttctgcctac atcaaaaata ccaagcagca gaacaatgct 721
gctcttgaaa gaggcctaac caaggctcta aagaaattgg atgactacct gaacacccct
781 ctaccagagg agattgacgc caacacttgt ggggaagaca aggggtcccg
gcgcaagttc 841 ctggatgggg atgagctgac cctggctgac tgcaatctgt
tgcccaagct ccatgtggtc 901 aagattgtgg ccaagaaata ccgcaactat
gatatcccgg ctgagatgac aggcctgtgg 961 cggtacctca agaacgccta
tgcccgtgat gagttcacca acacctgtgc agctgacagt
1021 gagatcgagt tggcctacgc tgatgtcgcc aaacgcctca gccgatcctg
agcacagcca 1081 ttttgcccca tccccgctgc agaaggactc aaccactccc
ctaagactcc agcttcatag 1141 actcctctgt atcactgcct tgaggcgcac
tttttataat caagcctcat cttgctggta 1201 tcatgggaac tccagcctgc
tatctttcat gaaggtcagc accatccctg gcctcctcac 1261 ataggaatct
agcagaaatg atagacacag tccacctttc ggccggccag cctgatctgg 1321
gctcagcatg tttggggtca gtcagtgttg gagagcccac atatgggatt gccactagct
1381 tcttctgcca atatcaaaat accttctcag atgctttaga aacatgcaac
accaactcct 1441 tttctaccct cctctccgtc catacctaca aggccaagga
caaacgccat cttcatcctt 1501 cttagaaaga gatctattac cccattaggg
gagacagaga gagtgaatgg aggagtaccg 1561 agctggctat ggacttgggt
gtctggcaaa cacagcttca gtctcactac ttctgacact 1621 ctggttattg
ggcactaagg gccagactgg aaagtcactt gagacacatt ctcagtttgt 1681
tgcagtgcca ggaatgctgc gctgctgctg ctgcgcacct ggcccatgct gtccctggct
1741 tccatgccgt ccaggccctg ccagaaaagg aaattggcat gcaattctaa
actgcagtga 1801 ctgggatggg aggggagggg agcagtgttg atgccaaaat
acccacgggg tctaccagcc 1861 atggggtttg cttgcttagg agtagttgtt
tcagaggtga ttacaggcct gggtttgact 1921 gtgcttacca atgagtggtt
tttgagctat gagaaagtgg atgggagtgg gaggaggaga 1981 gatgggtgaa
gacaaaagag ttctttatga gcctcgatgt tccctggtaa acttttaaaa 2041
aggccttctc tcatgatcta agtcttggac tggtggcatc atgtaactgc taaccttaca
2101 gtaaaaaccc aagaatgggt caaaaatgtc ttcccagttt ctccaagctg
cttctggaat 2161 gcaggtctgt cggctgggtg ctctccagca gctgctcctg
cctgattcaa ctgtagcctg 2221 taatgggtaa aagccacatt taggaggtgg
tctgatcata gaacacctta ggaagaaagt 2281 ccatgagact ttctgactag
gaaaccatgt ggtttgaact tgaagaaaaa tgtagaccca 2341 tctgggttaa
ttttcctaca atctgactca actgccaggt gaaaaaaaaa aggaaaaatt 2401
tttaagctaa tatttcactc ttttgtcatt ctccttaagt ttcatctcct aaaaagctta
2461 cccagcctga gcttggggac ctgtgcagag gaaactaaga aaaatgcact
catcaactcc 2521 ttctcccagt gaacgcccgg tgagaaaatc catttgccac
aggcccttac cttcaacaat 2581 cccccttcta tagtgttcgc tggtaaaggg
tgaggctccc aagtgctgga aagcccctgg 2641 acttggctca tttctcagca
agggcaggat agcacgggtc ctttccatag aaatatcaac 2701 aaattctaac
ccaagcaatc cctggaccta cctgcctcca gggatctctg aagaaaaaaa 2761
gtaacccatt gatcaaatca gaggagagga agcaggaggt ctcctagagc ccattgagga
2821 agaggaactt tctcagtagg acactttata agcctgagaa agctttgaaa
aggcggaatg 2881 agttgattca tttccacctc aaaaggaacc tttccaggtc
cccctggaaa ttgtgccctg 2941 gagatgttta acaaggagaa ctggtgagga
aagagtcctt ttttactgta gggaaaagcc 3001 ccaaactggc ctcctggggg
atgagggctg aaatgatccc gaaggccttt taattagtgt 3061 gaaatcctgc
tgtactcaga aatccttccc cgaatttaca gcacaggcag gatgacctaa 3121
gaggcagttt acttccctga gacccacagt tgggctgttc tggaaacaca tctgtgaatc
3181 atagccaatt gccacagaga aaacagaacc aagcctccgg tgaggccact
ccaccccaga 3241 gaagtctgca gaattccaag gactcggatt ggatgttcag
aattcagcaa ctggaaagtc 3301 cttaaaaaca aacaggccaa accaaatcaa
tattgctgtt tctagatgtc ccttctgtgg 3361 ttgagctagt tttacagaga
taaatatatt aagacaagga ggtgggggtg ttatatgatc 3421 aatgatagcc
atttgaaaga gagggaggag tacagaagga aggcacttct gggtacttaa 3481
ttcagaaatt tctttatatt tcagcactgg attatcatat aatgcaagtg actatggact
3541 aagagttagt tatggtgtct tatgactaga tttattatgg tatattaaag
taacaataat 3601 attaatatta ccttcctttt tttttttgtt tcaaaagaga
tctttctcca gatgcttcag 3661 cctgtctggc cttcttatca tatgtgcagc
acatcatgtc tcagcaacag tgtggtgagg 3721 tccttaggtg tcccaagaac
aactcaggga gcacgggagg gtctgcagtt gggaccccac 3781 aactatacag
ctatagggta ggaggcttcc ttttcattgg tcctgaatga atacaaatcg 3841
ctcagaaagc attttggtgg cacagaaagg ggatgtattt gtgttgagat cttattttat
3901 tttgtattta tttatcttct ttgacttgca cagcactatt gggggtgggg
gaagcagggt 3961 agtgggagac gaaggcagaa gcaagagtca aactcagaat
gactgagttg aattcactgt 4021 ctagtcagca atgcctgctt ctgagtttgg
cccagagaga aggtattgag taagatttta 4081 ataactgtaa aaagtaagct
ggataagtaa aatcatgatg gatccaaagc acagtttctt 4141 catctcctga
taaagaaagt caaatgcttg ataaattcag agtcacagat gtgagcatag 4201
ctatattctt ttaaacgaga ggtagagtga cctagcacta agcaaatgag ctgaaatgtc
4261 ggaaacagag tccatcagct tatttggcca cacgatccca aactagtttt
atcttgggaa 4321 atggccctgt cctcagcatt cccttcttgt gctggtgggg
ccagtgaagt cttgatctta 4381 tcagaaaaag gccacaccaa gtgcgagttt
tcccaggctg actttccagg cccttatcaa 4441 atgaaacaac agaagctctt
cacagttctg tgccccatgg ccactccaca gacagacaat 4501 accaagcatc
ttagaactgt cataagatag gtcatgcctg aaatagatct tgaccatatg 4561
agagtcccag aaatcagcaa ggcctggaca aatagaacta agagagaggc agaggcagga
4621 agctgcgggt ctatcttgta aagagtttag catcactgtg agagtgtgtg
tctaaaatta 4681 aattaaacta gaagcagcag gtgagtattt ggtaagtact
tctgtgactc gcctcaattc 4741 ccactggcca ggggccatct caactgcacg
gtgaatcaag atgctggtgt catcctcctt 4801 ggaaaaagga aatgttaact
catggttaaa actaagtaca atgattccca agggatcact 4861 ttcttatttt
tttaaatgac attaaggaga atcttaagaa agcatcagag aaagacatgt 4921
gcatgtgaag caccctgatt ctgatgttag gaaaacttaa gcgaacagga cctgctgcac
4981 acagccccat tgtcttctat ccatttctct ttatcattca aatcaagcaa
catgtgccct 5041 cctcatcaac acacattctt cccctttgtc agtatgcatc
tcccagctta gtgtcaggat 5101 actttcgatt cataattatg tatgatccaa
agtgtgcata atttcattta acgttaaaga 5161 aatagatcca attcctttct
tgcaaccaaa aataaataaa atacgttgcc tcaatataag 5221 gtttgggcta
ttctgtgttt ctatagaagc aatctgtttt tggtaaaatg tacttttaag 5281
gatccagtca tctgaagtat tttatgtaga gttagagatt tcacaatatt gactatacat
5341 atatttaaaa tataaattat ccagctgatg tttgaatttg tcttactttc
ctggccacct 5401 cgttgtccta ttttataagc tggggagtta actagcttaa
caaaagatgc ttagcttttg 5461 taaaagaaca agtgtttcat tttacaaaga
cactccaaat gatagttact tgattttctc 5521 gagaccttta actatggtga
tgaataacag gacttgcttt caagccttaa taaatgtaaa 5581 atgcctttta
atgaagatac agctgagtgt tttcctcatg aatctgaacc aattaccaat 5641
ttgtgttcca gtcttgattg gtattgactg attcaaataa agttggttta ttttcaaata
5701 tta GenBank Gene Name Gene Symbol Accession # SEQ ID NO PERP,
TP53 apoptosis PERP NM_022121 18 effector 1 gcttttgtgg cggcgcccgc
gctcgcaggc cactctctgc tgtcgcccgt cccgcgcgct 61 cctccgaccc
gctccgctcc gctccgctcg gccccgcgcc gcccgtcaac atgatccgct 121
gcggcctggc ctgcgagcgc tgccgctgga tcctgcccct gctcctactc agcgccatcg
181 ccttcgacat catcgcgctg gccggccgcg gctggttgca gtctagcgac
cacggccaga 241 cgtcctcgct gtggtggaaa tgctcccaag agggcggcgg
cagcgggtcc tacgaggagg 301 gctgtcagag cctcatggag tacgcgtggg
gtagagcagc ggctgccatg ctcttctgtg 361 gcttcatcat cctggtgatc
tgtttcatcc tctccttctt cgccctctgt ggaccccaga 421 tgcttgtctt
cctgagagtg attggaggtc tccttgcctt ggctgctgtg ttccagatca 481
tctccctggt aatttacccc gtgaagtaca cccagacctt cacccttcat gccaaccctg
541 ctgtcactta catctataac tgggcctacg gctttgggtg ggcagccacg
attatcctga 601 ttggctgtgc cttcttcttc tgctgcctcc ccaactacga
agatgacctt ctgggcaatg 661 ccaagcccag gtacttctac acatctgcct
aacttgggaa tgaatgtggg agaaaatcgc 721 tgctgctgag atggactcca
gaagaagaaa ctgtttctcc aggcgacttt gaacccattt 781 tttggcagtg
ttcatattat taaactagtc aaaaatgcta aaataatttg ggagaaaata 841
ttttttaagt agtgttatag tttcatgttt atcttttatt atgttttgtg aagttgtgtc
901 ttttcactaa ttacctatac tatgccaata tttcctatct atccataaca
tttatactac 961 atttgtaaga gaatatgcac gtgaaactta acactttata
aggtaaaaat gaggtttcca 1021 agatttaata atctgatcaa gttcttgtta
tttccaaata gaatggactc ggtctgttaa 1081 gggctaagga gaagaggaag
ataaggttaa aagttgttaa tgaccaaaca ttctaaaaga 1141 aatgcaaaaa
aaaagtttat tttcaagcct tcgaactatt taaggaaagc aaaatcattt 1201
cctaaatgca tatcatttgt gagaatttct cattaatatc ctgaatcatt cattttagct
1261 aaggcttcat gttgactcga tatgtcatct aggaaagtac tatttcatgg
tccaaacctg 1321 ttgccatagt tggtaaggct ttcctttaag tgtgaaatat
ttagatgaaa ttttctcttt 1381 taaagttctt tatagggtta gggtgtggga
aaatgctata ttaataaatc tgtagtgttt 1441 tgtgtttata tgttcagaac
cagagtagac tggattgaaa gatggactgg gtctaattta 1501 tcatgactga
tagatctgtt aagttgtgta gtaaagcatt aggagggtca ttcttgtcac 1561
aaaagtgcca ctaaaacagc ctcaggagaa taaatgactt gcttttctaa atctcaggtt
1621 tatctgggct ctatcatata gacaggcttc tgatagtttg caactgtaag
cagaaaccta 1681 catatagtta aaatcctggt ctttcttggt aaacagattt
taaatgtctg atataaaaca 1741 tgccacagga gaattcgggg atttgagttt
ctctgaatag catatatatg atgcatcgga 1801 taggtcatta tgatttttta
ccatttcgac ttacataatg aaaaccaatt cattttaaat 1861 atcagattat
tattttgtaa gttgtggaaa aagctaattg tagttttcat tatgaagttt 1921
tcccaataaa ccaggtattc t GenBank Gene Name Gene Symbol Accession #
SEQ ID NO spleen tyrosine kinase SYK NM_003177 19 1 aggaagagcc
gcgggcccgg cggctgaggc caccccggcg gcggctggag agcgaggagg 61
agcgggtggc cccgcgctgc gcccgccctc gcctcacctg gcgcaggtgg acacctgcgc
121 aggtgtgtgc cctccggccc ctgaagcatg gccagcagcg gcatggctga
cagcgccaac 181 cacctgccct tctttttcgg caacatcacc cgggaggagg
cagaagatta cctggtccag 241 gggggcatga gtgatgggct ttatttgctg
cgccagagcc gcaactacct gggtggcttc 301 gccctgtccg tggcccacgg
gaggaaggca caccactaca ccatcgagcg ggagctgaat 361 ggcacctacg
ccatcgccgg tggcaggacc catgccagcc ccgccgacct ctgccactac 421
cactcccagg agtctgatgg cctggtctgc ctcctcaaga agcccttcaa
ccggccccaa
481 ggggtgcagc ccaagactgg gccctttgag gatttgaagg aaaacctcat
cagggaatat 541 gtgaagcaga catggaacct gcagggtcag gctctggagc
aggccatcat cagtcagaag 601 cctcagctgg agaagctgat cgctaccaca
gcccatgaaa aaatgccttg gttccatgga 661 aaaatctctc gggaagaatc
tgagcaaatt gtcctgatag gatcaaagac aaatggaaag 721 ttcctgatcc
gagccagaga caacaacggc tcctacgccc tgtgcctgct gcacgaaggg 781
aaggtgctgc actatcgcat cgacaaagac aagacaggga agctctccat ccccgaggga
841 aagaagttcg acacgctctg gcagctagtc gagcattatt cttataaagc
agatggtttg 901 ttaagagttc ttactgtccc atgtcaaaaa atcggcacac
agggaaatgt taattttgga 961 ggccgtccac aacttccagg ttcccatcct
gcgacttggt cagcgggtgg aataatctca 1021 agaatcaaat catactcctt
cccaaagcct ggccacagaa agtcctcccc tgcccaaggg 1081 aaccggcaag
agagtactgt gtcattcaat ccgtatgagc cagaacttgc accctgggct 1141
gcagacaaag gcccccagag agaagcccta cccatggaca cagaggtgta cgagagcccc
1201 tacgcggacc ctgaggagat caggcccaag gaggtttacc tggaccgaaa
gctgctgacg 1261 ctggaagaca aagaactggg ctctggtaat tttggaactg
tgaaaaaggg ctactaccaa 1321 atgaaaaaag ttgtgaaaac cgtggctgtg
aaaatactga aaaacgaggc caatgacccc 1381 gctcttaaag atgagttatt
agcagaagca aatgtcatgc agcagctgga caacccgtac 1441 atcgtgcgca
tgatcgggat atgcgaggcc gagtcctgga tgctagttat ggagatggca 1501
gaacttggtc ccctcaataa gtatttgcag cagaacagac atgtcaagga taagaacatc
1561 atagaactgg ttcatcaggt ttccatgggc atgaagtact tggaggagag
caattttgtg 1621 cacagagatc tggctgcaag aaatgtgttg ctagttaccc
aacattatgc caagatcagt 1681 gatttcggac tctccaaagc actgcgtgct
gatgaaaact actacaaggc ccagacccat 1741 ggaaagtggc ctgtcaagtg
gtacgctccg gaatgcatca actactacaa gttctccagc 1801 aaaagcgatg
tctggagctt tggagtgttg atgtgggaag cattctccta tgggcagaag 1861
ccatatcgag ggatgaaagg aagtgaagtc accgctatgt tagagaaagg agagcggatg
1921 gggtgccctg cagggtgtcc aagagagatg tacgatctca tgaatctgtg
ctggacatac 1981 gatgtggaaa acaggcccgg attcgcagca gtggaactgc
ggctgcgcaa ttactactat 2041 gacgtggtga actaaccgct cccgcacctg
tcggtggctg cctttgatca caggagcaat 2101 cacaggaaaa tgtatccaga
ggaattgatt gtcagccacc tccctctgcc agtcgggaga 2161 gccaggcttg
gatggaacat gcccacaact tgtcacccaa agcctgtccc aggactcacc 2221
ctccacaaag caaaggcagt cccgggagaa aagacggatg gcaggatcca aggggctagc
2281 tggatttgtt tgttttcttg tctgtgtgat tttcatacag gttattttta
cgatctgttt 2341 ccaaatccct ttcatgtctt tccacttctc tgggtcccgg
ggtgcatttg ttactcatcg 2401 ggcccaggga cattgcagag tggcctagag
cactctcacc ccaagcggcc ttttccaaat 2461 gcccaaggat gccttagcat
gtgactcctg aagggaaggc aaaggcagag gaatttggct 2521 gcttctacgg
ccatgagact gatccctggc cactgaaaag ctttcctgac aataaaaatg 2581
ttttgaggct ttaaaaagaa aatcaagttt gaccagtgca gtttctaagc atgtagccag
2641 ttaaggaaag aaagaaaaaa GenBank Gene Name Gene Symbol Accession
# SEQ ID NO solute carrier family 12 SLC12A2 NM_001046 20
(sodium/potassium/chloride transporters), member 2 1 ggtggcctct
gtggccgtcc aggctagcgg cggcccgcag gcggcgggga gaaagactct 61
ctcacctggt cttgcggctg tggccaccgc cggccagggg tgtggagggc gtgctgccgg
121 agacgtccgc cgggctctgc agttccgccg ggggtcgggc agctatggag
ccgcggccca 181 cggcgccctc ctccggcgcc ccgggactgg ccggggtcgg
ggagacgccg tcagccgctg 241 cgctggccgc agccagggtg gaactgcccg
gcacggctgt gccctcggtg ccggaggatg 301 ctgcgcccgc gagccgggac
ggcggcgggg tccgcgatga gggccccgcg gcggccgggg 361 acgggctggg
cagacccttg gggcccaccc cgagccagag ccgtttccag gtggacctgg 421
tttccgagaa cgccgggcgg gccgctgctg cggcggcggc ggcggcggcg gcagcggcgg
481 cggctggtgc tggggcgggg gccaagcaga cccccgcgga cggggaagcc
agcggcgaga 541 gcgagccggc taaaggcagc gaggaagcca agggccgctt
ccgcgtgaac ttcgtggacc 601 cagctgcctc ctcgtcggct gaagacagcc
tgtcagatgc tgccggggtc ggagtcgacg 661 ggcccaacgt gagcttccag
aacggcgggg acacggtgct gagcgagggc agcagcctgc 721 actccggcgg
cggcggcggc agtgggcacc accagcacta ctattatgat acccacacca 781
acacctacta cctgcgcacc ttcggccaca acaccatgga cgctgtgccc aggatcgatc
841 actaccggca cacagccgcg cagctgggcg agaagctgct ccggcctagc
ctggcggagc 901 tccacgacga gctggaaaag gaaccttttg aggatggctt
tgcaaatggg gaagaaagta 961 ctccaaccag agatgctgtg gtcacgtata
ctgcagaaag taaaggagtc gtgaagtttg 1021 gctggatcaa gggtgtatta
gtacgttgta tgttaaacat ttggggtgtg atgcttttca 1081 ttagattgtc
atggattgtg ggtcaagctg gaataggtct atcagtcctt gtaataatga 1141
tggccactgt tgtgacaact atcacaggat tgtctacttc agcaatagca actaatggat
1201 ttgtaagagg aggaggagca tattatttaa tatctagaag tctagggcca
gaatttggtg 1261 gtgcaattgg tctaatcttc gcctttgcca acgctgttgc
agttgctatg tatgtggttg 1321 gatttgcaga aaccgtggtg gagttgctta
aggaacattc catacttatg atagatgaaa 1381 tcaatgatat ccgaattatt
ggagccatta cagtcgtgat tcttttaggt atctcagtag 1441 ctggaatgga
gtgggaagca aaagctcaga ttgttctttt ggtgatccta cttcttgcta 1501
ttggtgattt cgtcatagga acatttatcc cactggagag caagaagcca aaagggtttt
1561 ttggttataa atctgaaata tttaatgaga actttgggcc cgattttcga
gaggaagaga 1621 ctttcttttc tgtatttgcc atcttttttc ctgctgcaac
tggtattctg gctggagcaa 1681 atatctcagg tgatcttgca gatcctcagt
cagccatacc caaaggaaca ctcctagcca 1741 ttttaattac tacattggtt
tacgtaggaa ttgcagtatc tgtaggttct tgtgttgttc 1801 gagatgccac
tggaaacgtt aatgacacta tcgtaacaga gctaacaaac tgtacttctg 1861
cagcctgcaa attaaacttt gatttttcat cttgtgaaag cagtccttgt tcctatggcc
1921 taatgaacaa cttccaggta atgagtatgg tgtcaggatt tacaccacta
atttctgcag 1981 gtatattttc agccactctt tcttcagcat tagcatccct
agtgagtgct cccaaaatat 2041 ttcaggctct atgtaaggac aacatctacc
cagctttcca gatgtttgct aaaggttatg 2101 ggaaaaataa tgaacctctt
cgtggctaca tcttaacatt cttaattgca cttggattca 2161 tcttaattgc
tgaactgaat gttattgcac caattatctc aaacttcttc cttgcatcat 2221
atgcattgat caatttttca gtattccatg catcacttgc aaaatctcca ggatggcgtc
2281 ctgcattcaa atactacaac atgtggatat cacttcttgg agcaattctt
tgttgcatag 2341 taatgttcgt cattaactgg tgggctgcat tgctaacata
tgtgatagtc cttgggctgt 2401 atatttatgt tacctacaaa aaaccagatg
tgaattgggg atcctctaca caagccctga 2461 cttacctgaa tgcactgcag
cattcaattc gtctttctgg agtggaagac cacgtgaaaa 2521 actttaggcc
acagtgtctt gttatgacag gtgctccaaa ctcacgtcca gctttacttc 2581
atcttgttca tgatttcaca aaaaatgttg gtttgatgat ctgtggccat gtacatatgg
2641 gtcctcgaag acaagccatg aaagagatgt ccatcgatca agccaaatat
cagcgatggc 2701 ttattaagaa caaaatgaag gcattttatg ctccagtaca
tgcagatgac ttgagagaag 2761 gtgcacagta tttgatgcag gctgctggtc
ttggtcgtat gaagccaaac acacttgtcc 2821 ttggatttaa gaaagattgg
ttgcaagcag atatgaggga tgtggatatg tatataaact 2881 tatttcatga
tgcttttgac atacaatatg gagtagtggt tattcgccta aaagaaggtc 2941
tggatatatc tcatcttcaa ggacaagaag aattattgtc atcacaagag aaatctcctg
3001 gcaccaagga tgtggtagta agtgtggaat atagtaaaaa gtccgattta
gatacttcca 3061 aaccactcag tgaaaaacca attacacaca aagttgagga
agaggatggc aagactgcaa 3121 ctcaaccact gttgaaaaaa gaatccaaag
gccctattgt gcctttaaat gtagctgacc 3181 aaaagcttct tgaagctagt
acacagtttc agaaaaaaca aggaaagaat actattgatg 3241 tctggtggct
ttttgatgat ggaggtttga ccttattgat accttacctt ctgacgacca 3301
agaaaaaatg gaaagactgt aagatcagag tattcattgg tggaaagata aacagaatag
3361 accatgaccg gagagcgatg gctactttgc ttagcaagtt ccggatagac
ttttctgata 3421 tcatggttct aggagatatc aataccaaac caaagaaaga
aaatattata gcttttgagg 3481 aaatcattga gccatacaga cttcatgaag
atgataaaga gcaagatatt gcagataaaa 3541 tgaaagaaga tgaaccatgg
cgaataacag ataatgagct tgaactttat aagaccaaga 3601 cataccggca
gatcaggtta aatgagttat taaaggaaca ttcaagcaca gctaatatta 3661
ttgtcatgag tctcccagtt gcacgaaaag gtgctgtgtc tagtgctctc tacatggcat
3721 ggttagaagc tctatctaag gacctaccac caatcctcct agttcgtggg
aatcatcaga 3781 gtgtccttac cttctattca taaatgttct atacagtgga
cagccctcca gaatggtact 3841 tcagtgccta gtgtagtaac tgaaatcttc
aatgacacat taacatcaca atggcgaatg 3901 gtgacttttc tttcacgatt
tcattaattt gaaagcacac aggaaagttg ctccattgat 3961 aacgtgtatg
gagacttcgg ttttagtcaa ttccatatct caatcttaat ggtgattctt 4021
ctctgttgaa ctgaagtttg tgagagtagt tttcctttgc tacttgaata gcaataaaag
4081 cgtgttaact ttttgattga tgaaagaagt acaaaaagcc tttagccttg
aggtgccttc 4141 tgaaattaac caaatttcat ccatatatcc tcttttataa
acttatagaa tgtcaaactt 4201 tgccttcaac tgtttttatt tctagtctct
tccactttaa aacaaaatga acactgcttg 4261 tcttcttcca ttgaccattt
agtgttgagt actgtatgtg ttttgttaat tctataaagg 4321 tatctgttag
atattaaagg tgagaattag ggcaggttaa tcaaaaatgg ggaaggggaa 4381
atggtaacca aaaagtaacc ccatggtaag gtttatatga gtatatgtga atatagagct
4441 aggaaaaaaa gcccccccaa ataccttttt aacccctctg attggctatt
attactatat 4501 ttattattat ttattgaaac cttagggaag attgaagatt
catcccatac ttctatatac 4561 catgcttaaa aatcacgtca ttctttaaac
aaaaatactc aagatcattt atatttattt 4621 ggagagaaaa ctgtcctaat
ttagaatttc cctcaaatct gagggacttt taagaaatgc 4681 taacagattt
ttctggagga aatttagaca aaacaatgtc atttagtaga atatttcagt 4741
atttaagtgg aatttcagta tactgtacta tcctttataa gtcattaaaa taatgtttca
4801 tcaaatggtt aaatggacca ctggtttctt agagaaatgt ttttaggctt
aattcattca 4861 attgtcaagt acacttagtc ttaatacact caggtttgaa
cagattattc tgaatattaa 4921 aatttaatcc attcttaata ttttaaaact
tttgttaaga aaaactgcca gtttgtgctt 4981 ttgaaatgtc tgttttgaca
tcatagtcta gtaaaatttt gacagtgcat atgtactgtt 5041 actaaaagct
ttatatgaaa ttattaatgt gaagtttttc atttataatt caaggaagga
5101 tttcctgaaa acatttcaag ggatttatgt ctacatattt gtgtgtgtgt
gtgtatatat 5161 atgtaatatg catacacaga tgcatatgtg tatatataat
gaaatttatg ttgctggtat 5221 tttgcatttt aaagtgatca agattcatta
ggcaaacttt ggtttaagta aacatatgtt 5281 caaaatcaga ttaacagata
caggtttcat agagaacaaa ggtgatcatt tgaagggcat 5341 gctgtaattt
cacacaattt tccagttcaa aaatggagaa tacttcgcct aaaatactgt 5401
taagtgggtt aattgataca agtttctgtg gtggaaaatt tatgcaggtt ttcacgaatc
5461 cttttttttt tttttttttt tttttgagac ggagtcttgc tctgttgcca
cgctggaatg 5521 cagtaacgtg atcttggctc actgcgacct ccacctcccc
agttcaagcg attctcctgc 5581 ctcagcctcc ctagtagctg ggactacggg
tgcacgccac catgcccagc taatttttgt 5641 attttgagta gagacagggt
ttcaccgtgt tggctaggat ggtgtctatc tcttgacctt 5701 gtgatccacc
cgcctcagcc tcccagagtg ctgggattac aggtgcgagc cactgcgcct 5761
ggctggtttt catgaatctt gatagacatc tataacgtta ttattttcag tggtgtgcag
5821 catttttgct tcatgagtat gacctaggta tagagatctg ataacttgaa
ttcagaatat 5881 taagaaaatg aagtaactga ttttctaaaa aaaaaaaaaa
aaaaaatttc tacattataa 5941 ctcacagcat tgttccattg caggttttgc
aatgtttggg ggtaaagaca gtagaaatat 6001 tattcagtaa acaataatgt
gtgaactttt aagatggata atagggcatg gactgagtgc 6061 tgctatcttg
aaatgtgcac aggtacactt accttttttt tttttttttt taagtttttc 6121
ccattcagga aaacaacatt gtgatctgta ctacaggaac caaatgtcat gcgtcataca
6181 tgtgggtata aagtacataa aatatatcta actattcata atgtggggtg
ggtaatactg 6241 tctgtgaaat aatgtaagaa gcttttcact taaaaaaaat
gcattacttt cacttaacac 6301 tagacaccag gtcgaaaatt ttcaaggtta
tagtacttat ttcaacaatt cttagagatg 6361 ctagctagtg ttgaagctaa
aaatagcttt atttatgctg aattgtgatt tttttatgcc 6421 aaattttttt
tagttctaat cattgatgat agcttggaaa taaataatta tgccatggca 6481
tttgacagtt cattattcct ataagaatta aattgagttt agagagaatg gtggtgttga
6541 gctgattatt aacagttact gaaatcaaat atttatttgt tacattattc
catttgtatt 6601 ttaggtttcc ttttacattc tttttatatg cattctgaca
ttacatattt tttaagacta 6661 tggaaataat ttaaagattt aagctctggt
ggatgattat ctgctaagta agtctgaaaa 6721 tgtaatattt tgataatact
gtaatatacc tgtcacacaa atgcttttct aatgttttaa 6781 ccttgagtat
tgcagttgct gctttgtaca gaggttactg caataaagga agtggattca 6841
ttaaacctat ttaatgtcca GenBank Gene Name Gene Symbol Accession # SEQ
ID NO guanylate cyclase 2C GUCY2C NM_004963 21 (heat stable
enterotoxin receptor) 1 cgcaaagcaa gtgggcacaa ggagtatggt tctaacgtga
ttggggtcat gaagacgttg 61 ctgttggact tggctttgtg gtcactgctc
ttccagcccg ggtggctgtc ctttagttcc 121 caggtgagtc agaactgcca
caatggcagc tatgaaatca gcgtcctgat gatgggcaac 181 tcagcctttg
cagagcccct gaaaaacttg gaagatgcgg tgaatgaggg gctggaaata 241
gtgagaggac gtctgcaaaa tgctggccta aatgtgactg tgaacgctac tttcatgtat
301 tcggatggtc tgattcataa ctcaggcgac tgccggagta gcacctgtga
aggcctcgac 361 ctactcagga aaatttcaaa tgcacaacgg atgggctgtg
tcctcatagg gccctcatgt 421 acatactcca ccttccagat gtaccttgac
acagaattga gctaccccat gatctcagct 481 ggaagttttg gattgtcatg
tgactataaa gaaaccttaa ccaggctgat gtctccagct 541 agaaagttga
tgtacttctt ggttaacttt tggaaaacca acgatctgcc cttcaaaact 601
tattcctgga gcacttcgta tgtttacaag aatggtacag aaactgagga ctgtttctgg
661 taccttaatg ctctggaggc tagcgtttcc tatttctccc acgaactcgg
ctttaaggtg 721 gtgttaagac aagataagga gtttcaggat atcttaatgg
accacaacag gaaaagcaat 781 gtgattatta tgtgtggtgg tccagagttc
ctctacaagc tgaagggtga ccgagcagtg 841 gctgaagaca ttgtcattat
tctagtggat cttttcaatg accagtactt ggaggacaat 901 gtcacagccc
ctgactatat gaaaaatgtc cttgttctga cgctgtctcc tgggaattcc 961
cttctaaata gctctttctc caggaatcta tcaccaacaa aacgagactt tgctcttgcc
1021 tatttgaatg gaatcctgct ctttggacat atgctgaaga tatttcttga
aaatggagaa 1081 aatattacca cccccaaatt tgctcatgct ttcaggaatc
tcacttttga agggtatgac 1141 ggtccagtga ccttggatga ctggggggat
gttgacagta ccatggtgct tctgtatacc 1201 tctgtggaca ccaagaaata
caaggttctt ttgacctatg atacccacgt aaataagacc 1261 tatcctgtgg
atatgagccc cacattcact tggaagaact ctaaacttcc taatgatatt 1321
acaggccggg gccctcagat cctgatgatt gcagtcttca ccctcactgg agctgtggtg
1381 ctgctcctgc tcgtcgctct cctgatgctc agaaaatata gaaaagatta
tgaacttcgt 1441 cagaaaaaat ggtcccacat tcctcctgaa aatatctttc
ctctggagac caatgagacc 1501 aatcatgtta gcctcaagat cgatgatgac
aaaagacgag atacaatcca gagactacga 1561 cagtgcaaat acgacaaaaa
gcgagtgatt ctcaaagatc tcaagcacaa tgatggtaat 1621 ttcactgaaa
aacagaagat agaattgaac aagttgcttc agattgacta ttacaacctg 1681
accaagttct acggcacagt gaaacttgat accatgatct tcggggtgat agaatactgt
1741 gagagaggat ccctccggga agttttaaat gacacaattt cctaccctga
tggcacattc 1801 atggattggg agtttaagat ctctgtcttg tatgacattg
ctaagggaat gtcatatctg 1861 cactccagta agacagaagt ccatggtcgt
ctgaaatcta ccaactgcgt agtggacagt 1921 agaatggtgg tgaagatcac
tgattttggc tgcaattcca ttttacctcc aaaaaaggac 1981 ctgtggacag
ctccagagca cctccgccaa gccaacatct ctcagaaagg agatgtgtac 2041
agctatggga tcatcgcaca ggagatcatt ctgcggaaag aaaccttcta cactttgagc
2101 tgtcgggacc ggaatgagaa gattttcaga gtggaaaatt ccaatggaat
gaaacccttc 2161 cgcccagatt tattcttgga aacagcagag gaaaaagagc
tagaagtgta cctacttgta 2221 aaaaactgtt gggaggaaga tccagaaaag
agaccagatt tcaaaaaaat tgagactaca 2281 cttgccaaga tatttggact
ttttcatgac caaaaaaatg aaagctatat ggataccttg 2341 atccgacgtc
tacagctata ttctcgaaac ctggaacatc tggtagagga aaggacacag 2401
ctgtacaagg cagagaggga cagggctgac agacttaact ttatgttgct tccaaggcta
2461 gtggtaaagt ctctgaagga gaaaggcttt gtggagccgg aactatatga
ggaagttaca 2521 atctacttca gtgacattgt aggtttcact actatctgca
aatacagcac ccccatggaa 2581 gtggtggaca tgcttaatga catctataag
agttttgacc acattgttga tcatcatgat 2641 gtctacaagg tggaaaccat
cggtgatgcg tacatggtgg ctagtggttt gcctaagaga 2701 aatggcaatc
ggcatgcaat agacattgcc aagatggcct tggaaatcct cagcttcatg 2761
gggacctttg agctggagca tcttcctggc ctcccaatat ggattcgcat tggagttcac
2821 tctggtccct gtgctgctgg agttgtggga atcaagatgc ctcgttattg
tctatttgga 2881 gatacggtca acacagcctc taggatggaa tccactggcc
tccctttgag aattcacgtg 2941 agtggctcca ccatagccat cctgaagaga
actgagtgcc agttccttta tgaagtgaga 3001 ggagaaacat acttaaaggg
aagaggaaat gagactacct actggctgac tgggatgaag 3061 gaccagaaat
tcaacctgcc aacccctcct actgtggaga atcaacagcg tttgcaagca 3121
gaattttcag acatgattgc caactcttta cagaaaagac aggcagcagg gataagaagc
3181 caaaaaccca gacgggtagc cagctataaa aaaggcactc tggaatactt
gcagctgaat 3241 accacagaca aggagagcac ctatttttaa acctaaatga
ggtataagga ctcacacaaa 3301 ttaaaataca gctgcactga ggcagcgacc
tcaagtgtcc tgaaagctta cattttcctg 3361 agacctcaat gaagcagaaa
tgtacttagg cttggctgcc ctgtctggaa catggacttt 3421 cttgcatgaa
tcagatgtgt gttctcagtg aaataactac cttccactct ggaaccttat 3481
tccagcagtt gttccaggga gcttctacct ggaaaagaaa agaaatgaat agactatcta
3541 gaacttgaga agattttatt cttatttcat ttattttttg tttgtttatt
tttatcgttt 3601 ttgtttactg gctttccttc tgtattcata agatttttta
aattgtcata attatatttt 3661 aaataccca tcttcattaaa gtatatttaa
ctcataattt ttgcagaaaa tatgctatat 3721 attaggcaa gaataaaagct aaagg
GenBank Gene Name Gene Symbol Accession # SEQ ID NO transmembrane 4
TM4SF4 NM_004617 22 superfamily member 4 1 cttcaggtca gggagaatgt
ataaatgtcc attgccatcg aggttctgct atttttgaga 61 agctgaagca
actccaagga cacagttcac agaaatttgg ttctcagccc caaaatactg 121
attgaattgg agacaattac aaggactctc tggccaaaaa cccttgaaga ggccccgtga
181 aggaggcagt gaggagcttt tgattgctga cctgtgtcgt accaccccag
aatgtgcact 241 gggggctgtg ccagatgcct gggggggacc ctcattcccc
ttgctttttt tggcttcctg 301 gctaacatcc tgttattttt tcctggagga
aaagtgatag atgacaacga ccacctttcc 361 caagagatct ggtttttcgg
aggaatatta ggaagcggtg tcttgatgat cttccctgcg 421 ctggtgttct
tgggcctgaa gaacaatgac tgctgtgggt gctgcggcaa cgagggctgt 481
gggaagcgat ttgcgatgtt cacctccacg atatttgctg tggttggatt cttgggagct
541 ggatactcgt ttatcatctc agccatttca atcaacaagg gtcctaaatg
cctcatggcc 601 aatagtacat ggggctaccc cttccacgac ggggattatc
tcaatgatga ggccttatgg 661 aacaagtgcc gagagcctct caatgtggtt
ccctggaatc tgaccctctt ctccatcctg 721 ctggtcgtag gaggaatcca
gatggttctc tgcgccatcc aggtggtcaa tggcctcctg 781 gggaccctct
gtggggactg ccagtgttgt ggctgctgtg ggggagatgg acccgtttaa 841
acctccgaga tgagctgctc agactctaca gcatgacgac tacaatttct tttcataaaa
901 cttcttctct tcttggaatt attaattcct atctgcttcc tagctgataa
agcttagaaa 961 aggcagttat tccttctttc caaccagctt tgctcgagtt
agaattttgt tattttcaaa 1021 taaaaaatag tttggccact taacaaattt
gatttataaa tctttcaaat tagttccttt 1081 ttagaattta ccaacaggtt
caaagcatac ttttcatgat ttttttatta caaatgtaaa 1141 atgtataaag
tcacatgtac tgccatacta cttctttgta tataaagatg tttatatctt 1201
tggaagtttt acataaatca aaggaagaaa gcacatttaa aatgagaaac taagaccaat
1261 ttctgttttt aagaggaaaa agaatgattg atgtatccta agtattgtta
tttgttgtct 1321 ttttttgctg ccttgcttga gttgcttgtg actgatcttt
tgaggctgtc atcatggcta 1381 gggttctttt atgtatgtta aattaaaacc
tgaattcaga ggtaacgt GenBank Gene Name Gene Symbol Accession # SEQ
ID NO
transforming growth TGFA NM_003236 23 factor, alpha 1 ctggagagcc
tgctgcccgc ccgcccgtaa aatggtcccc tcggctggac agctcgccct 61
gttcgctctg ggtattgtgt tggctgcgtg ccaggccttg gagaacagca cgtccccgct
121 gagtgcagac ccgcccgtgg ctgcagcagt ggtgtcccat tttaatgact
gcccagattc 181 ccacactcag ttctgcttcc atggaacctg caggtttttg
gtgcaggagg acaagccagc 241 atgtgtctgc cattctgggt acgttggtgc
acgctgtgag catgcggacc tcctggccgt 301 ggtggctgcc agccagaaga
agcaggccat caccgccttg gtggtggtct ccatcgtggc 361 cctggctgtc
cttatcatca catgtgtgct gatacactgc tgccaggtcc gaaaacactg 421
tgagtggtgc cgggccctca tctgccggca cgagaagccc agcgccctcc tgaagggaag
481 aaccgcttgc tgccactcag aaacagtggt ctgaagagcc cagaggagga
gtttggccag 541 gtggactgtg gcagatcaat aaagaaaggc ttcttcagga
cagcactgcc agagatgcct 601 gggtgtgcca cagaccttcc tacttggcct
gtaatcacct gtgcagcctt ttgtgggcct 661 tcaaaactct gtcaagaact
ccgtctgctt ggggttattc agtgtgacct agagaagaaa 721 tcagcggacc
acgatttcaa gacttgttaa aaaagaactg caaagagacg gactcctgtt 781
cacctaggtg aggtgtgtgc agcagttggt gtctgagtcc acatgtgtgc agttgtcttc
841 tgccagccat ggattccagg ctatatattt ctttttaatg ggccacctcc
ccacaacaga 901 attctgccca acacaggaga tttctatagt tattgttttc
tgtcatttgc ctactgggga 961 agaaagtgaa ggaggggaaa ctgtttaata
tcacatgaag accctagctt taagagaagc 1021 tgtatcctct aaccacgaga
ctctcaacca gcccaacatc ttccatggac acatgacatt 1081 gaagaccatc
ccaagctatc gccacccttg gagatgatgt cttatttatt agatggataa 1141
tggttttatt tttaatctct taagtcaatg taaaaagtat aaaacccctt cagacttcta
1201 cattaatgat gtatgtgttg ctgactgaaa agctatactg attagaaatg
tctggcctct 1261 tcaagacagc taaggcttgg gaaaagtctt ccagggtgcg
gagatggaac cagaggctgg 1321 gttactggta ggaataaagg taggggttca
gaaatggtgc cattgaagcc acaaagccgg 1381 taaatgcctc aatacgttct
gggagaaaac ttagcaaatc catcagcagg gatctgtccc 1441 ctctgttggg
gagagaggaa gagtgtgtgt gtctacacag gataaaccca atacatattg 1501
tactgctcag tgattaaatg ggttcacttc ctcgtgagcc ctcggtaagt atgtttagaa
1561 atagaacatt agccacgagc cataggcatt tcaggccaaa tccatgaaag
ggggaccagt 1621 catttatttt ccattttgtt gcttggttgg tttgttgctt
tatttttaaa aggagaagtt 1681 taactttgct atttattttc gagcactagg
aaaactattc cagtaatttt tttttcctca 1741 tttccattca ggatgccggc
tttattaaca aaaactctaa caagtcacct ccactatgtg 1801 ggtcttcctt
tcccctcaag agaaggagca attgttcccc tgacatctgg gtccatctga 1861
cccatggggc ctgcctgtga gaaacagtgg gtcccttcaa atacatagtg gatagctcat
1921 ccctaggaat tttcattaaa atttggaaac agagtaatga agaaataata
tataaactcc 1981 ttatgtgagg aaatgctact aatatctgaa aagtgaaaga
tttctatgta ttaactctta 2041 agtgcaccta gcttattaca tcgtgaaagg
tacatttaaa atatgttaaa ttggcttgaa 2101 attttcagag aattttgtct
tcccctaatt cttcttcctt ggtctggaag aacaatttct 2161 atgaattttc
tctttatttt ttttttataa ttcagacaat tctatgaccc gtgtcttcat 2221
ttttggcact cttatttaac aatgccacac ctgaagcact tggatctgtt cagagctgac
2281 cccctagcaa cgtagttgac acagctccag gtttttaaat tactaaaata
agttcaagtt 2341 tacatccctt gggccagata tgtgggttga ggcttgactg
tagcatcctg cttagagacc 2401 aatcaatgga cactggtttt tagacctcta
tcaatcagta gttagcatcc aagagacttt 2461 gcagaggcgt aggaatgagg
ctggacagat ggcggaacga gaggttccct gcgaagactt 2521 gagatttagt
gtctgtgaat gttctagttc ctaggtccag caagtcacac ctgccagtgc 2581
cctcatcctt atgcctgtaa cacacatgca gtgagaggcc tcacatatac gcctccctag
2641 aagtgccttc caagtcagtc ctttggaaac cagcaggtct gaaaaagagg
ctgcatcaat 2701 gcaagcctgg ttggaccatt gtccatgcct caggatagaa
cagcctggct tatttgggga 2761 tttttcttct agaaatcaaa tgactgataa
gcattggctc cctctgccat ttaatggcaa 2821 tggtagtctt tggttagctg
caaaaatact ccatttcaag ttaaaaatgc atcttctaat 2881 ccatctctgc
aagctccctg tgtttccttg ccctttagaa aatgaattgt tcactacaat 2941
tagagaatca tttaacatcc tgacctggta agctgccaca cacctggcag tggggagcat
3001 cgctgtttcc aatggctcag gagacaatga aaagccccca tttaaaaaaa
taacaaacat 3061 tttttaaaag gcctccaata ctcttatgga gcctggattt
ttcccactgc tctacaggct 3121 gtgacttttt ttaagcatcc tgacaggaaa
tgttttcttc tacatggaaa gatagacagc 3181 agccaaccct gatctggaag
acagggcccc ggctggacac acgtggaacc aagccaggga 3241 tgggctggcc
attgtgtccc cgcaggagag atgggcagaa tggccctaga gttcttttcc 3301
ctgagaaagg agaaaaagat gggattgcca ctcacccacc cacactggta agggaggaga
3361 atttgtgctt ctggagcttc tcaagggatt gtgttttgca ggtacagaaa
actgcctgtt 3421 atcttcaagc caggttttcg agggcacatg ggtcaccagt
tgctttttca gtcaatttgg 3481 ccgggatgga ctaatgaggc tctaacactg
ctcaggagac ccctgccctc tagttggttc 3541 tgggctttga tctcttccaa
cctgcccagt cacagaagga ggaatgactc aaatgcccaa 3601 aaccaagaac
acattgcaga agtaagacaa acatgtatat ttttaaatgt tctaacataa 3661
gacctgttct ctctagccat tgatttacca ggctttctga aagatctagt ggttcacaca
3721 gagagagaga gagtactgaa aaagcaactc ctcttcttag tcttaataat
ttactaaaat 3781 ggtcaacttt tcattatctt tattataata aacctgatgc
ttttttttag aactccttac 3841 tctgatgtct gtatatgttg cactgaaaag
gttaatattt aatgttttaa tttattttgt 3901 gtggtaagtt aattttgatt
tctgtaatgt gttaatgtga ttagcagtta ttttccttaa 3961 tatctgaatt
atacttaaag agtagtgagc aatataagac gcaattgtgt ttttcagtaa 4021
tgtgcattgt tattgagttg tactgtacct tatttggaag gatgaaggaa tgaacctttt
4081 tttcctaaaa GenBank Gene Name Gene Symbol Accession # SEQ ID NO
fibroblast growth factor FGFBP1 NM_005130 24 binding protein 1 1
gaatagtcta ccccccttgc actctacctg acacagctgc agcctgcaat tcactcgcac
61 tgcctgggat tgcactggat ccgtgtgctc agaacaaggt gaacgcccag
ctgcagccat 121 gaagatctgt agcctcaccc tgctctcctt cctcctactg
gctgctcagg tgctcctggt 181 ggaggggaaa aaaaaagtga agaatggact
tcacagcaaa gtggtctcag aacaaaagga 241 cactctgggc aacacccaga
ttaagcagaa aagcaggccc gggaacaaag gcaagtttgt 301 caccaaagac
caagccaact gcagatgggc tgctactgag caggaggagg gcatctctct 361
caaggttgag tgcactcaat tggaccatga attttcctgt gtctttgctg gcaatccaac
421 ctcatgccta aagctcaagg atgagagagt ctattggaaa caagttgccc
ggaatctgcg 481 ctcacagaaa gacatctgta gatattccaa gacagctgtg
aaaaccagag tgtgcagaaa 541 ggattttcca gaatccagtc ttaagctagt
cagctccact ctatttggga acacaaagcc 601 caggaaggag aaaacagaga
tgtcccccag ggagcacatc aaaggcaaag agaccacccc 661 ctctagccta
gcagtgaccc agaccatggc caccaaagct cccgagtgtg tggaggaccc 721
agatatggca aaccagagga agactgccct ggagttctgt ggagagactt ggagctctct
781 ctgcacattc ttcctcagca tagtgcagga cacgtcatgc taatgaggtc
aaaagagaac 841 gggttccctt aagagatgtc atgtcgtaag tccctctgta
tactttaaag ctctctacag 901 tccccccaaa atatgaactt ttgtgcttag
tgagtgcaac gaaatattta aacaagtttt 961 gtattttttg cttttgtgtt
ttggaatttg ccttattttt cttggatgcg atgttcagag 1021 gctgtttcct
gcagcatgta tttccatggc ccacacagct atgtgtttga gcagcgaaga 1081
gtctttgagc tgaatgagcc agagtgataa tttcagtgca acgaactttc tgctgaatta
1141 atggtaataa aactctgggt gtttttcaga aatacattca GenBank Gene Name
Gene Symbol Accession # SEQ ID NO PTK6 protein tyrosine PTK6
NM_005975 25 kinase 6 1 gctgggccac agcctggtcc tgccgctgcg cccgcccgcc
atggtgtccc gggaccaggc 61 tcacctgggc cccaagtatg tgggcctctg
ggacttcaag tcccggacgg acgaggagct 121 gagcttccgc gcgggggacg
tcttccacgt ggccaggaag gaggagcagt ggtggtgggc 181 cacgctgctg
gacgaggcgg gtggggccgt ggcccagggc tatgtgcccc acaactacct 241
ggccgagagg gagacggtgg agtcggaacc gtggttcttt ggctgcatct cccgctcgga
301 agctgtgcgt cggctgcagg ccgagggcaa cgccacgggc gccttcctga
tcagggtcag 361 cgagaagccg agtgccgact acgtcctgtc ggtgcgggac
acgcaggctg tgcggcacta 421 caagatctgg cggcgtgccg ggggccggct
gcacctgaac gaggcggtgt ccttcctcag 481 cctgcccgag cttgtgaact
accacagggc ccagagcctg tcccacggcc tgcggctggc 541 cgcgccctgc
cggaagcacg agcctgagcc cctgccccat tgggatgact gggagaggcc 601
gagggaggag ttcacgctct gcaggaagct ggggtccggc tactttgggg aggtcttcga
661 ggggctctgg aaagaccggg tccaggtggc cattaaggtg atttctcgag
acaacctcct 721 gcaccagcag atgctgcagt cggagatcca ggccatgaag
aagctgcggc acaaacacat 781 cctggcgctg tacgccgtgg tgtccgtggg
ggaccccgtg tacatcatca cggagctcat 841 ggccaagggc agcctgctgg
agctgctccg cgactctgat gagaaagtcc tgcccgtttc 901 ggagctgctg
gacatcgcct ggcaggtggc tgagggcatg tgttacctgg agtcgcagaa 961
ttacatccac cgggacctgg ccgccaggaa catcctcgtc ggggaaaaca ccctctgcaa
1021 agttggggac ttcgggttag ccaggcttat caaggaggac gtctacctct
cccatgacca 1081 caatatcccc tacaagtgga cggcccctga agcgctctcc
cgaggccatt actccaccaa 1141 atccgacgtc tggtcctttg ggattctcct
gcatgagatg ttcagcaggg gtcaggtgcc 1201 ctacccaggc atgtccaacc
atgaggcctt cctgagggtg gacgccggct accgcatgcc 1261 ctgccctctg
gagtgcccgc ccagcgtgca caagctgatg ctgacatgct ggtgcaggga 1321
ccccgagcag agaccctgct tcaaggccct gcgggagagg ctctccagct tcaccagcta
1381 cgagaacccg acctgagctg ctgtggagcg ggcatggccg ggccctgctg
aggaggggcc 1441 tgggcagagg gcctggacct gggatcaagg cccacgcgct
tccctggggt ttactgaggt 1501 gatgggtgca ggaaaggttc acaaatgtgg
agtgtctgcg tccaatacac gcgtgtgctc 1561 ctctccttac tccatcgtgt
gtgccttggg tctcagctgc tgacacgcag cctgctctgg 1621 agcctgcaga
tgagatccgg gagactgaca cgaagccagc agaggtcaga ggggactctg 1681
accacagccc gctctctggc tgtctgtctg cagtgcccgg ctgagggtgg
gaggcaaaca
1741 cgccttgttc ctgctcttcc cagttcagct tggtgggaga aagtcattcg
cgtggctcgg 1801 gacgctcatg taaatttggt tttggtgctc aagggttctt
tcctcccagg ggcaggtgtt 1861 tctttcctgt ttgtcttgtg tcttgagagc
ttggccttat gaccagtgag aactctctcc 1921 ctggtctctg ccagcccaag
catcactgcc cgaggcgcca gctcagtttc accgtccacg 1981 tccacaaggg
gcttttccca ccttcacctt tgtcgctggg tcagtgctgg aaagcgcccc 2041
tcactcctgc gctgacaagg gcccttctct actgtctgtg gggtggttcc gggctggggg
2101 ggctgcctcc tttgcacctg attttgaagg tgtctctttc atccatggtt
aagtcataaa 2161 aagcttattg gttttggttt tgactcacct gaaagttttt
ttggtttaaa agaagaatag 2221 gcggggcacg gtggctcatg cctgtaatcc
cagcactttg ggaggctgag gcaggtggat 2281 cacgaggtca ggagatcgac
accatcctgg ctaacacggt gaaaccccgt ctctactaaa 2341 aaatacaaaa
aattagctgg gtgtggtggt gggggtgggc gcctgtagtc ccagctacgt 2401
gggaggctga ggcagcagac tggtgtgaac ccgggaggtg gagcttgcag tgagccgaga
2461 tcgcgccact gcactccagc ctgggcgaca gagcgagact ccatctcaaa GenBank
Gene Name Gene Symbol Accession # SEQ ID NO epithelial V-like EVA1
NM_005797 26 antigen 1 1 acaggcacag gtgaggaact caactcaaac
tcctctctct gggaaaacgc ggtgcttgct 61 cctcccggag tggccttggc
agggtgttgg agccctcggt ctgccccgtc cggtctctgg 121 ggccaaggct
gggtttccct catgtatggc aagagctcta ctcgtgcggt gcttcttctc 181
cttggcatac agctcacagc tctttggcct atagcagctg tggaaattta tacctcccgg
241 gtgctggagg ctgttaatgg gacagatgct cggttaaaat gcactttctc
cagctttgcc 301 cctgtgggtg atgctctaac agtgacctgg aattttcgtc
ctctagacgg gggacctgag 361 cagtttgtat tctactacca catagatccc
ttccaaccca tgagtgggcg gtttaaggac 421 cgggtgtctt gggatgggaa
tcctgagcgg tacgatgcct ccatccttct ctggaaactg 481 cagttcgacg
acaatgggac atacacctgc caggtgaaga acccacctga tgttgatggg 541
gtgatagggg agatccggct cagcgtcgtg cacactgtac gcttctctga gatccacttc
601 ctggctctgg ccattggctc tgcctgtgca ctgatgatca taatagtaat
tgtagtggtc 661 ctcttccagc attaccggaa aaagcgatgg gccgaaagag
ctcataaagt ggtggagata 721 aaatcaaaag aagaggaaag gctcaaccaa
gagaaaaagg tctctgttta tttagaagac 781 acagactaac aattttagat
ggaagctgag atgatttcca agaacaagaa ccctagtatt 841 tcttgaagtt
aatggaaact tttctttggc ttttccagtt gtgacccgtt ttccaaccag 901
ttctgcagca tattagattc tagacaagca acacccctct ggagccagca cagtgctcct
961 ccatatcacc agtcatacac agcctcatta ttaaggtctt atttaatttc
agagtgtaaa 1021 ttttttcaag tgctcattag gttttataaa caagaagcta
catttttgcc cttaagacac 1081 tacttacagt gttatgactt gtatacacat
atattggtat caaaagggat aaaagccaat 1141 ttgtctgtta catttccttt
cacgtatttc ttttagcagc acttctgcta ctaaagttaa 1201 tgtgtttact
ctctttcctt cccacattct caattaaaag gtgagctaag cctcctcggt 1261
gtttctgatt aacagtaaat cctaaattca aactgttaaa tgacattttt atttttatgt
1321 ctctccttaa ctatgagaca catcttgttt tactgaattt ctttcaatat
tccaggtgat 1381 agatttttgt tgttttgtta attaatccaa gatttacaat
agcacaacgc taaatcacac 1441 agtaactaca aaaggttaca tagatatgaa
aagattggca gaggccattg caggatgaat 1501 cacttgtcac ttttcttctg
tgctgggaaa aataatcaac aatgtgggtc tttcatgagc 1561 agtgacggat
agtttagctt actatgtttc ccccccaatt caatgatcta taacaacaga 1621
gcaaagtcta tgctcatttg cagactggaa tcattaagta atttaataaa aaaattgtga
1681 aacagcatat tacaagtttg aaaattcagg gctggtgaaa aaaatcaact
ctaaatgatg 1741 ataattttgt acagttttat ataaaactct gagaactaga
agaaattatt aacttttttt 1801 cttttttaat tctaattcac ttgtttattt
tgggggagga agactttggt atggagcaaa 1861 gaaataccaa aactacttta
aatggaataa aaccaacttt attctttttt tcccccatac 1921 tggtagataa
agcaaacttt ataagtgggc tattgaaaga aaagttacaa gcttaagata 1981
cagaagcatt tgttcaaagg atagaaagca tctaaaagtt taggctcaag atcaatcttt
2041 acagattgat attttcagtt tttaatcgac tggactgcag atgttttttc
ttttaacaaa 2101 ctggaatttt caaacagatt atctgtattt aaatgtatag
accttgatat ttttccaata 2161 ctatttttta aaaaattgta tgatttacat
atgaacctca gttctgaaat tcattacata 2221 tctgtctcat tctgcctttt
atactgtcta aaaaagcaaa gttttaaagt gcaattttaa 2281 aactgtaaat
tacatctgaa ggctatatat cctttaatca cattttatat tttttcttca 2341
caattctaac ctttgaaaat attataactg gatatttctt caaacagatg tcctggatga
2401 tggtccataa gaataatgaa gaagtagtta aaaatgtatg gacagttttt
ccggcaaaat 2461 ttgtagctta tgtcttggct aaatagtcaa ggggtaatat
gggcctgttg tttagtgtct 2521 ccttcctaaa gagcactttt gtattgtaat
ttatttttta ttatgcttta aacactatgt 2581 aaataaacct ttagtaataa
agaattatca gttataaaaa GenBank Gene Name Gene Symbol Accession # SEQ
ID NO EPH receptor A2 EPHA2 NM_004431 27 1 attaaggact cggggcagga
ggggcagaag ttgcgcgcag gccggcgggc gggagcggac 61 accgaggccg
gcgtgcaggc gtgcgggtgt gcgggagccg ggctcggggg gatcggaccg 121
agagcgagaa gcgcggcatg gagctccagg cagcccgcgc ctgcttcgcc ctgctgtggg
181 gctgtgcgct ggccgcggcc gcggcggcgc agggcaagga agtggtactg
ctggactttg 241 ctgcagctgg aggggagctc ggctggctca cacacccgta
tggcaaaggg tgggacctga 301 tgcagaacat catgaatgac atgccgatct
acatgtactc cgtgtgcaac gtgatgtctg 361 gcgaccagga caactggctc
cgcaccaact gggtgtaccg aggagaggct gagcgtatct 421 tcattgagct
caagtttact gtacgtgact gcaacagctt ccctggtggc gccagctcct 481
gcaaggagac tttcaacctc tactatgccg agtcggacct ggactacggc accaacttcc
541 agaagcgcct gttcaccaag attgacacca ttgcgcccga tgagatcacc
gtcagcagcg 601 acttcgaggc acgccacgtg aagctgaacg tggaggagcg
ctccgtgggg ccgctcaccc 661 gcaaaggctt ctacctggcc ttccaggata
tcggtgcctg tgtggcgctg ctctccgtcc 721 gtgtctacta caagaagtgc
cccgagctgc tgcagggcct ggcccacttc cctgagacca 781 tcgccggctc
tgatgcacct tccctggcca ctgtggccgg cacctgtgtg gaccatgccg 841
tggtgccacc ggggggtgaa gagccccgta tgcactgtgc agtggatggc gagtggctgg
901 tgcccattgg gcagtgcctg tgccaggcag gctacgagaa ggtggaggat
gcctgccagg 961 cctgctcgcc tggatttttt aagtttgagg catctgagag
cccctgcttg gagtgccctg 1021 agcacacgct gccatcccct gagggtgcca
cctcctgcga gtgtgaggaa ggcttcttcc 1081 gggcacctca ggacccagcg
tcgatgcctt gcacacgacc cccctccgcc ccacactacc 1141 tcacagccgt
gggcatgggt gccaaggtgg agctgcgctg gacgccccct caggacagcg 1201
ggggccgcga ggacattgtc tacagcgtca cctgcgaaca gtgctggccc gagtctgggg
1261 aatgcgggcc gtgtgaggcc agtgtgcgct actcggagcc tcctcacgga
ctgacccgca 1321 ccagtgtgac agtgagcgac ctggagcccc acatgaacta
caccttcacc gtggaggccc 1381 gcaatggcgt ctcaggcctg gtaaccagcc
gcagcttccg tactgccagt gtcagcatca 1441 accagacaga gccccccaag
gtgaggctgg agggccgcag caccacctcg cttagcgtct 1501 cctggagcat
ccccccgccg cagcagagcc gagtgtggaa gtacgaggtc acttaccgca 1561
agaagggaga ctccaacagc tacaatgtgc gccgcaccga gggtttctcc gtgaccctgg
1621 acgacctggc cccagacacc acctacctgg tccaggtgca ggcactgacg
caggagggcc 1681 agggggccgg cagcaaggtg cacgaattcc agacgctgtc
cccggaggga tctggcaact 1741 tggcggtgat tggcggcgtg gctgtcggtg
tggtcctgct tctggtgctg gcaggagttg 1801 gcttctttat ccaccgcagg
aggaagaacc agcgtgcccg ccagtccccg gaggacgttt 1861 acttctccaa
gtcagaacaa ctgaagcccc tgaagacata cgtggacccc cacacatatg 1921
aggaccccaa ccaggctgtg ttgaagttca ctaccgagat ccatccatcc tgtgtcactc
1981 ggcagaaggt gatcggagca ggagagtttg gggaggtgta caagggcatg
ctgaagacat 2041 cctcggggaa gaaggaggtg ccggtggcca tcaagacgct
gaaagccggc tacacagaga 2101 agcagcgagt ggacttcctc ggcgaggccg
gcatcatggg ccagttcagc caccacaaca 2161 tcatccgcct agagggcgtc
atctccaaat acaagcccat gatgatcatc actgagtaca 2221 tggagaatgg
ggccctggac aagttccttc gggagaagga tggcgagttc agcgtgctgc 2281
agctggtggg catgctgcgg ggcatcgcag ctggcatgaa gtacctggcc aacatgaact
2341 atgtgcaccg tgacctggct gcccgcaaca tcctcgtcaa cagcaacctg
gtctgcaagg 2401 tgtctgactt tggcctgtcc cgcgtgctgg aggacgaccc
cgaggccacc tacaccacca 2461 gtggcggcaa gatccccatc cgctggaccg
ccccggaggc catttcctac cggaagttca 2521 cctctgccag cgacgtgtgg
agctttggca ttgtcatgtg ggaggtgatg acctatggcg 2581 agcggcccta
ctgggagttg tccaaccacg aggtgatgaa agccatcaat gatggcttcc 2641
ggctccccac acccatggac tgcccctccg ccatctacca gctcatgatg cagtgctggc
2701 agcaggagcg tgcccgccgc cccaagttcg ctgacatcgt cagcatcctg
gacaagctca 2761 ttcgtgcccc tgactccctc aagaccctgg ctgactttga
cccccgcgtg tctatccggc 2821 tccccagcac gagcggctcg gagggggtgc
ccttccgcac ggtgtccgag tggctggagt 2881 ccatcaagat gcagcagtat
acggagcact tcatggcggc cggctacact gccatcgaga 2941 aggtggtgca
gatgaccaac gacgacatca agaggattgg ggtgcggctg cccggccacc 3001
agaagcgcat cgcctacagc ctgctgggac tcaaggacca ggtgaacact gtggggatcc
3061 ccatctgagc ctcgacaggg cctggagccc catcggccaa gaatacttga
agaaacagag 3121 tggcctccct gctgtgccat gctgggccac tggggacttt
atttatttct agttctttcc 3181 tccccctgca acttccgctg aggggtctcg
gatgacaccc tggcctgaac tgaggagatg 3241 accagggatg ctgggctggg
ccctctttcc ctgcgagacg cacacagctg agcacttagc 3301 aggcaccgcc
acgtcccagc atccctggag caggagcccc gccacagcct tcggacagac 3361
atataggata ttcccaagcc gaccttccct ccgccttctc ccacatgagg ccatctcagg
3421 agatggaggg cttggcccag cgccaagtaa acagggtacc tcaagcccca
tttcctcaca 3481 ctaagagggc agactgtgaa cttgactggg tgagacccaa
agcggtccct gtccctctag 3541 tgccttcttt agaccctcgg gccccatcct
catccctgac tggccaaacc cttgctttcc 3601 tgggcctttg caagatgctt
ggttgtgttg aggtttttaa atatatattt tgtactttgt 3661 ggagagaatg
tgtgtgtgtg gcagggggcc ccgccagggc tggggacaga gggtgtcaaa 3721
cattcgtgag ctggggactc agggaccggt gctgcaggag tgtcctgccc
atgccccagt
3781 cggccccatc tctcatcctt ttggataagt ttctattctg tcagtgttaa
agattttgtt 3841 ttgttggaca tttttttcga atcttaattt attatttttt
ttatatttat tgttagaaaa 3901 tgacttattt ctgctctgga ataaagttgc
agatgattca aaccgaaaaa GenBank Gene Name Gene Symbol Accession # SEQ
ID NO integrin, alpha 6 ITGA6 NM_000210 28 1 aacgggctca ttcagcggtc
gcgagctgcc cgcgaggggg agcggccgga cggagagcgc 61 gacccgtccc
gggggtgggg ccgggcgcag cggcgagagg aggcgaaggt ggctgcggta 121
gcagcagcgc ggcagcctcg gacccagccc ggagcgcagg gcggccgctg caggtccccg
181 ctcccctccc cgtgcgtccg cccatggccg ccgccgggca gctgtgcttg
ctctacctgt 241 cggcggggct cctgtcccgg ctcggcgcag ccttcaactt
ggacactcgg gaggacaacg 301 tgatccggaa atatggagac cccgggagcc
tcttcggctt ctcgctggcc atgcactggc 361 aactgcagcc cgaggacaag
cggctgttgc tcgtgggggc cccgcgggca gaagcgcttc 421 cactgcagag
agccaacaga acgggagggc tgtacagctg cgacatcacc gcccgggggc 481
catgcacgcg gatcgagttt gataacgatg ctgaccccac gtcagaaagc aaggaagatc
541 agtggatggg ggtcaccgtc cagagccaag gtccaggggg caaggtcgtg
acatgtgctc 601 accgatatga aaaaaggcag catgttaata cgaagcagga
atcccgagac atctttgggc 661 ggtgttatgt cctgagtcag aatctcagga
ttgaagacga tatggatggg ggagattgga 721 gcttttgtga tgggcgattg
agaggccatg agaaatttgg ctcttgccag caaggtgtag 781 cagctacttt
tactaaagac tttcattaca ttgtatttgg agccccgggt acttataact 841
ggaaagggat tgttcgtgta gagcaaaaga ataacacttt ttttgacatg aacatctttg
901 aagatgggcc ttatgaagtt ggtggagaga ctgagcatga tgaaagtctc
gttcctgttc 961 ctgctaacag ttacttaggt ttttctttgg actcagggaa
aggtattgtt tctaaagatg 1021 agatcacttt tgtatctggt gctcccagag
ccaatcacag tggagccgtg gttttgctga 1081 agagagacat gaagtctgca
catctcctcc ctgagcacat attcgatgga gaaggtctgg 1141 cctcttcatt
tggctatgat gtggcggtgg tggacctcaa caaggatggg tggcaagata 1201
tagttattgg agccccacag tattttgata gagatggaga agttggaggt gcagtgtatg
1261 tctacatgaa ccagcaaggc agatggaata atgtgaagcc aattcgtctt
aatggaacca 1321 aagattctat gtttggcatt gcagtaaaaa atattggaga
tattaatcaa gatggctacc 1381 cagatattgc agttggagct ccgtatgatg
acttgggaaa ggtttttatc tatcatggat 1441 ctgcaaatgg aataaatacc
aaaccaacac aggttctcaa gggtatatca ccttattttg 1501 gatattcaat
tgctggaaac atggaccttg atcgaaattc ctaccctgat gttgctgttg 1561
gttccctctc agattcagta actattttca gatcccggcc tgtgattaat attcagaaaa
1621 ccatcacagt aactcctaac agaattgacc tccgccagaa aacagcgtgt
ggggcgccta 1681 gtgggatatg cctccaggtt aaatcctgtt ttgaatatac
tgctaacccc gctggttata 1741 atccttcaat atcaattgtg ggcacacttg
aagctgaaaa agaaagaaga aaatctgggc 1801 tatcctcaag agttcagttt
cgaaaccaag gttctgagcc caaatatact caagaactaa 1861 ctctgaagag
gcagaaacag aaagtgtgca tggaggaaac cctgtggcta caggataata 1921
tcagagataa actgcgtccc attcccataa ctgcctcagt ggagatccaa gagccaagct
1981 ctcgtaggcg agtgaattca cttccagaag ttcttccaat tctgaattca
gatgaaccca 2041 agacagctca tattgatgtt cacttcttaa aagagggatg
tggagacgac aatgtatgta 2101 acagcaacct taaactagaa tataaatttt
gcacccgaga aggaaatcaa gacaaatttt 2161 cttatttacc aattcaaaaa
ggtgtaccag aactagttct aaaagatcag aaggatattg 2221 ctttagaaat
aacagtgaca aacagccctt ccaacccaag gaatcccaca aaagatggcg 2281
atgacgccca tgaggctaaa ctgattgcaa cgtttccaga cactttaacc tattctgcat
2341 atagagaact gagggctttc cctgagaaac agttgagttg tgttgccaac
cagaatggct 2401 cgcaagctga ctgtgagctc ggaaatcctt ttaaaagaaa
ttcaaatgtc actttttatt 2461 tggttttaag tacaactgaa gtcacctttg
acaccccaga tctggatatt aatctgaagt 2521 tagaaacaac aagcaatcaa
gataatttgg ctccaattac agctaaagca aaagtggtta 2581 ttgaactgct
tttatcggtc tcgggagttg ctaaaccttc ccaggtgtat tttggaggta 2641
cagttgttgg cgagcaagct atgaaatctg aagatgaagt gggaagttta atagagtatg
2701 aattcagggt aataaactta ggtaaacctc ttacaaacct cggcacagca
accttgaaca 2761 ttcagtggcc aaaagaaatt agcaatggga aatggttgct
ttatttggtg aaagtagaat 2821 ccaaaggatt ggaaaaggta acttgtgagc
cacaaaagga gataaactcc ctgaacctaa 2881 cggagtctca caactcaaga
aagaaacggg aaattactga aaaacagata gatgataaca 2941 gaaaattttc
tttatttgct gaaagaaaat accagactct taactgtagc gtgaacgtga 3001
actgtgtgaa catcagatgc ccgctgcggg ggctggacag caaggcgtct cttattttgc
3061 gctcgaggtt atggaacagc acatttctag aggaatattc caaactgaac
tacttggaca 3121 ttctcatgcg agccttcatt gatgtgactg ctgctgccga
aaatatcagg ctgccaaatg 3181 caggcactca ggttcgagtg actgtgtttc
cctcaaagac tgtagctcag tattcgggag 3241 taccttggtg gatcatccta
gtggctattc tcgctgggat cttgatgctt gctttattag 3301 tgtttatact
atggaagtgt ggtttcttca agagaaataa gaaagatcat tatgatgcca 3361
catatcacaa ggctgagatc catgctcagc catctgataa agagaggctt acttctgatg
3421 catagtattg atctacttct gtaattgtgt ggattcttta aacgctctag
gtacgatgac 3481 agtgttcccc gataccatgc tgtaaggatc cggaaagaag
agcgagagat caaagatgaa 3541 aagtatattg ataaccttga aaaaaaacag
tggatcacaa agtggaacga aaatgaaagc 3601 tactcatagc gggggcctaa
aaaaaaaaag cttcacagta cccaaactgc tttttccaac 3661 tcagaaattc
aatttggatt taaaagcctg ctcaatccct gaggactgat ttcagagtga 3721
ctacacacag tacgaaccta cagttttaac tgtggatatt gttacgtagc ctaaggctcc
3781 tgttttgcac agccaaattt aaaactgttg gaatggattt ttctttaact
gccgtaattt 3841 aactttctgg gttgccttta tttttggcgt ggctgactta
catcatgtgt tggggaaggg 3901 cctgcccagt tgcactcagg tgacatcctc
cagatagtgt agctgaggag gcacctacac 3961 tcacctgcac taacagagtg
gccgtcctaa cctcgggcct gctgcgcaga cgtccatcac 4021 gttagctgtc
ccacatcaca agactatgcc attggggtag ttgtgtttca acggaaagtg 4081
ctgtcttaaa ctaaatgtgc aatagaaggt gatgttgcca tcctaccgtc ttttcctgtt
4141 tcctagctgt gtgaatacct gctcacgtca aatgcataca agtttcattc
tccctttcac 4201 taaaacacac aggtgcaaca gacttgaatg ctagttatac
ttatttgtat atggtattta 4261 ttttttcttt tctttacaaa ccattttgtt
attgactaac aggccaaaga gtctccagtt 4321 tacccttcag gttggtttaa
tcaatcagaa ttagagcatg ggaggtcatc actttgacct 4381 aaattattta
ctgcaaaaag aaaatcttta taaatgtacc agagagagtt gttttaataa 4441
cttatctata aactataacc tctccttcat gacagcctcc accccacaac ccaaaaggtt
4501 taagaaatag aattataact gtaaagatgt ttatttcagg cattggatat
tttttacttt 4561 agaagcctgc ataatgtttc tggatttcat actgtaacat
tcaggaattc ttggagaaaa 4621 tgggtttatt cactgaactc tagtgcggtt
tactcactgc tgcaaatact gtatattcag 4681 gacttgaaag aaatggtgaa
tgcctatggt ggatccaaac tgatccagta taagactact 4741 gaatctgcta
ccaaaacagt taatcagtga gtcgatgttc tattttttgt tttgtttcct 4801
cccctatctg tattcccaaa aattactttg gggctaattt aacaagaact ttaaattgtg
4861 ttttaattgt aaaaatggca gggggtggaa ttattactct atacattcaa
cagagactga 4921 atagatatga aagctgattt tttttaatta ccatgcttca
caatgttaag ttatatgggg 4981 agcaacagca aacaggtgct aatttgtttt
ggatatagta taagcagtgt ctgtgttttg 5041 aaagaataga acacagtttg
tagtgccact gttgttttgg gggggctttt ttcttttcgg 5101 aaatcttaaa
ccttaagata ctaaggacgt tgttttggtt gtactttgga attcttagtc 5161
acaaaatata ttttgtttac aaaaatttct gtaaaacagg ttataacagt gtttaaagtc
5221 tcagtttctt gcttggggaa cttgtgtccc taatgtgttt agattgctag
attgctaagg 5281 agctgatact ttgacagtgt ttttagacct gtgttactaa
aaaaaagatg aatgtcctga 5341 aaagggtgtt gggagggtgg ttcaacaaag
aaacaaagat gttatggtgt ttagatttat 5401 ggttgttaaa aatgtcatct
caagtcaagt cactggtctg tttgcatttg atacattttt 5461 gtactaacta
gcattgtaaa attatttcat gattagaaat tacctgtgga tatttgtata 5521
aaagtgtgaa ataaattttt tataaaagtg ttcattgttt cgtaacacag cattgtatat
5581 gtgaagcaaa ctctaaaatt ataaatgaca acctgaatta tctatttcat
caaaccaaag 5641 ttcagtgttt ttatttttgg tgtctcatgt aatctcagat
cagccaaaga tactagtgcc 5701 aaagcaatgg gattcggggt ttttttctgt
tttcgctcta tgtaggtgat cctcaagtct 5761 ttcattttcc ttctttatga
ttaaaagaaa cctacaggtatttaacaacc GenBank Gene Name Gene Symbol
Accession # SEQ ID NO tumor necrosis factor TNFRSF21 NM_014452 29
receptor superfamily, member 21 1 gccaccacgt gtgtccctgc gcccggtggc
caccgactca gtccctcgcc gaccagtctg 61 ggcagcggag gagggtggtt
ggcagtggct ggaagcttcg ctatgggaag ttgttccttt 121 gctctctcgc
gcccagtcct cctccctggt tctcctcagc cgctgtcgga ggagagcacc 181
cggagacgcg ggctgcagtc gcggcggctt ctccccgcct gggcggccgc gccgctgggc
241 aggtgctgag cgcccctaga gcctcccttg ccgcctccct cctctgcccg
gccgcagcag 301 tgcacatggg gtgttggagg tagatgggct cccggcccgg
gaggcggcgg tggatgcggc 361 gctgggcaga agcagccgcc gattccagct
gccccgcgcg ccccgggcgc ccctgcgagt 421 ccccggttca gccatgggga
cctctccgag cagcagcacc gccctcgcct cctgcagccg 481 catcgcccgc
cgagccacag ccacgatgat cgcgggctcc cttctcctgc ttggattcct 541
tagcaccacc acagctcagc cagaacagaa ggcctcgaat ctcattggca cataccgcca
601 tgttgaccgt gccaccggcc aggtgctaac ctgtgacaag tgtccagcag
gaacctatgt 661 ctctgagcat tgtaccaaca caagcctgcg cgtctgcagc
agttgccctg tggggacctt 721 taccaggcat gagaatggca tagagaaatg
ccatgactgt agtcagccat gcccatggcc 781 aatgattgag aaattacctt
gtgctgcctt gactgaccga gaatgcactt gcccacctgg 841 catgttccag
tctaacgcta cctgtgcccc ccatacggtg tgtcctgtgg gttggggtgt 901
gcggaagaaa gggacagaga ctgaggatgt gcggtgtaag cagtgtgctc ggggtacctt
961 ctcagatgtg ccttctagtg tgatgaaatg caaagcatac acagactgtc
tgagtcagaa 1021 cctggtggtg atcaagccgg ggaccaagga gacagacaac
gtctgtggca cactcccgtc 1081 cttctccagc tccacctcac cttcccctgg
cacagccatc tttccacgcc ctgagcacat 1141 ggaaacccat gaagtccctt
cctccactta tgttcccaaa ggcatgaact caacagaatc
1201 caactcttct gcctctgtta gaccaaaggt actgagtagc atccaggaag
ggacagtccc 1261 tgacaacaca agctcagcaa gggggaagga agacgtgaac
aagaccctcc caaaccttca 1321 ggtagtcaac caccagcaag gcccccacca
cagacacatc ctgaagctgc tgccgtccat 1381 ggaggccact gggggcgaga
agtccagcac gcccatcaag ggccccaaga ggggacatcc 1441 tagacagaac
ctacacaagc attttgacat caatgagcat ttgccctgga tgattgtgct 1501
tttcctgctg ctggtgcttg tggtgattgt ggtgtgcagt atccggaaaa gctcgaggac
1561 tctgaaaaag gggccccggc aggatcccag tgccattgtg gaaaaggcag
ggctgaagaa 1621 atccatgact ccaacccaga accgggagaa atggatctac
tactgcaatg gccatggtat 1681 cgatatcctg aagcttgtag cagcccaagt
gggaagccag tggaaagata tctatcagtt 1741 tctttgcaat gccagtgaga
gggaggttgc tgctttctcc aatgggtaca cagccgacca 1801 cgagcgggcc
tacgcagctc tgcagcactg gaccatccgg ggccccgagg ccagcctcgc 1861
ccagctaatt agcgccctgc gccagcaccg gagaaacgat gttgtggaga agattcgtgg
1921 gctgatggaa gacaccaccc agctggaaac tgacaaacta gctctcccga
tgagccccag 1981 cccgcttagc ccgagcccca tccccagccc caacgcgaaa
cttgagaatt ccgctctcct 2041 gacggtggag ccttccccac aggacaagaa
caagggcttc ttcgtggatg agtcggagcc 2101 ccttctccgc tgtgactcta
catccagcgg ctcctccgcg ctgagcagga acggttcctt 2161 tattaccaaa
gaaaagaagg acacagtgtt gcggcaggta cgcctggacc cctgtgactt 2221
gcagcctatc tttgatgaca tgctccactt tctaaatcct gaggagctgc gggtgattga
2281 agagattccc caggctgagg acaaactaga ccggctattc gaaattattg
gagtcaagag 2341 ccaggaagcc agccagaccc tcctggactc tgtttatagc
catcttcctg acctgctgta 2401 gaacataggg atactgcatt ctggaaatta
ctcaatttag tggcagggtg gttttttaat 2461 tttcttctgt ttctgatttt
tgttgtttgg ggtgtgtgtg tgtgtttgtg tgtgtgtgtg 2521 tgtgtgtgtg
tgtgtgtgtg tttaacagag aatatggcca gtgcttgagt tctttctcct 2581
tctctctctc tctttttttt ttaaataact cttctgggaa gttggtttat aagcctttgc
2641 caggtgtaac tgttgtgaaa tacccaccac taaagttttt taagttccat
attttctcca 2701 ttttgccttc ttatgtattt tcaagattat tctgtgcact
ttaaatttac ttaacttacc 2761 ataaatgcag tgtgactttt cccacacact
ggattgtgag gctcttaact tcttaaaagt 2821 ataatggcat cttgtgaatc
ctataagcag tctttatgtc tcttaacatt cacacctact 2881 ttttaaaaac
aaatattatt actattttta ttattgtttg tcctttataa attttcttaa 2941
agattaagaa aatttaagac cccattgagt tactgtaatg caattcaact ttgagttatc
3001 ttttaaatat gtcttgtata gttcatattc atggctgaaa cttgaccaca
ctattgctga 3061 ttgtatggtt ttcacctgga caccgtgtag aatgcttgat
tacttgtact cttcttatgc 3121 taatatgctc tgggctggag aaatgaaatc
ctcaagccat caggatttgc tatttaagtg 3181 gcttgacaac tgggccacca
aagaacttga acttcacctt ttaggatttg agctgttctg 3241 gaacacattg
ctgcactttg gaaagtcaaa atcaagtgcc agtggcgccc tttccataga 3301
gaatttgccc agctttgctt taaaagatgt cttgtttttt atatacacat aatcaatagg
3361 tccaatctgc tctcaaggcc ttggtcctgg tgggattcct tcaccaatta
ctttaattaa 3421 aaatggctgc aactgtaaga acccttgtct gatatatttg
caactatgct cccatttaca 3481 aatgtacctt ctaatgctca gttgccaggt
tccaatgcaa aggtggcgtg gactcccttt 3541 gtgtgggtgg ggtttgtggg
tagtggtgaa ggaccgatat cagaaaaatg ccttcaagtg 3601 tactaattta
ttaataaaca ttaggtgttt gttaaaaaaa GenBank Gene Name Gene Symbol
Accession # SEQ ID NO transmembrane 4 TM4SF3 NM_004616 30
superfamily member 3 1 agtgccccag gagctatgac aagcaaagga acatacttgc
ctggagatag cctttgcgat 61 atttaaatgt ccgtggatac agaaatctct
gcaggcaagt tgctccagag catattgcag 121 gacaagcctg taacgaatag
ttaaattcac ggcatctgga ttcctaatcc ttttccgaaa 181 tggcaggtgt
gagtgcctgt ataaaatatt ctatgtttac cttcaacttc ttgttctggc 241
tatgtggtat cttgatccta gcattagcaa tatgggtacg agtaagcaat gactctcaag
301 caatttttgg ttctgaagat gtaggctcta gctcctacgt tgctgtggac
atattgattg 361 ctgtaggtgc catcatcatg attctgggct tcctgggatg
ctgcggtgct ataaaagaaa 421 gtcgctgcat gcttctgttg tttttcatag
gcttgcttct gatcctgctc ctgcaggtgg 481 cgacaggtat cctaggagct
gttttcaaat ctaagtctga tcgcattgtg aatgaaactc 541 tctatgaaaa
cacaaagctt ttgagcgcca caggggaaag tgaaaaacaa ttccaggaag 601
ccataattgt gtttcaagaa gagtttaaat gctgcggttt ggtcaatgga gctgctgatt
661 ggggaaataa ttttcaacac tatcctgaat tatgtgcctg tctagataag
cagagaccat 721 gccaaagcta taatggaaaa caagtttaca aagagacctg
tatttctttc ataaaagact 781 tcttggcaaa aaatttgatt atagttattg
gaatatcatt tggactggca gttattgaga 841 tactgggttt ggtgttttct
atggtcctgt attgccagat cgggaacaaa tgaatctgtg 901 gatgcatcaa
cctatcgtca gtcaaacccc tttaaaatgt tgctttggct ttgtaaattt 961
aaatatgtaa gtgctatata agtcaggagc agctgtcttt ttaaaatgtc tcggctagct
1021 agaccacaga tatcttctag acatattgaa cacatttaag atttgaggga
tataagggaa 1081 aatgatatga atgtgtattt ttactcaaaa taaaagtaac
tgtttacgtt GenBank Gene Name Gene Symbol Accession # SEQ ID NO
interleukin 18 IL18 NM_001562 31 (interferon-gamma- inducing
factor) 1 attctctccc cagcttgctg agccctttgc tcccctggcg actgcctgga
cagtcagcaa 61 ggaattgtct cccagtgcat tttgccctcc tggctgccaa
ctctggctgc taaagcggct 121 gccacctgct gcagtctaca cagcttcggg
aagaggaaag gaacctcaga ccttccagat 181 cgcttcctct cgcaacaaac
tatttgtcgc aggaataaag atggctgctg aaccagtaga 241 agacaattgc
atcaactttg tggcaatgaa atttattgac aatacgcttt actttatagc 301
tgaagatgat gaaaacctgg aatcagatta ctttggcaag cttgaatcta aattatcagt
361 cataagaaat ttgaatgacc aagttctctt cattgaccaa ggaaatcggc
ctctatttga 421 agatatgact gattctgact gtagagataa tgcaccccgg
accatattta ttataagtat 481 gtataaagat agccagccta gaggtatggc
tgtaactatc tctgtgaagt gtgagaaaat 541 ttcaactctc tcctgtgaga
acaaaattat ttcctttaag gaaatgaatc ctcctgataa 601 catcaaggat
acaaaaagtg acatcatatt ctttcagaga agtgtcccag gacatgataa 661
taagatgcaa tttgaatctt catcatacga aggatacttt ctagcttgtg aaaaagagag
721 agaccttttt aaactcattt tgaaaaaaga ggatgaattg ggggatagat
ctataatgtt 781 cactgttcaa aacgaagact agctattaaa atttcatgcc
gggcgcagtg gctcacgcct 841 gtaatcccag ccctttggga ggctgaggcg
ggcagatcac cagaggtcag gtgttcaaga 901 ccagcctgac caacatggtg
aaacctcatc tctactaaaa atacaaaaaa ttagctgagt 961 gtagtgacgc
atgccctcaa tcccagctac tcaagaggct gaggcaggag aatcacttgc 1021
actccggagg tagaggttgt ggtgagccga gattgcacca ttgcgctcta gcctgggcaa
1081 caacagcaaa actccatctc aaaaaataaa ataaataaat aaacaaataa
aaaattcata 1141 atgtg GenBank Gene Name Gene Symbol Accession # SEQ
ID NO bone morphogenetic BMP4 NM_130850 32 protein 4 1 gagggagggg
ccgccgggga agaggaggag gaaggaaaga aagaaagcga gggagggaaa 61
gaggaggaag gaagatgcga gaaggcagag gaggagggag ggagggaagg agcgcggagc
121 ccggcccgga agctaggagc cattccgtag tgccatcccg agcaacgcac
tgctgcagct 181 tccctgagcc tttccagcaa gtttgttcaa gattggctgt
caagaatcat ggactgttat 241 tatatgcctt gttttctgtc aagacaccat
gattcctggt aaccgaatgc tgatggtcgt 301 tttattatgc caagtcctgc
taggaggcgc gagccatgct agtttgatac ctgagacggg 361 gaagaaaaaa
gtcgccgaga ttcagggcca cgcgggagga cgccgctcag ggcagagcca 421
tgagctcctg cgggacttcg aggcgacact tctgcagatg tttgggctgc gccgccgccc
481 gcagcctagc aagagtgccg tcattccgga ctacatgcgg gatctttacc
ggcttcagtc 541 tggggaggag gaggaagagc agatccacag cactggtctt
gagtatcctg agcgcccggc 601 cagccgggcc aacaccgtga ggagcttcca
ccacgaagaa catctggaga acatcccagg 661 gaccagtgaa aactctgctt
ttcgtttcct ctttaacctc agcagcatcc ctgagaacga 721 ggcgatctcc
tctgcagagc ttcggctctt ccgggagcag gtggaccagg gccctgattg 781
ggaaaggggc ttccaccgta taaacattta tgaggttatg aagcccccag cagaagtggt
841 gcctgggcac ctcatcacac gactactgga cacgagactg gtccaccaca
atgtgacacg 901 gtgggaaact tttgatgtga gccctgcggt ccttcgctgg
acccgggaga agcagccaaa 961 ctatgggcta gccattgagg tgactcacct
ccatcagact cggacccacc agggccagca 1021 tgtcaggatt agccgatcgt
tacctcaagg gagtgggaat tgggcccagc tccggcccct 1081 cctggtcacc
tttggccatg atggccgggg ccatgccttg acccgacgcc ggagggccaa 1141
gcgtagccct aagcatcact cacagcgggc caggaagaag aataagaact gccggcgcca
1201 ctcgctctat gtggacttca gcgatgtggg ctggaatgac tggattgtgg
ccccaccagg 1261 ctaccaggcc ttctactgcc atggggactg cccctttcca
ctggctgacc acctcaactc 1321 aaccaaccat gccattgtgc agaccctggt
caattctgtc aattccagta tccccaaagc 1381 ctgttgtgtg cccactgaac
tgagtgccat ctccatgctg tacctggatg agtatgataa 1441 ggtggtactg
aaaaattatc aggagatggt agtagaggga tgtgggtgcc gctgagatca 1501
ggcagtcctt gaggatagac agatatacac accacacaca cacaccacat acaccacaca
1561 cacacgttcc catccactca cccacacact acacagactg cttccttata
gctggacttt 1621 tatttaaaaa aaaaaaaaaa aaaatggaaa aaatccctaa
acattcacct tgaccttatt 1681 tatgacttta cgtgcaaatg ttttgaccat
attgatcata tattttgaca aaatatattt 1741 ataactacgt attaaaagaa
aaaaataaaa tgagtcatta ttttaaaggt GenBank Gene Name Gene Symbol
Accession # SEQ ID NO sphingomyelin SMPDL3B NM_014474 33
phosphodiesterase, acid-like 3B 1 ccagatcata ccctgctggg caaaggagga
agagccagag gatccagacg ccttggagga 61 cttggaacac ctgtaacagg
acaaggagtt ctgctcaggc acgtggccac agaaaactac
121 ttaggaagcc tgtggtgaga acaacaacag tgcctgagaa tcccacggct
ctggggaagt 181 gagccccgag gatgaggctg ctcgcctggc tgattttcct
ggctaactgg ggaggtgcca 241 gggctgaacc agggaagttc tggcacatcg
ctgacctgca ccttgaccct gactacaagg 301 tatccaaaga ccccttccag
gtgtgcccat cagctggatc ccagccagtg cccgacgcag 361 gcccctgggg
tgactacctc tgtgattctc cctgggccct catcaactcc tccatctatg 421
ccatgaagga gattgagcca gagccagact tcattctctg gactggtgat gacacgcctc
481 atgtgcccga tgagaaactg ggagaggcag ctgtactgga aattgtggaa
cgcctgacca 541 agctcatcag agaggtcttt ccagatacta aagtctatgc
tgctttggga aatcatgatt 601 ttcaccccaa aaaccagttc ccagctggaa
gtaacaacat ctacaatcag atagcagaac 661 tatggaaacc ctggcttagt
aatgagtcca tcgctctctt caaaaaaggt gccttctact 721 gtgagaagct
gccgggtccc agcggggctg ggcgaattgt ggtcctcaac accaatctgt 781
actataccag caatgcgctg acagcagaca tggcggaccc tggccagcag ttccagtggc
841 tggaagatgt gctgaccgat gcatccaaag ctggggacat ggtgtacatt
gtcggccacg 901 tgcccccggg gttctttgag aagacgcaaa acaaggcatg
gttccgggag ggcttcaatg 961 aaaaatacct gaaggtggtc cggaagcatc
atcgcgtcat agcagggcag ttcttcgggc 1021 accaccacac cgacagcttt
cggatgctct atgatgatgc aggtgtcccc ataagcgcca 1081 tgttcatcac
acctggagtc accccatgga aaaccacatt acctggagtg gtcaatgggg 1141
ccaacaatcc agccatccgg gtgttcgaat atgaccgagc cacactgagc ctgaaggaca
1201 tggtgaccta cttcatgaac ctgagccagg cgaatgctca ggggacgccg
cgctgggagc 1261 tcgagtacca gctgaccgag gcctatgggg tgccggacgc
cagcgcccac tccatgcaca 1321 cagtgctgga ccgcatcgct ggcgaccaga
gcacactgca gcgctactac gtctataact 1381 cagtcagcta ctctgctggg
gtctgcgacg aggcctgcag catgcagcac gtgtgtgcca 1441 tgcgccaggt
ggacattgac gcttacacca cctgtctgta tgcctctggc accacgcccg 1501
tgccccagct cccgctgctg ctgatggccc tgctgggcct gtgcacgctc gtgctgtgac
1561 ctgccaggct caccttcttc ctggtaacgg gtaacggggg cagcgcccag
gatcacccag 1621 agctgggcct tccaccattt cctccgcgcc tgaggagtga
actgaaatag gacaaccgaa 1681 tcaggaagcg aagccccagg agctgcagcc
atccgtgatc gcgccactgc actccagcct 1741 gggcgacaaa gccagactct
ctccaaaaac aaaccagaaa cagaaaagaa atgacgaccc 1801 aagacccccc
tacaagcata cttcttttgc gtattatgtt ttactcacaa aacaaagctc 1861
atcatgcgtt tgaaaaaaaa GenBank Gene Name Gene Symbol Accession # SEQ
ID NO transmembrane TMPRSS2 NM_005656 34 protease, serine 2 1
cgcgagctaa gcaggaggcg gaggcggagg cggagggcga ggggcgggga gcgccgcctg
61 gagcgcggca ggtcatattg aacattccag atacctatca ttactcgatg
ctgttgataa 121 cagcaagatg gctttgaact cagggtcacc accagctatt
ggaccttact atgaaaacca 181 tggataccaa ccggaaaacc cctatcccgc
acagcccact gtggtcccca ctgtctacga 241 ggtgcatccg gctcagtact
acccgtcccc cgtgccccag tacgccccga gggtcctgac 301 gcaggcttcc
aaccccgtcg tctgcacgca gcccaaatcc ccatccggga cagtgtgcac 361
ctcaaagact aagaaagcac tgtgcatcac cttgaccctg gggaccttcc tcgtgggagc
421 tgcgctggcc gctggcctac tctggaagtt catgggcagc aagtgctcca
actctgggat 481 agagtgcgac tcctcaggta cctgcatcaa cccctctaac
tggtgtgatg gcgtgtcaca 541 ctgccccggc ggggaggacg agaatcggtg
tgttcgcctc tacggaccaa acttcatcct 601 tcagatgtac tcatctcaga
ggaagtcctg gcaccctgtg tgccaagacg actggaacga 661 gaactacggg
cgggcggcct gcagggacat gggctataag aataattttt actctagcca 721
aggaatagtg gatgacagcg gatccaccag ctttatgaaa ctgaacacaa gtgccggcaa
781 tgtcgatatc tataaaaaac tgtaccacag tgatgcctgt tcttcaaaag
cagtggtttc 841 tttacgctgt atagcctgcg gggtcaactt gaactcaagc
cgccagagca ggatcgtggg 901 cggtgagagc gcgctcccgg gggcctggcc
ctggcaggtc agcctgcacg tccagaacgt 961 ccacgtgtgc ggaggctcca
tcatcacccc cgagtggatc gtgacagccg cccactgcgt 1021 ggaaaaacct
cttaacaatc catggcattg gacggcattt gcggggattt tgagacaatc 1081
tttcatgttc tatggagccg gataccaagt agaaaaagtg atttctcatc caaattatga
1141 ctccaagacc aagaacaatg acattgcgct gatgaagctg cagaagcctc
tgactttcaa 1201 cgacctagtg aaaccagtgt gtctgcccaa cccaggcatg
atgctgcagc cagaacagct 1261 ctgctggatt tccgggtggg gggccaccga
ggagaaaggg aagacctcag aagtgctgaa 1321 cgctgccaag gtgcttctca
ttgagacaca gagatgcaac agcagatatg tctatgacaa 1381 cctgatcaca
ccagccatga tctgtgccgg cttcctgcag gggaacgtcg attcttgcca 1441
gggtgacagt ggagggcctc tggtcacttc gaagaacaat atctggtggc tgatagggga
1501 tacaagctgg ggttctggct gtgccaaagc ttacagacca ggagtgtacg
ggaatgtgat 1561 ggtattcacg gactggattt atcgacaaat gagggcagac
ggctaatcca catggtcttc 1621 gtccttgacg tcgttttaca agaaaacaat
ggggctggtt ttgcttcccc gtgcatgatt 1681 tactcttaga gatgattcag
aggtcacttc atttttatta aacagtgaac ttgtctggct 1741 ttggcactct
ctgccattct gtgcaggctg cagtggctcc cctgcccagc ctgctctccc 1801
taaccccttg tccgcaaggg gtgatggccg gctggttgtg ggcactggcg gtcaagtgtg
1861 gaggagaggg gtggaggctg ccccattgag atcttcctgc tgagtccttt
ccaggggcca 1921 attttggatg agcatggagc tgtcacctct cagctgctgg
atgacttgag atgaaaaagg 1981 agagacatgg aaagggagac agccaggtgg
cacctgcagc ggctgccctc tggggccact 2041 tggtagtgtc cccagcctac
ctctccacaa ggggattttg ctgatgggtt cttagagcct 2101 tagcagccct
ggatggtggc cagaaataaa gggaccagcc cttcatgggt ggtgacgtgg 2161
tagtcacttg taaggggaac agaaacattt ttgttcttat ggggtgagaa tatagacagt
2221 gcccttggtg cgagggaagc aattgaaaag gaacttgccc tgagcactcc
tggtgcaggt 2281 ctccacctgc acattgggtg gggctcctgg gagggagact
cagccttcct cctcatcctc 2341 cctgaccctg ctcctagcac cctggagagt
gcacatgccc cttggtcctg gcagggcgcc 2401 aagtctggca ccatgttggc
ctcttcaggc ctgctagtca ctggaaattg aggtccatgg 2461 gggaaatcaa
ggatgctcag tttaaggtac actgtttcca tgttatgttt ctacacattg 2521
ctacctcagt gctcctggaa acttagcttt tgatgtctcc aagtagtcca ccttcattta
2581 actctttgaa actgtatcac ctttgccaag taagagtggt ggcctatttc
agctgctttg 2641 acaaaatgac tggctcctga cttaacgttc tataaatgaa
tgtgctgaag caaagtgccc 2701 atggtggcgg cgaagaagag aaagatgtgt
tttgttttgg actctctgtg gtcccttcca 2761 atgctgtggg tttccaacca
ggggaagggt cccttttgca ttgccaagtg ccataaccat 2821 gagcactact
ctaccatggt tctgcctcct ggccaagcag gctggtttgc aagaatgaaa 2881
tgaatgattc tacagctagg acttaacctt gaaatggaaa gtcttgcaat cccatttgca
2941 ggatccgtct gtgcacatgc ctctgtagag agcagcattc ccagggacct
tggaaacagt 3001 tggcactgta aggtgcttgc tccccaagac acatcctaaa
aggtgttgta atggtgaaaa 3061 cgtcttcctt ctttattgcc ccttcttatt
tatgtgaaca actgtttgtc tttttttgta 3121 tcttttttaa actgtaaagt
tcaattgtga aaatgaatat catgcaaata aattatgcga 3181 tttttttttc
aaagcaaaaa GenBank Gene Name Gene Symbol Accession # SEQ ID NO
guanine deaminase GDA NM_004293 35 1 gtagggagcc agcccctggg
cgcggcctgc agggtaccgg caaccgcccg ggtaagcggg 61 ggcaggacaa
ggccggagcc tgtgtccgcc cggcagccgc ccgcagctgc agagagtccc 121
gctgcgtctc cgccgcgtgc gccctcctcg accagcagac ccgcgctgcg ctccgccgct
181 gacatgtgtg ccgctcagat gccgcccctg gcgcacatct tccgagggac
gttcgtccac 241 tccacctgga cctgccccat ggaggtgctg cgggatcacc
tcctcggcgt gagcgacagc 301 ggcaaaatag tgtttttaga agaagcatct
caacaggaaa aactggccaa agaatggtgc 361 ttcaagccgt gtgaaataag
agaactgagc caccatgagt tcttcatgcc tgggctggtt 421 gatacacaca
tccatgcctc tcagtattcc tttgctggaa gtagcataga cctgccactc 481
ttggagtggc tgaccaagta cacatttcct gcagaacaca gattccagaa catcgacttt
541 gcagaagaag tatataccag agttgtcagg agaacactaa agaatggaac
aaccacagct 601 tgttactttg caacaattca cactgactca tctctgctcc
ttgccgacat tacagataaa 661 tttggacagc gggcatttgt gggcaaagtt
tgcatggatt tgaatgacac ttttccagaa 721 tacaaggaga ccactgagga
atcgatcaag gaaactgaga gatttgtgtc agaaatgctc 781 caaaagaact
attctagagt gaagcccata gtgacaccac gtttttccct ctcctgctct 841
gagactttga tgggtgaact gggcaacatt gctaaaaccc gtgatttgca cattcagagc
901 catataagtg aaaatcgtga tgaagttgaa gctgtgaaaa acttataccc
cagttataaa 961 aactacacat ctgtgtatga taaaaacaat cttttgacaa
ataagacagt gatggcacac 1021 ggctgctacc tctctgcaga agaactgaac
gtattccatg aacgaggagc atccatcgca 1081 cactgtccca attctaattt
atcgctcagc agtggatttc taaatgtgct agaagtcctg 1141 aaacatgaag
tcaagatagg gctgggtaca gacgtggctg gtggctattc atattccatg 1201
cttgatgcaa tcagaagagc agtgatggtt tccaatatcc ttttaattaa taaggtaaat
1261 gagaaaagcc tcaccctcaa agaagtcttc agactagcta ctcttggagg
aagccaagcc 1321 ctggggctgg atggtgagat tggaaacttt gaagtgggca
aggaatttga tgccatcctg 1381 atcaacccca aagcatccga ctctcccatt
gacctgtttt atggggactt ttttggtgat 1441 atttctgagg ctgttatcca
gaagttcctc tatctaggag atgatcgaaa tattgaagag 1501 gtttatgtgg
gcggaaagca ggtggttccg ttttccagct cagtgtaaga ccctcgggcg 1561
tctacaaagt tctcctggga ttagcgtggt tctgcatctc ccttgtgccc aggtggagtt
1621 agaaagtcaa aaaatagtac cttgttcttg ggatgactat ccctttctgt
gtctagttac 1681 agtattcact tgacaaatag ttcgaaggaa gttgcactaa
ttctcaactc tggttgagag 1741 ggttcataaa tttcatgaaa atatctccct
ttggagctgc tcagacttac tttaagctca 1801 aacagaaggg aatgctatta
ctggtggtgt tcctacggta agacttaagc aaagcctttt 1861 tcatatttga
aaatgtggaa agaaaagatg ttcctaaaag gttagatatt ttgagctaat 1921
aattgcaaaa attagaagac tgaaaatgga cccatgagag tatattttta tgagggagca
1981 aaagttagac tgagaacaaa cgttagaaaa tcacttcaga ttgtgtttga
aaattatata 2041 ctgagcatac taatttaaaa agagaacttg ttgaaattta
aaacgtgttt ctaggttgac 2101 cttgtgtttt agaaatttgc acttaatgga
atttgcattt cagagatgtg ttagtgttgt
2161 gctttgcctt ctttggcgat gaatgtcaga aattgaatgc cacatgcttt
cataatatag 2221 ttttgtgctt caaagtgttt gacagaagtt gggtattaaa
gatttaaagt ctcttaggaa 2281 tattattcat gtaactccat ggcataaata
gttgtatttt tgtgtacttt aaaatcaact 2341 tataactgtg agatgttatt
gcttccattt tattagaaga gaaacaaatt ccatgcttta 2401 tggaatttat
gtagactgga gtcttcgtga actggggcaa atgctggcat ccaggagccg 2461
ccaatactaa caggacaggt tccattgcca tggcctattc cacccaaaca atatgttgta
2521 gtttctggaa attccatact cagatatcag tctgctagaa ctttaaaatg
aaggacaaat 2581 cctgttaaag aaatattgtt aaaaatcttt aaaccctgtg
tattgaaagc actctatttt 2641 ctaattttat ccagttttct gtttaactcc
ttataatgtt taggatatta aaattttagg 2701 ataatgaaga gtacataatg
tcctacttaa tatttatgtt aataggactt aattcttact 2761 agacatctag
gaacattaca aagcaaagac tatttttatg cttccataac ctagaattaa 2821
aaccaaatta tgaccttatg ataaatcttt aagtattggt gtgaatgtta tttaaattct
2881 atatttttct tatttaatta caaatactat aaatgagcaa ggaaaaggaa
tagactttct 2941 taatatatta taacactcat tcctagagct taggggtgac
tctttaatat taccttatag 3001 tagaaacttt atgtaatata gctaactccg
tatttacaga acaaaaaaac acagttcccc 3061 ctcctgtagt ataaatttta
ttttcacata cttagctaat ttagcagtaa ttggcccagt 3121 tttttcccta
atagaaatac ttttagattt gattatgtat acatgacacc taaagaggga 3181
acaaaagtta gttttatttt tttaataaac aacagagttt gttttgtgag ataagtatct
3241 tagtaaaccc aatttccagt cttagtctgt atttccaata tttctaattc
ctgagccacg 3301 tcaaagatgc cttgccaaat ttctccccat ttctctacgg
ggctagcaaa aatcttcagc 3361 tttatcactc aacccctgcc aaaggaactt
gattacatgg tgtctaacca aatgagcagg 3421 cttaggaatt tagatgagat
gtgtaagatt cacttacagg cagtagctgc ttctagcatt 3481 tgcaagatcc
tacactttta ccttctttaa gggtgtacat tttgatgttg aacatcagtt 3541
ttcatgtaga cttaggactc atgtgcagta aatataaata agtgtagcat cagaagcagt
3601 aggaatggcc gtatacaacc atcctgttaa acatttaaat ttagctctga
tagtgtgtta 3661 agacctgaat atctttccta gtaaaaatag gatgtgttga
aatatttata tgtactttga 3721 tctctccaca tcacttataa cttatgtgtt
ttatttctcc aagtgcggtg ttcctgaatg 3781 ttatgtatgc ttttttttct
gtaccacagg cattatctat acctggggcc agattttctg 3841 cactttgaaa
tgttgccttt gcctaatgta ggttgacttt ctgaattgtg gagaggcact 3901
tttccaagcc aatcttattt gtcacttttt gttttaatat cttgctctct gacaggaaag
3961 aaacaattca cttaccagcc tcctcacccc atcctccacc atttccttaa
tgttccatgg 4021 tattttcaac ggaatacact ttgaaaggta aaaacaattc
aaaagtatcg attatcataa 4081 attcacaaaa tatttttgca accagaacac
aaaagcaggc tagtcagcta aggtaaattt 4141 cattttcaaa cgagagggaa
acatgggaag taaaagatta ggatgtgaaa ggttgtccta 4201 aacagaccaa
ggagactgtt ccctaattta ttctcttggc tggttctctc attgaattat 4261
cagaccccaa gaggagatat tggaacaggc tcccttcatg ccaagggtct ttctaagtta
4321 atactgtgag cattgagccc ccattaaaac tcttttttac ttcagaaaga
attttacagg 4381 ttaaagggaa agaaatggtg ggaaactctc cccgtaatgc
ttagccaact ttaaagtgta 4441 cccttcaata tccccattgg caactgcagc
tgagatctta gagaggaaat ataaccggtg 4501 tgagatctag caatgcattt
tgaatcttca ctccctacca ggctcttcct atttttaatc 4561 tcttcacctc
agaactagac atatggagag ctttaaaggc aagctggaag gcacattgta 4621
tcaattctac cttgtgctat acgtaggaga gatccaaaat ttggatgctt ctggagactc
4681 ttagacatct tttcattgtt gtccattttt aaagttgatg attgctggaa
acattcacac 4741 gcttaaaagc aatggtgtga gttattaatg ggtaaactaa
gaagtgttat aggcaatgac 4801 ttgaaatggt ttttaaattg tatggattgt
taagaattgt tgaaaaaaaa tttttttttt 4861 ttggacagct tcaaggagat
gttagcaatt tcagatatac tagccagttt aggtatgact 4921 ttggaagtgc
agaaacagaa ggatactgtt agaaaatcct aacattggtc tccgtgcatg 4981
tgttcacacc tggtctcact gcctttcctt cccacagacc tgagtgtgaa agactgagag
5041 ttgaggagtt actttgtgga tcttgtccaa atttagtgaa atgtggaagt
caaccagacc 5101 aatgatggaa ttaaatgtaa attccaagag ggctttcaca
gtccacaggg ttcaaatgac 5161 ttgggtaaca gaagttattc ttagcttacc
tgttatgtga cagtgattta cctgtccatt 5221 tccaacccaa aagcctgtca
gaaagcattc tttagagaaa accactttac atttgttgtt 5281 aaactcctga
tcgctactct taagaatata catgtatgta ttcataggaa cattttttct 5341
caatatttgt atgattcgct tactgttatt gtgctgagtg agctcctgtg tgcttcagac
5401 aaaaataaat gagactttgt gtttacgtta GenBank Gene Name Gene Symbol
Accession # SEQ ID NO macrophage MST1R NM_002447 36 stimulating 1
receptor (c-met-related tyrosine kinase) 1 ggatcctcta gggtcccagc
tcgcctcgat ggagctcctc ccgccgctgc ctcagtcctt 61 cctgttgctg
ctgctgttgc ctgccaagcc cgcggcgggc gaggactggc agtgcccgcg 121
caccccctac gcggcctctc gcgactttga cgtgaagtac gtggtgccca gcttctccgc
181 cggaggcctg gtacaggcca tggtgaccta cgagggcgac agaaatgaga
gtgctgtgtt 241 tgtagccata cgcaatcgcc tgcatgtgct tgggcctgac
ctgaagtctg tccagagcct 301 ggccacgggc cctgctggag accctggctg
ccagacgtgt gcagcctgtg gcccaggacc 361 ccacggccct cccggtgaca
cagacacaaa ggtgctggtg ctggatcccg cgctgcctgc 421 gctggtcagt
tgtggctcca gcctgcaggg ccgctgcttc ctgcatgacc tagagcccca 481
agggacagcc gtgcatctgg cagcgccagc ctgcctcttc tcagcccacc ataaccggcc
541 cgatgactgc cccgactgtg tggccagccc attgggcacc cgtgtaactg
tggttgagca 601 aggccaggcc tcctatttct acgtggcatc ctcactggac
gcagccgtgg ctggcagctt 661 cagcccacgc tcagtgtcta tcaggcgtct
caaggctgac gcctcgggat tcgcaccggg 721 ctttgtggcg ttgtcagtgc
tgcccaagca tcttgtctcc tacagtattg aatacgtgca 781 cagcttccac
acgggagcct tcgtatactt cctgactgta cagccggcca gcgtgacaga 841
tgatcctagt gccctgcaca cacgcctggc acggcttagc gccactgagc cagagttggg
901 tgactatcgg gagctggtcc tcgactgcag atttgctcca aaacgcaggc
gccggggggc 961 cccagaaggc ggacagccct accctgtgct gcaggtggcc
cactccgctc cagtgggtgc 1021 ccaacttgcc actgagctga gcatcgccga
gggccaggaa gtactatttg gggtctttgt 1081 gactggcaag gatggtggtc
ctggcgtggg ccccaactct gtcgtctgtg ccttccccat 1141 tgacctgctg
gacacactaa ttgatgaggg tgtggagcgc tgttgtgaat ccccagtcca 1201
tccaggcctc cggcgaggcc tcgacttctt ccagtcgccc agtttttgcc ccaacccgcc
1261 tggcctggaa gccctcagcc ccaacaccag ctgccgccac ttccctctgc
tggtcagtag 1321 cagcttctca cgtgtggacc tattcaatgg gctgttggga
ccagtacagg tcactgcatt 1381 gtatgtgaca cgccttgaca acgtcacagt
ggcacacatg ggcacaatgg atgggcgtat 1441 cctgcaggtg gagctggtca
ggtcactaaa ctacttgctg tatgtgtcca acttctcact 1501 gggtgacagt
gggcagcccg tgcagcggga tgtcagtcgt cttggggacc acctactctt 1561
tgcctctggg gaccaggttt tccaggtacc tatccgaggc cctggctgcc gccacttcct
1621 gacctgtggg cgttgcctaa gggcatggca tttcatgggc tgtggctggt
gtgggaacat 1681 gtgcggccag cagaaggagt gtcctggctc ctggcaacag
gaccactgcc cacctaagct 1741 tactgagttc cacccccaca gtggacctct
aaggggcagt acaaggctga ccctgtgtgg 1801 ctccaacttc taccttcacc
cttctggtct ggtgcctgag ggaacccatc aggtcactgt 1861 gggccaaagt
ccctgccggc cactgcccaa ggacagctca aaactcagac cagtgccccg 1921
gaaagacttt gtagaggagt ttgagtgtga actggagccc ttgggcaccc aggcagtggg
1981 gcctaccaac gtcagcctca ccgtgactaa catgccaccg ggcaagcact
tccgggtaga 2041 cggcacctcc gtgctgagag gcttctcttt catggagcca
gtgctgatag cagtgcaacc 2101 cctctttggc ccacgggcag gaggcacctg
tctcactctt gaaggccaga gtctgtctgt 2161 aggcaccagc cgggctgtgc
tggtcaatgg gactgagtgt ctgctagcac gggtcagtga 2221 ggggcagctt
ttatgtgcca caccccctgg ggccacggtg gccagtgtcc cccttagcct 2281
gcaggtgggg ggtgcccagg tacctggttc ctggaccttc cagtacagag aagaccctgt
2341 cgtgctaagc atcagcccca actgtggcta catcaactcc cacatcacca
tctgtggcca 2401 gcatctaact tcagcatggc acttagtgct gtcattccat
gacgggctta gggcagtgga 2461 aagcaggtgt gagaggcagc ttccagagca
gcagctgtgc cgccttcctg aatatgtggt 2521 ccgagacccc cagggatggg
tggcagggaa tctgagtgcc cgaggggatg gagctgctgg 2581 ctttacactg
cctggctttc gcttcctacc cccaccccat ccacccagtg ccaacctagt 2641
tccactgaag cctgaggagc atgccattaa gtttgagtat attgggctgg gcgctgtggc
2701 tgactgtgtg ggtatcaacg tgaccgtggg tggtgagagc tgccagcacg
agttccgggg 2761 ggacatggtt gtctgccccc tgcccccatc cctgcagctt
ggccaggatg gtgccccatt 2821 gcaggtctgc gtagatggtg aatgtcatat
cctgggtaga gtggtgcggc cagggccaga 2881 tggggtccca cagagcacgc
tccttggtat cctgctgcct ttgctgctgc ttgtggctgc 2941 actggcgact
gcactggtct tcagctactg gtggcggagg aagcagctag ttcttcctcc 3001
caacctgaat gacctggcat ccctggacca gactgctgga gccacacccc tgcctattct
3061 gtactcgggc tctgactaca gaagtggcct tgcactccct gccattgatg
gtctggattc 3121 caccacttgt gtccatggag catccttctc cgatagtgaa
gatgaatcct gtgtgccact 3181 gctgcggaaa gagtccatcc agctaaggga
cctggactct gcgctcttgg ctgaggtcaa 3241 ggatgtgctg attccccatg
agcgggtggt cacccacagt gaccgagtca ttggcaaagg 3301 ccactttgga
gttgtctacc acggagaata catagaccag gcccagaatc gaatccaatg 3361
tgccatcaag tcactaagtc gcatcacaga gatgcagcag gtggaggcct tcctgcgaga
3421 ggggctgctc atgcgtggcc tgaaccaccc gaatgtgctg gctctcattg
gtatcatgtt 3481 gccacctgag ggcctgcccc atgtgctgct gccctatatg
tgccacggtg acctgctcca 3541 gttcatccgc tcacctcagc ggaaccccac
cgtgaaggac ctcatcagct ttggcctgca 3601 ggtagcccgc ggcatggagt
acctggcaga gcagaagttt gtgcacaggg acctggctgc 3661 gcggaactgc
atgctggacg agtcattcac agtcaaggtg gctgactttg gtttggcccg 3721
cgacatcctg gacagggagt actatagtgt tcaacagcat cgccacgctc gcctacctgt
3781 gaagtggatg gcgctggaga gcctgcagac ctatagattt accaccaagt
ctgatgtgtg 3841 gtcatttggt gtgctgctgt gggaactgct gacacggggt
gccccaccat accgccacat 3901 tgaccctttt gaccttaccc acttcctggc
ccagggtcgg cgcctgcccc agcctgagta 3961 ttgccctgat tctctgtacc
aagtgatgca gcaatgctgg gaggcagacc cagcagtgcg
4021 acccaccttc agagtactag tgggggaggt ggagcagata gtgtctgcac
tgcttgggga 4081 ccattatgtg cagctgccag caacctacat gaacttgggc
cccagcacct cgcatgagat 4141 gaatgtgcgt ccagaacagc cgcagttctc
acccatgcca gggaatgtac gccggccccg 4201 gccactctca gagcctcctc
ggcccacttg acttagttct tgggctggac ctgcttagct 4261 gccttgagct
aaccccaagg ctgcctctgg gccatgccag gccagagcag tggccctcca 4321
ccttgttcct gccctttaac tttcagaggc aataggtaaa tgggcccatt aggtccctca
4381 ctccacagag tgagccagtg agggcagtcc tgcaacatgt atttatggag
tgcctgctgt 4441 ggaccctgtc ttctgggcac agtggactca gcagtgacca
caccaacact gacccttgaa 4501 ccaataaagg aacaaatgac tattaaagca
caaaaaaaaa a GenBank Gene Name Gene Symbol Accession # SEQ ID NO
integrin, beta 4 ITGB4 NM_000213 37 1 gcgctgcccg cctcgtcccc
acccccccaa cccccgcgcc cgccctcgga cagtccctgc 61 tcgcccgcgc
gctgcagccc catctcctag cggcagccca ggcgcggagg gagcgagtcc 121
gccccgaggt aggtccagga cgggcgcaca gcagcagccg aggctggccg ggagagggag
181 gaagaggatg gcagggccac gccccagccc atgggccagg ctgctcctgg
cagccttgat 241 cagcgtcagc ctctctggga ccttggcaaa ccgctgcaag
aaggccccag tgaagagctg 301 cacggagtgt gtccgtgtgg ataaggactg
cgcctactgc acagacgaga tgttcaggga 361 ccggcgctgc aacacccagg
cggagctgct ggccgcgggc tgccagcggg agagcatcgt 421 ggtcatggag
agcagcttcc aaatcacaga ggagacccag attgacacca ccctgcggcg 481
cagccagatg tccccccaag gcctgcgggt ccgtctgcgg cccggtgagg agcggcattt
541 tgagctggag gtgtttgagc cactggagag ccccgtggac ctgtacatcc
tcatggactt 601 ctccaactcc atgtccgatg atctggacaa cctcaagaag
atggggcaga acctggctcg 661 ggtcctgagc cagctcacca gcgactacac
tattggattt ggcaagtttg tggacaaagt 721 cagcgtcccg cagacggaca
tgaggcctga gaagctgaag gagccctggc ccaacagtga 781 cccccccttc
tccttcaaga acgtcatcag cctgacagaa gatgtggatg agttccggaa 841
taaactgcag ggagagcgga tctcaggcaa cctggatgct cctgagggcg gcttcgatgc
901 catcctgcag acagctgtgt gcacgaggga cattggctgg cgcccggaca
gcacccacct 961 gctggtcttc tccaccgagt cagccttcca ctatgaggct
gatggcgcca acgtgctggc 1021 tggcatcatg agccgcaacg atgaacggtg
ccacctggac accacgggca cctacaccca 1081 gtacaggaca caggactacc
cgtcggtgcc caccctggtg cgcctgctcg ccaagcacaa 1141 catcatcccc
atctttgctg tcaccaacta ctcctatagc tactacgaga agcttcacac 1201
ctatttccct gtctcctcac tgggggtgct gcaggaggac tcgtccaaca tcgtggagct
1261 gctggaggag gccttcaatc ggatccgctc caacctggac atccgggccc
tagacagccc 1321 ccgaggcctt cggacagagg tcacctccaa gatgttccag
aagacgagga ctgggtcctt 1381 tcacatccgg cggggggaag tgggtatata
ccaggtgcag ctgcgggccc ttgagcacgt 1441 ggatgggacg cacgtgtgcc
agctgccgga ggaccagaag ggcaacatcc atctgaaacc 1501 ttccttctcc
gacggcctca agatggacgc gggcatcatc tgtgatgtgt gcacctgcga 1561
gctgcaaaaa gaggtgcggt cagctcgctg cagcttcaac ggagacttcg tgtgcggaca
1621 gtgtgtgtgc agcgagggct ggagtggcca gacctgcaac tgctccaccg
gctctctgag 1681 tgacattcag ccctgcctgc gggagggcga ggacaagccg
tgctccggcc gtggggagtg 1741 ccagtgcggg cactgtgtgt gctacggcga
aggccgctac gagggtcagt tctgcgagta 1801 tgacaacttc cagtgtcccc
gcacttccgg gttcctctgc aatgaccgag gacgctgctc 1861 catgggccag
tgtgtgtgtg agcctggttg gacaggccca agctgtgact gtcccctcag 1921
caatgccacc tgcatcgaca gcaatggggg catctgtaat ggacgtggcc actgtgagtg
1981 tggccgctgc cactgccacc agcagtcgct ctacacggac accatctgcg
agatcaacta 2041 ctcggcgatc cacccgggcc tctgcgagga cctacgctcc
tgcgtgcagt gccaggcgtg 2101 gggcaccggc gagaagaagg ggcgcacgtg
tgaggaatgc aacttcaagg tcaagatggt 2161 ggacgagctt aagagagccg
aggaggtggt ggtgcgctgc tccttccggg acgaggatga 2221 cgactgcacc
tacagctaca ccatggaagg tgacggcgcc cctgggccca acagcactgt 2281
cctggtgcac aagaagaagg actgccctcc gggctccttc tggtggctca tccccctgct
2341 cctcctcctc ctgccgctcc tggccctgct actgctgcta tgctggaagt
actgtgcctg 2401 ctgcaaggcc tgcctggcac ttctcccgtg ctgcaaccga
ggtcacatgg tgggctttaa 2461 ggaagaccac tacatgctgc gggagaacct
gatggcctct gaccacttgg acacgcccat 2521 gctgcgcagc gggaacctca
agggccgtga cgtggtccgc tggaaggtca ccaacaacat 2581 gcagcggcct
ggctttgcca ctcatgccgc cagcatcaac cccacagagc tggtgcccta 2641
cgggctgtcc ttgcgcctgg cccgcctttg caccgagaac ctgctgaagc ctgacactcg
2701 ggagtgcgcc cagctgcgcc aggaggtgga ggagaacctg aacgaggtct
acaggcagat 2761 ctccggtgta cacaagctcc agcagaccaa gttccggcag
cagcccaatg ccgggaaaaa 2821 gcaagaccac accattgtgg acacagtgct
gatggcgccc cgctcggcca agccggccct 2881 gctgaagctt acagagaagc
aggtggaaca gagggccttc cacgacctca aggtggcccc 2941 cggctactac
accctcactg cagaccagga cgcccggggc atggtggagt tccaggaggg 3001
cgtggagctg gtggacgtac gggtgcccct ctttatccgg cctgaggatg acgacgagaa
3061 gcagctgctg gtggaggcca tcgacgtgcc cgcaggcact gccaccctcg
gccgccgcct 3121 ggtaaacatc accatcatca aggagcaagc cagagacgtg
gtgtcctttg agcagcctga 3181 gttctcggtc agccgcgggg accaggtggc
ccgcatccct gtcatccggc gtgtcctgga 3241 cggcgggaag tcccaggtct
cctaccgcac acaggatggc accgcgcagg gcaaccggga 3301 ctacatcccc
gtggagggtg agctgctgtt ccagcctggg gaggcctgga aagagctgca 3361
ggtgaagctc ctggagctgc aagaagttga ctccctcctg cggggccgcc aggtccgccg
3421 tttccacgtc cagctcagca accctaagtt tggggcccac ctgggccagc
cccactccac 3481 caccatcatc atcagggacc cagatgaact ggaccggagc
ttcacgagtc agatgttgtc 3541 atcacagcca ccccctcacg gcgacctggg
cgccccgcag aaccccaatg ctaaggccgc 3601 tgggtccagg aagatccatt
tcaactggct gcccccttct ggcaagccaa tggggtacag 3661 ggtaaagtac
tggattcagg gtgactccga atccgaagcc cacctgctcg acagcaaggt 3721
gccctcagtg gagctcacca acctgtaccc gtattgcgac tatgagatga aggtgtgcgc
3781 ctacggggct cagggcgagg gaccctacag ctccctggtg tcctgccgca
cccaccagga 3841 agtgcccagc gagccagggc gtctggcctt caatgtcgtc
tcctccacgg tgacccagct 3901 gagctgggct gagccggctg agaccaacgg
tgagatcaca gcctacgagg tctgctatgg 3961 cctggtcaac gatgacaacc
gacctattgg gcccatgaag aaagtgctgg ttgacaaccc 4021 taagaaccgg
atgctgctta ttgagaacct tcgggagtcc cagccctacc gctacacggt 4081
gaaggcgcgc aacggggccg gctgggggcc tgagcgggag gccatcatca acctggccac
4141 ccagcccaag aggcccatgt ccatccccat catccctgac atccctatcg
tggacgccca 4201 gagcggggag gactacgaca gcttccttat gtacagcgat
gacgttctac gctctccatc 4261 gggcagccag aggcccagcg tctccgatga
cactggctgc ggctggaagt tcgagcccct 4321 gctgggggag gagctggacc
tgcggcgcgt cacgtggcgg ctgcccccgg agctcatccc 4381 gcgcctgtcg
gccagcagcg ggcgctcctc cgacgccgag gcgccccacg ggcccccgga 4441
cgacggcggc gcgggcggga agggcggcag cctgccccgc agtgcgacac ccgggccccc
4501 cggagagcac ctggtgaatg gccggatgga ctttgccttc ccgggcagca
ccaactccct 4561 gcacaggatg accacgacca gtgctgctgc ctatggcacc
cacctgagcc cacacgtgcc 4621 ccaccgcgtg ctaagcacat cctccaccct
cacacgggac tacaactcac tgacccgctc 4681 agaacactca cactcgacca
cactgcccag ggactactcc accctcacct ccgtctcctc 4741 ccacgactct
cgcctgactg ctggtgtgcc cgacacgccc acccgcctgg tgttctctgc 4801
cctggggccc acatctctca gagtgagctg gcaggagccg cggtgcgagc ggccgctgca
4861 gggctacagt gtggagtacc agctgctgaa cggcggtgag ctgcatcggc
tcaacatccc 4921 caaccctgcc cagacctcgg tggtggtgga agacctcctg
cccaaccact cctacgtgtt 4981 ccgcgtgcgg gcccagagcc aggaaggctg
gggccgagag cgtgagggtg tcatcaccat 5041 tgaatcccag gtgcacccgc
agagcccact gtgtcccctg ccaggctccg ccttcacttt 5101 gagcactccc
agtgccccag gcccgctggt gttcactgcc ctgagcccag actcgctgca 5161
gctgagctgg gagcggccac ggaggcccaa tggggatatc gtcggctacc tggtgacctg
5221 tgagatggcc caaggaggag ggccagccac cgcattccgg gtggatggag
acagccccga 5281 gagccggctg accgtgccgg gcctcagcga gaacgtgccc
tacaagttca aggtgcaggc 5341 caggaccact gagggcttcg ggccagagcg
cgagggcatc atcaccatag agtcccagga 5401 tggaggaccc ttcccgcagc
tgggcagccg tgccgggctc ttccagcacc cgctgcaaag 5461 cgagtacagc
agcatcacca ccacccacac cagcgccacc gagcccttcc tagtggatgg 5521
gctgaccctg ggggcccagc acctggaggc aggcggctcc ctcacccggc atgtgaccca
5581 ggagtttgtg agccggacac tgaccaccag cggaaccctt agcacccaca
tggaccaaca 5641 gttcttccaa acttgaccgc accctgcccc acccccgcca
cgtcccacta ggcgtcctcc 5701 cgactcctct cccggagcct cctcagctac
tccatccttg cacccctggg ggcccagccc 5761 acccgcatgc acagagcagg
ggctaggtgt ctcctgggag gcatgaaggg ggcaaggtcc 5821 gtcctctgtg
ggcccaaacc tatttgtaac caaagagctg ggagcagcac aaggacccag 5881
cctttgttct gcacttaata aatggttttg ctactgctaa GenBank Gene Name Gene
Symbol Accession # SEQ ID NO annexin A3 ANXA3 NM_005139 38 1
gggtggggaa gcttagagac cggtgaggga gcagagctgg ggcgcctgtg tacagggata
61 gagcccggcg gcagcagggc gcggcttccc tttcccgggg cctggggccg
caatcaggtg 121 gagtcgagag gccggaggag gggcaggagg aaggggtgcg
gtcgcgatcc ggacccggag 181 ccagcgcgga gcacctgcgc ccgcggctga
caccttcgct cgcagtttgt tcgcagttta 241 ctcgcacacc agtttccccc
accgcgcttt ggattagtgt gatctcagct caaggcaaag 301 gtgggatatc
atggcatcta tctgggttgg acaccgagga acagtaagag attatccaga 361
ctttagccca tcagtggatg ctgaagctat tcagaaagca atcagaggaa ttggaactga
421 tgagaaaatg ctcatcagca ttctgactga gaggtcaaat gcacagcggc
agctgattgt 481 taaggaatat caagcagcat atggaaagga gctgaaagat
gacttgaagg gtgatctctc 541 tggccacttt gagcatctca tggtggccct
agtgactcca ccagcagtct ttgatgcaaa 601 gcagctaaag aaatccatga
agggcgcggg aacaaacgaa gatgccttga ttgaaatctt 661 aactaccagg
acaagcaggc aaatgaagga tatctctcaa gcctattata cagtatacaa
721 gaagagtctt ggagatgaca ttagttccga aacatctggt gacttccgga
aagctctgtt 781 gactttggca gatggcagaa gagatgaaag tctgaaagtg
gatgagcatc tggccaaaca 841 agatgcccag attctctata aagctggtga
gaacagatgg ggcacggatg aagacaaatt 901 cactgagatc ctgtgtttaa
ggagctttcc tcaattaaaa ctaacatttg atgaatacag 961 aaatatcagc
caaaaggaca ttgtggacag cataaaagga gaattatctg ggcattttga 1021
agacttactg ttggccatag ttaattgtgt gaggaacacg ccggcctttt tagccgaaag
1081 actgcatcga gccttgaagg gtattggaac tgatgagttt actctgaacc
gaataatggt 1141 gtccagatca gaaattgacc ttttggacat tcgaacagag
ttcaagaagc attatggcta 1201 ttccctatat tcagcaatta aatcggatac
ttctggagac tatgaaatca cactcttaaa 1261 aatctgtggt ggagatgact
gaaccaagaa gataatctcc aaaggtccac gatgggcttt 1321 cccaacagct
ccaccttact tcttctcata ctatttaaga gaacaagcaa atataaacag 1381
caacttgtgt tcctaacagg aattttcatt gttctataac aacaacaaca aaagcgatta
1441 ttattttaga gcatctcatt tataatgtag cagctcataa atgaaattga
aaatggtatt 1501 aaagatctgc aactactatc caacttatat ttctgctttc
aaagttaaga atctttatag 1561 ttctactcca ttaaatataa agcaagataa
taaaaattgt tgcttttgtt aaaagtaaaa GenBank Gene Name Gene Symbol
Accession # SEQ ID NO chemokine (C-C motif) CCL15 NM_032965 39
ligand 15 1 tgcagactga tatggattca ccactgctaa cacctcctgg ttggaactac
aggaatagaa 61 ctggaaaggg aaaaaaggca gcattcacca catcccaatc
ctgaatccaa gagtctaaga 121 tagtccccca ctcctatctc aggcttagag
gattagatta atctcctgga gggaagactc 181 ttccttgaaa catttttttt
tatctgcctg tagctattgg gataattcgg gaaatccaca 241 gggacagttc
aagtcatctt tgtcctctac tttctgttgc actctcagcc ttgttctctt 301
tttagaaact gcatggtaac tattatatag ctaaagaaga gcattctgac ctctgccctg
361 ggacttcctg gatcctcctc ttcttataaa tacaagggca gagctggtat
cccggggagc 421 caggaagcag tgagcccagg agtcctcggc cagccctgcc
tgcccaccag gaggatgaag 481 gtctccgtgg ctgccctctc ctgcctcatg
cttgttgctg tccttggatc ccaggcccag 541 ttcataaatg atgcagagac
agagttaatg atgtcaaagc ttccactgga aaatccagta 601 gttctgaaca
gctttcactt tgctgctgac tgctgcacct cctacatctc acaaagcatc 661
ccgtgttcac tcatgaaaag ttattttgaa acgagcagcg agtgctccaa gccaggtgtc
721 atattcctca ccaagaaggg gcggcaagtc tgtgccaaac ccagtggtcc
gggagttcag 781 gattgcatga aaaagctgaa gccctactca atataataat
aaagagacaa aagaggccag 841 ccacccacct ccaacacctc ctgtgagttt
cttggtctga aatacttaaa aaatatatat 901 attgttgtgt ctggtaatga
aagtaatgca tctaataaag agtattcaat ttttt GenBank Gene Name Gene
Symbol Accession # SEQ ID NO dipeptidase 1 (renal) DPEP1 NM_004413
40 1 cgggggggta ctgtgcgagc cctcaaggag gtggctgttc tgtagctgga
gagctccgtg 61 ggtggcagga ctgaacttga acaccagaaa caacccccaa
gccttgtgac ctgggaggca 121 ggaggcgggt ctgtctccct gggacttggg
tggctgagcc gaggtactcg ggaccctgtc 181 ccgcgcatgg cagagtggct
cctcacagcc tgaagctcat ccttctgcac gggccagcca 241 ggccagcaca
gaggcaccag ggcagcagtg cacacaggtc cccggggacc ccaccatgtg 301
gagcggatgg tggctgtggc cccttgtggc cgtctgcact gcagacttct ttcgggacga
361 ggcagagagg atcatgaggg actcccctgt cattgatggg cacaatgacc
tcccctggca 421 gctgctggat atgttcaaca accggctgca ggacgagagg
gccaacctga ccaccttggc 481 cggcacacac accaacatcc ccaagctgag
ggccggcttt gtgggaggcc agttctggtc 541 cgtgtacacg ccctgcgaca
cccagaacaa agacgccgtg cggaggacgc tggagcagat 601 ggacgtggtc
caccgcatgt gccggatgta cccggagacc ttcctgtatg tcaccagcag 661
tgcaggcatt cggcaggcct tccgggaagg gaaggtggcc agcctgatcg gcgtggaggg
721 cggccactcc attgacagca gtttgggcgt cctgcgggca ctctatcagc
tgggcatgcg 781 gtacctgacc ctcacccaca gctgcaacac gccctgggct
gacaactggc tggtggacac 841 gggagacagc gagccccaga gccaaggctt
gtcacccttt gggcagcgtg tggtgaagga 901 gctgaaccgt ctgggggtcc
tcatcgactt ggctcacgtg tctgtggcca ccatgaaggc 961 caccctgcag
ctgtccagag ccccggtcat cttcagccac tcctcggcct acagcgtgtg 1021
cgcaagccgg cgcaacgtgc ctgacgacgt cctgaggctg gtgaaacaga cagacagcct
1081 ggtgatggtg aacttctaca acaattacat ttcctgcacc aacaaggcca
acctgtccca 1141 agtggccgac catctggatc acatcaagga ggtggcagga
gccagagccg tgggttttgg 1201 tggggacttt gatggtgttc caagggtccc
tgaggggctg gaggacgtct ccaagtatcc 1261 agacctgatc gctgagctgc
tcaggaggaa ctggacggag gcggaggtca agggcgcact 1321 ggctgacaac
ctgctgaggg tcttcgaggc tgtggaacag gccagcaacc tcacacaggc 1381
tcccgaggag gagcccatcc cgctggacca gctgggtggc tcctgcagga cccattacgg
1441 ctactcctct ggggcttcca gcctccatcg ccactggggg ctcctgctgg
cctccctcgc 1501 tcccctggtc ctctgtctgt ctctcctgtg aaacctggga
gaccagagtc ccctttaggg 1561 ttcccggagc tccgggaaga cccgcccatc
ccaggactcc agatgccagg agccctgctg 1621 cccacatgca aggaccagca
tctcctgaga ggacgcctgg gcttacctgg ggggcaggat 1681 gcctggggac
agttcaggac acacacacag taggcccgca ataaaagcaa cacccctt GenBank Gene
Name Gene Symbol Accession # SEQ ID NO NADPH oxidase NOXO1
NM_172167 41 organizer 1 1 agccatggca ggcccccgat acccagtttc
agtgcaaggg gcagccctgg tgcagatcaa 61 gaggctccaa acgtttgcct
tctctgtgcg ctggtcagac ggcagcgaca ccttcgtgcg 121 caggagttgg
gacgaattca ggcagctcaa gaagaccctc aaggagacct tcccggtgga 181
ggcgggcctg ctgcggagat ctgaccgcgt tctcccaaag cttctcgatg caccactgtt
241 gggacgcgtg gggcgcacga gccgcggcct ggcgcgcctg cagctgttgg
aaacctattc 301 tcggaggctg ctggcgactg cagagcgcgt ggcacggagc
ccgacgatca ctggcttctt 361 cgcaccgcaa cccctggacc tggagcccgc
gctgccaccc ggcagccggg tgatcctgcc 421 caccccagag gagcagcctc
tttctcgcgc tgcgggccgc ctctccatcc acagtctgga 481 ggctcagagc
ctgcgctgcc tgcagccctt ctgtacccag gacacgcggg ataggccttt 541
tcaggcgcag gcccaggaga gcctggacgt gctgctgcgg cacccctcag gctggtggct
601 ggtggagaac gaagaccggc agaccgcctg gtttccagcg ccctacctgg
aggaggcggc 661 cccgggccaa ggccgggagg gaggcccgtc cctagggagc
agcggtcccc agttctgtgc 721 ttcccgcgcc tacgagagca gccgcgcaga
tgagctgtcc gtgcccgcgg gggcgcgcgt 781 gcgcgtgttg gaaacgtcag
accgcggctg gtggctatgc aggtacggcg accgggcggg 841 cctactcccc
gcggtgctgc tgcggccgga agggctgggc gctctcctga gcgggacggg 901
gttccgtgga ggagacgacc cggcgggtga ggcccggggc ttccctgaac cctcccaggc
961 caccgcccct ccccccaccg tgcccacccg accttcgccg ggcgccatcc
agagccgctg 1021 ctgcaccgtc acacgcaggg ccctggagcg gcgcccacgg
cgccagggcc gccctcgagg 1081 gtgcgtggac tctgtgccgc accccacgac
ggagcagtga gcgcgaggat cc GenBank Gene Name Gene Symbol Accession #
SEQ ID NO interferon, alpha- IFI27 NM_005532 42 inducible protein
27 1 gggaacacat ccaagcttaa gacggtgagg tcagcttcac attctcagga
actctccttc 61 tttgggtctg gctgaagttg aggatctctt actctctagg
ccacggaatt aacccgagca 121 ggcatggagg cctctgctct cacctcatca
gcagtgacca gtgtggccaa agtggtcagg 181 gtggcctctg gctctgccgt
agttttgccc ctggccagga ttgctacagt tgtgattgga 241 ggagttgtgg
ctgtgcccat ggtgctcagt gccatgggct tcactgcggc gggaatcgcc 301
tcgtcctcca tagcagccaa gatgatgtcc gcggcggcca ttgccaatgg gggtggagtt
361 gcctcgggca gccttgtggc tactctgcag tcactgggag caactggact
ctccggattg 421 accaagttca tcctgggctc cattgggtct gccattgcgg
ctgtcattgc gaggttctac 481 tagctccctg cccctcgccc tgcagagaag
agaaccatgc caggggagaa ggcacccagc 541 catcctgacc cagcgaggag
ccaactatcc caaatatacc tggggtgaaa tataccaaat 601 tctgcatctc
cagaggaaaa taagaaataa agatgaattg ttgcaactct tcaaaa GenBank Gene
Name Gene Symbol Accession # SEQ ID NO cytochrome P450, CYP3A43
NM_057095 43 family 3, subfamily A, polypeptide 43 1 acctctgggc
agagaaacaa agctctatat gcacagccca gcaaagagca gcacacagct 61
gaaagaaaaa ctcagaagac agagctgaaa aagaaaactg gtgatggatc tcattccaaa
121 ctttgccatg gaaacatggg ttcttgtggc taccagcctg gtactcctct
atatttatgg 181 gacccattca cataaacttt ttaagaagct gggaattcct
gggccaaccc ctctgccttt 241 tctgggaact attttgttct accttagggg
tctttggaat tttgacagag aatgtaatga 301 aaaatacgga gaaatgtggg
ggctgtatga ggggcaacag cccatgctgg tcatcatgga 361 tcccgacatg
atcaaaacag tgttagtgaa agaatgttac tctgtcttca caaaccagat 421
gcctttaggt ccaatgggat ttctgaaaag tgccttaagt tttgctgaag atgaagaatg
481 gaagagaata cgaacattgc tatctccagc tttcaccagt gtaaaattca
aggaaatggt 541 ccccatcatt tcccaatgtg gagatatgtt ggtgagaagc
ctgaggcagg aagcagagaa 601 cagcaagtcc atcaacttga aagatttctt
tggggcctac accatggatg taatcactgg 661 cacattattt ggagtgaact
tggattctct caacaatcca caagatccct ttctgaaaaa 721 tatgaagaag
cttttaaaat tggatttttt ggatcccttt ttactcttaa tatcactctt 781
tccatttctt accccagttt ttgaagccct aaatatcggt ttgtttccaa aagatgttac
841 ccatttttta aaaaattcca ttgaaaggat gaaagaaagt cgcctcaaag
ataaacaaaa 901 gcatcgagta gatttctttc aacagatgat cgactcccag
aattccaaag aaacaaagtc 961 ccataaagct ctgtctgatc tggagcttgt
ggcccagtca attatcatca tttttgctgc 1021 ctatgacaca actagcacca
ctctcccctt cattatgtat gaactggcca ctcaccctga 1081 tgtccagcag
aaactgcagg aggagattga cgcagtttta cccaataagg cacctgtcac 1141
ctacgatgcc ctggtacaga tggagtacct tgacatggtg gtgaatgaaa cgctcagatt
1201 attcccagtt gttagtagag ttacgagagt ctgcaagaaa gatattgaaa
tcaatggagt
1261 gttcattccc aaagggttag cagtgatggt tccaatctat gctcttcacc
atgacccaaa 1321 gtactggaca gagcctgaga agttctgccc tgaaaggttc
agtaagaaga acaaggacag 1381 catagatctt tacagataca taccttttgg
agctggaccc cgaaactgca ttggcatgag 1441 gtttgctctc acaaacataa
aacttgctgt cattagagca ctgcagaact tctccttcaa 1501 accttgtaaa
gagactcaga tcccactgaa attagacaat ctaccaattc ttcaaccaga 1561
aaaacctatt gttctaaaag tgcacttaag agatgggatt acaagtggac cctgactttc
1621 cctaaggact tccactttgt tcaagaaagc tgtatcccag aacactagac
acttcaaatt 1681 gttttgtgaa taaaactcag aaatgaagat gagcttaatt
aacctagtat actgggtgaa 1741 taattagaaa ttctctacat tcattgagct
ctcattgtct gggtagagta ttacacgttg 1801 catactacaa agcaggtgac
aaatcaatgc caaataagta cagtcatctt ctctagttct 1861 cataagacta
tctccccgcc acctatagtt agtaccctca agtcctcctg agctgtgatc 1921
agagaataaa catttctcaa caattttacc aacaattttt aatgaaaagg aaaattatac
1981 ttgtgattct cgtagtgaca tttatattac atgttccatt tgtgatattc
tataataagt 2041 attatattga gaaagtcaac aagcacctct ttacaaaact
gttatctgat gtcttcctgc 2101 atattaagga tgaatctaca gaattagatc
aataaggatc aacaaataaa tatttttggt 2161 catt GenBank Gene Name Gene
Symbol Accession # SEQ ID NO plakophilin 2 PKP2 NM_004572 44 1
gtggcggctt cgcccgcgag tccagaggca ggcgagcagc tcggtcgccc ccaccggccc
61 catggcagcc cccggcgccc cagctgagta cggctacatc cggaccgtcc
tgggccagca 121 gatcctggga caactggaca gctccagcct ggcgctgccc
tccgaggcca agctgaagct 181 ggcggggagc agcggccgcg gcggccagac
agtcaagagc ctgcggatcc aggagcaggt 241 gcagcagacc ctcgcccgga
agggccgcag ctccgtgggc aacggaaatc ttcaccgaac 301 cagcagtgtt
cctgagtatg tctacaacct acacttggtt gaaaatgatt ttgttggagg 361
ccgttcccct gttcctaaaa cctatgacat gctaaaggct ggcacaactg ccacttatga
421 aggtcgctgg ggaagaggaa cagcacagta cagctcccag aagtccgtgg
aagaaaggtc 481 cttgaggcat cctctgagga gactggagat ttctcctgac
agcagcccgg agagggctca 541 ctacacgcac agcgattacc agtacagcca
gagaagccag gctgggcaca ccctgcacca 601 ccaagaaagc aggcgggccg
ccctcctagt gccaccgaga tatgctcgtt ccgagatcgt 661 gggggtcagc
cgtgctggca ccacaagcag gcagcgccac tttgacacat accacagaca 721
gtaccagcat ggctctgtta gcgacaccgt ttttgacagc atccctgcca acccggccct
781 gctcacgtac cccaggccag ggaccagccg cagcatgggc aacctcttgg
agaaggagaa 841 ctacctgacg gcagggctca ctgtcgggca ggtcaggccg
ctggtgcccc tgcagcccgt 901 cactcagaac agggcttcca ggtcctcctg
gcatcagagc tccttccaca gcacccgcac 961 gctgagggaa gctgggccca
gtgtcgccgt ggattccagc gggaggagag cgcacttgac 1021 tgtcggccag
gcggccgcag ggggaagtgg gaatctgctc actgagagaa gcactttcac 1081
tgactcccag ctggggaatg cagacatgga gatgactctg gagcgagcag tgagtatgct
1141 cgaggcagac cacatgccgc catccaggat ttctgctgca gctactttca
tacagcacga 1201 gtgcttccag aaatctgaag ctcggaagag ggttaaccag
cttcgtggca tcctcaagct 1261 tctgcagctc ctaaaagttc agaatgaaga
cgttcagcga gctgtgtgtg gggccttgag 1321 aaacttagta tttgaagaca
atgacaacaa attggaggtg gctgaactaa atggggtacc 1381 tcggctgctc
caggtgctga agcaaaccag agacttggag actaaaaaac aaataacaga 1441
ccatacagtc aatttaagaa gtaggaatgg ctggccgggc gcggtggctc acgcctgtaa
1501 tcccagcact ttgggaggcc aaggcgggcg gatcacgagg tcaggagttc
gagaccagcc 1561 tgaccaacat ggtttgctgt ggaatttgtc atctaatgac
aaactcaaga atctcatgat 1621 aacagaagca ttgcttacgc tgacggagaa
tatcatcatc cccttttctg ggtggcctga 1681 aggagactac ccaaaagcaa
atggtttgct cgattttgac atattctaca acgtcactgg 1741 atgcctaaga
aacatgagtt ctgctggcgc tgatgggaga aaagcgatga gaagatgtga 1801
cggactcatt gactcactgg tccattatgt cagaggaacc attgcagatt accagccaga
1861 tgacaaggcc acggagaatt gtgtgtgcat tcttcataac ctctcctacc
agctggaggc 1921 agagctccca gagaaatatt cccagaatat ctatattcaa
aaccggaata tccagactga 1981 caacaacaaa agtattggat gttttggcag
tcgaagcagg aaagtaaaag agcaatacca 2041 ggacgtgccg atgccggagg
aaaagagcaa ccccaagggc gtggagtggc tgtggcattc 2101 cattgttata
aggatgtatc tgtccttgat cgccaaaagt gtccgcaact acacacaaga 2161
agcatcctta ggagctctgc agaacctcac ggccggaagt ggaccaatgc cgacatcagt
2221 ggctcagaca gttgtccaga aggaaagtgg cctgcagcac acccgaaaga
tgctgcatgt 2281 tggtgaccca agtgtgaaaa agacagccat ctcgctgctg
aggaatctgt cccggaatct 2341 ttctctgcag aatgaaattg ccaaagaaac
tctccctgat ttggtttcca tcattcctga 2401 cacagtcccg agtactgacc
ttctcattga aactacagcc tctgcctgtt acacattgaa 2461 caacataatc
caaaacagtt accagaatgc acgcgacctt ctaaacaccg ggggcatcca 2521
gaaaattatg gccattagtg caggcgatgc ctatgcctcc aacaaagcaa gtaaagctgc
2581 ttccgtcctt ctgtattctc tgtgggcaca cacggaactg catcatgcct
acaagaaggc 2641 tcagtttaag aagacagatt ttgtcaacag ccggactgcc
aaagcctacc actcccttaa 2701 agactgagga aaatgacaaa gtattctcgg
ctgcaaaaat ccccaaagga aaacacctat 2761 ttttctacta cccagcccaa
gaaacctcaa aagcatgcct tgtttctatc cttctctatt 2821 tccgtggtcc
cctgaatcca gaaaacaaat agaacataat tttatgagtc ttccagaaga 2881
cctttgcaag tttgccacca gtagataccg gccacaggct cgacaaatag tggtctttgt
2941 tattagggct tatggtacat ggcttcctgg aatcaaaatg tgaattcatg
tggaagggac 3001 attaatccaa taaataagga aagaagctgt tgcattactg
ggattttaaa agtttgattt 3061 acatttatat tccttttctg gttcccatgt
tttgtcactc atgtgcacat tgcttcgcca 3121 ttgggcctcc agtgtattgt
tctgcagtgt tgaaacagaa tggaaatgac aagaaatatc 3181 tgcagttatc
caggagaaag tataatggca aaattattgg tttctttctt tactttgtgc 3241
ttgtttttat ccccttgggt tgtttttctc tgatttttaa ataaacttaa gaaatttaga
3301 ttacagagta tgcatgactg taagaaaaag aaattgagag gaagtgatca
tagcaaatta 3361 aagaagtctt ttcctcccag aacttaaagt aaaataaaaa
ataaataaat aaataaaatc 3421 ttttccacag agaaaggcaa ctgtgatgat
aaaatttaac gttcccccaa acactgagtc 3481 aatgagattt ttctcaggag
atactttacc tataacaacg ccgttaaatc caaatctctt 3541 ctaaacgatg
gcattctatg taatgccttt cctggacttt tttggccact gccctggact 3601
agtgaaagaa tggactctat ctttatctgc aagaggaact aaggccttct atcagactgc
3661 ctggccagcc tggggcactg aaaatacggc tcatgttaat gagttacatt
atcagccagc 3721 ccagccttgc ccaccattta agaaatatca cagagccact
agatctcata tgatcttctt 3781 caagccatta ttttaactca agaaaactct
agagaagaaa agtgaagaag tcatgttgaa 3841 gaagatgtaa gaatgtgtca
agaccatcca gaaatgatat gagaaatact gatattttaa 3901 atggttgaca
tcatccagcg aaatgaatct acattaaatg ttgttttaac tgcgctatga 3961
ttaaaaccat tcatatagag ttagtcttta caactactat tctgttattt ttttttttaa
4021 tctgacaaca tttgtcctaa gtaagataag caaaaaaatt cttcaactcc
ttttggcaag 4081 aaaactgtaa cagaaaataa attttgaatg tgtacttaag
tctttattat atttgaagca 4141 attttttttc aattttaaaa gctgaatgaa
gacaacttag gttgctaacc tagttcaaaa 4201 tgaaattatt tagataccaa
tttttaaaat actggagaga atttatatgt ctttttccag 4261 agttctgatg
ataagcattt ggagtgcatt tattcctcca gataataaat gtgtgttcag 4321
aactttttgt gttttttaag gcattaataa agccttcgat aatattaaat acaaaatgaa
Sequence CWU 1
1
4412376DNAHomo sapiens 1tgaatagttt gctggtagca agacggatga agacctatat
gggagattct ttatctctag 60agctagcata tttacttgca tactttgttt cttttccaca
tggatatttt actgctaaat 120ggcagaggtg ggagggagat gtcacacagt
accataaccc catattgaaa acaagaaacc 180accagaaagt ttgcagctaa
ggggcagggg attcagttcc tacgcccact cagcactaac 240tacttgcggg
cctggttgct tagaagctct acctctcttt cattatctgt aaaatagaaa
300caatacttag gactttagtt ggaacatgag gattgaataa gatcacgcta
ttcatgtgac 360tttttatcgg ctagaacagc aacagacact gctgtgggtg
agttacttag aaaagtttag 420ttatcagtga ttagcccaaa aacacatcag
tcaaaaatag aatccactgg atttttgtct 480ctctttttag agacagggtc
tcactgtcgc ccaggctgga gtacagtggc atgatcattg 540ttcactgcag
cctcaaattc ctgggctcaa gcaatcctcg cacctcagcc tcctgagtag
600ccgggactat aggcacatgc cacctcacct ggcttgtgtg tgtgtgtgtg
tgtgtgtgtg 660tgtgtgtgtg tgtgtgtgta gagacaggat cttgatgtgt
cgcctaggct ggtctcaaac 720tcctggcctc aagtgatctt cccacctcag
cctccaaaac tgttgggatt ataggcgtga 780gccactgtgc ccagcctaac
tgggttttta tgagaggaaa atagaaaatg ctcttctaga 840agagagagaa
caagagcaca aaataatctg gactcacaaa aattcagcaa gctccaagaa
900agggggatgg agggaacgct ggcaaaaatt taaatgccat taggatattt
agcaagttat 960tactgtttgg taaaaatgca tcatcaccct gtgtgcaaaa
tgcttgcaaa gtagtctaaa 1020tgtctttgga gatgggtgtt ttactgcttt
tttccaaaaa caaattgttt attatggttg 1080cagaaatgca gccattacgg
tcacataaat ttctaaaaag cctaccaaag gttgcaagca 1140gtcttctgcc
actgggcagg ccagcagttc agacccagcg aggttgccag gaacaaatcc
1200aggaaatact gggaagaaca agacaagaga attacctaaa agagcaaaca
attcaagtaa 1260atcctgtagc tattaccact taaaatccgt agctcaagat
tcctgtttca ccaccttata 1320cacttaagca attatactta agcctttttt
tagtcctaag tgaagaacta catcagaatc 1380aggataagta ttttgcctgg
gaaatttggc tgcatatgaa tggagaagac atttacatcc 1440tatgttctgg
cactttctga aagatctaat taaacatgtt gatgtgccaa tttaatcaag
1500atgagagatc cctgctggtg tcaccctcta gaacctgcac ttggtgtttt
gactttccag 1560aagaaaaaaa tgcaactttg gttagggggc agtggttgga
tcacacagtt gtctttcgtt 1620tcctaccaca gtaattcata tttaaatatg
cttttagatt agtgtggata ctattgctgc 1680tgtgttgcta cctgaccttt
ttctgggggg ggtacctcag aaatgagcat ttgagggcaa 1740gcgaaaaagc
cctcttcatc ctccagaggc aacaaagagg cagcagaaat ggggaaagat
1800tgtgagaggc agggcttggg tctagacctg gacttaggca agatatgttg
ccctcaaccc 1860tgagttttct tatatgtaaa aagggaaggt tgggctggac
tagatgaggt caagatttgc 1920cattctggga ggctgatatt ccagagaatc
aaaattaatc ctaaaccaaa gctttatggc 1980tgctacagag acatgtcaca
tttctgagac ttgtcaccaa gagtttgtcc ctcagacttt 2040ggcgctgttg
aatgcaaaga caaggatggc caccttctgg ttcttgcctg ttgtcctcag
2100ctgagagcag tctcggtaaa ggtggcaaag attctgtgac ctcagaccgg
ggaccaaatg 2160cttgggagtc tgatggccgg gctgggccac cattctcata
gctctcattc tgtttggagc 2220aaccaaagga tttgtgtgaa gttatttgga
aaaggacctt aactgagcag taatcttttt 2280tctgtatatt tggaatgttt
ttcattctga cctgttctgt cagtgattct actgaaaaac 2340aatttaatca
atataaaaat gttcaagcta tgcaac 237625310DNAHomo sapiens 2ctccggcgcc
cgctctgccc gccgctgggt ccgaccgcgc tcgccttcct tgcagccgcg 60cctcggcccc
atggacgccc tgtgcggttc cggggagctc ggctccaagt tctgggactc
120caacctgtct gtgcacacag aaaacccgga cctcactccc tgcttccaga
actccctgct 180ggcctgggtg ccctgcatct acctgtgggt cgccctgccc
tgctacttgc tctacctgcg 240gcaccattgt cgtggctaca tcatcctctc
ccacctgtcc aagctcaaga tggtcctggg 300tgtcctgctg tggtgcgtct
cctgggcgga ccttttttac tccttccatg gcctggtcca 360tggccgggcc
cctgcccctg ttttctttgt cacccccttg gtggtggggg tcaccatgct
420gctggccacc ctgctgatac agtatgagcg gctgcagggc gtacagtctt
cgggggtcct 480cattatcttc tggttcctgt gtgtggtctg cgccatcgtc
ccattccgct ccaagatcct 540tttagccaag gcagagggtg agatctcaga
ccccttccgc ttcaccacct tctacatcca 600ctttgccctg gtactctcta
ccctcatctt ggcctgcttc agggagaaac ctccattttt 660ctccgcaaag
aatgtcgacc ctaaccccta ccctgagacc agcgctggct ttctctcccg
720cctgtttttc tggtggttca caaagatggc catctatggc taccggcatc
ccctggagga 780gaaggacctc tggtccctaa aggaagagga cagatcccag
atggtggtgc agcagctgct 840ggaggcatgg aggaagcagg aaaagcagac
ggcacgacac aaggcttcag cagcacctgg 900gaaaaatgcc tccggcgagg
acgaggtgct gctgggtgcc cggcccaggc cccggaagcc 960ctccttcctg
aaggccctgc tggccacctt cggctccagc ttcctcatca gtgcctgctt
1020caagcttatc caggacctgc tctccttcat caatccacag ctgctcagca
tcctgatcag 1080gtttatctcc aaccccatgg ccccctcctg gtggggcttc
ctggtggctg ggctgatgtt 1140cctgtgctcc atgatgcagt cgctgatctt
acaacactat taccactaca tctttgtgac 1200tggggtgaag tttcgtactg
ggatcatggg tgtcatctac aggaaggctc tggttatcac 1260caactcagtc
aaacgtgcgt ccactgtggg ggaaattgtc aacctcatgt cagtggatgc
1320ccagcgcttc atggaccttg cccccttcct caatctgctg tggtcagcac
ccctgcagat 1380catcctggcg atctacttcc tctggcagaa cctaggtccc
tctgtcctgg ctggagtcgc 1440tttcatggtc ttgctgattc cactcaacgg
agctgtggcc gtgaagatgc gcgccttcca 1500ggtaaagcaa atgaaattga
aggactcgcg catcaagctg atgagtgaga tcctgaacgg 1560catcaaggtg
ctgaagctgt acgcctggga gcccagcttc ctgaagcagg tggagggcat
1620caggcagggt gagctccagc tgctgcgcac ggcggcctac ctccacacca
caaccacctt 1680cacctggatg tgcagcccct tcctggtgac cctgatcacc
ctctgggtgt acgtgtacgt 1740ggacccaaac aatgtgctgg acgccgagaa
ggcctttgtg tctgtgtcct tgtttaatat 1800cttaagactt cccctcaaca
tgctgcccca gttaatcagc aacctgactc aggccagtgt 1860gtctctgaaa
cggatccagc aattcctgag ccaagaggaa cttgaccccc agagtgtgga
1920aagaaagacc atctccccag gctatgccat caccatacac agtggcacct
tcacctgggc 1980ccaggacctg ccccccactc tgcacagcct agacatccag
gtcccgaaag gggcactggt 2040ggccgtggtg gggcctgtgg gctgtgggaa
gtcctccctg gtgtctgccc tgctgggaga 2100gatggagaag ctagaaggca
aagtgcacat gaagggctcc gtggcctatg tgccccagca 2160ggcatggatc
cagaactgca ctcttcagga aaacgtgctt ttcggcaaag ccctgaaccc
2220caagcgctac cagcagactc tggaggcctg tgccttgcta gctgacctgg
agatgctgcc 2280tggtggggat cagacagaga ttggagagaa gggcattaac
ctgtctgggg gccagcggca 2340gcgggtcagt ctggctcgag ctgtttacag
tgatgccgat attttcttgc tggatgaccc 2400actgtccgcg gtggactctc
atgtggccaa gcacatcttt gaccacgtca tcgggccaga 2460aggcgtgctg
gcaggcaaga cgcgagtgct ggtgacgcac ggcattagct tcctgcccca
2520gacagacttc atcattgtgc tagctgatgg acaggtgtct gagatgggcc
cgtacccagc 2580cctgctgcag cgcaacggct cctttgccaa ctttctctgc
aactatgccc ccgatgagga 2640ccaagggcac ctggaggaca gctggaccgc
gttggaaggt gcagaggata aggaggcact 2700gctgattgaa gacacactca
gcaaccacac ggatctgaca gacaatgatc cagtcaccta 2760tgtggtccag
aagcagttta tgagacagct gagtgccctg tcctcagatg gggagggaca
2820gggtcggcct gtaccccgga ggcacctggg tccatcagag aaggtgcagg
tgacagaggc 2880gaaggcagat ggggcactga cccaggagga gaaagcagcc
attggcactg tggagctcag 2940tgtgttctgg gattatgcca aggccgtggg
gctctgtacc acgctggcca tctgtctcct 3000gtatgtgggt caaagtgcgg
ctgccattgg agccaatgtg tggctcagtg cctggacaaa 3060tgatgccatg
gcagacagta gacagaacaa cacttccctg aggctgggcg tctatgctgc
3120tttaggaatt ctgcaagggt tcttggtgat gctggcagcc atggccatgg
cagcgggtgg 3180catccaggct gcccgtgtgt tgcaccaggc actgctgcac
aacaagatac gctcgccaca 3240gtccttcttt gacaccacac catcaggccg
catcctgaac tgcttctcca aggacatcta 3300tgtcgttgat gaggttctgg
cccctgtcat cctcatgctg ctcaattcct tcttcaacgc 3360catctccact
cttgtggtca tcatggccag cacgccgctc ttcactgtgg tcatcctgcc
3420cctggctgtg ctctacacct tagtgcagcg cttctatgca gccacatcac
ggcaactgaa 3480gcggctggaa tcagtcagcc gctcacctat ctactcccac
ttttcggaga cagtgactgg 3540tgccagtgtc atccgggcct acaaccgcag
ccgggatttt gagatcatca gtgatactaa 3600ggtggatgcc aaccagagaa
gctgctaccc ctacatcatc tccaaccggt cagaagccgc 3660ctccctcgct
ccctgctcct ccaggaattc ccagcaggct ctctggtgtt cagggtcctt
3720gtccctcctt tcccctaagc agaaaactgg ccctgccctg cccctgcccc
atttcctcct 3780catctgatcc cccataggcg gctgagcatc ggagtggagt
tcgtggggaa ctgcgtggtg 3840ctctttgctg cactatttgc cgtcatcggg
aggagcagcc tgaacccggg gctggtgggc 3900ctttctgtgt cctactcctt
gcaggtgaca tttgctctga actggatgat acgaatgatg 3960tcagatttgg
aatctaacat cgtggctgtg gagagggtca aggagtactc caagacagag
4020acagaggcgc cctgggtggt ggaaggcagc cgccctcccg aaggttggcc
cccacgtggg 4080gaggtggagt tccggaatta ttctgtgcgc taccggccgg
gcctagacct ggtgctgaga 4140gacctgagtc tgcatgtgca cggtggcgag
aaggtgggga tcgtgggccg cactggggct 4200ggcaagtctt ccatgaccct
ttgcctgttc cgcatcctgg aggcggcaaa gggtgaaatc 4260cgcattgatg
gcctcaatgt ggcagacatc ggcctccatg acctgcgctc tcagctgacc
4320atcatcccgc aggaccccat cctgttctcg gggaccctgc gcatgaacct
ggaccccttc 4380ggcagctact cagaggagga catttggtgg gctttggagc
tgtcccacct gcacacgttt 4440gtgagctccc agccggcagg cctggacttc
cagtgctcag agggcgggga gaatctcagc 4500gtgggccaga ggcagctcgt
gtgcctggcc cgagccctgc tccgcaagag ccgcatcctg 4560gttttagacg
aggccacagc tgccatcgac ctggagactg acaacctcat ccaggctacc
4620atccgcaccc agtttgatac ctgcactgtc ctgaccatcg cacaccggct
taacactatc 4680atggactaca ccagggtcct ggtcctggac aaaggagtag
tagctgaatt tgattctcca 4740gccaacctca ttgcagctag aggcatcttc
tacgggatgg ccagagatgc tggacttgcc 4800taaaatatat tcctgagatt
tcctcctggc ctttcctggt tttcatcagg aaggaaatga 4860caccaaatat
gtccgcagaa tggacttgat agcaaacact gggggcacct taagattttg
4920cacctgtaaa gtgccttaca gggtaactgt gctgaatgct ttagatgagg
aaatgatccc 4980caagtggtga atgacacgcc taaggtcaca gctagtttga
gccagttaga ctagtccccc 5040ggtctcccga ttcccaactg agtgttattt
gcacactgca ctgttttcaa ataacgattt 5100tatgaaatga cctctgtcct
ccctctgatt tttcatattt tcctaaagtt tcgtttctgt 5160tttttaataa
aaagcttttt cctcctggaa cagaagacag ctgctgggtc aggccacccc
5220taggaactca gtcctgtact ctggggtgct gcctgaatcc attaaaaatg
ggagtactga 5280tgaaataaaa ctacatggtc aacagtaaaa 531035490DNAHomo
sapiens 3gtgggggcca ggcagcacag atgaagcatt tacctatcta ggtaagtcag
gaggagctca 60aaaggagaag aaaacagtag gaggcagggg aagcagcctc tgtctccatc
tctgcccttt 120gaaacaaaag ggtatttctt ttctctcttc agcccccaac
ccagtggagg cccggcttgg 180gacattgttc acttcccctc gcttcccctc
tagaagcccc ctttgccatc cctgcacctt 240gtttcgggtg atgcccgaga
gggagctgtg gccagcgggg actggctcag aacccgtgac 300ccgtgtcggc
agctgtgaca gcatgatgag cagcacctcc acccgctctg gatctagtga
360tagcagctac gacttcctgt ccactgaaga gaaggagtgt ctgctcttcc
tggaggagac 420cattggctca ctggacacgg aggctgacag cggactgtcc
actgacgagt ctgagccagc 480cacaactccc agaggtttcc gagcactgcc
cataacccaa cccactcccc ggggaggtcc 540agaggagacc atcactcagc
aaggacgaac gccaaggaca gtaactgagt ccagctcatc 600ccaccctcct
gagccccagg gcctaggcct caggtctggc tcctacagcc tccctaggaa
660tatccacatt gccagaagcc agaacttcag gaaaagcacc acccaggcta
gcagtcacaa 720ccctggagaa ccggggaggc ttgcgccaga gcctgagaaa
gaacaggtca gccagagcag 780ccaacccagg caggcacctg ccagccccca
ggaggctgcc cttgacttgg acgtggtgct 840catccctccg ccagaagctt
tccgggacac ccagccagag cagtgtaggg aagccagcct 900gcccgagggg
ccaggacagc agggccacac accccagctc cacacaccat ccagctccca
960ggaaagagag cagactcctt cagaagccat gtcccaaaaa gccaaggaaa
cagtctcaac 1020caggtacaca caaccccagc ctcctcctgc agggttgcct
cagaatgcaa gagctgaaga 1080tgctcccctc tcatcagggg aggacccaaa
cagccgacta gctcccctca caacccctaa 1140gccccggaag ctgccaccta
atattgttct gaagagcagc cgaagcagtt tccacagtga 1200cccccagcac
tggctgtccc gccacactga ggctgcccct ggagattctg gcctgatctc
1260ctgttcactg caagagcaga gaaaagcacg taaagaagct ctagagaagc
tggggctacc 1320ccaggatcaa gatgagcctg gactccactt aagtaagccc
accagctcca tcagacccaa 1380ggagacacgg gcccagcatc tgtccccagc
tccaggtctg gctcagcctg cagctccagc 1440ccaggcctca gcagctattc
ctgctgctgg gaaggctctg gctcaagctc cggctccagc 1500tccaggtcca
gctcagggac ctttgccaat gaagtctcca gctccaggca atgttgcagc
1560tagcaaatct atgccaattc ctatccctaa ggccccaagg gcaaacagtg
ccctgactcc 1620accgaagcca gagtcagggc tgactctcca ggagagcaac
acccctggcc tgagacagat 1680gaacttcaag tccaacactc tggagcgctc
aggcgtggga ctgagcagct acctttcaac 1740tgagaaagat gccagcccca
aaaccagcac ttctctggga aagggctcct tcttggacaa 1800gatctcgccc
agtgtcttac gtaattctcg gccccgcccg gcctccctgg gcacggggaa
1860agattttgca ggtatccagg taggcaagct ggctgacctg gagcaggagc
agagctccaa 1920gcgcctgtcc taccaaggac agagccgtga caagcttcct
cgccccccct gtgtcagtgt 1980caagatctcc ccaaagggtg tccccaatga
acacagaagg gaggccctga agaagctggg 2040actgttgaag gagtagactc
tgcgaccagt acagaccctg tcctggctga acaagaagag 2100acacatgctc
cacttgggag cctttgccac cacgcaactc agggctcaag atgaatggga
2160gggagagatt tgagtccaag catacattta tattcagtgt tgtgccattg
agttcccatg 2220tggatcattc tgaaggtgat ctccacaaga gggtgtgtgt
gtgtgtgttt ggtgtgtgtg 2280tggagggggg gccgctggat acatcactga
agctattgat ataacacaat gagtcactgt 2340tcagaatttt gctcttgtta
gatgttttct tacattgggt agagtccagc ctagtgagag 2400ctgagtgaag
gggctggcca tgcctgagac aaaaagtcaa atgagacaat ggacgtgtca
2460atgacttgaa aaaaagtcac atccagcaaa tgcagggtca catgaaatat
gggcctcctg 2520gaatccctac agtggatgga gactggctca taccttgcca
gatccctctc tcagttccag 2580ccttctggac aaggcctggg ctaagaggag
ctgattcgtt atctcttcac ccactgccct 2640ctcagtatca ccagtcccaa
agacaggata cgtccctgta acccaatctc tcggttgatt 2700gatagcagaa
cagctcttgt tggtctgaga aggcaggata agtgaccaca tatttatgcc
2760actacctcca ccagggagag tccttctcca caggcttgat aaattcaatc
accaactgtg 2820ctgtcgtccc tgactctgct actcccgttc ttcctgcttt
cctgctccgt atctcagtct 2880gcactgaccc cagggctggg ctgacatcaa
gatgggagcc cagcccacgg gctttataaa 2940cacccaagaa ccgtttcaga
tcttctctgt gctgatgcag gtagttttaa atttttctca 3000gttccagtga
tagaaaaccc acacaataca tcctctgcca gtcttaatag aatatcagag
3060gtaagagggg cctcagagaa gctctgacgc agtgctgctg gggaagggaa
gtgactaacc 3120ccgggtcagc ctgccattta gggaaagagc tgaggttctt
acccttgttg catgctgcca 3180cctctcctta gccagtgctc ttgtacatcc
acacagcacc ctaaggagcc atagtcacca 3240tcaaagactc aaccctaagg
cccttcaaga tctcaaagtg ccttctgaag catcagagat 3300taaatattgt
tcaaactaat agttattgct gtggctttta attttatctt tggaagatag
3360ctatatggta actcatcatt aaccagaaca cctctcccct caaattccgt
gaccaagttg 3420tgcagcttga gcaaatgccg aaagagggta ttatgggtgg
gtggtgtggg cttgcaaata 3480caagcttgga ggtgagacat ggccagacat
gactcctgct tccccttagg aagtaaatct 3540tacttatggt tgtgaactgc
ttggagtcca ggatgcccag atgtgagggg cagatgaagg 3600gaatgttgct
ggaaaggtgc cttttaaggc tgctgagaat ttctggactg tgtcctgatg
3660gacgcagcac catcaaagcc cagaatttct gaaaacggtg acaaggttaa
cataaggaca 3720acaaatactc caccctgtca tggtatgtga ggtgtgggtg
tggcggtttc tgtgtacgtt 3780tgctcataca cgcacatcca aaagcctgtg
cctcattcct ggccatgggt gaggacttgg 3840tctgtcacgg ctgatgagga
ctcccacaac cggccaagtt atgtcttatt atacaccccc 3900agaaagagag
aaagctgcct tctggaggac tgattccaca tgctatattc agctgagttg
3960atttctgtgt ctatttcaac ccataacctg aagaatgatc accttattcc
ttattcatta 4020attttcttga ttaataggga aacttgggaa tagctataaa
gtaaaacttg ggtggaacct 4080ggggccctgg catcacacaa gtgtgattag
gatggtcaag gtcatcagga gtacagccta 4140ttatattccc acatcctgag
aaaggtcatt tctcccacac acgacaaagt cacagacatc 4200ctgcacctgc
cactaggcat cctcatccta ctgacatgcc catttctcca gttttcttaa
4260tctgagactc ccttcccttg ttttttaaag ataccgtgct tctccacatc
ctcatccttc 4320aaggagcata ttttgctctt aggatggtct ttgggattca
agaatagaat aataaatcca 4380aacttggtca ttcccatttt gaagagatgc
aagagggccc agtgaggaca tccgcctccc 4440tgaaagtggt gctagacaga
gctgaggtca ttgtatctgt gtatccacat aggatttctc 4500ttaattcagc
ttgaattgat ggggagggag gtaagagtag ggtcagagtt actcatccct
4560tttcaaagaa ttgtgggtgg aagtttgtaa aggccattca tttgattttc
aaaatcaaag 4620cgacagctct acttccactt ggccttagat ctctgctata
ccctgccata gccttgatgc 4680cactgggcac aagccacctg ccaaatacag
gagtggcctc tcccagcctg gcatgatagg 4740ggggtctgtg ccctcagatg
tgttgacagc tgctcttctg aattgccaca cctgtgctac 4800acttggaatt
ctgtgctctg actctgcagg gtaggaccac gtgccatctc acacagaggt
4860caaccgatga gcccactcac tcgtacatgc cttcttccac agtgggaagc
atgatctggc 4920aggggccgcc ctgtaggctg gggatgggct gctgtgtgaa
tgttgacgtt cgtttcatgg 4980agaaagggga ggtgaaagat tgaagagcag
gttcctgtca atgttctgag ttcgagctgg 5040aggtgtagat tgaatagtct
acatggtctg tgagtgtgtg agatgaaccc ttccatcctt 5100tgacacctgg
ttgtatgtgt aggctaagaa ggaaggaccc tcctgtcagt gtgcaaagct
5160gtaatctcat ggactagagg agagggggcc aaggggatgg acaggagaag
tcatgcagaa 5220tctaagcagg aatgcagata gaacacatct aggctctttt
ccccaggaga gtgatgatgg 5280agcatataga tctggctcaa attcagcctc
catcacttac cagtcaggaa ccctggcgat 5340atcactttaa ctttctgaac
ctcagagtct tcacctataa gacggggaaa ataataccac 5400cctttcaaga
ttgttgagat aaataagtga tataaaacat gtaaagctta gttctggcca
5460cagtgtagct actcaataaa tgataatact 549041270DNAHomo sapiens
4ctcctctccg cgcggggcgg gctccgcgcc acgtgactcc gcggccgggc cgggacgcga
60cgggacgcgc tgggaccggc gtcgggggtc gcggggacca tgcagcggag cctccctgcc
120cttcgctatc ctgacgctgg tgaacgcccc gtacaagcga ggattttact
gcggggatga 180ctccatccgg tacccctacc gtccagatac catcacccac
gggctcatgg ctggggtcac 240catcacggcc accgtcatcc ttgtctcggc
cggggaagcc tacctggtgt acacagaccg 300gctctattct cgctcggact
tcaacaacta cgtggctgct gtatacaagg tgctggggac 360cttcctgttt
ggggctgccg tgagccagtc tctgacagac ctggccaagt acatgattgg
420gcgtctgagg cccaacttcc tagccgtctg cgaccccgac tggagccggg
tcaactgctc 480ggtctatgtg cagctggaga aggtgtgcag gggaaaccct
gctgatgtca ccgaggccag 540gttgtctttc tactcgggac actcttcctt
tgggatgtac tgcatggtgt tcttggcgct 600gtatgtgcag gcacgactct
gttggaagtg ggcacggctg ctgcgaccca cagtccagtt 660cttcctggtg
gcctttgccc tctacgtggg ctacacccgc gtgtctgatt acaaacacca
720ctggagcgat gtccttgttg gcctcctgca gggggcactg gtggctgccc
tcactgtctg 780ctacatctca gacttcttca aagcccgacc cccacagcac
tgtctgaagg aggaggagct 840ggaacggaag cccagcctgt cactgacgtt
gaccctgggc gaggctgacc acaaccacta 900tggatacccg cactcctcct
cctgaggccg gaccccgccc aggcagggag ctgctgtgag 960tccagctgag
gcccacccag gtggtccctc cagccctggt taggcactga gggctctgga
1020cgggctccag gaaccctggg ctgatgggag cagtgagcgg gctccgctgc
cccctgccct 1080gcactggacc aggagtctgg agatgcctgg gtagccctca
gcatttggag gggaacctgt 1140tcccgtcggt ccccaaatat ccccttcttt
ttatggggtt aaggaaggga ccgagagatc 1200agatagttgc tgttttgtaa
aatgtaatgt atatgtggtt tttagtaaaa tagggcacct 1260gtttcacaaa
127051500DNAHomo sapiens 5gcgcgcctcg ccggcgcctc catcccggat
ccttgctgca gcgtcagcgc cgccgcccgt 60gcctttcctc ttcctcctcc tcctccttgg
catccgcctc ttcttcctcc tgcgtcctcc 120cccgctgcct ccgctgctcc
cgacgcggag cccggagccc gcgccgagcc cctggcctcg 180cggtgccatg
ctgccccggc ggcggcgctg aaggatggcg acgccgctgc ctccgccctc
240cccgcggcac ctgcggctgc tgcggctgct gctctccggc ctcgtcctcg
gcgccgccct 300gcgtggagcc gccgccggcc acccggatgt agccgcctgt
cccgggagcc tggactgtgc 360cctgaagagg cgggcaaggt
gtcctcctgg tgcacatgcc tgtgggccct gccttcagcc 420cttccaggag
gaccagcaag ggctctgtgt gcccaggatg cgccggcctc caggcggggg
480ccggccccag cccagactgg aagatgagat tgacttcctg gcccaggagc
ttgcccggaa 540ggagtctgga cactcaactc cgcccctacc caaggaccga
cagcggctcc cggagcctgc 600caccctgggc ttctcggcac gggggcaggg
gctggagctg ggcctcccct ccactccagg 660aacccccacg cccacgcccc
acacctccat gggctcccct gtgtcatccg acccggtgca 720catgtcgccc
ctggagcccc ggggagggca aggcgacggc ctcgcccttg tgctgatcct
780ggcgttctgt gtggccggtg cagccgccct ctccgtagcc tccctctgct
ggtgcaggct 840gcatcgtgag atccgcctga ctcagaaggc cgactacgcc
actgcgaagg cccctggctc 900acctgcagct ccccggatct cgcctgggga
ccaacggctg gcacagagcg cggagatgta 960ccactaccag caccaacggc
aacagatgct gtgcctggag cggcataaag agccacccaa 1020ggagctggac
acggcctcct cggatgagga gaatgaggac ggagacttca cggtgtacga
1080gtgcccgggc ctggccccga ccggggaaat ggaggtgcgc aaccctctgt
tcgaccacgc 1140cgcactgtcc gcgcccctgc cggcccccag ctcaccgcct
gcactgccat gacctggagg 1200cagacagacg cccacctgct ccccgacctc
gaggcccccg gggaggggca gggcctggag 1260cttcccacta aaaacatgtt
ttgatgctgt gtgcttttgg ctgggcctcg ggctccaggc 1320cctgggaccc
cttgccaggg agacccccga acctttgtgc caggacacct cctggtcccc
1380tgcacctctc ctgttcggtt tagaccccca aactggaggg ggcatggaga
accgtagagc 1440gcaggaacgg gtgggtaatt ctagagacaa aagccaatta
aagtccattt cagaaaaaaa 150064005DNAHomo sapiens 6gggcaacagt
ctgcccacct gtggacacca gatcctggga gctcctggtt agcaagtgag 60atctctggga
tgtcagtgag gctggttgaa gaccagaggt aaactgcaga ggtcaccacc
120cccaccatgt cccaggtgat gtccagccca ctgctggcag gaggccatgc
tgtcagcttg 180gcgccttgtg atgagcccag gaggaccctg cacccagcac
ccagccccag cctgccaccc 240cagtgttctt actacaccac ggaaggctgg
ggagcccagg ccctgatggc ccccgtgccc 300tgcatggggc cccctggccg
actccagcaa gccccacagg tggaggccaa agccacctgc 360ttcctgccgt
cccctggtga gaaggccttg gggaccccag aggaccttga ctcctacatt
420gacttctcac tggagagcct caatcagatg atcctggaac tggaccccac
cttccagctg 480cttcccccag ggactggggg ctcccaggct gagctggccc
agagcaccat gtcaatgaga 540aagaaggagg aatctgaagc cttggacata
aagtacatcg aggtgacctc cgccagatca 600aggtgccacg attggcccca
gcactgctcc agcccctctg tcaccccgcc cttcggctcc 660cctcgcagtg
gtggcctcct cctttccaga gacgtccccc gagagacacg aagcagcagt
720gagagcctca tcttctctgg gaaccagggc agggggcacc agcgccctct
gcccccctca 780gagggtctct cccctcgacc cccaaattcc cccagcatct
caatcccttg catggggagc 840aaggcctcga gcccccatgg tttgggctcc
ccgctggtgg cttctccaag actggagaag 900cggctgggag gcctggcccc
acagcggggc agcaggatct ctgtgctgtc agccagccca 960gtgtctgatg
tcagctatat gtttggaagc agccagtccc tcctgcactc cagcaactcc
1020agccatcagt catcttccag atccttggaa agtccagcca actcttcctc
cagcctccac 1080agccttggct cagtgtccct gtgtacaaga cccagtgact
tccaggctcc cagaaacccc 1140accctaacca tgggccaacc cagaacaccc
cactctccac cactggccaa agaacatgcc 1200agcatctgcc ccccatccat
caccaactcc atggtggaca tacccattgt gctgatcaac 1260ggctgcccag
aaccagggtc ttctccaccc cagcggaccc caggacacca gaactccgtt
1320caacctggag ctgcttctcc cagcaacccc tgtccagcca ccaggagcaa
cagccagacc 1380ctgtcagatg ccccctttac cacatgccca gagggtcccg
ccagggacat gcagcccacc 1440atgaagttcg tgatggacac atctaaatac
tggtttaagc caaacatcac ccgagagcaa 1500gcaatcgagc tgctgaggaa
ggaggagcca ggggcttttg tcataaggga cagctcttca 1560taccgaggct
ccttcggcct ggccctgaag gtgcaggagg ttcccgcgtc tgctcagaat
1620cgaccaggtg aggacagcaa tgacctcatc cgacacttcc tcatcgagtc
gtctgccaaa 1680ggagtgcatc tcaaaggagc agatgaggag ccctactttg
ggagcctctc tgccttcgtg 1740tgccagcatt ccatcatggc cctggccctg
ccctgcaaac tcaccatccc acagagagaa 1800ctgggaggtg cagatggggc
ctcggactct acagacagcc cagcctcctg ccagaagaaa 1860tctgcgggct
gccacaccct gtacctgagc tcagtgagcg tggagaccct gactggagcc
1920ctggccgtgc agaaagccat ctccaccacc tttgagaggg acatcctccc
cacgcccacc 1980gtggtccact tcgaagtcac agagcagggc atcactctga
ctgatgtcca gaggaaggtg 2040tttttccggc gccattaccc actcaccacc
ctccgcttct gtggtatgga ccctgagcaa 2100cggaagtggc agaagtactg
caaaccctcc tggatctttg ggtttgtggc caagagccag 2160acagagcctc
aggagaacgt atgccacctc tttgcggagt atgacatggt ccagccagcc
2220tcgcaggtca tcggcctggt gactgctctg ctgcaggacg cagaaaggat
gtaggggaga 2280gactgcctgt gcacctaacc aacacctcca ggggctcgct
aaggagcccc cctccacccc 2340ctgaatgggt gtggcttgtg gccatattga
cagaccaatc tatgggacta gggggattgg 2400catcaagttg acacccttga
acctgctatg gccttcagca gtcaccatca tccagacccc 2460ccgggcctca
gtttcctcaa tcatagaaga agaccaatag acaagatcag ctgttcttag
2520atgctggtgg gcatttgaac atgctcctcc atgattctga agcatgcaca
cctctgaaga 2580cccctgcatg aaaataacct ccaaggaccc tctgacccca
tcgacctggg ccctgcccac 2640acaacagtct gagcaagaga cctgcagccc
ctgtttcgtg gcagacagca ggtgcctggc 2700ggtgacccac ggggctcctg
gcttgcagct ggtgatggtc aagaactgac tacaaaacag 2760gaatggatag
actctatttc cttccatatc tgttcctctg ttccttttcc cactttctgg
2820gtggcttttt gggtccaccc agccaggatg ctgcaggcca agctgggtgt
ggtatttagg 2880gcagctcagc agggggaact tgtccccatg gtcagaggag
acccagctgt cctgcacccc 2940cttgcagatg agtatcaccc catcttttct
ttccacttgg tttttatttt tatttttttt 3000gagacagagt ctcactgtca
cccaggctga actgcagtgg tgtgatctag gctcactgca 3060acctccacct
cccaggttca agcaattatc ctgcctcagg ctcccgagta gctgggatta
3120caggcatgtg caactcaccc agctaatttt gtatttttag tagagacagg
gtttcaccat 3180gttggccagg ctggtcttga actcctgacc gcaggtaatc
cacctgcttc ggcctcccaa 3240agtgctggga ttacaggcgc aagccaccca
gcccagcttc tttccattcc ttgataggcg 3300agtattccaa agctggtatc
gtagctgccc taatgttgca tattaggcgg cgggggcaga 3360gataagggcc
atctctctgt gattctgcct cagctcctgt cttgctgagc cctcccccaa
3420cccacgctcc aacacacaca cacacacaca cacacacaca cacacacaca
cacacacaca 3480cacgcccctc tactgctatg tggcttcaac cagcctcaca
gccacacggg ggaagcagag 3540agtcaagaat gcaaagaggc cgcttcccta
agaggcttgg aggagctggg ctctatccca 3600cacccacccc caccccaccc
ccacccagcc tccagaagct ggaaccattt ctcccgcagg 3660cctgagttcc
taaggaaacc accctaccgg ggtggaaggg agggtcaggg aagaaaccca
3720ctcttgctct acgaggagca agtgcctgcc ccctcccagc agccagccct
gccaaagttg 3780cattatcttt ggccaaggct gggcctgacg gttatgattt
cagccctggg cctgcaggag 3840aggctgagat cagcccaccc agccagtggt
cgagcactgc cccgccgcca aagtctgcag 3900aatgtgagat gaggttctca
aggtcacagg ccccagtccc agcctggggg ctggcagagg 3960cccccatata
ctctgctaca gctcctatca tgaaaaataa aatgt 400571090DNAHomo sapiens
7ctctgcttcc ttacagcacc cccacctgcc agagctgatc ctccctaggc cctgcctaac
60cttgagttgg cccccaatcc ctctggctgc agaagtcccc ttacccccaa tgagaggagg
120ggcaggacca gatcttttga gagctgaggg ttgagggcat tgagccaaca
cacagatttg 180tcgcctctgt ccccgaagac acctgcaccc tccatgcgga
gccaagatgg ggaatggaac 240tgaggaagat tataactttg tcttcaaggt
ggtgctgatc ggcgaatcag gtgtggggaa 300gaccaatcta ctctcccgat
tcacgcgcaa tgagttcagc cacgacagcc gcaccaccat 360cggggttgag
ttctccaccc gcactgtgat gttgggcacc gctgctgtca aggctcagat
420ctgggacaca gctggcctgg agcggtaccg agccatcacc tcggcgtact
atcgtggtgc 480agtgggggcc ctcctggtgt ttgacctaac caagcaccag
acctatgctg tggtggagcg 540atggctgaag gagctctatg accatgctga
agccacgatc gtcgtcatgc tcgtgggtaa 600caaaagtgac ctcagccagg
cccgggaagt gcccactgag gaggcccgaa tgttcgctga 660aaacaatgga
ctgctcttcc tggagacctc agccctggac tctaccaatg ttgagctagc
720ctttgagact gtcctgaaag aaatctttgc gaaggtgtcc aagcagagac
agaacagcat 780ccggaccaat gccatcactc tgggcagtgc ccaggctgga
caggagcctg gccctgggga 840gaagagggcc tgttgcatca gcctctgacc
ttggccagca ccacctgccc ccactggctt 900tttggtgccc cttgtcccca
cttcagcccc aggacctttc cttgcccttt ggttccagat 960atcagactgt
tccctgttca cagcaccctc agggtcttaa ggtcttcatg ccctatcaca
1020aatacctctt ttatctgtcc acccctcaca gactaggacc ctcaaataaa
gctgttttat 1080atcaaaaaaa 109084260DNAHomo sapiens 8gcccagcctg
cctggagaaa agtgtctgct cctagccaag atctcctcat cacaaaagta 60atgtgggcca
tggagtcagg ccacctcctc tgggctctgc tgttcatgca gtccttgtgg
120cctcaactga ctgatggagc cactcgagtc tactacctgg gcatccggga
tgtgcagtgg 180aactatgctc ccaagggaag aaatgtcatc acgaaccagc
ctctggacag tgacatagtg 240gcttccagct tcttaaagtc tgacaagaac
cggatagggg gaacctacaa gaagaccatc 300tataaagaat acaaggatga
ctcatacaca gatgaagtgg cccagcctgc ctggttgggc 360ttcctggggc
cagtgttgca ggctgaagtg ggggatgtca ttcttattca cctgaagaat
420tttgccactc gtccctatac catccaccct catggtgtct tctacgagaa
ggactctgaa 480ggttccctat acccagatgg ctcctctggg ccactgaaag
ctgatgactc tgttcccccg 540gggggcagcc atatctacaa ctggaccatt
ccagaaggcc atgcacccac cgatgctgac 600ccagcgtgcc tcacctggat
ctaccattct catgtagatg ctccacgaga cattgcaact 660ggcctaattg
ggcctctcat cacctgtaaa agaggagccc tggatgggaa ctcccctcct
720caacgccagg atgtagacca tgatttcttc ctcctcttca gtgtggtaga
tgagaacctc 780agctggcatc tcaatgagaa cattgccact tactgctcag
atcctgcttc agtggacaaa 840gaagatgaga catttcagga gagcaatagg
atgcatgcaa tcaatggctt tgtttttggg 900aatttacctg agctgaacat
gtgtgcacag aaacgtgtgg cctggcactt gtttggcatg 960ggcaatgaaa
ttgatgtcca cacagcattt ttccatggac agatgctgac tacccgtgga
1020caccacactg atgtggctaa catctttcca gccacctttg tgactgctga
gatggtgccc 1080tgggaacctg gtacctggtt aattagctgc caagtgaaca
gtcactttcg agatggcatg 1140caggcactct acaaggtcaa gtcttgctcc
atggcccctc ctgtggacct gctcacaggc 1200aaagttcgac agtacttcat
tgaggcccat gagattcaat gggactatgg cccgatgggg 1260catgatggga
gtactgggaa gaatttgaga gagccaggca gtatctcaga taagtttttc
1320cagaagagct ccagccgaat tgggggcact tactggaaag tgcgatatga
agcctttcaa 1380gatgagacat tccaagagaa gatgcatttg gaggaagata
ggcatcttgg aatcctgggg 1440ccagtgatcc gggctgaggt gggtgacacc
attcaggtgg tcttctacaa ccgtgcctcc 1500cagccattca gcatgcagcc
ccatggggtc ttttatgaga aagactatga aggcactgtg 1560tacaatgatg
gctcatctta ccctggcttg gttgccaagc cctttgagaa agtaacatac
1620cgctggacag tcccccctca tgccggtccc actgctcagg atcctgcttg
tctcacttgg 1680atgtacttct ctgctgcaga tcccataaga gacacaaatt
ctggcctggt gggcccgctg 1740ctggtgtgca gggctggtgc cttgggtgca
gatggcaagc agaaaggggt ggataaagaa 1800ttctttcttc tcttcactgt
gttggatgag aacaagagct ggtacagcaa tgccaatcaa 1860gcagctgcta
tgttggattt ccgactgctt tcagaggata ttgagggctt ccaagactcc
1920aatcggatgc atgccattaa tgggtttctg ttctctaacc tgcccaggct
ggacatgtgc 1980aagggtgaca cagtggcctg gcacctgctc ggcctgggca
cagagactga tgtgcatgga 2040gtcatgttcc agggcaacac tgtgcagctt
cagggcatga ggaagggtgc agctatgctc 2100tttcctcata cctttgtcat
ggccatcatg cagcctgaca accttgggac atttgagatt 2160tattgccagg
caggcagcca tcgagaagca gggatgaggg caatctataa tgtctcccag
2220tgtcctggcc accaagccac ccctcgccaa cgctaccaag ctgcaagaat
ctactatatc 2280atggcagaag aagtagagtg ggactattgc cctgaccgga
gctgggaacg ggaatggcac 2340aaccagtctg agaaggacag ttatggttac
attttcctga gcaacaagga tgggctcctg 2400ggttccagat acaagaaagc
tgtattcagg gaatacactg atggtacatt caggatccct 2460cggccaagga
ctggaccaga agaacacttg ggaatcttgg gtccacttat caaaggtgaa
2520gttggtgata tcctgactgt ggtattcaag aataatgcca gccgccccta
ctctgtgcat 2580gctcatggag tgctagaatc tactactgtc tggccactgg
ctgctgagcc tggtgaggtg 2640gtcacttatc agtggaacat cccagagagg
tctggccctg ggcccaatga ctctgcttgt 2700gtttcctgga tctattattc
tgcagtggat cccatcaagg acatgtatag tggcctggtg 2760gggcccttgg
ctatctgcca aaagggcatc ctggagcccc atggaggacg gagtgacatg
2820gatcgggaat ttgcattgtt gttcttgatt tttgatgaaa ataagtcttg
gtatttggag 2880gaaaatgtgg caacccatgg gtcccaggat ccaggcagta
ttaacctaca ggatgaaact 2940ttcttggaga gcaataaaat gcatgcaatc
aatgggaaac tctatgccaa ccttaggggt 3000cttaccatgt accaaggaga
acgagtggcc tggtacatgc tggccatggg ccaagatgtg 3060gatctacaca
ccatccactt tcatgcagag agcttcctct atcggaatgg cgagaactac
3120cgggcagatg tggtggatct gttcccaggg acttttgagg ttgtggagat
ggtggccagc 3180aaccctggga catggctgat gcactgccat gtgactgacc
atgtccatgc tggcatggag 3240accctcttca ctgttttttc tcgaacagaa
cacttaagcc ctctcaccgt catcaccaaa 3300gagactgaaa aagcagtgcc
ccccagagac attgaagaag gcaatgtgaa gatgctgggc 3360atgcagatcc
ccataaagaa tgttgagatg ctggcctctg ttttggttgc cattagtgtc
3420acccttctgc tcgttgttct ggctcttggt ggagtggttt ggtaccaaca
tcgacagaga 3480aagctacgac gcaataggag gtccatcctg gatgacagct
tcaagcttct gtctttcaaa 3540cagtaacatc tggagcctgg agatatcctc
aggaagcaca tctgtagtgc actcccagca 3600ggccatggac tagtcactaa
ccccacactc aaaggggcat gggtggtgga gaagcagaag 3660gagcaatcaa
gcttatctgg atatttcttt ctttatttat tttacatgga aataatatga
3720tttcactttt tctttagttt ctttgctcta cgtgggcacc tggcactaag
ggagtacctt 3780attatcctac atcgcaaatt tcaacagcta cattatattt
ccttctgaca cttggaaggt 3840attgaaattt ctagaaatgt atccttctca
caaagtagag accaagagaa aaactcattg 3900attgggtttc tacttctttc
aaggactcag gaaatttcac tttgaactga ggccaagtga 3960gctgttaaga
taacccacac ttaaactaaa ggctaagaat ataggcttga tgggaaattg
4020aaggtaggct gagtattggg aatccaaatt gaattttgat tctccttggc
agtgaactac 4080tttgaagaag tggtcaatgg gttgttgctg ccatgagcat
gtacaacctc tggagctaga 4140agctcctcag gaaagccagt tctccaagtt
cttaacctgt ggcactgaaa ggaatgttga 4200gttacctctt catgttttag
acagcaaacc ctatccatta aagtacttgt tagaacactg 426093250DNAHomo
sapiens 9gcgggcggag gcggggcgcg gagaagtggc ggaggtggaa gcggaggcgt
acccgcccct 60ggggacgtca ttggtggcgg aggcaatggc cggcaaccag ctgtaagcga
ggcacggaag 120acatatgctt gtgagacaaa ggtgtctctg aaactatgga
tggtacaaga acttcacttg 180acattgaaga gtactcggat actgaggtac
agaaaaacca agtactaact ctggaagaat 240ggcaagacaa gtgggtgaac
ggcaagactg cttttcatca ggaacaagga catcagctat 300taaagaagca
tttagatact ttccttaaag gcaagagtgg actgagggta ttttttcctc
360tttgcggaaa agcggttgag atgaaatggt ttgcagaccg gggacacagt
gtagttggtg 420tggaaatcag tgaacttggg atacaagaat tttttacaga
gcagaatctt tcttactcag 480aagaaccaat caccgaaatt cctggaacca
aagtatttaa gagttcttcg gggaacattt 540cattgtactg ttgcagtatt
tttgatcttc ccaggacaaa tattggcaaa tttgacatga 600tttgggatag
aggagcatta gttgccatca atccaggtga tcgcaaatgc tatgcagata
660caatgttttc cctcctggga aagaagtttc agtatctcct gtgtgttctt
tcttatgatc 720caactaaaca tccaggtcca ccattttatg ttccacatgc
tgaaattgaa aggttgtttg 780gtaaaatatg caatatacgt tgtcttgaga
aggttgatgc ttttgaagaa cgacataaaa 840gttggggaat tgactgtctt
tttgaaaagt tatatctact tacagaaaag taaatgagac 900atagataaaa
taaaatcaca ctgacatgtt tttgaggaat tgaaaattat gctaaagcct
960gaaaatgtaa tggatgaatt tttaaaattg tttataaatc atatgataga
tctttactaa 1020aaatggcttt ttagtaaagc catttacttt ttctaaaaaa
gttttagaag aaaaagatgt 1080aactaaactt ttaaagtagc tcctttggag
aggagattat gatgtgaaag attatgccta 1140tgtgtcttgc agattgcaag
atattttacc aatcagcatg tgttacctgt acaattaaaa 1200aaatatttca
aaatgcaatg catattaaat ataatacaca cagaaaaact ggcatttatt
1260ttgttttatt tttttgagat ggagtttcgt tcttgttgcc caacctggag
tgcaatggtg 1320caatctcagc tcactgcaac ctctgcctcc caggttcagg
tgattctcct gcctcagcct 1380cctgagtagc tgggattaca ggtgtgcgcc
accacgccca gctaattttt tgtattttta 1440gtagagacag ggtttcacca
tgttggtcag gctgatctcg agctcctgac ctcaggtgat 1500ctacccacct
cggcctccca aagtgctggg attacaggcg tgagccactg cacctggcct
1560gacattcttt atgaaattta gaattgttga agaactataa catttcagta
gggttcaagg 1620tggtcccaaa agttatataa aagattagtt tttactataa
acccttgtct tttactcaga 1680tcctagcatc ccttttcaca tggtttctcc
atgtatataa cagaatcaag aaacaaattt 1740taattaaaca atctgtaaca
gaatcaagaa acaaatacat tttaattaaa caatctatat 1800ggaacaaaca
ttcccaaatt ctaagaataa atttttcttt aagttttctc tgagtttggc
1860aattgttgtt ttttataatt taatctgttt aaatcatcag gtcttataaa
atataatgta 1920cttagagctg gattcatggc tgtttattat gaaaggttag
atttctcagt tcttctttaa 1980ccacattttg ttatatcaga cagtcctcta
taactctgta ctacccaaca actaaatggt 2040ttagattgtt tagctcatgt
taataggatg gttgtgtatt ataaaaaacg agttacgtgt 2100gtgtgtgcac
gcatgcacgc acatgtgctg gcttaaaggt tgttaatgca aggtttgggg
2160tcccctttaa cactggtgaa agctacggta ctctccccag agatatgtct
tgtcagcctc 2220tctagttccc cttggcctgc atgtacaaac ttctacccta
gaagctctct gccatcgatg 2280tattctaata gatttgtaag gctattaatt
tgaagcaact ccttgctcac agtgattctt 2340gcttctctga gacctgctcc
cagtcgatac tgtgggcttc agaagccatg actccccaac 2400tctgcctgta
tcaccggttg aatggacaac taacccgagc tggaccaaca caattctctc
2460cagagacttt tgattttact tttatgtaga gacagggtct cactttgttg
cccacgctga 2520tgttgaactt gacgtgaggc ctcaagcagt cctcctgtct
tggccaccca aagtgctagg 2580attacaggta tgagccattg cgctggccct
cttcataggc ttttggactt gggaatagaa 2640aagcaacccc gtctctacta
aaaatacaaa aaaattagcc aggcgtggtg gcacgtgcct 2700gtaatcccag
ctacttggga ggctgaggca ggagaatcac ttgaacctag gaggcggagg
2760ttgcagtgag ctgagatcat gccactgcac gcaagcctgg gcaacagagc
aagactctgt 2820ctcaaaagaa agaaaaagaa aagaaaaaaa agaaaggcaa
gttgactgct gaaaggggaa 2880tctgtgtacg cctgggagct gtggggcagc
cacattccag cacatggatc tgagaaacag 2940aacgctgatc tgcagaaaga
gatgagaacc aaagagaggc cacctgcgtc ctgggtccat 3000tttcatcctc
cctgaagccc agctgcccag ggtggggaga aacaccctgt gtccatggga
3060tagagtcctt tccgcttgca gttgtgccca aagaatctta aatacaaatg
agatatcctt 3120aggtagttga tcatttatgt aatatgtgtc ttcactgggg
aatactgact tcctaaaatc 3180tcaagatgga agatatacca catgtaaatt
attttagagc aattaaattg ttttcaggat 3240tttccaaaaa 3250102810DNAHomo
sapiens 10ggcctcgagg gacaggacgt gaagatagtt gggtttggag gcggccgcca
ggcccaggcc 60cggtggacct gccgccatgc aggacggtaa cttcctgctg tcggccctgc
agcctgaggc 120cggcgtgtgc tccctggcgc tgccctctga cctgcagctg
gaccgccggg gcgccgaggg 180gccggaggcc gagcggctgc gggcagcccg
cgtccaggag caggtccgcg cccgcctctt 240gcagctggga cagcagccgc
ggcacaacgg ggccgctgag cccgagcctg aggccgagac 300tgccagaggc
acatccaggg ggcagtacca caccctgcag gctggcttca gctctcgctc
360tcagggcctg agtggggaca agacctcggg cttccggccc atcgccaagc
cggcctacag 420cccagcctcc tggtcctccc gctccgccgt ggatctgagc
tgcagtcgga ggctgagttc 480agcccacaac gggggcagcg cctttggggc
cgctgggtac gggggtgccc agcccacccc 540tcccatgccc accaggcccg
tgtccttcca tgagcgcggt ggggttggga gccgggccga 600ctatgacaca
ctctccctgc gctcgctgcg gctggggccc gggggcctgg acgaccgcta
660cagcctggtg tctgagcagc tggagcccgc ggccacctcc acctacaggg
cctttgcgta 720cgagcgccag gccagctcca gctccagccg ggcagggggg
ctggactggc ccgaggccac 780tgaggtttcc ccgagccgga ccatccgtgc
ccctgccgtg cggaccctgc agcgattcca 840gagcagccac cggagccgcg
gggtaggcgg ggcagtgccg ggggccgtcc tggagccagt 900ggctcgagcg
ccatctgtgc gcagcctcag cctcagcctg gctgactcgg gccacctgcc
960ggacgtgcat gggttcaaca gctacggtag ccaccgaacc ctgcagagac
tcagcagcgg 1020ttttgatgac attgacctgc cctcagcagt caagtacctc
atggcttcag accccaacct 1080gcaggtgctg ggagcggcct acatccagca
caagtgctac
agcgatgcag ccgccaagaa 1140gcaggcccgc agccttcagg ccgtgcctag
gctggtgaag ctcttcaacc acgccaacca 1200ggaagtgcag cgccatgcca
caggtgccat gcgcaacctc atctacgaca acgctgacaa 1260caagctggcc
ctggtggagg agaacgggat cttcgagctg ctgcggacac tgcgggagca
1320ggatgatgag cttcgcaaaa atgtcacagg gatcctgtgg aacctttcat
ccagcgacca 1380cctgaaggac cgcctggcca gagacacgct ggagcagctc
acagacctgg tgttgagccc 1440cctgtcgggg gctgggggtc cccccctcat
ccagcagaac gcctcggagg cggagatctt 1500ctacaacgcc accggcttcc
tcaggaacct cagctcagcc tctcaggcca ctcgccagaa 1560gatgcgggag
tgccacgggc tggtggacgc cctggtcacc tctatcaacc acgccctgga
1620cgcgggcaaa tgcgaggaca agagcgtgga gaacgcggtg tgcgtcctgc
ggaacctgtc 1680ctaccgcctc tacgacgaga tgccgccgtc cgcgctgcag
cggctggagg gtcgcggccg 1740cagggacctg gcgggggcgc cgccgggaga
ggtcgtgggc tgcttcacgc cgcagagccg 1800gcggctgcgc gagctgcccc
tcgccgccga tgcgctcacc ttcgcggagg tgtccaagga 1860ccccaagggc
ctcgagtggc tgtggagccc ccagatcgtg gggctgtaca accggctgct
1920gcagcgctgc gagctcaacc ggcacacgac ggaggcggcc gccggggcgc
tgcagaacat 1980cacggcaggc gaccgcaggt gggcgggggt gctgagccgc
ctggccctgg agcaggagcg 2040tattctgaac cccctgctag accgtgtcag
gaccgccgac caccaccagc tgcgctcact 2100gactggcctc atccgaaacc
tgtctcggaa cgctaggaac aaggacgaga tgtccacgaa 2160ggtggtgagc
cacctgatcg agaagctgcc gggcagcgtg ggtgagaagt cgcccccagc
2220cgaggtgctg gtcaacatca tagctgtgct caacaacctg gtggtggcca
gccccatcgc 2280tgcccgagac ctgctgtatt ttgacggact ccgaaagctc
atcttcatca agaagaagcg 2340ggacagcccc gacagtgaga agtcctcccg
ggcagcatcc agcctcctgg ccaacctgtg 2400gcagtacaac aagctccacc
gtgacttccg ggcgaagggc tatcggaagg aggacttcct 2460gggcccatag
gtgaagcctt ctggaggaga aggtgacgtg gcccagcgtc caagggacag
2520actcagctcc aggctgcttg gcagcccagc ctggaggaga aggctaatga
cggaggggcc 2580cctcgctggg gcccctgtgt gcatctttga gggtcctggg
ccaccaggag gggcagggtc 2640ttatagctgg ggacttggct tccgcagggc
agggggtggg gcagggctca aggctgctct 2700ggtgtatggg gtggtgaccc
agtcacattg gcagaggtgg gggttggctg tggcctggca 2760gtatcttggg
atagccagca ctgggaataa agatggccat gaacagtcaa 2810113131DNAHomo
sapiens 11agtgtttatc agaacttagc cagggccagc caagcaggca cagatgctct
gctatgaaat 60gccacgcagg cagagactga caagcggtag gaactgagct ttccccttgg
actgctgctt 120cctgctgtgt tcaggggagg gggtcacttt ctggcaactc
tgctgctgct gctgctgctg 180ctgctacttc agcttcctct ccactcaagg
taagcaggct aagggagggc aggctgctag 240ggaaagcttt gtaccatgaa
caggatccga aagtttttcc gaggaagtgg gcgagtcttg 300gcatttatct
ttgtagcttc tgtcatctgg ctcctctttg acatggcagc tctccgcctc
360tcattcagtg agatcaacac tcgggtcatc aaggaagaca ttgtgaggag
ggagcggata 420ggattcagag ttcagccaga ccaaggaaaa attttttaca
gcagcataaa agagatgaaa 480cctcccctaa ggggacatgg gaaaggggca
tggggcaaag agaatgttag aaaaactgag 540gagagtgtgc tcaaggttga
ggtggacttg gaccaaaccc agagggaaag aaaaatgcag 600aatgccctgg
gaaggggcaa ggttgtgccg ttgtggcatc ctgcacatct gcagaccctc
660cctgtgactc ctaacaagca gaagacagac gggagaggca ccaaacctga
agcctcctct 720caccagggga caccaaagca aacgacagct cagggggctc
caaagacctc attcatagca 780gcaaaaggaa ctcaggtagt caaaatatca
gtacacatgg gacgtgtcag tttaaaacag 840gagccccgga agagtcatag
tcccagcagt gacacatcaa aactagcagc tgaaagggac 900ttgaatgtga
ccatcagtct tagtactgat agaccaaagc agcgatcaca ggcagtagca
960aacgagaggg cacaccctgc cagcacagca gtgccgaagt ctggggaagc
catggcctta 1020aacaaaacta agactcagag caaagaagtc aatgcaaata
aacacaaagc caatacgagt 1080cttccttttc ctaagttcac tgtcaattca
aatcgcttaa ggaagcaatc tattaatgag 1140acacctttgg gaagtttgtc
aaaggatgat ggagctagag gggctcatgg gaagaaactc 1200aatttctctg
aaagccatct tgtgattata accaaagagg aagagcaaaa ggcagacccc
1260aaagaggtct ctaattctaa aaccaaaaca atatttccta aagtattggg
taaaagccaa 1320agtaaacaca tttccaggaa tagaagtgag atgtcttcct
cttcacttgc tccacataga 1380gtgccactgt cccaaactaa ccatgcttta
actggagggc tagagccagc aaaaatcaac 1440ataactgcca aagccccctc
tacagaatac aaccagagtc atataaaagc ccttttacct 1500gaagacagtg
gaacgcacca ggtgttaaga attgatgtga cactttctcc aagggacccc
1560aaagctccag ggcagtttgg gcgtcctgta gttgtccccc atggaaagga
gaaggaggca 1620gaaagaagat ggaaagaagg aaacttcaat gtctacctta
gcgatttgat cccagtggat 1680agagccattg aagacaccag acctgctgga
tgtgcagagc agctagttca caataacctc 1740ccaaccacca gtgtcatcat
gtgctttgtg gatgaagtgt ggtccactct cctgagatct 1800gttcacagtg
tcatcaatcg ctctcctcca cacctcatca aggagattct gctggtagat
1860gacttcagca ccaaagacta tctaaaagat aatttggata aatacatgtc
ccagtttcca 1920aaagttcgga ttcttcgcct caaagagaga catggcttaa
taagggccag gctggcagga 1980gcacagaatg caacaggtga tgtgttgaca
tttttagatt ctcatgtgga atgtaacgtt 2040ggttggttgg aacctcttct
ggaaagagtt tatttaagta gaaagaaagt ggcctgtcca 2100gtaatcgaag
tcatcaatga taaggatatg agttacatga cagtggataa ctttcaaaga
2160ggcatctttg tgtggcccat gaactttggt tggagaacaa ttcctccaga
tgtcattgca 2220aaaaacagaa ttaaagaaac tgatacaata aggtgccctg
tcatggctgg tggattgttt 2280tctattgaca aaagttactt ttttgaactt
ggaacatacg accctggcct tgatgtttgg 2340ggtggggaaa atatggagct
ctcattcaag gtgtggatgt gtggtggtga aattgagatc 2400attccctgct
cccgagtggg ccatatattc agaaatgaca atccatattc cttccccaaa
2460gaccggatga agacagtgga gcggaacttg gtgcgggttg ccgaggtctg
gctggatgag 2520tataaggagc tgttctatgg ccacggagac cacctcatcg
accaagggct agatgttggc 2580aacctcaccc agcaaaggga gctgcgaaag
aaactgaagt gcaaaagttt caaatggtac 2640ttggagaatg tctttcctga
cttaagggct cccattgtga gagctagtgg tgtgcttatt 2700aatgtggctt
tgggtaaatg catttccatt gaaaacacta cagtcattct ggaagactgc
2760gatgggagca aagagcttca acaatttaat tacacctggt taagacttat
taaatgtgga 2820gaatggtgta tagcccccat ccctgataaa ggagccgtaa
ggctgcaccc ttgtgataac 2880agaaacaaag ggctaaaatg gctgcataaa
tcaacatcag tctttcatcc agaactggtg 2940aatcacattg tttttgaaaa
caatcagcaa ttattatgct tggaaggaaa tttttctcaa 3000aagatcctga
aagtagctgc ctgtgaccca gtgaagccat atcaaaagtg gaaatttgaa
3060aaatattatg aagcctgaag tgtaactgat gtttttatat agtaaaccca
ttaaatactg 3120tgaaaataac a 3131124640DNAHomo sapiens 12ggggctgagg
gtggagagag gaagggaagg aagaaaaggg gagccttcct ggccagggta 60accggcacta
agaggcctca ctccaagccc ccgaggagcc tgtggtgggg ctggagaccc
120ggctcaggcc cctccaccac ccttaaagtc ctcagaaggt gggaactgaa
ctggcacagg 180atgggaaccg gctgtgcgct ggccacttga ttttgccagc
tgccctgtaa ttcagctggt 240gaggaaactg aggcacagac tgaggtagaa
tgattcgcca gtcactcagc aagtcagcag 300acggggagga ctgaatccca
gcctgagagc accgaagctt gtatccctgc aataccgagc 360cccaagcctg
cgagccccgg tgcccatctc tgagttaggc cgtcttggaa gggttccctt
420cctcctacaa gatggtgtgt gaggagcctt caatacgacc cggggtgtaa
agtgtccaac 480tctagtaggg gcctgatggc atccccgccg agtcccagga
gagagagaga agaccccttc 540ctggagtcca gggctcccgg gaagaaacac
tggcatttgt ccctttgctt cggcttctgg 600aggcagagac tctgagccca
gggagagcct tctgcagccc catttcctca aaaatccaac 660ctgcccaggt
ggcgggtcat gagctgtgct caggaagctg gaatctgacc ctggtggcgt
720cgggcccagt ctccatggca gccgagcatt tattacccgg gcctccaccc
agcttggcag 780actttagact tgaggctgga ggaaagggaa ctgaacgcgg
ttctgggagc agcaagccca 840cgggtagcag ccgaggcccc agaatggcca
agtttctttc ccaagaccaa attaatgagt 900acaaggaatg cttctccctg
tatgacaagc agcagagggg gaagataaaa gccaccgacc 960tcatggtggc
catgaggtgc ctgggggcca gcccgacgcc aggggaggtg cagcggcacc
1020tgcagaccca cgggatagac ggaaatggag agctggattt ctccactttt
ctgaccatta 1080tgcacatgca aataaaacaa gaagacccaa agaaagaaat
tcttctagcc atgttgatgg 1140tggacaagga gaagaaaggt tacgtcatgg
cgtccgacct gcggtcaaaa ctcacgagtc 1200tgggggagaa gctcacccac
aaggaagtgg atgatctctt cagggaagca gatatcgaac 1260ccaatggcaa
agtgaagtat gatgaattta tccacaagat cacccttcct ggacgggact
1320attgaaggag gagaatggga gagcctcccc tgggcctgaa aacttggagc
aattaatttt 1380ttttaaaaag tgttcttttc acttgggaga gatggcaaac
acagtggcaa gacaacatta 1440cccaactata gaagagaggc taactagcaa
caataataga tgatttcagc catggtatga 1500gtagatcttt aataaaagat
ttgtattgat tttattaact accgtgagtc cggccctttc 1560aagcatggaa
ggagcctgcg gtttggagtc tggcctgggt tccagtcctg gctctgctgc
1620ttcccactgt gactttgggc aaatcatttc actcctcaaa gcccccccac
acaagctgga 1680ttcccacttc ttacctcatg gagcctgttg aggaaggatt
gagctgatga cttaagggca 1740atctaccaag agacttattc tgtatttggg
ggctagaacc atcttccata tttccaagat 1800tttccaagat gaagccagtg
ctagctgaga agcagcaatg aacagaaagc tgtaacactt 1860atgacaacaa
ttcttgcagt gccagaggcc catttacaaa ttctcatttc catctcaaca
1920gatatagtga catagctcag gctattcatt cataaacaca gagtgtagag
tgaaaacact 1980agagtgaaaa cacatgctac aatgaggcag catcagctga
gagcaggaag agcgatctac 2040tttacacccc acaccaaagg aaaccagatg
tgagctgcta aattgactgg ccttgcagag 2100ctcaagaagg gggcttccaa
tgctgtgaga attccgagct gttccctggg ctctgttaac 2160aggcagagag
gttccgggat ggtctgctca agtggcccac actggtcatt gccttaagcc
2220acctccccag gacttacgga gagaaataag gggatgtaac cagcaatggc
cagggtacaa 2280cagccctgga aaacagtagt aggagcacta ggctttctgg
gagtccatcc agctggagtg 2340gctttgagtg agttacacag ctagaaggtg
ccaggttggt gctgccagag attcagaggt 2400gccatacact tgtcaaatct
ggatcattcg tagtgccagc acagtcctaa aagggctgga 2460gtaccacacc
aacacaggta ggggtgcagg gcttcaagta caaagatttg catccatgta
2520tgtatcaaaa gtgggttctc tgggctgtgg ctttgtctag tagtaccaca
gtggctaaag 2580tagaagaaaa ccaaatcaaa tgggatgtgt cttttgggag
gatgtacaag acacaaatct 2640ttcactaggc accgggcaca gggaaaactg
cagggaacaa gagttgtagt gttagtgcaa 2700ctgtctcaac gatgctgtgt
ggcttcagac ccaaacaagg ccctgaggaa ggagactctc 2760atttccccaa
gcataactgc aaggagagga ggaattccta ggagccaaag agttttgtgg
2820ggtgagggta aataaatggc ccaaatgcca actaggtgaa gttgtgacca
tctggctggg 2880aagcccaggt ccacacagtg taggagcaga tgttttgtgg
ggtctgaggt ttacgagatt 2940tggctgcctt aagaatacaa aaacagaaat
gcagaatttc tggggctgct cctaggacca 3000gaacaagtga agggtcctgg
tgcttaaact tcattacctt catggtaaat ccaccagagg 3060gccggttaga
tgctggcccc gccgagagaa ctgctgtcac tttcaggcaa agctcaaagg
3120tcctaggccc acagttcttt tgagctccag tcatggacat taggaagtaa
atcctgcaca 3180gccaacctgg aataccaaag attagatggg agatagatac
caatgattta gatggcacag 3240gaagagcaag ttctggatat aataaatgag
ggtactttcc gtcaaagctt ttctatgtct 3300atatttatca ctgaatagtc
ccagtatggt tttaaagcaa gttttatgaa tctcatttgc 3360ctaacaggaa
tctgaaatat aacttgccaa aaacacacag ttggtgtgga atggtcatta
3420gaacctgggg ctcctcttca cggactccct gctcattaag ggattcagtg
gtccagagtc 3480taagatccta ttaagtgttt gattcaaacc tctacccgag
gaagggctgt taccttactc 3540ctggtcctgg tttcaagctc attcctgaaa
ttccagctgg tttctctagc acctagtgtt 3600gtttacaaga aggccacggt
gctcttagca ttcaaactgc agatactaaa cagatgctgt 3660gatttattaa
agagttagcc atatttcaac aagaaaggga aatgatggct atattcatta
3720cttacctcaa agcatgctgc aagaaaatta gttagttact tgtcatgctt
tgaaatctct 3780ggatgaaagg tgctttggaa gcacaaacca ttatcacttg
tctcataggg attgtcccct 3840tgaacatcca gcagtgttat tttacagaag
acaaattaac tgaaggcttt tcttttatta 3900catctaaaga gctctacata
aacaggtaac attcaatagg taaacaattt ttttccaatg 3960catgtaataa
atattttcac ttggtacttt tatacaaact gacattgtct actatacatt
4020tttaaaagcc attttactgg tttggcatgc ggtatggaaa ttctaagaga
gaaagtttta 4080aggcaatgaa tcacagattt aagttcatgg aatttatggt
aactttatct gtttatgtac 4140attttcccct ttgttaaaca attaacagca
gcacactctg ggaccaccag ctattttccc 4200tctctttctg aaatctaagc
tttgtattta attaaaaaac agaattcaac atctattgat 4260aaaacaaaat
tcttactaaa ataatttcaa atgtgcttta aaaagtcctg aagatcttga
4320aagttttatg tgtttaaaat tgaaattgtc taaaaaaatg ctctttccac
attaatttag 4380ttaggatata ttttcactcc atttcagaca cttgactcaa
aggaaaatct gccaaagaat 4440ccgatttttc agagcttacg tgaatctttc
ctcagtaaag atacagaatt gtgatcatgt 4500ctaaataatt agtaaagcaa
ttttaatgct caaaatagtc aaccaagtat ggcatggttc 4560tggttcagat
tttttttttt taagatgtat ccaataacac tcacgaagta attaaaagcc
4620actttaaccc tgctaaaaaa 4640132300DNAHomo sapiens 13cattttataa
tgaagcctgg tcaactctcc ttcggacagt ttacagtgtc cttgagacat 60ccccggatat
cctgctagaa gaagtgatcc ttgtagatga ctacagtgat agagagcacc
120tgaaggagcg cttggccaat gagctttcgg gactgcccaa ggtgcgcctg
atccgcgcca 180acaagagaga gggcctggtg cgagcccggc tgctgggggc
gtctgcggcg aggggcgatg 240ttctgacctt cctggactgt cactgtgagt
gccacgaagg gtggctggag ccgctgctgc 300agaggatcca tgaagaggag
tcggcagtgg tgtgcccggt gattgatgtg atcgactgga 360acaccttcga
atacctgggg aactccgggg agccccagat cggcggtttc gactggaggc
420tggtgttcac gtggcacaca gttcctgaga gggagaggat acggatgcaa
tcccccgtcg 480atgtcatcag gtctccaaca atggctggtg ggctgtttgc
tgtgagtaag aaatattttg 540aatatctggg gtcttatgat acaggaatgg
aagtttgggg aggagaaaac ctcgaatttt 600cctttaggat ctggcagtgt
ggtggggttc tggaaacaca cccatgttcc catgttggcc 660atgttttccc
caagcaagct ccctactccc gcaacaaggc tctggccaac agtgttcgtg
720cagctgaagt atggatggat gaatttaaag agctctacta ccatcgcaac
ccccgtgccc 780gcttggaacc ttttggggat gtgacagaga ggaagcagct
ccgggacaag ctccagtgta 840aagacttcaa gtggttcttg gagactgtgt
atccagaact gcatgtgcct gaggacaggc 900ctggcttctt cgggatgctc
cagaacaaag gactaacaga ctactgcttt gactataacc 960ctcccgatga
aaaccagatt gtgggacacc aggtcattct gtacctctgt catgggatgg
1020gccagaatca gtttttcgag tacacgtccc agaaagaaat acgctataac
acccaccagc 1080ctgagggctg cattgctgtg gaagcaggaa tggataccct
tatcatgcat ctctgcgaag 1140aaactgcccc agagaatcag aagttcatct
tgcaggagga tggatcttta tttcacgaac 1200agtccaagaa atgtgtccag
gctgcgagga aggagtcgag tgacagtttc gttccactct 1260tacgagactg
caccaactcg gatcatcaga aatggttctt caaagagcgc atgttatgaa
1320gcctcgtgta tcaaggagcc catcgaagga gactgtggag ccaggactct
gcccaacaaa 1380gacttagcta agcagtgacc agaacccacc aaaaactagg
ctgcattgct ttgaagaggc 1440aatcattttg ccatttgtga aagttgtgtt
ggatttagta aaaatgtgaa taagctttgt 1500acttattttg agaacttttt
aaatgttcca aaatacccta ttttcaaagg gtaatcgtaa 1560gatgttaacc
cttggtattt agaaaattaa aaccttataa tatttttcta tcaagatgta
1620tattttacag tcgtgccttt tactctcatt agcaaaaaag ataaagattt
tattttggta 1680tttacaagaa ttcccaggta cgaagatatc tgcatgggtg
gaaatcaggt tcaagcaacg 1740tactttgcat taactgataa tacctcagct
gcggggttaa agttttccca gtatagagag 1800actgtcacta ggaacattgt
attgatttat tcaggtcatt gagatcttct agatgtattt 1860taaaaagaat
gctttttggt tatgtgttgc taccacagtt aacactccat aatgttcatg
1920tcagccaaag aggactaacc aaagctgaaa tctcagagaa caatttgctt
tactaagctg 1980agtcaacttg agagcgaact tctaacaatg ccgcactgta
gtgtggctgg ttctaccact 2040atgactttaa aacatgttta tatcattttt
aatttttatg atacggtagt gtcagggaga 2100aatgtaatgt tctatatgaa
attccttttt caagtttgtt cattaataac agttattaat 2160ttaaatcagc
gttagagttt gtgctgctgc aactgctgtg aaaatttctc tgagtaattc
2220tgatttgtga atgatcccag accaaccctg agattttgtc aacctgatta
agtcaatatg 2280aatgattaaa aagatgtgag 2300142440DNAHomo sapiens
14aaggctcctc agccgagcgc cgagcggtcg atcgccgtag ctcccgcagc ctgcgatctc
60cagtctgtgg ctcctaccag ccattgtagg ccaataatcc gttatggagc atgcctttac
120cccgttggag cccctgcttt ccactgggaa tttgaagtac tgccttgtaa
ttcttaatca 180gcctttggac aactattttc gtcatctttg gaacaaagct
cttttaagag cctgtgccga 240tggaggtgcc aaccgcttat atgatatcac
cgaaggagag agagaaagct ttttgcctga 300attcatcaat ggagactttg
attctattag gcctgaagtc agagaatact atgctactaa 360gggatgtgag
ctcatttcaa ctcctgatca agaccacact gactttacta agtgccttaa
420aatgctccaa aagaagatag aagaaaaaga cttaaaggtt gatgtgatcg
tgacactggg 480aggccttgct gggcgttttg accagattat ggcatctgtg
aataccttgt tccaagcgac 540tcacatcact ccttttccaa ttataataat
ccaagaggaa tcgctgatct acctgctcca 600accaggaaag cacaggttgc
atgtagacac tggaatggag ggtgattggt gtggccttat 660tcctgttgga
cagccttgta tgcaggttac aaccacaggc ctcaagtgga acctcacaaa
720tgatgtgctt gcttttggaa cattggtcag tacttccaat acctacgacg
ggtctggtgt 780tgtgactgtg gaaactgacc acccactcct ctggaccatg
gccatcaaaa gctaacctgt 840tgactggcat ccataagtgt gcctctgcct
tatctcattt ctcaacagtt cattgctcaa 900caagaacgat tcacctgggt
ttgcaagaat ctaaacctct ctaggggaag cccactgggt 960ttaaagatgt
tagtgtttag ataatacagg taacattata aatgacagat ctcaatttta
1020tagtagtggg aaagatacat gctaagaaag caaataagct ctattatatt
cggttggaac 1080ctaatgggaa tcattccact atacaattca gtactgatta
ttcttcttac attattaatc 1140attccattta tcctagaaaa ttgtttttaa
tttgaatcag agaaaactgt tgaggttcct 1200cttggagtct agaacatcct
taaatgtcta acaacaaggg ctacctctga gtacctttta 1260gtattagttt
tctgtatatg atatatatta tcttatactg aaaaaaaatt cctttcagat
1320tggggtgtta gaagtgcacc aggtcactct gaccttatta ctgtctttgg
tattgtctta 1380aataaatcaa gaatcattga cctaattgtt aaatttaaaa
ataggtagtt agcaataggt 1440ggaaagagaa atgatgtgaa agataaatga
tgattcgtgg agccctactc acacattaac 1500ccccaaattc aaaagtaaga
atgcaaaagt ctagaggggg taacagtctg catcatcatc 1560acaacctaaa
tggagaaagc tgtgcagagg aaacttaagc ataaaaattg aattcgtttc
1620tgacatacct tagactgaaa aactgttggt tcatccagaa gtgtattcat
attaccagaa 1680aatgagtttg tctatgggga tacatgaact tcatatacta
aggagcctaa ctccaaagcc 1740tgcgttctca tcccagtctg atattcacct
aagtttccgg acccttttcc ttagctgtaa 1800aatggaagcg gttggactga
tggtgtctga ggttctttcc cacactgaaa ttctaaatat 1860tgacacttag
cagtcatagg gctgataata cacacagtta ctgacttagc ctaaacaacc
1920tggtgcatcg aaatgtattc acctttcttt tgtaaagaga ccatcttcta
tcttctttcc 1980acctttctct gttttatgaa accaactgtt gacatacaaa
ccatgattga aggagaacct 2040gtccaacatg ttttatgtac acaaatccct
atgttgctat aagaaaagtg aaagtaactg 2100ttttcttctt ggtgctatga
cagtgtgaga ctcaggttgt ctgtagagaa tgaaaggagc 2160agtggcccgc
gtgattgtgg catttaagga gcagtggccc atgtgactgt ggcattttcg
2220gcacttttca ttactttctg cttgaccgga agttgaggct tagctatgtt
tccatcttca 2280gtttctgaag actagttata tattccttac tagaaatata
ttcataatat ataaaagaaa 2340tatatctgtg attttaaaat tttgctacca
aagaatgcat gttctgtgtg ccctgaaaat 2400gttaccagtg ttaataaatg
gatacttatc aaaaaagaaa 244015475DNAHomo sapiens 15acacatctgc
tcctgctctc tctcctccag cgaccctagc catgagaacc ctcaccatcc 60tcactgctgt
tctcctcgtg gccctccagg ccaaggctga gccactccaa gctgaggatg
120atccactgca ggcaaaagct tatgaggctg atgcccagga gcagcgtggg
gcaaatgacc 180aggactttgc cgtctccttt gcagaggatg caagctcaag
tcttagagct ttgggctcaa 240caagggcttt cacttgccat tgcagaaggt
cctgttattc aacagaatat tcctatggga 300cctgcactgt catgggtatt
aaccacagat tctgctgcct ctgagggatg agaacagaga 360gaaatatatt
cataatttac tttatgacct agaaggaaac tgtcgtgtgt cccatacatt
420gccatcaact ttgtttcctc atctcaaata aagtcctttc agcaaaaaaa aaaaa
475163650DNAHomo sapiens 16gcgctaggta gagcgccggg acctgtgaca
gggctggtag cagcgcagag gaaaggcggc 60ttttagccag gtatttcagt gtctgtagac
aagatggaat
catctccatt taatagacgg 120caatggacct cactatcatt gagggtaaca
gccaaagaac tttctcttgt caacaagaac 180aagtcatcgg ctattgtgga
aatattctcc aagtaccaga aagcagctga agaaacaaac 240atggagaaga
agagaagtaa caccgaaaat ctctcccagc actttagaaa ggggaccctg
300actgtgttaa agaagaagtg ggagaaccca gggctgggag cagagtctca
cacagactct 360ctacggaaca gcagcactga gattaggcac agagcagacc
atcctcctgc tgaagtgaca 420agccacgctg cttctggagc caaagctgac
caagaagaac aaatccaccc cagatctaga 480ctcaggtcac ctcctgaagc
cctcgttcag ggtcgatatc cccacatcaa ggacggtgag 540gatcttaaag
accactcaac agaaagtaaa aaaatggaaa attgtctagg agaatccagg
600catgaagtag aaaaatcaga aatcagtgaa aacacagatg cttcgggcaa
aatagagaaa 660tataatgttc cgctgaacag gcttaagatg atgtttgaga
aaggtgaacc aactcaaact 720aagattctcc gggcccaaag ccgaagtgca
agtggaagga agatctctga aaacagctat 780tctctagatg acctggaaat
aggcccaggt cagttgtcat cttctacatt tgactcggag 840aaaaatgaga
gtagacgaaa tctggaactt ccacgcctct cagaaacctc tataaaggat
900cgaatggcca agtaccaggc agctgtgtcc aaacaaagca gctcaaccaa
ctatacaaat 960gagctgaaag ccagtggtgg cgaaatcaaa attcataaaa
tggagcaaaa ggagaatgtg 1020cccccaggtc ctgaggtctg catcacccat
caggaagggg aaaagatttc tgcaaatgag 1080aatagcctgg cagtccgttc
cacccctgcc gaagatgact cccgtgactc ccaggttaag 1140agtgaggttc
aacagcctgt ccatcccaag ccactaagtc cagattccag agcctccagt
1200ctttctgaaa gttctcctcc caaagcaatg aagaagtttc aggcacctgc
aagagagacc 1260tgcgtggaat gtcagaagac agtctatcca atggagcgtc
tcttggccaa ccagcaggtg 1320tttcacatca gctgcttccg ttgctcctat
tgcaacaaca aactcagtct aggaacatat 1380gcatctttac atggaagaat
ctattgtaag cctcacttca atcaactctt taaatctaag 1440ggcaactatg
atgaaggctt tgggcacaga ccacacaagg atctatgggc aagcaaaaat
1500gaaaacgaag agattttgga gagaccagcc cagcttgcaa atgcaaggga
gacccctcac 1560agcccagggg tagaagatgc ccctattgct aaggtgggtg
tcctggctgc aagtatggaa 1620gccaaggcct cctctcagca ggagaaggaa
gacaagccag ctgaaaccaa gaagctgagg 1680atcgcctggc caccccccac
tgaacttgga agttcaggaa gtgccttgga ggaagggatc 1740aaaatgtcaa
agcccaaatg gcctcctgaa gacgaaatca gcaagcccga agttcctgag
1800gatgtcgatc tagatctgaa gaagctaaga cgatcttctt cactgaagga
aagaagccgc 1860ccattcactg tagcagcttc atttcaaagc acctctgtca
agagcccaaa aactgtgtcc 1920ccacctatca ggaaaggctg gagcatgtca
gagcagagtg aagagtctgt gggtggaaga 1980gttgcagaaa ggaaacaagt
ggaaaatgcc aaggcttcta agaagaatgg gaatgtggga 2040aaaacaacct
ggcaaaacaa agaatctaaa ggagagacag ggaagagaag taaggaaggt
2100catagtttgg agatggagaa tgagaatctt gtagaaaatg gtgcagactc
cgatgaagat 2160gataacagct tcctcaaaca acaatctcca caagaaccca
agtctctgaa ttggtcgagt 2220tttgtagaca acacctttgc tgaagaattc
actactcaga atcagaaatc ccaggatgtg 2280gaactctggg agggagaagt
ggtcaaagag ctctctgtgg aagaacagat aaagagaaat 2340cggtattatg
atgaggatga ggatgaagag tgacaaattg caatgatgct gggccttaaa
2400ttcatgttag tgttagcgag ccactgccct ttgtcaaaat gtgatgcaca
taagcaggta 2460tcccagcatg aaatgtaatt tacttggaag taactttgga
aaagaattcc ttcttaaaat 2520caaaaacaaa acaaaaaaac acaaaaaaca
cattctaaat actagagata actttactta 2580aattcttcat tttagcagtg
atgatatgcg taagtgctgt aaggcttgta actggggaaa 2640tattccacct
gataatagcc cagattctac tgtattccca aaaggcaata ttaaggtaga
2700tagatgatta gtagtatatt gttacacact attttggaat tagagaacat
acagaaggaa 2760tttaggggct taaacattac gactgaatgc actttagtat
aaagggcaca gtttgtatat 2820ttttaaatga ataccaattt aattttttag
tatttacctg ttaagagatt atttagtctt 2880taaatttttt aggttaattt
tcttgctgtg atatatatga ggaatttact actttatgtc 2940ctgctctcta
aactacatcc tgaactcgac gtcctgaggt ataatacaac agagcacttt
3000ttgaggcaat tgaaaaacca acctacactc ttcggtgctt agagagatct
gctgtctccc 3060aaataagctt ttgtatctgc cagtgaattt actgtactcc
aaatgattgc tttcttttct 3120ggtgatatct gtgcttctca taattactga
aagctgcaat attttagtaa taccttcggg 3180atcactgtcc cccatcttcc
gtgttagagc aaagtgaaga gtttaaagga ggaagaagaa 3240agaactgtct
tacaccactt gagctcagac ctctaaaccc tgtatttccc ttatgatgtc
3300ccctttttga gacactaatt tttaaatact tactagctct gaaatatatt
gatttttatc 3360acagtattct cagggtgaaa ttaaaccaac tataggcctt
tttcttggga tgattttcta 3420gtcttaaggt ttggggacat tataaacttg
agtacatttg ttgtacacag ttgatattcc 3480aaattgtatg gatgggaggg
agaggtgtct taagctgtag gcttttcttt gtactgcatt 3540tatagagatt
tagctttaat attttttaga gatgtaaaac attctgcttt cttagtctta
3600cctagtctga aacattttta ttcaataaag attttaatta aaatttgaaa
3650175703DNAHomo sapiens 17gacagtcgcg gatcctgtga cacctccggg
cagcccggca cttgttgctc ccacgacctg 60ttgtcattcc cttaacccgg ctttccccgt
ggccccccgc ctcctcccgg cttcgctcct 120tttcatgtga gcatctggga
cactgatctc tcagaccccg ctgctcgggc tggagaatag 180atggttttgt
gaaaaattaa acaccgccct gaagaggagc cccgctgggc agcggcagga
240gcgcagagtg ctggcccagg tgctgcagag gtggcgcctc cccggcccgg
gacggtagcc 300ccgggcgcca acggcatgac agactcggcg acagctaacg
gggacgacag ggaccccgag 360atcgagctct ttgtgaaggc tggaatcgat
ggagaaagca tcggcaactg tcctttctct 420cagcgcctct tcatgatcct
ctggctgaaa ggagtcgtgt tcaatgtcac cactgtggat 480ctgaaaagaa
agccagctga cctgcacaac ctagcccccg gcacgcaccc gcccttcctg
540accttcaacg gggacgtgaa gacagacgtc aataagatcg aggagttcct
ggaggagacc 600ttgacccctg aaaagtaccc caaactggct gcaaaacacc
gggaatccaa cacagcgggc 660atcgacatct tttccaagtt ttctgcctac
atcaaaaata ccaagcagca gaacaatgct 720gctcttgaaa gaggcctaac
caaggctcta aagaaattgg atgactacct gaacacccct 780ctaccagagg
agattgacgc caacacttgt ggggaagaca aggggtcccg gcgcaagttc
840ctggatgggg atgagctgac cctggctgac tgcaatctgt tgcccaagct
ccatgtggtc 900aagattgtgg ccaagaaata ccgcaactat gatatcccgg
ctgagatgac aggcctgtgg 960cggtacctca agaacgccta tgcccgtgat
gagttcacca acacctgtgc agctgacagt 1020gagatcgagt tggcctacgc
tgatgtcgcc aaacgcctca gccgatcctg agcacagcca 1080ttttgcccca
tccccgctgc agaaggactc aaccactccc ctaagactcc agcttcatag
1140actcctctgt atcactgcct tgaggcgcac tttttataat caagcctcat
cttgctggta 1200tcatgggaac tccagcctgc tatctttcat gaaggtcagc
accatccctg gcctcctcac 1260ataggaatct agcagaaatg atagacacag
tccacctttc ggccggccag cctgatctgg 1320gctcagcatg tttggggtca
gtcagtgttg gagagcccac atatgggatt gccactagct 1380tcttctgcca
atatcaaaat accttctcag atgctttaga aacatgcaac accaactcct
1440tttctaccct cctctccgtc catacctaca aggccaagga caaacgccat
cttcatcctt 1500cttagaaaga gatctattac cccattaggg gagacagaga
gagtgaatgg aggagtaccg 1560agctggctat ggacttgggt gtctggcaaa
cacagcttca gtctcactac ttctgacact 1620ctggttattg ggcactaagg
gccagactgg aaagtcactt gagacacatt ctcagtttgt 1680tgcagtgcca
ggaatgctgc gctgctgctg ctgcgcacct ggcccatgct gtccctggct
1740tccatgccgt ccaggccctg ccagaaaagg aaattggcat gcaattctaa
actgcagtga 1800ctgggatggg aggggagggg agcagtgttg atgccaaaat
acccacgggg tctaccagcc 1860atggggtttg cttgcttagg agtagttgtt
tcagaggtga ttacaggcct gggtttgact 1920gtgcttacca atgagtggtt
tttgagctat gagaaagtgg atgggagtgg gaggaggaga 1980gatgggtgaa
gacaaaagag ttctttatga gcctcgatgt tccctggtaa acttttaaaa
2040aggccttctc tcatgatcta agtcttggac tggtggcatc atgtaactgc
taaccttaca 2100gtaaaaaccc aagaatgggt caaaaatgtc ttcccagttt
ctccaagctg cttctggaat 2160gcaggtctgt cggctgggtg ctctccagca
gctgctcctg cctgattcaa ctgtagcctg 2220taatgggtaa aagccacatt
taggaggtgg tctgatcata gaacacctta ggaagaaagt 2280ccatgagact
ttctgactag gaaaccatgt ggtttgaact tgaagaaaaa tgtagaccca
2340tctgggttaa ttttcctaca atctgactca actgccaggt gaaaaaaaaa
aggaaaaatt 2400tttaagctaa tatttcactc ttttgtcatt ctccttaagt
ttcatctcct aaaaagctta 2460cccagcctga gcttggggac ctgtgcagag
gaaactaaga aaaatgcact catcaactcc 2520ttctcccagt gaacgcccgg
tgagaaaatc catttgccac aggcccttac cttcaacaat 2580cccccttcta
tagtgttcgc tggtaaaggg tgaggctccc aagtgctgga aagcccctgg
2640acttggctca tttctcagca agggcaggat agcacgggtc ctttccatag
aaatatcaac 2700aaattctaac ccaagcaatc cctggaccta cctgcctcca
gggatctctg aagaaaaaaa 2760gtaacccatt gatcaaatca gaggagagga
agcaggaggt ctcctagagc ccattgagga 2820agaggaactt tctcagtagg
acactttata agcctgagaa agctttgaaa aggcggaatg 2880agttgattca
tttccacctc aaaaggaacc tttccaggtc cccctggaaa ttgtgccctg
2940gagatgttta acaaggagaa ctggtgagga aagagtcctt ttttactgta
gggaaaagcc 3000ccaaactggc ctcctggggg atgagggctg aaatgatccc
gaaggccttt taattagtgt 3060gaaatcctgc tgtactcaga aatccttccc
cgaatttaca gcacaggcag gatgacctaa 3120gaggcagttt acttccctga
gacccacagt tgggctgttc tggaaacaca tctgtgaatc 3180atagccaatt
gccacagaga aaacagaacc aagcctccgg tgaggccact ccaccccaga
3240gaagtctgca gaattccaag gactcggatt ggatgttcag aattcagcaa
ctggaaagtc 3300cttaaaaaca aacaggccaa accaaatcaa tattgctgtt
tctagatgtc ccttctgtgg 3360ttgagctagt tttacagaga taaatatatt
aagacaagga ggtgggggtg ttatatgatc 3420aatgatagcc atttgaaaga
gagggaggag tacagaagga aggcacttct gggtacttaa 3480ttcagaaatt
tctttatatt tcagcactgg attatcatat aatgcaagtg actatggact
3540aagagttagt tatggtgtct tatgactaga tttattatgg tatattaaag
taacaataat 3600attaatatta ccttcctttt tttttttgtt tcaaaagaga
tctttctcca gatgcttcag 3660cctgtctggc cttcttatca tatgtgcagc
acatcatgtc tcagcaacag tgtggtgagg 3720tccttaggtg tcccaagaac
aactcaggga gcacgggagg gtctgcagtt gggaccccac 3780aactatacag
ctatagggta ggaggcttcc ttttcattgg tcctgaatga atacaaatcg
3840ctcagaaagc attttggtgg cacagaaagg ggatgtattt gtgttgagat
cttattttat 3900tttgtattta tttatcttct ttgacttgca cagcactatt
gggggtgggg gaagcagggt 3960agtgggagac gaaggcagaa gcaagagtca
aactcagaat gactgagttg aattcactgt 4020ctagtcagca atgcctgctt
ctgagtttgg cccagagaga aggtattgag taagatttta 4080ataactgtaa
aaagtaagct ggataagtaa aatcatgatg gatccaaagc acagtttctt
4140catctcctga taaagaaagt caaatgcttg ataaattcag agtcacagat
gtgagcatag 4200ctatattctt ttaaacgaga ggtagagtga cctagcacta
agcaaatgag ctgaaatgtc 4260ggaaacagag tccatcagct tatttggcca
cacgatccca aactagtttt atcttgggaa 4320atggccctgt cctcagcatt
cccttcttgt gctggtgggg ccagtgaagt cttgatctta 4380tcagaaaaag
gccacaccaa gtgcgagttt tcccaggctg actttccagg cccttatcaa
4440atgaaacaac agaagctctt cacagttctg tgccccatgg ccactccaca
gacagacaat 4500accaagcatc ttagaactgt cataagatag gtcatgcctg
aaatagatct tgaccatatg 4560agagtcccag aaatcagcaa ggcctggaca
aatagaacta agagagaggc agaggcagga 4620agctgcgggt ctatcttgta
aagagtttag catcactgtg agagtgtgtg tctaaaatta 4680aattaaacta
gaagcagcag gtgagtattt ggtaagtact tctgtgactc gcctcaattc
4740ccactggcca ggggccatct caactgcacg gtgaatcaag atgctggtgt
catcctcctt 4800ggaaaaagga aatgttaact catggttaaa actaagtaca
atgattccca agggatcact 4860ttcttatttt tttaaatgac attaaggaga
atcttaagaa agcatcagag aaagacatgt 4920gcatgtgaag caccctgatt
ctgatgttag gaaaacttaa gcgaacagga cctgctgcac 4980acagccccat
tgtcttctat ccatttctct ttatcattca aatcaagcaa catgtgccct
5040cctcatcaac acacattctt cccctttgtc agtatgcatc tcccagctta
gtgtcaggat 5100actttcgatt cataattatg tatgatccaa agtgtgcata
atttcattta acgttaaaga 5160aatagatcca attcctttct tgcaaccaaa
aataaataaa atacgttgcc tcaatataag 5220gtttgggcta ttctgtgttt
ctatagaagc aatctgtttt tggtaaaatg tacttttaag 5280gatccagtca
tctgaagtat tttatgtaga gttagagatt tcacaatatt gactatacat
5340atatttaaaa tataaattat ccagctgatg tttgaatttg tcttactttc
ctggccacct 5400cgttgtccta ttttataagc tggggagtta actagcttaa
caaaagatgc ttagcttttg 5460taaaagaaca agtgtttcat tttacaaaga
cactccaaat gatagttact tgattttctc 5520gagaccttta actatggtga
tgaataacag gacttgcttt caagccttaa taaatgtaaa 5580atgcctttta
atgaagatac agctgagtgt tttcctcatg aatctgaacc aattaccaat
5640ttgtgttcca gtcttgattg gtattgactg attcaaataa agttggttta
ttttcaaata 5700tta 5703181941DNAHomo sapiens 18gcttttgtgg
cggcgcccgc gctcgcaggc cactctctgc tgtcgcccgt cccgcgcgct 60cctccgaccc
gctccgctcc gctccgctcg gccccgcgcc gcccgtcaac atgatccgct
120gcggcctggc ctgcgagcgc tgccgctgga tcctgcccct gctcctactc
agcgccatcg 180ccttcgacat catcgcgctg gccggccgcg gctggttgca
gtctagcgac cacggccaga 240cgtcctcgct gtggtggaaa tgctcccaag
agggcggcgg cagcgggtcc tacgaggagg 300gctgtcagag cctcatggag
tacgcgtggg gtagagcagc ggctgccatg ctcttctgtg 360gcttcatcat
cctggtgatc tgtttcatcc tctccttctt cgccctctgt ggaccccaga
420tgcttgtctt cctgagagtg attggaggtc tccttgcctt ggctgctgtg
ttccagatca 480tctccctggt aatttacccc gtgaagtaca cccagacctt
cacccttcat gccaaccctg 540ctgtcactta catctataac tgggcctacg
gctttgggtg ggcagccacg attatcctga 600ttggctgtgc cttcttcttc
tgctgcctcc ccaactacga agatgacctt ctgggcaatg 660ccaagcccag
gtacttctac acatctgcct aacttgggaa tgaatgtggg agaaaatcgc
720tgctgctgag atggactcca gaagaagaaa ctgtttctcc aggcgacttt
gaacccattt 780tttggcagtg ttcatattat taaactagtc aaaaatgcta
aaataatttg ggagaaaata 840ttttttaagt agtgttatag tttcatgttt
atcttttatt atgttttgtg aagttgtgtc 900ttttcactaa ttacctatac
tatgccaata tttcctatct atccataaca tttatactac 960atttgtaaga
gaatatgcac gtgaaactta acactttata aggtaaaaat gaggtttcca
1020agatttaata atctgatcaa gttcttgtta tttccaaata gaatggactc
ggtctgttaa 1080gggctaagga gaagaggaag ataaggttaa aagttgttaa
tgaccaaaca ttctaaaaga 1140aatgcaaaaa aaaagtttat tttcaagcct
tcgaactatt taaggaaagc aaaatcattt 1200cctaaatgca tatcatttgt
gagaatttct cattaatatc ctgaatcatt cattttagct 1260aaggcttcat
gttgactcga tatgtcatct aggaaagtac tatttcatgg tccaaacctg
1320ttgccatagt tggtaaggct ttcctttaag tgtgaaatat ttagatgaaa
ttttctcttt 1380taaagttctt tatagggtta gggtgtggga aaatgctata
ttaataaatc tgtagtgttt 1440tgtgtttata tgttcagaac cagagtagac
tggattgaaa gatggactgg gtctaattta 1500tcatgactga tagatctgtt
aagttgtgta gtaaagcatt aggagggtca ttcttgtcac 1560aaaagtgcca
ctaaaacagc ctcaggagaa taaatgactt gcttttctaa atctcaggtt
1620tatctgggct ctatcatata gacaggcttc tgatagtttg caactgtaag
cagaaaccta 1680catatagtta aaatcctggt ctttcttggt aaacagattt
taaatgtctg atataaaaca 1740tgccacagga gaattcgggg atttgagttt
ctctgaatag catatatatg atgcatcgga 1800taggtcatta tgatttttta
ccatttcgac ttacataatg aaaaccaatt cattttaaat 1860atcagattat
tattttgtaa gttgtggaaa aagctaattg tagttttcat tatgaagttt
1920tcccaataaa ccaggtattc t 1941192660DNAHomo sapiens 19aggaagagcc
gcgggcccgg cggctgaggc caccccggcg gcggctggag agcgaggagg 60agcgggtggc
cccgcgctgc gcccgccctc gcctcacctg gcgcaggtgg acacctgcgc
120aggtgtgtgc cctccggccc ctgaagcatg gccagcagcg gcatggctga
cagcgccaac 180cacctgccct tctttttcgg caacatcacc cgggaggagg
cagaagatta cctggtccag 240gggggcatga gtgatgggct ttatttgctg
cgccagagcc gcaactacct gggtggcttc 300gccctgtccg tggcccacgg
gaggaaggca caccactaca ccatcgagcg ggagctgaat 360ggcacctacg
ccatcgccgg tggcaggacc catgccagcc ccgccgacct ctgccactac
420cactcccagg agtctgatgg cctggtctgc ctcctcaaga agcccttcaa
ccggccccaa 480ggggtgcagc ccaagactgg gccctttgag gatttgaagg
aaaacctcat cagggaatat 540gtgaagcaga catggaacct gcagggtcag
gctctggagc aggccatcat cagtcagaag 600cctcagctgg agaagctgat
cgctaccaca gcccatgaaa aaatgccttg gttccatgga 660aaaatctctc
gggaagaatc tgagcaaatt gtcctgatag gatcaaagac aaatggaaag
720ttcctgatcc gagccagaga caacaacggc tcctacgccc tgtgcctgct
gcacgaaggg 780aaggtgctgc actatcgcat cgacaaagac aagacaggga
agctctccat ccccgaggga 840aagaagttcg acacgctctg gcagctagtc
gagcattatt cttataaagc agatggtttg 900ttaagagttc ttactgtccc
atgtcaaaaa atcggcacac agggaaatgt taattttgga 960ggccgtccac
aacttccagg ttcccatcct gcgacttggt cagcgggtgg aataatctca
1020agaatcaaat catactcctt cccaaagcct ggccacagaa agtcctcccc
tgcccaaggg 1080aaccggcaag agagtactgt gtcattcaat ccgtatgagc
cagaacttgc accctgggct 1140gcagacaaag gcccccagag agaagcccta
cccatggaca cagaggtgta cgagagcccc 1200tacgcggacc ctgaggagat
caggcccaag gaggtttacc tggaccgaaa gctgctgacg 1260ctggaagaca
aagaactggg ctctggtaat tttggaactg tgaaaaaggg ctactaccaa
1320atgaaaaaag ttgtgaaaac cgtggctgtg aaaatactga aaaacgaggc
caatgacccc 1380gctcttaaag atgagttatt agcagaagca aatgtcatgc
agcagctgga caacccgtac 1440atcgtgcgca tgatcgggat atgcgaggcc
gagtcctgga tgctagttat ggagatggca 1500gaacttggtc ccctcaataa
gtatttgcag cagaacagac atgtcaagga taagaacatc 1560atagaactgg
ttcatcaggt ttccatgggc atgaagtact tggaggagag caattttgtg
1620cacagagatc tggctgcaag aaatgtgttg ctagttaccc aacattatgc
caagatcagt 1680gatttcggac tctccaaagc actgcgtgct gatgaaaact
actacaaggc ccagacccat 1740ggaaagtggc ctgtcaagtg gtacgctccg
gaatgcatca actactacaa gttctccagc 1800aaaagcgatg tctggagctt
tggagtgttg atgtgggaag cattctccta tgggcagaag 1860ccatatcgag
ggatgaaagg aagtgaagtc accgctatgt tagagaaagg agagcggatg
1920gggtgccctg cagggtgtcc aagagagatg tacgatctca tgaatctgtg
ctggacatac 1980gatgtggaaa acaggcccgg attcgcagca gtggaactgc
ggctgcgcaa ttactactat 2040gacgtggtga actaaccgct cccgcacctg
tcggtggctg cctttgatca caggagcaat 2100cacaggaaaa tgtatccaga
ggaattgatt gtcagccacc tccctctgcc agtcgggaga 2160gccaggcttg
gatggaacat gcccacaact tgtcacccaa agcctgtccc aggactcacc
2220ctccacaaag caaaggcagt cccgggagaa aagacggatg gcaggatcca
aggggctagc 2280tggatttgtt tgttttcttg tctgtgtgat tttcatacag
gttattttta cgatctgttt 2340ccaaatccct ttcatgtctt tccacttctc
tgggtcccgg ggtgcatttg ttactcatcg 2400ggcccaggga cattgcagag
tggcctagag cactctcacc ccaagcggcc ttttccaaat 2460gcccaaggat
gccttagcat gtgactcctg aagggaaggc aaaggcagag gaatttggct
2520gcttctacgg ccatgagact gatccctggc cactgaaaag ctttcctgac
aataaaaatg 2580ttttgaggct ttaaaaagaa aatcaagttt gaccagtgca
gtttctaagc atgtagccag 2640ttaaggaaag aaagaaaaaa 2660206860DNAHomo
sapiens 20ggtggcctct gtggccgtcc aggctagcgg cggcccgcag gcggcgggga
gaaagactct 60ctcacctggt cttgcggctg tggccaccgc cggccagggg tgtggagggc
gtgctgccgg 120agacgtccgc cgggctctgc agttccgccg ggggtcgggc
agctatggag ccgcggccca 180cggcgccctc ctccggcgcc ccgggactgg
ccggggtcgg ggagacgccg tcagccgctg 240cgctggccgc agccagggtg
gaactgcccg gcacggctgt gccctcggtg ccggaggatg 300ctgcgcccgc
gagccgggac ggcggcgggg tccgcgatga gggccccgcg gcggccgggg
360acgggctggg cagacccttg gggcccaccc cgagccagag ccgtttccag
gtggacctgg 420tttccgagaa cgccgggcgg gccgctgctg cggcggcggc
ggcggcggcg gcagcggcgg 480cggctggtgc tggggcgggg gccaagcaga
cccccgcgga cggggaagcc agcggcgaga 540gcgagccggc taaaggcagc
gaggaagcca agggccgctt ccgcgtgaac ttcgtggacc 600cagctgcctc
ctcgtcggct gaagacagcc tgtcagatgc tgccggggtc ggagtcgacg
660ggcccaacgt gagcttccag aacggcgggg acacggtgct gagcgagggc
agcagcctgc 720actccggcgg cggcggcggc agtgggcacc accagcacta
ctattatgat acccacacca 780acacctacta cctgcgcacc ttcggccaca
acaccatgga cgctgtgccc aggatcgatc 840actaccggca cacagccgcg
cagctgggcg agaagctgct ccggcctagc ctggcggagc 900tccacgacga
gctggaaaag gaaccttttg aggatggctt tgcaaatggg gaagaaagta
960ctccaaccag agatgctgtg
gtcacgtata ctgcagaaag taaaggagtc gtgaagtttg 1020gctggatcaa
gggtgtatta gtacgttgta tgttaaacat ttggggtgtg atgcttttca
1080ttagattgtc atggattgtg ggtcaagctg gaataggtct atcagtcctt
gtaataatga 1140tggccactgt tgtgacaact atcacaggat tgtctacttc
agcaatagca actaatggat 1200ttgtaagagg aggaggagca tattatttaa
tatctagaag tctagggcca gaatttggtg 1260gtgcaattgg tctaatcttc
gcctttgcca acgctgttgc agttgctatg tatgtggttg 1320gatttgcaga
aaccgtggtg gagttgctta aggaacattc catacttatg atagatgaaa
1380tcaatgatat ccgaattatt ggagccatta cagtcgtgat tcttttaggt
atctcagtag 1440ctggaatgga gtgggaagca aaagctcaga ttgttctttt
ggtgatccta cttcttgcta 1500ttggtgattt cgtcatagga acatttatcc
cactggagag caagaagcca aaagggtttt 1560ttggttataa atctgaaata
tttaatgaga actttgggcc cgattttcga gaggaagaga 1620ctttcttttc
tgtatttgcc atcttttttc ctgctgcaac tggtattctg gctggagcaa
1680atatctcagg tgatcttgca gatcctcagt cagccatacc caaaggaaca
ctcctagcca 1740ttttaattac tacattggtt tacgtaggaa ttgcagtatc
tgtaggttct tgtgttgttc 1800gagatgccac tggaaacgtt aatgacacta
tcgtaacaga gctaacaaac tgtacttctg 1860cagcctgcaa attaaacttt
gatttttcat cttgtgaaag cagtccttgt tcctatggcc 1920taatgaacaa
cttccaggta atgagtatgg tgtcaggatt tacaccacta atttctgcag
1980gtatattttc agccactctt tcttcagcat tagcatccct agtgagtgct
cccaaaatat 2040ttcaggctct atgtaaggac aacatctacc cagctttcca
gatgtttgct aaaggttatg 2100ggaaaaataa tgaacctctt cgtggctaca
tcttaacatt cttaattgca cttggattca 2160tcttaattgc tgaactgaat
gttattgcac caattatctc aaacttcttc cttgcatcat 2220atgcattgat
caatttttca gtattccatg catcacttgc aaaatctcca ggatggcgtc
2280ctgcattcaa atactacaac atgtggatat cacttcttgg agcaattctt
tgttgcatag 2340taatgttcgt cattaactgg tgggctgcat tgctaacata
tgtgatagtc cttgggctgt 2400atatttatgt tacctacaaa aaaccagatg
tgaattgggg atcctctaca caagccctga 2460cttacctgaa tgcactgcag
cattcaattc gtctttctgg agtggaagac cacgtgaaaa 2520actttaggcc
acagtgtctt gttatgacag gtgctccaaa ctcacgtcca gctttacttc
2580atcttgttca tgatttcaca aaaaatgttg gtttgatgat ctgtggccat
gtacatatgg 2640gtcctcgaag acaagccatg aaagagatgt ccatcgatca
agccaaatat cagcgatggc 2700ttattaagaa caaaatgaag gcattttatg
ctccagtaca tgcagatgac ttgagagaag 2760gtgcacagta tttgatgcag
gctgctggtc ttggtcgtat gaagccaaac acacttgtcc 2820ttggatttaa
gaaagattgg ttgcaagcag atatgaggga tgtggatatg tatataaact
2880tatttcatga tgcttttgac atacaatatg gagtagtggt tattcgccta
aaagaaggtc 2940tggatatatc tcatcttcaa ggacaagaag aattattgtc
atcacaagag aaatctcctg 3000gcaccaagga tgtggtagta agtgtggaat
atagtaaaaa gtccgattta gatacttcca 3060aaccactcag tgaaaaacca
attacacaca aagttgagga agaggatggc aagactgcaa 3120ctcaaccact
gttgaaaaaa gaatccaaag gccctattgt gcctttaaat gtagctgacc
3180aaaagcttct tgaagctagt acacagtttc agaaaaaaca aggaaagaat
actattgatg 3240tctggtggct ttttgatgat ggaggtttga ccttattgat
accttacctt ctgacgacca 3300agaaaaaatg gaaagactgt aagatcagag
tattcattgg tggaaagata aacagaatag 3360accatgaccg gagagcgatg
gctactttgc ttagcaagtt ccggatagac ttttctgata 3420tcatggttct
aggagatatc aataccaaac caaagaaaga aaatattata gcttttgagg
3480aaatcattga gccatacaga cttcatgaag atgataaaga gcaagatatt
gcagataaaa 3540tgaaagaaga tgaaccatgg cgaataacag ataatgagct
tgaactttat aagaccaaga 3600cataccggca gatcaggtta aatgagttat
taaaggaaca ttcaagcaca gctaatatta 3660ttgtcatgag tctcccagtt
gcacgaaaag gtgctgtgtc tagtgctctc tacatggcat 3720ggttagaagc
tctatctaag gacctaccac caatcctcct agttcgtggg aatcatcaga
3780gtgtccttac cttctattca taaatgttct atacagtgga cagccctcca
gaatggtact 3840tcagtgccta gtgtagtaac tgaaatcttc aatgacacat
taacatcaca atggcgaatg 3900gtgacttttc tttcacgatt tcattaattt
gaaagcacac aggaaagttg ctccattgat 3960aacgtgtatg gagacttcgg
ttttagtcaa ttccatatct caatcttaat ggtgattctt 4020ctctgttgaa
ctgaagtttg tgagagtagt tttcctttgc tacttgaata gcaataaaag
4080cgtgttaact ttttgattga tgaaagaagt acaaaaagcc tttagccttg
aggtgccttc 4140tgaaattaac caaatttcat ccatatatcc tcttttataa
acttatagaa tgtcaaactt 4200tgccttcaac tgtttttatt tctagtctct
tccactttaa aacaaaatga acactgcttg 4260tcttcttcca ttgaccattt
agtgttgagt actgtatgtg ttttgttaat tctataaagg 4320tatctgttag
atattaaagg tgagaattag ggcaggttaa tcaaaaatgg ggaaggggaa
4380atggtaacca aaaagtaacc ccatggtaag gtttatatga gtatatgtga
atatagagct 4440aggaaaaaaa gcccccccaa ataccttttt aacccctctg
attggctatt attactatat 4500ttattattat ttattgaaac cttagggaag
attgaagatt catcccatac ttctatatac 4560catgcttaaa aatcacgtca
ttctttaaac aaaaatactc aagatcattt atatttattt 4620ggagagaaaa
ctgtcctaat ttagaatttc cctcaaatct gagggacttt taagaaatgc
4680taacagattt ttctggagga aatttagaca aaacaatgtc atttagtaga
atatttcagt 4740atttaagtgg aatttcagta tactgtacta tcctttataa
gtcattaaaa taatgtttca 4800tcaaatggtt aaatggacca ctggtttctt
agagaaatgt ttttaggctt aattcattca 4860attgtcaagt acacttagtc
ttaatacact caggtttgaa cagattattc tgaatattaa 4920aatttaatcc
attcttaata ttttaaaact tttgttaaga aaaactgcca gtttgtgctt
4980ttgaaatgtc tgttttgaca tcatagtcta gtaaaatttt gacagtgcat
atgtactgtt 5040actaaaagct ttatatgaaa ttattaatgt gaagtttttc
atttataatt caaggaagga 5100tttcctgaaa acatttcaag ggatttatgt
ctacatattt gtgtgtgtgt gtgtatatat 5160atgtaatatg catacacaga
tgcatatgtg tatatataat gaaatttatg ttgctggtat 5220tttgcatttt
aaagtgatca agattcatta ggcaaacttt ggtttaagta aacatatgtt
5280caaaatcaga ttaacagata caggtttcat agagaacaaa ggtgatcatt
tgaagggcat 5340gctgtaattt cacacaattt tccagttcaa aaatggagaa
tacttcgcct aaaatactgt 5400taagtgggtt aattgataca agtttctgtg
gtggaaaatt tatgcaggtt ttcacgaatc 5460cttttttttt tttttttttt
tttttgagac ggagtcttgc tctgttgcca cgctggaatg 5520cagtaacgtg
atcttggctc actgcgacct ccacctcccc agttcaagcg attctcctgc
5580ctcagcctcc ctagtagctg ggactacggg tgcacgccac catgcccagc
taatttttgt 5640attttgagta gagacagggt ttcaccgtgt tggctaggat
ggtgtctatc tcttgacctt 5700gtgatccacc cgcctcagcc tcccagagtg
ctgggattac aggtgcgagc cactgcgcct 5760ggctggtttt catgaatctt
gatagacatc tataacgtta ttattttcag tggtgtgcag 5820catttttgct
tcatgagtat gacctaggta tagagatctg ataacttgaa ttcagaatat
5880taagaaaatg aagtaactga ttttctaaaa aaaaaaaaaa aaaaaatttc
tacattataa 5940ctcacagcat tgttccattg caggttttgc aatgtttggg
ggtaaagaca gtagaaatat 6000tattcagtaa acaataatgt gtgaactttt
aagatggata atagggcatg gactgagtgc 6060tgctatcttg aaatgtgcac
aggtacactt accttttttt tttttttttt taagtttttc 6120ccattcagga
aaacaacatt gtgatctgta ctacaggaac caaatgtcat gcgtcataca
6180tgtgggtata aagtacataa aatatatcta actattcata atgtggggtg
ggtaatactg 6240tctgtgaaat aatgtaagaa gcttttcact taaaaaaaat
gcattacttt cacttaacac 6300tagacaccag gtcgaaaatt ttcaaggtta
tagtacttat ttcaacaatt cttagagatg 6360ctagctagtg ttgaagctaa
aaatagcttt atttatgctg aattgtgatt tttttatgcc 6420aaattttttt
tagttctaat cattgatgat agcttggaaa taaataatta tgccatggca
6480tttgacagtt cattattcct ataagaatta aattgagttt agagagaatg
gtggtgttga 6540gctgattatt aacagttact gaaatcaaat atttatttgt
tacattattc catttgtatt 6600ttaggtttcc ttttacattc tttttatatg
cattctgaca ttacatattt tttaagacta 6660tggaaataat ttaaagattt
aagctctggt ggatgattat ctgctaagta agtctgaaaa 6720tgtaatattt
tgataatact gtaatatacc tgtcacacaa atgcttttct aatgttttaa
6780ccttgagtat tgcagttgct gctttgtaca gaggttactg caataaagga
agtggattca 6840ttaaacctat ttaatgtcca 6860213745DNAHomo sapiens
21cgcaaagcaa gtgggcacaa ggagtatggt tctaacgtga ttggggtcat gaagacgttg
60ctgttggact tggctttgtg gtcactgctc ttccagcccg ggtggctgtc ctttagttcc
120caggtgagtc agaactgcca caatggcagc tatgaaatca gcgtcctgat
gatgggcaac 180tcagcctttg cagagcccct gaaaaacttg gaagatgcgg
tgaatgaggg gctggaaata 240gtgagaggac gtctgcaaaa tgctggccta
aatgtgactg tgaacgctac tttcatgtat 300tcggatggtc tgattcataa
ctcaggcgac tgccggagta gcacctgtga aggcctcgac 360ctactcagga
aaatttcaaa tgcacaacgg atgggctgtg tcctcatagg gccctcatgt
420acatactcca ccttccagat gtaccttgac acagaattga gctaccccat
gatctcagct 480ggaagttttg gattgtcatg tgactataaa gaaaccttaa
ccaggctgat gtctccagct 540agaaagttga tgtacttctt ggttaacttt
tggaaaacca acgatctgcc cttcaaaact 600tattcctgga gcacttcgta
tgtttacaag aatggtacag aaactgagga ctgtttctgg 660taccttaatg
ctctggaggc tagcgtttcc tatttctccc acgaactcgg ctttaaggtg
720gtgttaagac aagataagga gtttcaggat atcttaatgg accacaacag
gaaaagcaat 780gtgattatta tgtgtggtgg tccagagttc ctctacaagc
tgaagggtga ccgagcagtg 840gctgaagaca ttgtcattat tctagtggat
cttttcaatg accagtactt ggaggacaat 900gtcacagccc ctgactatat
gaaaaatgtc cttgttctga cgctgtctcc tgggaattcc 960cttctaaata
gctctttctc caggaatcta tcaccaacaa aacgagactt tgctcttgcc
1020tatttgaatg gaatcctgct ctttggacat atgctgaaga tatttcttga
aaatggagaa 1080aatattacca cccccaaatt tgctcatgct ttcaggaatc
tcacttttga agggtatgac 1140ggtccagtga ccttggatga ctggggggat
gttgacagta ccatggtgct tctgtatacc 1200tctgtggaca ccaagaaata
caaggttctt ttgacctatg atacccacgt aaataagacc 1260tatcctgtgg
atatgagccc cacattcact tggaagaact ctaaacttcc taatgatatt
1320acaggccggg gccctcagat cctgatgatt gcagtcttca ccctcactgg
agctgtggtg 1380ctgctcctgc tcgtcgctct cctgatgctc agaaaatata
gaaaagatta tgaacttcgt 1440cagaaaaaat ggtcccacat tcctcctgaa
aatatctttc ctctggagac caatgagacc 1500aatcatgtta gcctcaagat
cgatgatgac aaaagacgag atacaatcca gagactacga 1560cagtgcaaat
acgacaaaaa gcgagtgatt ctcaaagatc tcaagcacaa tgatggtaat
1620ttcactgaaa aacagaagat agaattgaac aagttgcttc agattgacta
ttacaacctg 1680accaagttct acggcacagt gaaacttgat accatgatct
tcggggtgat agaatactgt 1740gagagaggat ccctccggga agttttaaat
gacacaattt cctaccctga tggcacattc 1800atggattggg agtttaagat
ctctgtcttg tatgacattg ctaagggaat gtcatatctg 1860cactccagta
agacagaagt ccatggtcgt ctgaaatcta ccaactgcgt agtggacagt
1920agaatggtgg tgaagatcac tgattttggc tgcaattcca ttttacctcc
aaaaaaggac 1980ctgtggacag ctccagagca cctccgccaa gccaacatct
ctcagaaagg agatgtgtac 2040agctatggga tcatcgcaca ggagatcatt
ctgcggaaag aaaccttcta cactttgagc 2100tgtcgggacc ggaatgagaa
gattttcaga gtggaaaatt ccaatggaat gaaacccttc 2160cgcccagatt
tattcttgga aacagcagag gaaaaagagc tagaagtgta cctacttgta
2220aaaaactgtt gggaggaaga tccagaaaag agaccagatt tcaaaaaaat
tgagactaca 2280cttgccaaga tatttggact ttttcatgac caaaaaaatg
aaagctatat ggataccttg 2340atccgacgtc tacagctata ttctcgaaac
ctggaacatc tggtagagga aaggacacag 2400ctgtacaagg cagagaggga
cagggctgac agacttaact ttatgttgct tccaaggcta 2460gtggtaaagt
ctctgaagga gaaaggcttt gtggagccgg aactatatga ggaagttaca
2520atctacttca gtgacattgt aggtttcact actatctgca aatacagcac
ccccatggaa 2580gtggtggaca tgcttaatga catctataag agttttgacc
acattgttga tcatcatgat 2640gtctacaagg tggaaaccat cggtgatgcg
tacatggtgg ctagtggttt gcctaagaga 2700aatggcaatc ggcatgcaat
agacattgcc aagatggcct tggaaatcct cagcttcatg 2760gggacctttg
agctggagca tcttcctggc ctcccaatat ggattcgcat tggagttcac
2820tctggtccct gtgctgctgg agttgtggga atcaagatgc ctcgttattg
tctatttgga 2880gatacggtca acacagcctc taggatggaa tccactggcc
tccctttgag aattcacgtg 2940agtggctcca ccatagccat cctgaagaga
actgagtgcc agttccttta tgaagtgaga 3000ggagaaacat acttaaaggg
aagaggaaat gagactacct actggctgac tgggatgaag 3060gaccagaaat
tcaacctgcc aacccctcct actgtggaga atcaacagcg tttgcaagca
3120gaattttcag acatgattgc caactcttta cagaaaagac aggcagcagg
gataagaagc 3180caaaaaccca gacgggtagc cagctataaa aaaggcactc
tggaatactt gcagctgaat 3240accacagaca aggagagcac ctatttttaa
acctaaatga ggtataagga ctcacacaaa 3300ttaaaataca gctgcactga
ggcagcgacc tcaagtgtcc tgaaagctta cattttcctg 3360agacctcaat
gaagcagaaa tgtacttagg cttggctgcc ctgtctggaa catggacttt
3420cttgcatgaa tcagatgtgt gttctcagtg aaataactac cttccactct
ggaaccttat 3480tccagcagtt gttccaggga gcttctacct ggaaaagaaa
agaaatgaat agactatcta 3540gaacttgaga agattttatt cttatttcat
ttattttttg tttgtttatt tttatcgttt 3600ttgtttactg gctttccttc
tgtattcata agatttttta aattgtcata attatatttt 3660aaatacccat
cttcattaaa gtatatttaa ctcataattt ttgcagaaaa tatgctatat
3720attaggcaag aataaaagct aaagg 3745221428DNAHomo sapiens
22cttcaggtca gggagaatgt ataaatgtcc attgccatcg aggttctgct atttttgaga
60agctgaagca actccaagga cacagttcac agaaatttgg ttctcagccc caaaatactg
120attgaattgg agacaattac aaggactctc tggccaaaaa cccttgaaga
ggccccgtga 180aggaggcagt gaggagcttt tgattgctga cctgtgtcgt
accaccccag aatgtgcact 240gggggctgtg ccagatgcct gggggggacc
ctcattcccc ttgctttttt tggcttcctg 300gctaacatcc tgttattttt
tcctggagga aaagtgatag atgacaacga ccacctttcc 360caagagatct
ggtttttcgg aggaatatta ggaagcggtg tcttgatgat cttccctgcg
420ctggtgttct tgggcctgaa gaacaatgac tgctgtgggt gctgcggcaa
cgagggctgt 480gggaagcgat ttgcgatgtt cacctccacg atatttgctg
tggttggatt cttgggagct 540ggatactcgt ttatcatctc agccatttca
atcaacaagg gtcctaaatg cctcatggcc 600aatagtacat ggggctaccc
cttccacgac ggggattatc tcaatgatga ggccttatgg 660aacaagtgcc
gagagcctct caatgtggtt ccctggaatc tgaccctctt ctccatcctg
720ctggtcgtag gaggaatcca gatggttctc tgcgccatcc aggtggtcaa
tggcctcctg 780gggaccctct gtggggactg ccagtgttgt ggctgctgtg
ggggagatgg acccgtttaa 840acctccgaga tgagctgctc agactctaca
gcatgacgac tacaatttct tttcataaaa 900cttcttctct tcttggaatt
attaattcct atctgcttcc tagctgataa agcttagaaa 960aggcagttat
tccttctttc caaccagctt tgctcgagtt agaattttgt tattttcaaa
1020taaaaaatag tttggccact taacaaattt gatttataaa tctttcaaat
tagttccttt 1080ttagaattta ccaacaggtt caaagcatac ttttcatgat
ttttttatta caaatgtaaa 1140atgtataaag tcacatgtac tgccatacta
cttctttgta tataaagatg tttatatctt 1200tggaagtttt acataaatca
aaggaagaaa gcacatttaa aatgagaaac taagaccaat 1260ttctgttttt
aagaggaaaa agaatgattg atgtatccta agtattgtta tttgttgtct
1320ttttttgctg ccttgcttga gttgcttgtg actgatcttt tgaggctgtc
atcatggcta 1380gggttctttt atgtatgtta aattaaaacc tgaattcaga ggtaacgt
1428234090DNAHomo sapiens 23ctggagagcc tgctgcccgc ccgcccgtaa
aatggtcccc tcggctggac agctcgccct 60gttcgctctg ggtattgtgt tggctgcgtg
ccaggccttg gagaacagca cgtccccgct 120gagtgcagac ccgcccgtgg
ctgcagcagt ggtgtcccat tttaatgact gcccagattc 180ccacactcag
ttctgcttcc atggaacctg caggtttttg gtgcaggagg acaagccagc
240atgtgtctgc cattctgggt acgttggtgc acgctgtgag catgcggacc
tcctggccgt 300ggtggctgcc agccagaaga agcaggccat caccgccttg
gtggtggtct ccatcgtggc 360cctggctgtc cttatcatca catgtgtgct
gatacactgc tgccaggtcc gaaaacactg 420tgagtggtgc cgggccctca
tctgccggca cgagaagccc agcgccctcc tgaagggaag 480aaccgcttgc
tgccactcag aaacagtggt ctgaagagcc cagaggagga gtttggccag
540gtggactgtg gcagatcaat aaagaaaggc ttcttcagga cagcactgcc
agagatgcct 600gggtgtgcca cagaccttcc tacttggcct gtaatcacct
gtgcagcctt ttgtgggcct 660tcaaaactct gtcaagaact ccgtctgctt
ggggttattc agtgtgacct agagaagaaa 720tcagcggacc acgatttcaa
gacttgttaa aaaagaactg caaagagacg gactcctgtt 780cacctaggtg
aggtgtgtgc agcagttggt gtctgagtcc acatgtgtgc agttgtcttc
840tgccagccat ggattccagg ctatatattt ctttttaatg ggccacctcc
ccacaacaga 900attctgccca acacaggaga tttctatagt tattgttttc
tgtcatttgc ctactgggga 960agaaagtgaa ggaggggaaa ctgtttaata
tcacatgaag accctagctt taagagaagc 1020tgtatcctct aaccacgaga
ctctcaacca gcccaacatc ttccatggac acatgacatt 1080gaagaccatc
ccaagctatc gccacccttg gagatgatgt cttatttatt agatggataa
1140tggttttatt tttaatctct taagtcaatg taaaaagtat aaaacccctt
cagacttcta 1200cattaatgat gtatgtgttg ctgactgaaa agctatactg
attagaaatg tctggcctct 1260tcaagacagc taaggcttgg gaaaagtctt
ccagggtgcg gagatggaac cagaggctgg 1320gttactggta ggaataaagg
taggggttca gaaatggtgc cattgaagcc acaaagccgg 1380taaatgcctc
aatacgttct gggagaaaac ttagcaaatc catcagcagg gatctgtccc
1440ctctgttggg gagagaggaa gagtgtgtgt gtctacacag gataaaccca
atacatattg 1500tactgctcag tgattaaatg ggttcacttc ctcgtgagcc
ctcggtaagt atgtttagaa 1560atagaacatt agccacgagc cataggcatt
tcaggccaaa tccatgaaag ggggaccagt 1620catttatttt ccattttgtt
gcttggttgg tttgttgctt tatttttaaa aggagaagtt 1680taactttgct
atttattttc gagcactagg aaaactattc cagtaatttt tttttcctca
1740tttccattca ggatgccggc tttattaaca aaaactctaa caagtcacct
ccactatgtg 1800ggtcttcctt tcccctcaag agaaggagca attgttcccc
tgacatctgg gtccatctga 1860cccatggggc ctgcctgtga gaaacagtgg
gtcccttcaa atacatagtg gatagctcat 1920ccctaggaat tttcattaaa
atttggaaac agagtaatga agaaataata tataaactcc 1980ttatgtgagg
aaatgctact aatatctgaa aagtgaaaga tttctatgta ttaactctta
2040agtgcaccta gcttattaca tcgtgaaagg tacatttaaa atatgttaaa
ttggcttgaa 2100attttcagag aattttgtct tcccctaatt cttcttcctt
ggtctggaag aacaatttct 2160atgaattttc tctttatttt ttttttataa
ttcagacaat tctatgaccc gtgtcttcat 2220ttttggcact cttatttaac
aatgccacac ctgaagcact tggatctgtt cagagctgac 2280cccctagcaa
cgtagttgac acagctccag gtttttaaat tactaaaata agttcaagtt
2340tacatccctt gggccagata tgtgggttga ggcttgactg tagcatcctg
cttagagacc 2400aatcaatgga cactggtttt tagacctcta tcaatcagta
gttagcatcc aagagacttt 2460gcagaggcgt aggaatgagg ctggacagat
ggcggaacga gaggttccct gcgaagactt 2520gagatttagt gtctgtgaat
gttctagttc ctaggtccag caagtcacac ctgccagtgc 2580cctcatcctt
atgcctgtaa cacacatgca gtgagaggcc tcacatatac gcctccctag
2640aagtgccttc caagtcagtc ctttggaaac cagcaggtct gaaaaagagg
ctgcatcaat 2700gcaagcctgg ttggaccatt gtccatgcct caggatagaa
cagcctggct tatttgggga 2760tttttcttct agaaatcaaa tgactgataa
gcattggctc cctctgccat ttaatggcaa 2820tggtagtctt tggttagctg
caaaaatact ccatttcaag ttaaaaatgc atcttctaat 2880ccatctctgc
aagctccctg tgtttccttg ccctttagaa aatgaattgt tcactacaat
2940tagagaatca tttaacatcc tgacctggta agctgccaca cacctggcag
tggggagcat 3000cgctgtttcc aatggctcag gagacaatga aaagccccca
tttaaaaaaa taacaaacat 3060tttttaaaag gcctccaata ctcttatgga
gcctggattt ttcccactgc tctacaggct 3120gtgacttttt ttaagcatcc
tgacaggaaa tgttttcttc tacatggaaa gatagacagc 3180agccaaccct
gatctggaag acagggcccc ggctggacac acgtggaacc aagccaggga
3240tgggctggcc attgtgtccc cgcaggagag atgggcagaa tggccctaga
gttcttttcc 3300ctgagaaagg agaaaaagat gggattgcca ctcacccacc
cacactggta agggaggaga 3360atttgtgctt ctggagcttc tcaagggatt
gtgttttgca ggtacagaaa actgcctgtt 3420atcttcaagc caggttttcg
agggcacatg ggtcaccagt tgctttttca gtcaatttgg 3480ccgggatgga
ctaatgaggc tctaacactg ctcaggagac ccctgccctc tagttggttc
3540tgggctttga tctcttccaa cctgcccagt cacagaagga ggaatgactc
aaatgcccaa 3600aaccaagaac acattgcaga agtaagacaa acatgtatat
ttttaaatgt tctaacataa 3660gacctgttct ctctagccat tgatttacca
ggctttctga aagatctagt ggttcacaca 3720gagagagaga gagtactgaa
aaagcaactc ctcttcttag tcttaataat ttactaaaat 3780ggtcaacttt
tcattatctt tattataata aacctgatgc ttttttttag aactccttac
3840tctgatgtct gtatatgttg
cactgaaaag gttaatattt aatgttttaa tttattttgt 3900gtggtaagtt
aattttgatt tctgtaatgt gttaatgtga ttagcagtta ttttccttaa
3960tatctgaatt atacttaaag agtagtgagc aatataagac gcaattgtgt
ttttcagtaa 4020tgtgcattgt tattgagttg tactgtacct tatttggaag
gatgaaggaa tgaacctttt 4080tttcctaaaa 4090241180DNAHomo sapiens
24gaatagtcta ccccccttgc actctacctg acacagctgc agcctgcaat tcactcgcac
60tgcctgggat tgcactggat ccgtgtgctc agaacaaggt gaacgcccag ctgcagccat
120gaagatctgt agcctcaccc tgctctcctt cctcctactg gctgctcagg
tgctcctggt 180ggaggggaaa aaaaaagtga agaatggact tcacagcaaa
gtggtctcag aacaaaagga 240cactctgggc aacacccaga ttaagcagaa
aagcaggccc gggaacaaag gcaagtttgt 300caccaaagac caagccaact
gcagatgggc tgctactgag caggaggagg gcatctctct 360caaggttgag
tgcactcaat tggaccatga attttcctgt gtctttgctg gcaatccaac
420ctcatgccta aagctcaagg atgagagagt ctattggaaa caagttgccc
ggaatctgcg 480ctcacagaaa gacatctgta gatattccaa gacagctgtg
aaaaccagag tgtgcagaaa 540ggattttcca gaatccagtc ttaagctagt
cagctccact ctatttggga acacaaagcc 600caggaaggag aaaacagaga
tgtcccccag ggagcacatc aaaggcaaag agaccacccc 660ctctagccta
gcagtgaccc agaccatggc caccaaagct cccgagtgtg tggaggaccc
720agatatggca aaccagagga agactgccct ggagttctgt ggagagactt
ggagctctct 780ctgcacattc ttcctcagca tagtgcagga cacgtcatgc
taatgaggtc aaaagagaac 840gggttccctt aagagatgtc atgtcgtaag
tccctctgta tactttaaag ctctctacag 900tccccccaaa atatgaactt
ttgtgcttag tgagtgcaac gaaatattta aacaagtttt 960gtattttttg
cttttgtgtt ttggaatttg ccttattttt cttggatgcg atgttcagag
1020gctgtttcct gcagcatgta tttccatggc ccacacagct atgtgtttga
gcagcgaaga 1080gtctttgagc tgaatgagcc agagtgataa tttcagtgca
acgaactttc tgctgaatta 1140atggtaataa aactctgggt gtttttcaga
aatacattca 1180252510DNAHomo sapiens 25gctgggccac agcctggtcc
tgccgctgcg cccgcccgcc atggtgtccc gggaccaggc 60tcacctgggc cccaagtatg
tgggcctctg ggacttcaag tcccggacgg acgaggagct 120gagcttccgc
gcgggggacg tcttccacgt ggccaggaag gaggagcagt ggtggtgggc
180cacgctgctg gacgaggcgg gtggggccgt ggcccagggc tatgtgcccc
acaactacct 240ggccgagagg gagacggtgg agtcggaacc gtggttcttt
ggctgcatct cccgctcgga 300agctgtgcgt cggctgcagg ccgagggcaa
cgccacgggc gccttcctga tcagggtcag 360cgagaagccg agtgccgact
acgtcctgtc ggtgcgggac acgcaggctg tgcggcacta 420caagatctgg
cggcgtgccg ggggccggct gcacctgaac gaggcggtgt ccttcctcag
480cctgcccgag cttgtgaact accacagggc ccagagcctg tcccacggcc
tgcggctggc 540cgcgccctgc cggaagcacg agcctgagcc cctgccccat
tgggatgact gggagaggcc 600gagggaggag ttcacgctct gcaggaagct
ggggtccggc tactttgggg aggtcttcga 660ggggctctgg aaagaccggg
tccaggtggc cattaaggtg atttctcgag acaacctcct 720gcaccagcag
atgctgcagt cggagatcca ggccatgaag aagctgcggc acaaacacat
780cctggcgctg tacgccgtgg tgtccgtggg ggaccccgtg tacatcatca
cggagctcat 840ggccaagggc agcctgctgg agctgctccg cgactctgat
gagaaagtcc tgcccgtttc 900ggagctgctg gacatcgcct ggcaggtggc
tgagggcatg tgttacctgg agtcgcagaa 960ttacatccac cgggacctgg
ccgccaggaa catcctcgtc ggggaaaaca ccctctgcaa 1020agttggggac
ttcgggttag ccaggcttat caaggaggac gtctacctct cccatgacca
1080caatatcccc tacaagtgga cggcccctga agcgctctcc cgaggccatt
actccaccaa 1140atccgacgtc tggtcctttg ggattctcct gcatgagatg
ttcagcaggg gtcaggtgcc 1200ctacccaggc atgtccaacc atgaggcctt
cctgagggtg gacgccggct accgcatgcc 1260ctgccctctg gagtgcccgc
ccagcgtgca caagctgatg ctgacatgct ggtgcaggga 1320ccccgagcag
agaccctgct tcaaggccct gcgggagagg ctctccagct tcaccagcta
1380cgagaacccg acctgagctg ctgtggagcg ggcatggccg ggccctgctg
aggaggggcc 1440tgggcagagg gcctggacct gggatcaagg cccacgcgct
tccctggggt ttactgaggt 1500gatgggtgca ggaaaggttc acaaatgtgg
agtgtctgcg tccaatacac gcgtgtgctc 1560ctctccttac tccatcgtgt
gtgccttggg tctcagctgc tgacacgcag cctgctctgg 1620agcctgcaga
tgagatccgg gagactgaca cgaagccagc agaggtcaga ggggactctg
1680accacagccc gctctctggc tgtctgtctg cagtgcccgg ctgagggtgg
gaggcaaaca 1740cgccttgttc ctgctcttcc cagttcagct tggtgggaga
aagtcattcg cgtggctcgg 1800gacgctcatg taaatttggt tttggtgctc
aagggttctt tcctcccagg ggcaggtgtt 1860tctttcctgt ttgtcttgtg
tcttgagagc ttggccttat gaccagtgag aactctctcc 1920ctggtctctg
ccagcccaag catcactgcc cgaggcgcca gctcagtttc accgtccacg
1980tccacaaggg gcttttccca ccttcacctt tgtcgctggg tcagtgctgg
aaagcgcccc 2040tcactcctgc gctgacaagg gcccttctct actgtctgtg
gggtggttcc gggctggggg 2100ggctgcctcc tttgcacctg attttgaagg
tgtctctttc atccatggtt aagtcataaa 2160aagcttattg gttttggttt
tgactcacct gaaagttttt ttggtttaaa agaagaatag 2220gcggggcacg
gtggctcatg cctgtaatcc cagcactttg ggaggctgag gcaggtggat
2280cacgaggtca ggagatcgac accatcctgg ctaacacggt gaaaccccgt
ctctactaaa 2340aaatacaaaa aattagctgg gtgtggtggt gggggtgggc
gcctgtagtc ccagctacgt 2400gggaggctga ggcagcagac tggtgtgaac
ccgggaggtg gagcttgcag tgagccgaga 2460tcgcgccact gcactccagc
ctgggcgaca gagcgagact ccatctcaaa 2510262620DNAHomo sapiens
26acaggcacag gtgaggaact caactcaaac tcctctctct gggaaaacgc ggtgcttgct
60cctcccggag tggccttggc agggtgttgg agccctcggt ctgccccgtc cggtctctgg
120ggccaaggct gggtttccct catgtatggc aagagctcta ctcgtgcggt
gcttcttctc 180cttggcatac agctcacagc tctttggcct atagcagctg
tggaaattta tacctcccgg 240gtgctggagg ctgttaatgg gacagatgct
cggttaaaat gcactttctc cagctttgcc 300cctgtgggtg atgctctaac
agtgacctgg aattttcgtc ctctagacgg gggacctgag 360cagtttgtat
tctactacca catagatccc ttccaaccca tgagtgggcg gtttaaggac
420cgggtgtctt gggatgggaa tcctgagcgg tacgatgcct ccatccttct
ctggaaactg 480cagttcgacg acaatgggac atacacctgc caggtgaaga
acccacctga tgttgatggg 540gtgatagggg agatccggct cagcgtcgtg
cacactgtac gcttctctga gatccacttc 600ctggctctgg ccattggctc
tgcctgtgca ctgatgatca taatagtaat tgtagtggtc 660ctcttccagc
attaccggaa aaagcgatgg gccgaaagag ctcataaagt ggtggagata
720aaatcaaaag aagaggaaag gctcaaccaa gagaaaaagg tctctgttta
tttagaagac 780acagactaac aattttagat ggaagctgag atgatttcca
agaacaagaa ccctagtatt 840tcttgaagtt aatggaaact tttctttggc
ttttccagtt gtgacccgtt ttccaaccag 900ttctgcagca tattagattc
tagacaagca acacccctct ggagccagca cagtgctcct 960ccatatcacc
agtcatacac agcctcatta ttaaggtctt atttaatttc agagtgtaaa
1020ttttttcaag tgctcattag gttttataaa caagaagcta catttttgcc
cttaagacac 1080tacttacagt gttatgactt gtatacacat atattggtat
caaaagggat aaaagccaat 1140ttgtctgtta catttccttt cacgtatttc
ttttagcagc acttctgcta ctaaagttaa 1200tgtgtttact ctctttcctt
cccacattct caattaaaag gtgagctaag cctcctcggt 1260gtttctgatt
aacagtaaat cctaaattca aactgttaaa tgacattttt atttttatgt
1320ctctccttaa ctatgagaca catcttgttt tactgaattt ctttcaatat
tccaggtgat 1380agatttttgt tgttttgtta attaatccaa gatttacaat
agcacaacgc taaatcacac 1440agtaactaca aaaggttaca tagatatgaa
aagattggca gaggccattg caggatgaat 1500cacttgtcac ttttcttctg
tgctgggaaa aataatcaac aatgtgggtc tttcatgagc 1560agtgacggat
agtttagctt actatgtttc ccccccaatt caatgatcta taacaacaga
1620gcaaagtcta tgctcatttg cagactggaa tcattaagta atttaataaa
aaaattgtga 1680aacagcatat tacaagtttg aaaattcagg gctggtgaaa
aaaatcaact ctaaatgatg 1740ataattttgt acagttttat ataaaactct
gagaactaga agaaattatt aacttttttt 1800cttttttaat tctaattcac
ttgtttattt tgggggagga agactttggt atggagcaaa 1860gaaataccaa
aactacttta aatggaataa aaccaacttt attctttttt tcccccatac
1920tggtagataa agcaaacttt ataagtgggc tattgaaaga aaagttacaa
gcttaagata 1980cagaagcatt tgttcaaagg atagaaagca tctaaaagtt
taggctcaag atcaatcttt 2040acagattgat attttcagtt tttaatcgac
tggactgcag atgttttttc ttttaacaaa 2100ctggaatttt caaacagatt
atctgtattt aaatgtatag accttgatat ttttccaata 2160ctatttttta
aaaaattgta tgatttacat atgaacctca gttctgaaat tcattacata
2220tctgtctcat tctgcctttt atactgtcta aaaaagcaaa gttttaaagt
gcaattttaa 2280aactgtaaat tacatctgaa ggctatatat cctttaatca
cattttatat tttttcttca 2340caattctaac ctttgaaaat attataactg
gatatttctt caaacagatg tcctggatga 2400tggtccataa gaataatgaa
gaagtagtta aaaatgtatg gacagttttt ccggcaaaat 2460ttgtagctta
tgtcttggct aaatagtcaa ggggtaatat gggcctgttg tttagtgtct
2520ccttcctaaa gagcactttt gtattgtaat ttatttttta ttatgcttta
aacactatgt 2580aaataaacct ttagtaataa agaattatca gttataaaaa
2620273950DNAHomo sapiens 27attaaggact cggggcagga ggggcagaag
ttgcgcgcag gccggcgggc gggagcggac 60accgaggccg gcgtgcaggc gtgcgggtgt
gcgggagccg ggctcggggg gatcggaccg 120agagcgagaa gcgcggcatg
gagctccagg cagcccgcgc ctgcttcgcc ctgctgtggg 180gctgtgcgct
ggccgcggcc gcggcggcgc agggcaagga agtggtactg ctggactttg
240ctgcagctgg aggggagctc ggctggctca cacacccgta tggcaaaggg
tgggacctga 300tgcagaacat catgaatgac atgccgatct acatgtactc
cgtgtgcaac gtgatgtctg 360gcgaccagga caactggctc cgcaccaact
gggtgtaccg aggagaggct gagcgtatct 420tcattgagct caagtttact
gtacgtgact gcaacagctt ccctggtggc gccagctcct 480gcaaggagac
tttcaacctc tactatgccg agtcggacct ggactacggc accaacttcc
540agaagcgcct gttcaccaag attgacacca ttgcgcccga tgagatcacc
gtcagcagcg 600acttcgaggc acgccacgtg aagctgaacg tggaggagcg
ctccgtgggg ccgctcaccc 660gcaaaggctt ctacctggcc ttccaggata
tcggtgcctg tgtggcgctg ctctccgtcc 720gtgtctacta caagaagtgc
cccgagctgc tgcagggcct ggcccacttc cctgagacca 780tcgccggctc
tgatgcacct tccctggcca ctgtggccgg cacctgtgtg gaccatgccg
840tggtgccacc ggggggtgaa gagccccgta tgcactgtgc agtggatggc
gagtggctgg 900tgcccattgg gcagtgcctg tgccaggcag gctacgagaa
ggtggaggat gcctgccagg 960cctgctcgcc tggatttttt aagtttgagg
catctgagag cccctgcttg gagtgccctg 1020agcacacgct gccatcccct
gagggtgcca cctcctgcga gtgtgaggaa ggcttcttcc 1080gggcacctca
ggacccagcg tcgatgcctt gcacacgacc cccctccgcc ccacactacc
1140tcacagccgt gggcatgggt gccaaggtgg agctgcgctg gacgccccct
caggacagcg 1200ggggccgcga ggacattgtc tacagcgtca cctgcgaaca
gtgctggccc gagtctgggg 1260aatgcgggcc gtgtgaggcc agtgtgcgct
actcggagcc tcctcacgga ctgacccgca 1320ccagtgtgac agtgagcgac
ctggagcccc acatgaacta caccttcacc gtggaggccc 1380gcaatggcgt
ctcaggcctg gtaaccagcc gcagcttccg tactgccagt gtcagcatca
1440accagacaga gccccccaag gtgaggctgg agggccgcag caccacctcg
cttagcgtct 1500cctggagcat ccccccgccg cagcagagcc gagtgtggaa
gtacgaggtc acttaccgca 1560agaagggaga ctccaacagc tacaatgtgc
gccgcaccga gggtttctcc gtgaccctgg 1620acgacctggc cccagacacc
acctacctgg tccaggtgca ggcactgacg caggagggcc 1680agggggccgg
cagcaaggtg cacgaattcc agacgctgtc cccggaggga tctggcaact
1740tggcggtgat tggcggcgtg gctgtcggtg tggtcctgct tctggtgctg
gcaggagttg 1800gcttctttat ccaccgcagg aggaagaacc agcgtgcccg
ccagtccccg gaggacgttt 1860acttctccaa gtcagaacaa ctgaagcccc
tgaagacata cgtggacccc cacacatatg 1920aggaccccaa ccaggctgtg
ttgaagttca ctaccgagat ccatccatcc tgtgtcactc 1980ggcagaaggt
gatcggagca ggagagtttg gggaggtgta caagggcatg ctgaagacat
2040cctcggggaa gaaggaggtg ccggtggcca tcaagacgct gaaagccggc
tacacagaga 2100agcagcgagt ggacttcctc ggcgaggccg gcatcatggg
ccagttcagc caccacaaca 2160tcatccgcct agagggcgtc atctccaaat
acaagcccat gatgatcatc actgagtaca 2220tggagaatgg ggccctggac
aagttccttc gggagaagga tggcgagttc agcgtgctgc 2280agctggtggg
catgctgcgg ggcatcgcag ctggcatgaa gtacctggcc aacatgaact
2340atgtgcaccg tgacctggct gcccgcaaca tcctcgtcaa cagcaacctg
gtctgcaagg 2400tgtctgactt tggcctgtcc cgcgtgctgg aggacgaccc
cgaggccacc tacaccacca 2460gtggcggcaa gatccccatc cgctggaccg
ccccggaggc catttcctac cggaagttca 2520cctctgccag cgacgtgtgg
agctttggca ttgtcatgtg ggaggtgatg acctatggcg 2580agcggcccta
ctgggagttg tccaaccacg aggtgatgaa agccatcaat gatggcttcc
2640ggctccccac acccatggac tgcccctccg ccatctacca gctcatgatg
cagtgctggc 2700agcaggagcg tgcccgccgc cccaagttcg ctgacatcgt
cagcatcctg gacaagctca 2760ttcgtgcccc tgactccctc aagaccctgg
ctgactttga cccccgcgtg tctatccggc 2820tccccagcac gagcggctcg
gagggggtgc ccttccgcac ggtgtccgag tggctggagt 2880ccatcaagat
gcagcagtat acggagcact tcatggcggc cggctacact gccatcgaga
2940aggtggtgca gatgaccaac gacgacatca agaggattgg ggtgcggctg
cccggccacc 3000agaagcgcat cgcctacagc ctgctgggac tcaaggacca
ggtgaacact gtggggatcc 3060ccatctgagc ctcgacaggg cctggagccc
catcggccaa gaatacttga agaaacagag 3120tggcctccct gctgtgccat
gctgggccac tggggacttt atttatttct agttctttcc 3180tccccctgca
acttccgctg aggggtctcg gatgacaccc tggcctgaac tgaggagatg
3240accagggatg ctgggctggg ccctctttcc ctgcgagacg cacacagctg
agcacttagc 3300aggcaccgcc acgtcccagc atccctggag caggagcccc
gccacagcct tcggacagac 3360atataggata ttcccaagcc gaccttccct
ccgccttctc ccacatgagg ccatctcagg 3420agatggaggg cttggcccag
cgccaagtaa acagggtacc tcaagcccca tttcctcaca 3480ctaagagggc
agactgtgaa cttgactggg tgagacccaa agcggtccct gtccctctag
3540tgccttcttt agaccctcgg gccccatcct catccctgac tggccaaacc
cttgctttcc 3600tgggcctttg caagatgctt ggttgtgttg aggtttttaa
atatatattt tgtactttgt 3660ggagagaatg tgtgtgtgtg gcagggggcc
ccgccagggc tggggacaga gggtgtcaaa 3720cattcgtgag ctggggactc
agggaccggt gctgcaggag tgtcctgccc atgccccagt 3780cggccccatc
tctcatcctt ttggataagt ttctattctg tcagtgttaa agattttgtt
3840ttgttggaca tttttttcga atcttaattt attatttttt ttatatttat
tgttagaaaa 3900tgacttattt ctgctctgga ataaagttgc agatgattca
aaccgaaaaa 3950285810DNAHomo sapiens 28aacgggctca ttcagcggtc
gcgagctgcc cgcgaggggg agcggccgga cggagagcgc 60gacccgtccc gggggtgggg
ccgggcgcag cggcgagagg aggcgaaggt ggctgcggta 120gcagcagcgc
ggcagcctcg gacccagccc ggagcgcagg gcggccgctg caggtccccg
180ctcccctccc cgtgcgtccg cccatggccg ccgccgggca gctgtgcttg
ctctacctgt 240cggcggggct cctgtcccgg ctcggcgcag ccttcaactt
ggacactcgg gaggacaacg 300tgatccggaa atatggagac cccgggagcc
tcttcggctt ctcgctggcc atgcactggc 360aactgcagcc cgaggacaag
cggctgttgc tcgtgggggc cccgcgggca gaagcgcttc 420cactgcagag
agccaacaga acgggagggc tgtacagctg cgacatcacc gcccgggggc
480catgcacgcg gatcgagttt gataacgatg ctgaccccac gtcagaaagc
aaggaagatc 540agtggatggg ggtcaccgtc cagagccaag gtccaggggg
caaggtcgtg acatgtgctc 600accgatatga aaaaaggcag catgttaata
cgaagcagga atcccgagac atctttgggc 660ggtgttatgt cctgagtcag
aatctcagga ttgaagacga tatggatggg ggagattgga 720gcttttgtga
tgggcgattg agaggccatg agaaatttgg ctcttgccag caaggtgtag
780cagctacttt tactaaagac tttcattaca ttgtatttgg agccccgggt
acttataact 840ggaaagggat tgttcgtgta gagcaaaaga ataacacttt
ttttgacatg aacatctttg 900aagatgggcc ttatgaagtt ggtggagaga
ctgagcatga tgaaagtctc gttcctgttc 960ctgctaacag ttacttaggt
ttttctttgg actcagggaa aggtattgtt tctaaagatg 1020agatcacttt
tgtatctggt gctcccagag ccaatcacag tggagccgtg gttttgctga
1080agagagacat gaagtctgca catctcctcc ctgagcacat attcgatgga
gaaggtctgg 1140cctcttcatt tggctatgat gtggcggtgg tggacctcaa
caaggatggg tggcaagata 1200tagttattgg agccccacag tattttgata
gagatggaga agttggaggt gcagtgtatg 1260tctacatgaa ccagcaaggc
agatggaata atgtgaagcc aattcgtctt aatggaacca 1320aagattctat
gtttggcatt gcagtaaaaa atattggaga tattaatcaa gatggctacc
1380cagatattgc agttggagct ccgtatgatg acttgggaaa ggtttttatc
tatcatggat 1440ctgcaaatgg aataaatacc aaaccaacac aggttctcaa
gggtatatca ccttattttg 1500gatattcaat tgctggaaac atggaccttg
atcgaaattc ctaccctgat gttgctgttg 1560gttccctctc agattcagta
actattttca gatcccggcc tgtgattaat attcagaaaa 1620ccatcacagt
aactcctaac agaattgacc tccgccagaa aacagcgtgt ggggcgccta
1680gtgggatatg cctccaggtt aaatcctgtt ttgaatatac tgctaacccc
gctggttata 1740atccttcaat atcaattgtg ggcacacttg aagctgaaaa
agaaagaaga aaatctgggc 1800tatcctcaag agttcagttt cgaaaccaag
gttctgagcc caaatatact caagaactaa 1860ctctgaagag gcagaaacag
aaagtgtgca tggaggaaac cctgtggcta caggataata 1920tcagagataa
actgcgtccc attcccataa ctgcctcagt ggagatccaa gagccaagct
1980ctcgtaggcg agtgaattca cttccagaag ttcttccaat tctgaattca
gatgaaccca 2040agacagctca tattgatgtt cacttcttaa aagagggatg
tggagacgac aatgtatgta 2100acagcaacct taaactagaa tataaatttt
gcacccgaga aggaaatcaa gacaaatttt 2160cttatttacc aattcaaaaa
ggtgtaccag aactagttct aaaagatcag aaggatattg 2220ctttagaaat
aacagtgaca aacagccctt ccaacccaag gaatcccaca aaagatggcg
2280atgacgccca tgaggctaaa ctgattgcaa cgtttccaga cactttaacc
tattctgcat 2340atagagaact gagggctttc cctgagaaac agttgagttg
tgttgccaac cagaatggct 2400cgcaagctga ctgtgagctc ggaaatcctt
ttaaaagaaa ttcaaatgtc actttttatt 2460tggttttaag tacaactgaa
gtcacctttg acaccccaga tctggatatt aatctgaagt 2520tagaaacaac
aagcaatcaa gataatttgg ctccaattac agctaaagca aaagtggtta
2580ttgaactgct tttatcggtc tcgggagttg ctaaaccttc ccaggtgtat
tttggaggta 2640cagttgttgg cgagcaagct atgaaatctg aagatgaagt
gggaagttta atagagtatg 2700aattcagggt aataaactta ggtaaacctc
ttacaaacct cggcacagca accttgaaca 2760ttcagtggcc aaaagaaatt
agcaatggga aatggttgct ttatttggtg aaagtagaat 2820ccaaaggatt
ggaaaaggta acttgtgagc cacaaaagga gataaactcc ctgaacctaa
2880cggagtctca caactcaaga aagaaacggg aaattactga aaaacagata
gatgataaca 2940gaaaattttc tttatttgct gaaagaaaat accagactct
taactgtagc gtgaacgtga 3000actgtgtgaa catcagatgc ccgctgcggg
ggctggacag caaggcgtct cttattttgc 3060gctcgaggtt atggaacagc
acatttctag aggaatattc caaactgaac tacttggaca 3120ttctcatgcg
agccttcatt gatgtgactg ctgctgccga aaatatcagg ctgccaaatg
3180caggcactca ggttcgagtg actgtgtttc cctcaaagac tgtagctcag
tattcgggag 3240taccttggtg gatcatccta gtggctattc tcgctgggat
cttgatgctt gctttattag 3300tgtttatact atggaagtgt ggtttcttca
agagaaataa gaaagatcat tatgatgcca 3360catatcacaa ggctgagatc
catgctcagc catctgataa agagaggctt acttctgatg 3420catagtattg
atctacttct gtaattgtgt ggattcttta aacgctctag gtacgatgac
3480agtgttcccc gataccatgc tgtaaggatc cggaaagaag agcgagagat
caaagatgaa 3540aagtatattg ataaccttga aaaaaaacag tggatcacaa
agtggaacga aaatgaaagc 3600tactcatagc gggggcctaa aaaaaaaaag
cttcacagta cccaaactgc tttttccaac 3660tcagaaattc aatttggatt
taaaagcctg ctcaatccct gaggactgat ttcagagtga 3720ctacacacag
tacgaaccta cagttttaac tgtggatatt gttacgtagc ctaaggctcc
3780tgttttgcac agccaaattt aaaactgttg gaatggattt ttctttaact
gccgtaattt 3840aactttctgg gttgccttta tttttggcgt ggctgactta
catcatgtgt tggggaaggg 3900cctgcccagt tgcactcagg tgacatcctc
cagatagtgt agctgaggag gcacctacac 3960tcacctgcac taacagagtg
gccgtcctaa cctcgggcct gctgcgcaga cgtccatcac 4020gttagctgtc
ccacatcaca agactatgcc attggggtag ttgtgtttca acggaaagtg
4080ctgtcttaaa ctaaatgtgc aatagaaggt gatgttgcca tcctaccgtc
ttttcctgtt 4140tcctagctgt gtgaatacct gctcacgtca aatgcataca
agtttcattc tccctttcac 4200taaaacacac aggtgcaaca gacttgaatg
ctagttatac ttatttgtat atggtattta 4260ttttttcttt tctttacaaa
ccattttgtt attgactaac aggccaaaga gtctccagtt 4320tacccttcag
gttggtttaa tcaatcagaa ttagagcatg
ggaggtcatc actttgacct 4380aaattattta ctgcaaaaag aaaatcttta
taaatgtacc agagagagtt gttttaataa 4440cttatctata aactataacc
tctccttcat gacagcctcc accccacaac ccaaaaggtt 4500taagaaatag
aattataact gtaaagatgt ttatttcagg cattggatat tttttacttt
4560agaagcctgc ataatgtttc tggatttcat actgtaacat tcaggaattc
ttggagaaaa 4620tgggtttatt cactgaactc tagtgcggtt tactcactgc
tgcaaatact gtatattcag 4680gacttgaaag aaatggtgaa tgcctatggt
ggatccaaac tgatccagta taagactact 4740gaatctgcta ccaaaacagt
taatcagtga gtcgatgttc tattttttgt tttgtttcct 4800cccctatctg
tattcccaaa aattactttg gggctaattt aacaagaact ttaaattgtg
4860ttttaattgt aaaaatggca gggggtggaa ttattactct atacattcaa
cagagactga 4920atagatatga aagctgattt tttttaatta ccatgcttca
caatgttaag ttatatgggg 4980agcaacagca aacaggtgct aatttgtttt
ggatatagta taagcagtgt ctgtgttttg 5040aaagaataga acacagtttg
tagtgccact gttgttttgg gggggctttt ttcttttcgg 5100aaatcttaaa
ccttaagata ctaaggacgt tgttttggtt gtactttgga attcttagtc
5160acaaaatata ttttgtttac aaaaatttct gtaaaacagg ttataacagt
gtttaaagtc 5220tcagtttctt gcttggggaa cttgtgtccc taatgtgttt
agattgctag attgctaagg 5280agctgatact ttgacagtgt ttttagacct
gtgttactaa aaaaaagatg aatgtcctga 5340aaagggtgtt gggagggtgg
ttcaacaaag aaacaaagat gttatggtgt ttagatttat 5400ggttgttaaa
aatgtcatct caagtcaagt cactggtctg tttgcatttg atacattttt
5460gtactaacta gcattgtaaa attatttcat gattagaaat tacctgtgga
tatttgtata 5520aaagtgtgaa ataaattttt tataaaagtg ttcattgttt
cgtaacacag cattgtatat 5580gtgaagcaaa ctctaaaatt ataaatgaca
acctgaatta tctatttcat caaaccaaag 5640ttcagtgttt ttatttttgg
tgtctcatgt aatctcagat cagccaaaga tactagtgcc 5700aaagcaatgg
gattcggggt ttttttctgt tttcgctcta tgtaggtgat cctcaagtct
5760ttcattttcc ttctttatga ttaaaagaaa cctacaggta tttaacaacc
5810293640DNAHomo sapiens 29gccaccacgt gtgtccctgc gcccggtggc
caccgactca gtccctcgcc gaccagtctg 60ggcagcggag gagggtggtt ggcagtggct
ggaagcttcg ctatgggaag ttgttccttt 120gctctctcgc gcccagtcct
cctccctggt tctcctcagc cgctgtcgga ggagagcacc 180cggagacgcg
ggctgcagtc gcggcggctt ctccccgcct gggcggccgc gccgctgggc
240aggtgctgag cgcccctaga gcctcccttg ccgcctccct cctctgcccg
gccgcagcag 300tgcacatggg gtgttggagg tagatgggct cccggcccgg
gaggcggcgg tggatgcggc 360gctgggcaga agcagccgcc gattccagct
gccccgcgcg ccccgggcgc ccctgcgagt 420ccccggttca gccatgggga
cctctccgag cagcagcacc gccctcgcct cctgcagccg 480catcgcccgc
cgagccacag ccacgatgat cgcgggctcc cttctcctgc ttggattcct
540tagcaccacc acagctcagc cagaacagaa ggcctcgaat ctcattggca
cataccgcca 600tgttgaccgt gccaccggcc aggtgctaac ctgtgacaag
tgtccagcag gaacctatgt 660ctctgagcat tgtaccaaca caagcctgcg
cgtctgcagc agttgccctg tggggacctt 720taccaggcat gagaatggca
tagagaaatg ccatgactgt agtcagccat gcccatggcc 780aatgattgag
aaattacctt gtgctgcctt gactgaccga gaatgcactt gcccacctgg
840catgttccag tctaacgcta cctgtgcccc ccatacggtg tgtcctgtgg
gttggggtgt 900gcggaagaaa gggacagaga ctgaggatgt gcggtgtaag
cagtgtgctc ggggtacctt 960ctcagatgtg ccttctagtg tgatgaaatg
caaagcatac acagactgtc tgagtcagaa 1020cctggtggtg atcaagccgg
ggaccaagga gacagacaac gtctgtggca cactcccgtc 1080cttctccagc
tccacctcac cttcccctgg cacagccatc tttccacgcc ctgagcacat
1140ggaaacccat gaagtccctt cctccactta tgttcccaaa ggcatgaact
caacagaatc 1200caactcttct gcctctgtta gaccaaaggt actgagtagc
atccaggaag ggacagtccc 1260tgacaacaca agctcagcaa gggggaagga
agacgtgaac aagaccctcc caaaccttca 1320ggtagtcaac caccagcaag
gcccccacca cagacacatc ctgaagctgc tgccgtccat 1380ggaggccact
gggggcgaga agtccagcac gcccatcaag ggccccaaga ggggacatcc
1440tagacagaac ctacacaagc attttgacat caatgagcat ttgccctgga
tgattgtgct 1500tttcctgctg ctggtgcttg tggtgattgt ggtgtgcagt
atccggaaaa gctcgaggac 1560tctgaaaaag gggccccggc aggatcccag
tgccattgtg gaaaaggcag ggctgaagaa 1620atccatgact ccaacccaga
accgggagaa atggatctac tactgcaatg gccatggtat 1680cgatatcctg
aagcttgtag cagcccaagt gggaagccag tggaaagata tctatcagtt
1740tctttgcaat gccagtgaga gggaggttgc tgctttctcc aatgggtaca
cagccgacca 1800cgagcgggcc tacgcagctc tgcagcactg gaccatccgg
ggccccgagg ccagcctcgc 1860ccagctaatt agcgccctgc gccagcaccg
gagaaacgat gttgtggaga agattcgtgg 1920gctgatggaa gacaccaccc
agctggaaac tgacaaacta gctctcccga tgagccccag 1980cccgcttagc
ccgagcccca tccccagccc caacgcgaaa cttgagaatt ccgctctcct
2040gacggtggag ccttccccac aggacaagaa caagggcttc ttcgtggatg
agtcggagcc 2100ccttctccgc tgtgactcta catccagcgg ctcctccgcg
ctgagcagga acggttcctt 2160tattaccaaa gaaaagaagg acacagtgtt
gcggcaggta cgcctggacc cctgtgactt 2220gcagcctatc tttgatgaca
tgctccactt tctaaatcct gaggagctgc gggtgattga 2280agagattccc
caggctgagg acaaactaga ccggctattc gaaattattg gagtcaagag
2340ccaggaagcc agccagaccc tcctggactc tgtttatagc catcttcctg
acctgctgta 2400gaacataggg atactgcatt ctggaaatta ctcaatttag
tggcagggtg gttttttaat 2460tttcttctgt ttctgatttt tgttgtttgg
ggtgtgtgtg tgtgtttgtg tgtgtgtgtg 2520tgtgtgtgtg tgtgtgtgtg
tttaacagag aatatggcca gtgcttgagt tctttctcct 2580tctctctctc
tctttttttt ttaaataact cttctgggaa gttggtttat aagcctttgc
2640caggtgtaac tgttgtgaaa tacccaccac taaagttttt taagttccat
attttctcca 2700ttttgccttc ttatgtattt tcaagattat tctgtgcact
ttaaatttac ttaacttacc 2760ataaatgcag tgtgactttt cccacacact
ggattgtgag gctcttaact tcttaaaagt 2820ataatggcat cttgtgaatc
ctataagcag tctttatgtc tcttaacatt cacacctact 2880ttttaaaaac
aaatattatt actattttta ttattgtttg tcctttataa attttcttaa
2940agattaagaa aatttaagac cccattgagt tactgtaatg caattcaact
ttgagttatc 3000ttttaaatat gtcttgtata gttcatattc atggctgaaa
cttgaccaca ctattgctga 3060ttgtatggtt ttcacctgga caccgtgtag
aatgcttgat tacttgtact cttcttatgc 3120taatatgctc tgggctggag
aaatgaaatc ctcaagccat caggatttgc tatttaagtg 3180gcttgacaac
tgggccacca aagaacttga acttcacctt ttaggatttg agctgttctg
3240gaacacattg ctgcactttg gaaagtcaaa atcaagtgcc agtggcgccc
tttccataga 3300gaatttgccc agctttgctt taaaagatgt cttgtttttt
atatacacat aatcaatagg 3360tccaatctgc tctcaaggcc ttggtcctgg
tgggattcct tcaccaatta ctttaattaa 3420aaatggctgc aactgtaaga
acccttgtct gatatatttg caactatgct cccatttaca 3480aatgtacctt
ctaatgctca gttgccaggt tccaatgcaa aggtggcgtg gactcccttt
3540gtgtgggtgg ggtttgtggg tagtggtgaa ggaccgatat cagaaaaatg
ccttcaagtg 3600tactaattta ttaataaaca ttaggtgttt gttaaaaaaa
3640301130DNAHomo sapiens 30agtgccccag gagctatgac aagcaaagga
acatacttgc ctggagatag cctttgcgat 60atttaaatgt ccgtggatac agaaatctct
gcaggcaagt tgctccagag catattgcag 120gacaagcctg taacgaatag
ttaaattcac ggcatctgga ttcctaatcc ttttccgaaa 180tggcaggtgt
gagtgcctgt ataaaatatt ctatgtttac cttcaacttc ttgttctggc
240tatgtggtat cttgatccta gcattagcaa tatgggtacg agtaagcaat
gactctcaag 300caatttttgg ttctgaagat gtaggctcta gctcctacgt
tgctgtggac atattgattg 360ctgtaggtgc catcatcatg attctgggct
tcctgggatg ctgcggtgct ataaaagaaa 420gtcgctgcat gcttctgttg
tttttcatag gcttgcttct gatcctgctc ctgcaggtgg 480cgacaggtat
cctaggagct gttttcaaat ctaagtctga tcgcattgtg aatgaaactc
540tctatgaaaa cacaaagctt ttgagcgcca caggggaaag tgaaaaacaa
ttccaggaag 600ccataattgt gtttcaagaa gagtttaaat gctgcggttt
ggtcaatgga gctgctgatt 660ggggaaataa ttttcaacac tatcctgaat
tatgtgcctg tctagataag cagagaccat 720gccaaagcta taatggaaaa
caagtttaca aagagacctg tatttctttc ataaaagact 780tcttggcaaa
aaatttgatt atagttattg gaatatcatt tggactggca gttattgaga
840tactgggttt ggtgttttct atggtcctgt attgccagat cgggaacaaa
tgaatctgtg 900gatgcatcaa cctatcgtca gtcaaacccc tttaaaatgt
tgctttggct ttgtaaattt 960aaatatgtaa gtgctatata agtcaggagc
agctgtcttt ttaaaatgtc tcggctagct 1020agaccacaga tatcttctag
acatattgaa cacatttaag atttgaggga tataagggaa 1080aatgatatga
atgtgtattt ttactcaaaa taaaagtaac tgtttacgtt 1130311145DNAHomo
sapiens 31attctctccc cagcttgctg agccctttgc tcccctggcg actgcctgga
cagtcagcaa 60ggaattgtct cccagtgcat tttgccctcc tggctgccaa ctctggctgc
taaagcggct 120gccacctgct gcagtctaca cagcttcggg aagaggaaag
gaacctcaga ccttccagat 180cgcttcctct cgcaacaaac tatttgtcgc
aggaataaag atggctgctg aaccagtaga 240agacaattgc atcaactttg
tggcaatgaa atttattgac aatacgcttt actttatagc 300tgaagatgat
gaaaacctgg aatcagatta ctttggcaag cttgaatcta aattatcagt
360cataagaaat ttgaatgacc aagttctctt cattgaccaa ggaaatcggc
ctctatttga 420agatatgact gattctgact gtagagataa tgcaccccgg
accatattta ttataagtat 480gtataaagat agccagccta gaggtatggc
tgtaactatc tctgtgaagt gtgagaaaat 540ttcaactctc tcctgtgaga
acaaaattat ttcctttaag gaaatgaatc ctcctgataa 600catcaaggat
acaaaaagtg acatcatatt ctttcagaga agtgtcccag gacatgataa
660taagatgcaa tttgaatctt catcatacga aggatacttt ctagcttgtg
aaaaagagag 720agaccttttt aaactcattt tgaaaaaaga ggatgaattg
ggggatagat ctataatgtt 780cactgttcaa aacgaagact agctattaaa
atttcatgcc gggcgcagtg gctcacgcct 840gtaatcccag ccctttggga
ggctgaggcg ggcagatcac cagaggtcag gtgttcaaga 900ccagcctgac
caacatggtg aaacctcatc tctactaaaa atacaaaaaa ttagctgagt
960gtagtgacgc atgccctcaa tcccagctac tcaagaggct gaggcaggag
aatcacttgc 1020actccggagg tagaggttgt ggtgagccga gattgcacca
ttgcgctcta gcctgggcaa 1080caacagcaaa actccatctc aaaaaataaa
ataaataaat aaacaaataa aaaattcata 1140atgtg 1145321790DNAHomo
sapiens 32gagggagggg ccgccgggga agaggaggag gaaggaaaga aagaaagcga
gggagggaaa 60gaggaggaag gaagatgcga gaaggcagag gaggagggag ggagggaagg
agcgcggagc 120ccggcccgga agctaggagc cattccgtag tgccatcccg
agcaacgcac tgctgcagct 180tccctgagcc tttccagcaa gtttgttcaa
gattggctgt caagaatcat ggactgttat 240tatatgcctt gttttctgtc
aagacaccat gattcctggt aaccgaatgc tgatggtcgt 300tttattatgc
caagtcctgc taggaggcgc gagccatgct agtttgatac ctgagacggg
360gaagaaaaaa gtcgccgaga ttcagggcca cgcgggagga cgccgctcag
ggcagagcca 420tgagctcctg cgggacttcg aggcgacact tctgcagatg
tttgggctgc gccgccgccc 480gcagcctagc aagagtgccg tcattccgga
ctacatgcgg gatctttacc ggcttcagtc 540tggggaggag gaggaagagc
agatccacag cactggtctt gagtatcctg agcgcccggc 600cagccgggcc
aacaccgtga ggagcttcca ccacgaagaa catctggaga acatcccagg
660gaccagtgaa aactctgctt ttcgtttcct ctttaacctc agcagcatcc
ctgagaacga 720ggcgatctcc tctgcagagc ttcggctctt ccgggagcag
gtggaccagg gccctgattg 780ggaaaggggc ttccaccgta taaacattta
tgaggttatg aagcccccag cagaagtggt 840gcctgggcac ctcatcacac
gactactgga cacgagactg gtccaccaca atgtgacacg 900gtgggaaact
tttgatgtga gccctgcggt ccttcgctgg acccgggaga agcagccaaa
960ctatgggcta gccattgagg tgactcacct ccatcagact cggacccacc
agggccagca 1020tgtcaggatt agccgatcgt tacctcaagg gagtgggaat
tgggcccagc tccggcccct 1080cctggtcacc tttggccatg atggccgggg
ccatgccttg acccgacgcc ggagggccaa 1140gcgtagccct aagcatcact
cacagcgggc caggaagaag aataagaact gccggcgcca 1200ctcgctctat
gtggacttca gcgatgtggg ctggaatgac tggattgtgg ccccaccagg
1260ctaccaggcc ttctactgcc atggggactg cccctttcca ctggctgacc
acctcaactc 1320aaccaaccat gccattgtgc agaccctggt caattctgtc
aattccagta tccccaaagc 1380ctgttgtgtg cccactgaac tgagtgccat
ctccatgctg tacctggatg agtatgataa 1440ggtggtactg aaaaattatc
aggagatggt agtagaggga tgtgggtgcc gctgagatca 1500ggcagtcctt
gaggatagac agatatacac accacacaca cacaccacat acaccacaca
1560cacacgttcc catccactca cccacacact acacagactg cttccttata
gctggacttt 1620tatttaaaaa aaaaaaaaaa aaaatggaaa aaatccctaa
acattcacct tgaccttatt 1680tatgacttta cgtgcaaatg ttttgaccat
attgatcata tattttgaca aaatatattt 1740ataactacgt attaaaagaa
aaaaataaaa tgagtcatta ttttaaaggt 1790331880DNAHomo sapiens
33ccagatcata ccctgctggg caaaggagga agagccagag gatccagacg ccttggagga
60cttggaacac ctgtaacagg acaaggagtt ctgctcaggc acgtggccac agaaaactac
120ttaggaagcc tgtggtgaga acaacaacag tgcctgagaa tcccacggct
ctggggaagt 180gagccccgag gatgaggctg ctcgcctggc tgattttcct
ggctaactgg ggaggtgcca 240gggctgaacc agggaagttc tggcacatcg
ctgacctgca ccttgaccct gactacaagg 300tatccaaaga ccccttccag
gtgtgcccat cagctggatc ccagccagtg cccgacgcag 360gcccctgggg
tgactacctc tgtgattctc cctgggccct catcaactcc tccatctatg
420ccatgaagga gattgagcca gagccagact tcattctctg gactggtgat
gacacgcctc 480atgtgcccga tgagaaactg ggagaggcag ctgtactgga
aattgtggaa cgcctgacca 540agctcatcag agaggtcttt ccagatacta
aagtctatgc tgctttggga aatcatgatt 600ttcaccccaa aaaccagttc
ccagctggaa gtaacaacat ctacaatcag atagcagaac 660tatggaaacc
ctggcttagt aatgagtcca tcgctctctt caaaaaaggt gccttctact
720gtgagaagct gccgggtccc agcggggctg ggcgaattgt ggtcctcaac
accaatctgt 780actataccag caatgcgctg acagcagaca tggcggaccc
tggccagcag ttccagtggc 840tggaagatgt gctgaccgat gcatccaaag
ctggggacat ggtgtacatt gtcggccacg 900tgcccccggg gttctttgag
aagacgcaaa acaaggcatg gttccgggag ggcttcaatg 960aaaaatacct
gaaggtggtc cggaagcatc atcgcgtcat agcagggcag ttcttcgggc
1020accaccacac cgacagcttt cggatgctct atgatgatgc aggtgtcccc
ataagcgcca 1080tgttcatcac acctggagtc accccatgga aaaccacatt
acctggagtg gtcaatgggg 1140ccaacaatcc agccatccgg gtgttcgaat
atgaccgagc cacactgagc ctgaaggaca 1200tggtgaccta cttcatgaac
ctgagccagg cgaatgctca ggggacgccg cgctgggagc 1260tcgagtacca
gctgaccgag gcctatgggg tgccggacgc cagcgcccac tccatgcaca
1320cagtgctgga ccgcatcgct ggcgaccaga gcacactgca gcgctactac
gtctataact 1380cagtcagcta ctctgctggg gtctgcgacg aggcctgcag
catgcagcac gtgtgtgcca 1440tgcgccaggt ggacattgac gcttacacca
cctgtctgta tgcctctggc accacgcccg 1500tgccccagct cccgctgctg
ctgatggccc tgctgggcct gtgcacgctc gtgctgtgac 1560ctgccaggct
caccttcttc ctggtaacgg gtaacggggg cagcgcccag gatcacccag
1620agctgggcct tccaccattt cctccgcgcc tgaggagtga actgaaatag
gacaaccgaa 1680tcaggaagcg aagccccagg agctgcagcc atccgtgatc
gcgccactgc actccagcct 1740gggcgacaaa gccagactct ctccaaaaac
aaaccagaaa cagaaaagaa atgacgaccc 1800aagacccccc tacaagcata
cttcttttgc gtattatgtt ttactcacaa aacaaagctc 1860atcatgcgtt
tgaaaaaaaa 1880343200DNAHomo sapiens 34cgcgagctaa gcaggaggcg
gaggcggagg cggagggcga ggggcgggga gcgccgcctg 60gagcgcggca ggtcatattg
aacattccag atacctatca ttactcgatg ctgttgataa 120cagcaagatg
gctttgaact cagggtcacc accagctatt ggaccttact atgaaaacca
180tggataccaa ccggaaaacc cctatcccgc acagcccact gtggtcccca
ctgtctacga 240ggtgcatccg gctcagtact acccgtcccc cgtgccccag
tacgccccga gggtcctgac 300gcaggcttcc aaccccgtcg tctgcacgca
gcccaaatcc ccatccggga cagtgtgcac 360ctcaaagact aagaaagcac
tgtgcatcac cttgaccctg gggaccttcc tcgtgggagc 420tgcgctggcc
gctggcctac tctggaagtt catgggcagc aagtgctcca actctgggat
480agagtgcgac tcctcaggta cctgcatcaa cccctctaac tggtgtgatg
gcgtgtcaca 540ctgccccggc ggggaggacg agaatcggtg tgttcgcctc
tacggaccaa acttcatcct 600tcagatgtac tcatctcaga ggaagtcctg
gcaccctgtg tgccaagacg actggaacga 660gaactacggg cgggcggcct
gcagggacat gggctataag aataattttt actctagcca 720aggaatagtg
gatgacagcg gatccaccag ctttatgaaa ctgaacacaa gtgccggcaa
780tgtcgatatc tataaaaaac tgtaccacag tgatgcctgt tcttcaaaag
cagtggtttc 840tttacgctgt atagcctgcg gggtcaactt gaactcaagc
cgccagagca ggatcgtggg 900cggtgagagc gcgctcccgg gggcctggcc
ctggcaggtc agcctgcacg tccagaacgt 960ccacgtgtgc ggaggctcca
tcatcacccc cgagtggatc gtgacagccg cccactgcgt 1020ggaaaaacct
cttaacaatc catggcattg gacggcattt gcggggattt tgagacaatc
1080tttcatgttc tatggagccg gataccaagt agaaaaagtg atttctcatc
caaattatga 1140ctccaagacc aagaacaatg acattgcgct gatgaagctg
cagaagcctc tgactttcaa 1200cgacctagtg aaaccagtgt gtctgcccaa
cccaggcatg atgctgcagc cagaacagct 1260ctgctggatt tccgggtggg
gggccaccga ggagaaaggg aagacctcag aagtgctgaa 1320cgctgccaag
gtgcttctca ttgagacaca gagatgcaac agcagatatg tctatgacaa
1380cctgatcaca ccagccatga tctgtgccgg cttcctgcag gggaacgtcg
attcttgcca 1440gggtgacagt ggagggcctc tggtcacttc gaagaacaat
atctggtggc tgatagggga 1500tacaagctgg ggttctggct gtgccaaagc
ttacagacca ggagtgtacg ggaatgtgat 1560ggtattcacg gactggattt
atcgacaaat gagggcagac ggctaatcca catggtcttc 1620gtccttgacg
tcgttttaca agaaaacaat ggggctggtt ttgcttcccc gtgcatgatt
1680tactcttaga gatgattcag aggtcacttc atttttatta aacagtgaac
ttgtctggct 1740ttggcactct ctgccattct gtgcaggctg cagtggctcc
cctgcccagc ctgctctccc 1800taaccccttg tccgcaaggg gtgatggccg
gctggttgtg ggcactggcg gtcaagtgtg 1860gaggagaggg gtggaggctg
ccccattgag atcttcctgc tgagtccttt ccaggggcca 1920attttggatg
agcatggagc tgtcacctct cagctgctgg atgacttgag atgaaaaagg
1980agagacatgg aaagggagac agccaggtgg cacctgcagc ggctgccctc
tggggccact 2040tggtagtgtc cccagcctac ctctccacaa ggggattttg
ctgatgggtt cttagagcct 2100tagcagccct ggatggtggc cagaaataaa
gggaccagcc cttcatgggt ggtgacgtgg 2160tagtcacttg taaggggaac
agaaacattt ttgttcttat ggggtgagaa tatagacagt 2220gcccttggtg
cgagggaagc aattgaaaag gaacttgccc tgagcactcc tggtgcaggt
2280ctccacctgc acattgggtg gggctcctgg gagggagact cagccttcct
cctcatcctc 2340cctgaccctg ctcctagcac cctggagagt gcacatgccc
cttggtcctg gcagggcgcc 2400aagtctggca ccatgttggc ctcttcaggc
ctgctagtca ctggaaattg aggtccatgg 2460gggaaatcaa ggatgctcag
tttaaggtac actgtttcca tgttatgttt ctacacattg 2520ctacctcagt
gctcctggaa acttagcttt tgatgtctcc aagtagtcca ccttcattta
2580actctttgaa actgtatcac ctttgccaag taagagtggt ggcctatttc
agctgctttg 2640acaaaatgac tggctcctga cttaacgttc tataaatgaa
tgtgctgaag caaagtgccc 2700atggtggcgg cgaagaagag aaagatgtgt
tttgttttgg actctctgtg gtcccttcca 2760atgctgtggg tttccaacca
ggggaagggt cccttttgca ttgccaagtg ccataaccat 2820gagcactact
ctaccatggt tctgcctcct ggccaagcag gctggtttgc aagaatgaaa
2880tgaatgattc tacagctagg acttaacctt gaaatggaaa gtcttgcaat
cccatttgca 2940ggatccgtct gtgcacatgc ctctgtagag agcagcattc
ccagggacct tggaaacagt 3000tggcactgta aggtgcttgc tccccaagac
acatcctaaa aggtgttgta atggtgaaaa 3060cgtcttcctt ctttattgcc
ccttcttatt tatgtgaaca actgtttgtc tttttttgta 3120tcttttttaa
actgtaaagt tcaattgtga aaatgaatat catgcaaata aattatgcga
3180tttttttttc aaagcaaaaa 3200355430DNAHomo sapiens 35gtagggagcc
agcccctggg cgcggcctgc agggtaccgg caaccgcccg ggtaagcggg 60ggcaggacaa
ggccggagcc tgtgtccgcc cggcagccgc ccgcagctgc agagagtccc
120gctgcgtctc cgccgcgtgc gccctcctcg accagcagac ccgcgctgcg
ctccgccgct 180gacatgtgtg ccgctcagat gccgcccctg gcgcacatct
tccgagggac gttcgtccac 240tccacctgga cctgccccat ggaggtgctg
cgggatcacc tcctcggcgt gagcgacagc 300ggcaaaatag tgtttttaga
agaagcatct caacaggaaa aactggccaa agaatggtgc 360ttcaagccgt
gtgaaataag agaactgagc caccatgagt tcttcatgcc tgggctggtt
420gatacacaca tccatgcctc tcagtattcc tttgctggaa gtagcataga
cctgccactc 480ttggagtggc tgaccaagta
cacatttcct gcagaacaca gattccagaa catcgacttt 540gcagaagaag
tatataccag agttgtcagg agaacactaa agaatggaac aaccacagct
600tgttactttg caacaattca cactgactca tctctgctcc ttgccgacat
tacagataaa 660tttggacagc gggcatttgt gggcaaagtt tgcatggatt
tgaatgacac ttttccagaa 720tacaaggaga ccactgagga atcgatcaag
gaaactgaga gatttgtgtc agaaatgctc 780caaaagaact attctagagt
gaagcccata gtgacaccac gtttttccct ctcctgctct 840gagactttga
tgggtgaact gggcaacatt gctaaaaccc gtgatttgca cattcagagc
900catataagtg aaaatcgtga tgaagttgaa gctgtgaaaa acttataccc
cagttataaa 960aactacacat ctgtgtatga taaaaacaat cttttgacaa
ataagacagt gatggcacac 1020ggctgctacc tctctgcaga agaactgaac
gtattccatg aacgaggagc atccatcgca 1080cactgtccca attctaattt
atcgctcagc agtggatttc taaatgtgct agaagtcctg 1140aaacatgaag
tcaagatagg gctgggtaca gacgtggctg gtggctattc atattccatg
1200cttgatgcaa tcagaagagc agtgatggtt tccaatatcc ttttaattaa
taaggtaaat 1260gagaaaagcc tcaccctcaa agaagtcttc agactagcta
ctcttggagg aagccaagcc 1320ctggggctgg atggtgagat tggaaacttt
gaagtgggca aggaatttga tgccatcctg 1380atcaacccca aagcatccga
ctctcccatt gacctgtttt atggggactt ttttggtgat 1440atttctgagg
ctgttatcca gaagttcctc tatctaggag atgatcgaaa tattgaagag
1500gtttatgtgg gcggaaagca ggtggttccg ttttccagct cagtgtaaga
ccctcgggcg 1560tctacaaagt tctcctggga ttagcgtggt tctgcatctc
ccttgtgccc aggtggagtt 1620agaaagtcaa aaaatagtac cttgttcttg
ggatgactat ccctttctgt gtctagttac 1680agtattcact tgacaaatag
ttcgaaggaa gttgcactaa ttctcaactc tggttgagag 1740ggttcataaa
tttcatgaaa atatctccct ttggagctgc tcagacttac tttaagctca
1800aacagaaggg aatgctatta ctggtggtgt tcctacggta agacttaagc
aaagcctttt 1860tcatatttga aaatgtggaa agaaaagatg ttcctaaaag
gttagatatt ttgagctaat 1920aattgcaaaa attagaagac tgaaaatgga
cccatgagag tatattttta tgagggagca 1980aaagttagac tgagaacaaa
cgttagaaaa tcacttcaga ttgtgtttga aaattatata 2040ctgagcatac
taatttaaaa agagaacttg ttgaaattta aaacgtgttt ctaggttgac
2100cttgtgtttt agaaatttgc acttaatgga atttgcattt cagagatgtg
ttagtgttgt 2160gctttgcctt ctttggcgat gaatgtcaga aattgaatgc
cacatgcttt cataatatag 2220ttttgtgctt caaagtgttt gacagaagtt
gggtattaaa gatttaaagt ctcttaggaa 2280tattattcat gtaactccat
ggcataaata gttgtatttt tgtgtacttt aaaatcaact 2340tataactgtg
agatgttatt gcttccattt tattagaaga gaaacaaatt ccatgcttta
2400tggaatttat gtagactgga gtcttcgtga actggggcaa atgctggcat
ccaggagccg 2460ccaatactaa caggacaggt tccattgcca tggcctattc
cacccaaaca atatgttgta 2520gtttctggaa attccatact cagatatcag
tctgctagaa ctttaaaatg aaggacaaat 2580cctgttaaag aaatattgtt
aaaaatcttt aaaccctgtg tattgaaagc actctatttt 2640ctaattttat
ccagttttct gtttaactcc ttataatgtt taggatatta aaattttagg
2700ataatgaaga gtacataatg tcctacttaa tatttatgtt aataggactt
aattcttact 2760agacatctag gaacattaca aagcaaagac tatttttatg
cttccataac ctagaattaa 2820aaccaaatta tgaccttatg ataaatcttt
aagtattggt gtgaatgtta tttaaattct 2880atatttttct tatttaatta
caaatactat aaatgagcaa ggaaaaggaa tagactttct 2940taatatatta
taacactcat tcctagagct taggggtgac tctttaatat taccttatag
3000tagaaacttt atgtaatata gctaactccg tatttacaga acaaaaaaac
acagttcccc 3060ctcctgtagt ataaatttta ttttcacata cttagctaat
ttagcagtaa ttggcccagt 3120tttttcccta atagaaatac ttttagattt
gattatgtat acatgacacc taaagaggga 3180acaaaagtta gttttatttt
tttaataaac aacagagttt gttttgtgag ataagtatct 3240tagtaaaccc
aatttccagt cttagtctgt atttccaata tttctaattc ctgagccacg
3300tcaaagatgc cttgccaaat ttctccccat ttctctacgg ggctagcaaa
aatcttcagc 3360tttatcactc aacccctgcc aaaggaactt gattacatgg
tgtctaacca aatgagcagg 3420cttaggaatt tagatgagat gtgtaagatt
cacttacagg cagtagctgc ttctagcatt 3480tgcaagatcc tacactttta
ccttctttaa gggtgtacat tttgatgttg aacatcagtt 3540ttcatgtaga
cttaggactc atgtgcagta aatataaata agtgtagcat cagaagcagt
3600aggaatggcc gtatacaacc atcctgttaa acatttaaat ttagctctga
tagtgtgtta 3660agacctgaat atctttccta gtaaaaatag gatgtgttga
aatatttata tgtactttga 3720tctctccaca tcacttataa cttatgtgtt
ttatttctcc aagtgcggtg ttcctgaatg 3780ttatgtatgc ttttttttct
gtaccacagg cattatctat acctggggcc agattttctg 3840cactttgaaa
tgttgccttt gcctaatgta ggttgacttt ctgaattgtg gagaggcact
3900tttccaagcc aatcttattt gtcacttttt gttttaatat cttgctctct
gacaggaaag 3960aaacaattca cttaccagcc tcctcacccc atcctccacc
atttccttaa tgttccatgg 4020tattttcaac ggaatacact ttgaaaggta
aaaacaattc aaaagtatcg attatcataa 4080attcacaaaa tatttttgca
accagaacac aaaagcaggc tagtcagcta aggtaaattt 4140cattttcaaa
cgagagggaa acatgggaag taaaagatta ggatgtgaaa ggttgtccta
4200aacagaccaa ggagactgtt ccctaattta ttctcttggc tggttctctc
attgaattat 4260cagaccccaa gaggagatat tggaacaggc tcccttcatg
ccaagggtct ttctaagtta 4320atactgtgag cattgagccc ccattaaaac
tcttttttac ttcagaaaga attttacagg 4380ttaaagggaa agaaatggtg
ggaaactctc cccgtaatgc ttagccaact ttaaagtgta 4440cccttcaata
tccccattgg caactgcagc tgagatctta gagaggaaat ataaccggtg
4500tgagatctag caatgcattt tgaatcttca ctccctacca ggctcttcct
atttttaatc 4560tcttcacctc agaactagac atatggagag ctttaaaggc
aagctggaag gcacattgta 4620tcaattctac cttgtgctat acgtaggaga
gatccaaaat ttggatgctt ctggagactc 4680ttagacatct tttcattgtt
gtccattttt aaagttgatg attgctggaa acattcacac 4740gcttaaaagc
aatggtgtga gttattaatg ggtaaactaa gaagtgttat aggcaatgac
4800ttgaaatggt ttttaaattg tatggattgt taagaattgt tgaaaaaaaa
tttttttttt 4860ttggacagct tcaaggagat gttagcaatt tcagatatac
tagccagttt aggtatgact 4920ttggaagtgc agaaacagaa ggatactgtt
agaaaatcct aacattggtc tccgtgcatg 4980tgttcacacc tggtctcact
gcctttcctt cccacagacc tgagtgtgaa agactgagag 5040ttgaggagtt
actttgtgga tcttgtccaa atttagtgaa atgtggaagt caaccagacc
5100aatgatggaa ttaaatgtaa attccaagag ggctttcaca gtccacaggg
ttcaaatgac 5160ttgggtaaca gaagttattc ttagcttacc tgttatgtga
cagtgattta cctgtccatt 5220tccaacccaa aagcctgtca gaaagcattc
tttagagaaa accactttac atttgttgtt 5280aaactcctga tcgctactct
taagaatata catgtatgta ttcataggaa cattttttct 5340caatatttgt
atgattcgct tactgttatt gtgctgagtg agctcctgtg tgcttcagac
5400aaaaataaat gagactttgt gtttacgtta 5430364541DNAHomo sapiens
36ggatcctcta gggtcccagc tcgcctcgat ggagctcctc ccgccgctgc ctcagtcctt
60cctgttgctg ctgctgttgc ctgccaagcc cgcggcgggc gaggactggc agtgcccgcg
120caccccctac gcggcctctc gcgactttga cgtgaagtac gtggtgccca
gcttctccgc 180cggaggcctg gtacaggcca tggtgaccta cgagggcgac
agaaatgaga gtgctgtgtt 240tgtagccata cgcaatcgcc tgcatgtgct
tgggcctgac ctgaagtctg tccagagcct 300ggccacgggc cctgctggag
accctggctg ccagacgtgt gcagcctgtg gcccaggacc 360ccacggccct
cccggtgaca cagacacaaa ggtgctggtg ctggatcccg cgctgcctgc
420gctggtcagt tgtggctcca gcctgcaggg ccgctgcttc ctgcatgacc
tagagcccca 480agggacagcc gtgcatctgg cagcgccagc ctgcctcttc
tcagcccacc ataaccggcc 540cgatgactgc cccgactgtg tggccagccc
attgggcacc cgtgtaactg tggttgagca 600aggccaggcc tcctatttct
acgtggcatc ctcactggac gcagccgtgg ctggcagctt 660cagcccacgc
tcagtgtcta tcaggcgtct caaggctgac gcctcgggat tcgcaccggg
720ctttgtggcg ttgtcagtgc tgcccaagca tcttgtctcc tacagtattg
aatacgtgca 780cagcttccac acgggagcct tcgtatactt cctgactgta
cagccggcca gcgtgacaga 840tgatcctagt gccctgcaca cacgcctggc
acggcttagc gccactgagc cagagttggg 900tgactatcgg gagctggtcc
tcgactgcag atttgctcca aaacgcaggc gccggggggc 960cccagaaggc
ggacagccct accctgtgct gcaggtggcc cactccgctc cagtgggtgc
1020ccaacttgcc actgagctga gcatcgccga gggccaggaa gtactatttg
gggtctttgt 1080gactggcaag gatggtggtc ctggcgtggg ccccaactct
gtcgtctgtg ccttccccat 1140tgacctgctg gacacactaa ttgatgaggg
tgtggagcgc tgttgtgaat ccccagtcca 1200tccaggcctc cggcgaggcc
tcgacttctt ccagtcgccc agtttttgcc ccaacccgcc 1260tggcctggaa
gccctcagcc ccaacaccag ctgccgccac ttccctctgc tggtcagtag
1320cagcttctca cgtgtggacc tattcaatgg gctgttggga ccagtacagg
tcactgcatt 1380gtatgtgaca cgccttgaca acgtcacagt ggcacacatg
ggcacaatgg atgggcgtat 1440cctgcaggtg gagctggtca ggtcactaaa
ctacttgctg tatgtgtcca acttctcact 1500gggtgacagt gggcagcccg
tgcagcggga tgtcagtcgt cttggggacc acctactctt 1560tgcctctggg
gaccaggttt tccaggtacc tatccgaggc cctggctgcc gccacttcct
1620gacctgtggg cgttgcctaa gggcatggca tttcatgggc tgtggctggt
gtgggaacat 1680gtgcggccag cagaaggagt gtcctggctc ctggcaacag
gaccactgcc cacctaagct 1740tactgagttc cacccccaca gtggacctct
aaggggcagt acaaggctga ccctgtgtgg 1800ctccaacttc taccttcacc
cttctggtct ggtgcctgag ggaacccatc aggtcactgt 1860gggccaaagt
ccctgccggc cactgcccaa ggacagctca aaactcagac cagtgccccg
1920gaaagacttt gtagaggagt ttgagtgtga actggagccc ttgggcaccc
aggcagtggg 1980gcctaccaac gtcagcctca ccgtgactaa catgccaccg
ggcaagcact tccgggtaga 2040cggcacctcc gtgctgagag gcttctcttt
catggagcca gtgctgatag cagtgcaacc 2100cctctttggc ccacgggcag
gaggcacctg tctcactctt gaaggccaga gtctgtctgt 2160aggcaccagc
cgggctgtgc tggtcaatgg gactgagtgt ctgctagcac gggtcagtga
2220ggggcagctt ttatgtgcca caccccctgg ggccacggtg gccagtgtcc
cccttagcct 2280gcaggtgggg ggtgcccagg tacctggttc ctggaccttc
cagtacagag aagaccctgt 2340cgtgctaagc atcagcccca actgtggcta
catcaactcc cacatcacca tctgtggcca 2400gcatctaact tcagcatggc
acttagtgct gtcattccat gacgggctta gggcagtgga 2460aagcaggtgt
gagaggcagc ttccagagca gcagctgtgc cgccttcctg aatatgtggt
2520ccgagacccc cagggatggg tggcagggaa tctgagtgcc cgaggggatg
gagctgctgg 2580ctttacactg cctggctttc gcttcctacc cccaccccat
ccacccagtg ccaacctagt 2640tccactgaag cctgaggagc atgccattaa
gtttgagtat attgggctgg gcgctgtggc 2700tgactgtgtg ggtatcaacg
tgaccgtggg tggtgagagc tgccagcacg agttccgggg 2760ggacatggtt
gtctgccccc tgcccccatc cctgcagctt ggccaggatg gtgccccatt
2820gcaggtctgc gtagatggtg aatgtcatat cctgggtaga gtggtgcggc
cagggccaga 2880tggggtccca cagagcacgc tccttggtat cctgctgcct
ttgctgctgc ttgtggctgc 2940actggcgact gcactggtct tcagctactg
gtggcggagg aagcagctag ttcttcctcc 3000caacctgaat gacctggcat
ccctggacca gactgctgga gccacacccc tgcctattct 3060gtactcgggc
tctgactaca gaagtggcct tgcactccct gccattgatg gtctggattc
3120caccacttgt gtccatggag catccttctc cgatagtgaa gatgaatcct
gtgtgccact 3180gctgcggaaa gagtccatcc agctaaggga cctggactct
gcgctcttgg ctgaggtcaa 3240ggatgtgctg attccccatg agcgggtggt
cacccacagt gaccgagtca ttggcaaagg 3300ccactttgga gttgtctacc
acggagaata catagaccag gcccagaatc gaatccaatg 3360tgccatcaag
tcactaagtc gcatcacaga gatgcagcag gtggaggcct tcctgcgaga
3420ggggctgctc atgcgtggcc tgaaccaccc gaatgtgctg gctctcattg
gtatcatgtt 3480gccacctgag ggcctgcccc atgtgctgct gccctatatg
tgccacggtg acctgctcca 3540gttcatccgc tcacctcagc ggaaccccac
cgtgaaggac ctcatcagct ttggcctgca 3600ggtagcccgc ggcatggagt
acctggcaga gcagaagttt gtgcacaggg acctggctgc 3660gcggaactgc
atgctggacg agtcattcac agtcaaggtg gctgactttg gtttggcccg
3720cgacatcctg gacagggagt actatagtgt tcaacagcat cgccacgctc
gcctacctgt 3780gaagtggatg gcgctggaga gcctgcagac ctatagattt
accaccaagt ctgatgtgtg 3840gtcatttggt gtgctgctgt gggaactgct
gacacggggt gccccaccat accgccacat 3900tgaccctttt gaccttaccc
acttcctggc ccagggtcgg cgcctgcccc agcctgagta 3960ttgccctgat
tctctgtacc aagtgatgca gcaatgctgg gaggcagacc cagcagtgcg
4020acccaccttc agagtactag tgggggaggt ggagcagata gtgtctgcac
tgcttgggga 4080ccattatgtg cagctgccag caacctacat gaacttgggc
cccagcacct cgcatgagat 4140gaatgtgcgt ccagaacagc cgcagttctc
acccatgcca gggaatgtac gccggccccg 4200gccactctca gagcctcctc
ggcccacttg acttagttct tgggctggac ctgcttagct 4260gccttgagct
aaccccaagg ctgcctctgg gccatgccag gccagagcag tggccctcca
4320ccttgttcct gccctttaac tttcagaggc aataggtaaa tgggcccatt
aggtccctca 4380ctccacagag tgagccagtg agggcagtcc tgcaacatgt
atttatggag tgcctgctgt 4440ggaccctgtc ttctgggcac agtggactca
gcagtgacca caccaacact gacccttgaa 4500ccaataaagg aacaaatgac
tattaaagca caaaaaaaaa a 4541375920DNAHomo sapiens 37gcgctgcccg
cctcgtcccc acccccccaa cccccgcgcc cgccctcgga cagtccctgc 60tcgcccgcgc
gctgcagccc catctcctag cggcagccca ggcgcggagg gagcgagtcc
120gccccgaggt aggtccagga cgggcgcaca gcagcagccg aggctggccg
ggagagggag 180gaagaggatg gcagggccac gccccagccc atgggccagg
ctgctcctgg cagccttgat 240cagcgtcagc ctctctggga ccttggcaaa
ccgctgcaag aaggccccag tgaagagctg 300cacggagtgt gtccgtgtgg
ataaggactg cgcctactgc acagacgaga tgttcaggga 360ccggcgctgc
aacacccagg cggagctgct ggccgcgggc tgccagcggg agagcatcgt
420ggtcatggag agcagcttcc aaatcacaga ggagacccag attgacacca
ccctgcggcg 480cagccagatg tccccccaag gcctgcgggt ccgtctgcgg
cccggtgagg agcggcattt 540tgagctggag gtgtttgagc cactggagag
ccccgtggac ctgtacatcc tcatggactt 600ctccaactcc atgtccgatg
atctggacaa cctcaagaag atggggcaga acctggctcg 660ggtcctgagc
cagctcacca gcgactacac tattggattt ggcaagtttg tggacaaagt
720cagcgtcccg cagacggaca tgaggcctga gaagctgaag gagccctggc
ccaacagtga 780cccccccttc tccttcaaga acgtcatcag cctgacagaa
gatgtggatg agttccggaa 840taaactgcag ggagagcgga tctcaggcaa
cctggatgct cctgagggcg gcttcgatgc 900catcctgcag acagctgtgt
gcacgaggga cattggctgg cgcccggaca gcacccacct 960gctggtcttc
tccaccgagt cagccttcca ctatgaggct gatggcgcca acgtgctggc
1020tggcatcatg agccgcaacg atgaacggtg ccacctggac accacgggca
cctacaccca 1080gtacaggaca caggactacc cgtcggtgcc caccctggtg
cgcctgctcg ccaagcacaa 1140catcatcccc atctttgctg tcaccaacta
ctcctatagc tactacgaga agcttcacac 1200ctatttccct gtctcctcac
tgggggtgct gcaggaggac tcgtccaaca tcgtggagct 1260gctggaggag
gccttcaatc ggatccgctc caacctggac atccgggccc tagacagccc
1320ccgaggcctt cggacagagg tcacctccaa gatgttccag aagacgagga
ctgggtcctt 1380tcacatccgg cggggggaag tgggtatata ccaggtgcag
ctgcgggccc ttgagcacgt 1440ggatgggacg cacgtgtgcc agctgccgga
ggaccagaag ggcaacatcc atctgaaacc 1500ttccttctcc gacggcctca
agatggacgc gggcatcatc tgtgatgtgt gcacctgcga 1560gctgcaaaaa
gaggtgcggt cagctcgctg cagcttcaac ggagacttcg tgtgcggaca
1620gtgtgtgtgc agcgagggct ggagtggcca gacctgcaac tgctccaccg
gctctctgag 1680tgacattcag ccctgcctgc gggagggcga ggacaagccg
tgctccggcc gtggggagtg 1740ccagtgcggg cactgtgtgt gctacggcga
aggccgctac gagggtcagt tctgcgagta 1800tgacaacttc cagtgtcccc
gcacttccgg gttcctctgc aatgaccgag gacgctgctc 1860catgggccag
tgtgtgtgtg agcctggttg gacaggccca agctgtgact gtcccctcag
1920caatgccacc tgcatcgaca gcaatggggg catctgtaat ggacgtggcc
actgtgagtg 1980tggccgctgc cactgccacc agcagtcgct ctacacggac
accatctgcg agatcaacta 2040ctcggcgatc cacccgggcc tctgcgagga
cctacgctcc tgcgtgcagt gccaggcgtg 2100gggcaccggc gagaagaagg
ggcgcacgtg tgaggaatgc aacttcaagg tcaagatggt 2160ggacgagctt
aagagagccg aggaggtggt ggtgcgctgc tccttccggg acgaggatga
2220cgactgcacc tacagctaca ccatggaagg tgacggcgcc cctgggccca
acagcactgt 2280cctggtgcac aagaagaagg actgccctcc gggctccttc
tggtggctca tccccctgct 2340cctcctcctc ctgccgctcc tggccctgct
actgctgcta tgctggaagt actgtgcctg 2400ctgcaaggcc tgcctggcac
ttctcccgtg ctgcaaccga ggtcacatgg tgggctttaa 2460ggaagaccac
tacatgctgc gggagaacct gatggcctct gaccacttgg acacgcccat
2520gctgcgcagc gggaacctca agggccgtga cgtggtccgc tggaaggtca
ccaacaacat 2580gcagcggcct ggctttgcca ctcatgccgc cagcatcaac
cccacagagc tggtgcccta 2640cgggctgtcc ttgcgcctgg cccgcctttg
caccgagaac ctgctgaagc ctgacactcg 2700ggagtgcgcc cagctgcgcc
aggaggtgga ggagaacctg aacgaggtct acaggcagat 2760ctccggtgta
cacaagctcc agcagaccaa gttccggcag cagcccaatg ccgggaaaaa
2820gcaagaccac accattgtgg acacagtgct gatggcgccc cgctcggcca
agccggccct 2880gctgaagctt acagagaagc aggtggaaca gagggccttc
cacgacctca aggtggcccc 2940cggctactac accctcactg cagaccagga
cgcccggggc atggtggagt tccaggaggg 3000cgtggagctg gtggacgtac
gggtgcccct ctttatccgg cctgaggatg acgacgagaa 3060gcagctgctg
gtggaggcca tcgacgtgcc cgcaggcact gccaccctcg gccgccgcct
3120ggtaaacatc accatcatca aggagcaagc cagagacgtg gtgtcctttg
agcagcctga 3180gttctcggtc agccgcgggg accaggtggc ccgcatccct
gtcatccggc gtgtcctgga 3240cggcgggaag tcccaggtct cctaccgcac
acaggatggc accgcgcagg gcaaccggga 3300ctacatcccc gtggagggtg
agctgctgtt ccagcctggg gaggcctgga aagagctgca 3360ggtgaagctc
ctggagctgc aagaagttga ctccctcctg cggggccgcc aggtccgccg
3420tttccacgtc cagctcagca accctaagtt tggggcccac ctgggccagc
cccactccac 3480caccatcatc atcagggacc cagatgaact ggaccggagc
ttcacgagtc agatgttgtc 3540atcacagcca ccccctcacg gcgacctggg
cgccccgcag aaccccaatg ctaaggccgc 3600tgggtccagg aagatccatt
tcaactggct gcccccttct ggcaagccaa tggggtacag 3660ggtaaagtac
tggattcagg gtgactccga atccgaagcc cacctgctcg acagcaaggt
3720gccctcagtg gagctcacca acctgtaccc gtattgcgac tatgagatga
aggtgtgcgc 3780ctacggggct cagggcgagg gaccctacag ctccctggtg
tcctgccgca cccaccagga 3840agtgcccagc gagccagggc gtctggcctt
caatgtcgtc tcctccacgg tgacccagct 3900gagctgggct gagccggctg
agaccaacgg tgagatcaca gcctacgagg tctgctatgg 3960cctggtcaac
gatgacaacc gacctattgg gcccatgaag aaagtgctgg ttgacaaccc
4020taagaaccgg atgctgctta ttgagaacct tcgggagtcc cagccctacc
gctacacggt 4080gaaggcgcgc aacggggccg gctgggggcc tgagcgggag
gccatcatca acctggccac 4140ccagcccaag aggcccatgt ccatccccat
catccctgac atccctatcg tggacgccca 4200gagcggggag gactacgaca
gcttccttat gtacagcgat gacgttctac gctctccatc 4260gggcagccag
aggcccagcg tctccgatga cactggctgc ggctggaagt tcgagcccct
4320gctgggggag gagctggacc tgcggcgcgt cacgtggcgg ctgcccccgg
agctcatccc 4380gcgcctgtcg gccagcagcg ggcgctcctc cgacgccgag
gcgccccacg ggcccccgga 4440cgacggcggc gcgggcggga agggcggcag
cctgccccgc agtgcgacac ccgggccccc 4500cggagagcac ctggtgaatg
gccggatgga ctttgccttc ccgggcagca ccaactccct 4560gcacaggatg
accacgacca gtgctgctgc ctatggcacc cacctgagcc cacacgtgcc
4620ccaccgcgtg ctaagcacat cctccaccct cacacgggac tacaactcac
tgacccgctc 4680agaacactca cactcgacca cactgcccag ggactactcc
accctcacct ccgtctcctc 4740ccacgactct cgcctgactg ctggtgtgcc
cgacacgccc acccgcctgg tgttctctgc 4800cctggggccc acatctctca
gagtgagctg gcaggagccg cggtgcgagc ggccgctgca 4860gggctacagt
gtggagtacc agctgctgaa cggcggtgag ctgcatcggc tcaacatccc
4920caaccctgcc cagacctcgg tggtggtgga agacctcctg cccaaccact
cctacgtgtt 4980ccgcgtgcgg gcccagagcc aggaaggctg gggccgagag
cgtgagggtg tcatcaccat 5040tgaatcccag gtgcacccgc agagcccact
gtgtcccctg ccaggctccg ccttcacttt 5100gagcactccc agtgccccag
gcccgctggt gttcactgcc ctgagcccag actcgctgca 5160gctgagctgg
gagcggccac ggaggcccaa tggggatatc gtcggctacc tggtgacctg
5220tgagatggcc caaggaggag ggccagccac cgcattccgg gtggatggag
acagccccga 5280gagccggctg accgtgccgg gcctcagcga gaacgtgccc
tacaagttca aggtgcaggc 5340caggaccact gagggcttcg ggccagagcg
cgagggcatc atcaccatag agtcccagga 5400tggaggaccc ttcccgcagc
tgggcagccg tgccgggctc ttccagcacc cgctgcaaag 5460cgagtacagc
agcatcacca ccacccacac cagcgccacc
gagcccttcc tagtggatgg 5520gctgaccctg ggggcccagc acctggaggc
aggcggctcc ctcacccggc atgtgaccca 5580ggagtttgtg agccggacac
tgaccaccag cggaaccctt agcacccaca tggaccaaca 5640gttcttccaa
acttgaccgc accctgcccc acccccgcca cgtcccacta ggcgtcctcc
5700cgactcctct cccggagcct cctcagctac tccatccttg cacccctggg
ggcccagccc 5760acccgcatgc acagagcagg ggctaggtgt ctcctgggag
gcatgaaggg ggcaaggtcc 5820gtcctctgtg ggcccaaacc tatttgtaac
caaagagctg ggagcagcac aaggacccag 5880cctttgttct gcacttaata
aatggttttg ctactgctaa 5920381620DNAHomo sapiens 38gggtggggaa
gcttagagac cggtgaggga gcagagctgg ggcgcctgtg tacagggata 60gagcccggcg
gcagcagggc gcggcttccc tttcccgggg cctggggccg caatcaggtg
120gagtcgagag gccggaggag gggcaggagg aaggggtgcg gtcgcgatcc
ggacccggag 180ccagcgcgga gcacctgcgc ccgcggctga caccttcgct
cgcagtttgt tcgcagttta 240ctcgcacacc agtttccccc accgcgcttt
ggattagtgt gatctcagct caaggcaaag 300gtgggatatc atggcatcta
tctgggttgg acaccgagga acagtaagag attatccaga 360ctttagccca
tcagtggatg ctgaagctat tcagaaagca atcagaggaa ttggaactga
420tgagaaaatg ctcatcagca ttctgactga gaggtcaaat gcacagcggc
agctgattgt 480taaggaatat caagcagcat atggaaagga gctgaaagat
gacttgaagg gtgatctctc 540tggccacttt gagcatctca tggtggccct
agtgactcca ccagcagtct ttgatgcaaa 600gcagctaaag aaatccatga
agggcgcggg aacaaacgaa gatgccttga ttgaaatctt 660aactaccagg
acaagcaggc aaatgaagga tatctctcaa gcctattata cagtatacaa
720gaagagtctt ggagatgaca ttagttccga aacatctggt gacttccgga
aagctctgtt 780gactttggca gatggcagaa gagatgaaag tctgaaagtg
gatgagcatc tggccaaaca 840agatgcccag attctctata aagctggtga
gaacagatgg ggcacggatg aagacaaatt 900cactgagatc ctgtgtttaa
ggagctttcc tcaattaaaa ctaacatttg atgaatacag 960aaatatcagc
caaaaggaca ttgtggacag cataaaagga gaattatctg ggcattttga
1020agacttactg ttggccatag ttaattgtgt gaggaacacg ccggcctttt
tagccgaaag 1080actgcatcga gccttgaagg gtattggaac tgatgagttt
actctgaacc gaataatggt 1140gtccagatca gaaattgacc ttttggacat
tcgaacagag ttcaagaagc attatggcta 1200ttccctatat tcagcaatta
aatcggatac ttctggagac tatgaaatca cactcttaaa 1260aatctgtggt
ggagatgact gaaccaagaa gataatctcc aaaggtccac gatgggcttt
1320cccaacagct ccaccttact tcttctcata ctatttaaga gaacaagcaa
atataaacag 1380caacttgtgt tcctaacagg aattttcatt gttctataac
aacaacaaca aaagcgatta 1440ttattttaga gcatctcatt tataatgtag
cagctcataa atgaaattga aaatggtatt 1500aaagatctgc aactactatc
caacttatat ttctgctttc aaagttaaga atctttatag 1560ttctactcca
ttaaatataa agcaagataa taaaaattgt tgcttttgtt aaaagtaaaa
162039955DNAHomo sapiens 39tgcagactga tatggattca ccactgctaa
cacctcctgg ttggaactac aggaatagaa 60ctggaaaggg aaaaaaggca gcattcacca
catcccaatc ctgaatccaa gagtctaaga 120tagtccccca ctcctatctc
aggcttagag gattagatta atctcctgga gggaagactc 180ttccttgaaa
catttttttt tatctgcctg tagctattgg gataattcgg gaaatccaca
240gggacagttc aagtcatctt tgtcctctac tttctgttgc actctcagcc
ttgttctctt 300tttagaaact gcatggtaac tattatatag ctaaagaaga
gcattctgac ctctgccctg 360ggacttcctg gatcctcctc ttcttataaa
tacaagggca gagctggtat cccggggagc 420caggaagcag tgagcccagg
agtcctcggc cagccctgcc tgcccaccag gaggatgaag 480gtctccgtgg
ctgccctctc ctgcctcatg cttgttgctg tccttggatc ccaggcccag
540ttcataaatg atgcagagac agagttaatg atgtcaaagc ttccactgga
aaatccagta 600gttctgaaca gctttcactt tgctgctgac tgctgcacct
cctacatctc acaaagcatc 660ccgtgttcac tcatgaaaag ttattttgaa
acgagcagcg agtgctccaa gccaggtgtc 720atattcctca ccaagaaggg
gcggcaagtc tgtgccaaac ccagtggtcc gggagttcag 780gattgcatga
aaaagctgaa gccctactca atataataat aaagagacaa aagaggccag
840ccacccacct ccaacacctc ctgtgagttt cttggtctga aatacttaaa
aaatatatat 900attgttgtgt ctggtaatga aagtaatgca tctaataaag
agtattcaat ttttt 955401738DNAHomo sapiens 40cgggggggta ctgtgcgagc
cctcaaggag gtggctgttc tgtagctgga gagctccgtg 60ggtggcagga ctgaacttga
acaccagaaa caacccccaa gccttgtgac ctgggaggca 120ggaggcgggt
ctgtctccct gggacttggg tggctgagcc gaggtactcg ggaccctgtc
180ccgcgcatgg cagagtggct cctcacagcc tgaagctcat ccttctgcac
gggccagcca 240ggccagcaca gaggcaccag ggcagcagtg cacacaggtc
cccggggacc ccaccatgtg 300gagcggatgg tggctgtggc cccttgtggc
cgtctgcact gcagacttct ttcgggacga 360ggcagagagg atcatgaggg
actcccctgt cattgatggg cacaatgacc tcccctggca 420gctgctggat
atgttcaaca accggctgca ggacgagagg gccaacctga ccaccttggc
480cggcacacac accaacatcc ccaagctgag ggccggcttt gtgggaggcc
agttctggtc 540cgtgtacacg ccctgcgaca cccagaacaa agacgccgtg
cggaggacgc tggagcagat 600ggacgtggtc caccgcatgt gccggatgta
cccggagacc ttcctgtatg tcaccagcag 660tgcaggcatt cggcaggcct
tccgggaagg gaaggtggcc agcctgatcg gcgtggaggg 720cggccactcc
attgacagca gtttgggcgt cctgcgggca ctctatcagc tgggcatgcg
780gtacctgacc ctcacccaca gctgcaacac gccctgggct gacaactggc
tggtggacac 840gggagacagc gagccccaga gccaaggctt gtcacccttt
gggcagcgtg tggtgaagga 900gctgaaccgt ctgggggtcc tcatcgactt
ggctcacgtg tctgtggcca ccatgaaggc 960caccctgcag ctgtccagag
ccccggtcat cttcagccac tcctcggcct acagcgtgtg 1020cgcaagccgg
cgcaacgtgc ctgacgacgt cctgaggctg gtgaaacaga cagacagcct
1080ggtgatggtg aacttctaca acaattacat ttcctgcacc aacaaggcca
acctgtccca 1140agtggccgac catctggatc acatcaagga ggtggcagga
gccagagccg tgggttttgg 1200tggggacttt gatggtgttc caagggtccc
tgaggggctg gaggacgtct ccaagtatcc 1260agacctgatc gctgagctgc
tcaggaggaa ctggacggag gcggaggtca agggcgcact 1320ggctgacaac
ctgctgaggg tcttcgaggc tgtggaacag gccagcaacc tcacacaggc
1380tcccgaggag gagcccatcc cgctggacca gctgggtggc tcctgcagga
cccattacgg 1440ctactcctct ggggcttcca gcctccatcg ccactggggg
ctcctgctgg cctccctcgc 1500tcccctggtc ctctgtctgt ctctcctgtg
aaacctggga gaccagagtc ccctttaggg 1560ttcccggagc tccgggaaga
cccgcccatc ccaggactcc agatgccagg agccctgctg 1620cccacatgca
aggaccagca tctcctgaga ggacgcctgg gcttacctgg ggggcaggat
1680gcctggggac agttcaggac acacacacag taggcccgca ataaaagcaa cacccctt
1738411132DNAHomo sapiens 41agccatggca ggcccccgat acccagtttc
agtgcaaggg gcagccctgg tgcagatcaa 60gaggctccaa acgtttgcct tctctgtgcg
ctggtcagac ggcagcgaca ccttcgtgcg 120caggagttgg gacgaattca
ggcagctcaa gaagaccctc aaggagacct tcccggtgga 180ggcgggcctg
ctgcggagat ctgaccgcgt tctcccaaag cttctcgatg caccactgtt
240gggacgcgtg gggcgcacga gccgcggcct ggcgcgcctg cagctgttgg
aaacctattc 300tcggaggctg ctggcgactg cagagcgcgt ggcacggagc
ccgacgatca ctggcttctt 360cgcaccgcaa cccctggacc tggagcccgc
gctgccaccc ggcagccggg tgatcctgcc 420caccccagag gagcagcctc
tttctcgcgc tgcgggccgc ctctccatcc acagtctgga 480ggctcagagc
ctgcgctgcc tgcagccctt ctgtacccag gacacgcggg ataggccttt
540tcaggcgcag gcccaggaga gcctggacgt gctgctgcgg cacccctcag
gctggtggct 600ggtggagaac gaagaccggc agaccgcctg gtttccagcg
ccctacctgg aggaggcggc 660cccgggccaa ggccgggagg gaggcccgtc
cctagggagc agcggtcccc agttctgtgc 720ttcccgcgcc tacgagagca
gccgcgcaga tgagctgtcc gtgcccgcgg gggcgcgcgt 780gcgcgtgttg
gaaacgtcag accgcggctg gtggctatgc aggtacggcg accgggcggg
840cctactcccc gcggtgctgc tgcggccgga agggctgggc gctctcctga
gcgggacggg 900gttccgtgga ggagacgacc cggcgggtga ggcccggggc
ttccctgaac cctcccaggc 960caccgcccct ccccccaccg tgcccacccg
accttcgccg ggcgccatcc agagccgctg 1020ctgcaccgtc acacgcaggg
ccctggagcg gcgcccacgg cgccagggcc gccctcgagg 1080gtgcgtggac
tctgtgccgc accccacgac ggagcagtga gcgcgaggat cc 113242656DNAHomo
sapiens 42gggaacacat ccaagcttaa gacggtgagg tcagcttcac attctcagga
actctccttc 60tttgggtctg gctgaagttg aggatctctt actctctagg ccacggaatt
aacccgagca 120ggcatggagg cctctgctct cacctcatca gcagtgacca
gtgtggccaa agtggtcagg 180gtggcctctg gctctgccgt agttttgccc
ctggccagga ttgctacagt tgtgattgga 240ggagttgtgg ctgtgcccat
ggtgctcagt gccatgggct tcactgcggc gggaatcgcc 300tcgtcctcca
tagcagccaa gatgatgtcc gcggcggcca ttgccaatgg gggtggagtt
360gcctcgggca gccttgtggc tactctgcag tcactgggag caactggact
ctccggattg 420accaagttca tcctgggctc cattgggtct gccattgcgg
ctgtcattgc gaggttctac 480tagctccctg cccctcgccc tgcagagaag
agaaccatgc caggggagaa ggcacccagc 540catcctgacc cagcgaggag
ccaactatcc caaatatacc tggggtgaaa tataccaaat 600tctgcatctc
cagaggaaaa taagaaataa agatgaattg ttgcaactct tcaaaa 656432164DNAHomo
sapiens 43acctctgggc agagaaacaa agctctatat gcacagccca gcaaagagca
gcacacagct 60gaaagaaaaa ctcagaagac agagctgaaa aagaaaactg gtgatggatc
tcattccaaa 120ctttgccatg gaaacatggg ttcttgtggc taccagcctg
gtactcctct atatttatgg 180gacccattca cataaacttt ttaagaagct
gggaattcct gggccaaccc ctctgccttt 240tctgggaact attttgttct
accttagggg tctttggaat tttgacagag aatgtaatga 300aaaatacgga
gaaatgtggg ggctgtatga ggggcaacag cccatgctgg tcatcatgga
360tcccgacatg atcaaaacag tgttagtgaa agaatgttac tctgtcttca
caaaccagat 420gcctttaggt ccaatgggat ttctgaaaag tgccttaagt
tttgctgaag atgaagaatg 480gaagagaata cgaacattgc tatctccagc
tttcaccagt gtaaaattca aggaaatggt 540ccccatcatt tcccaatgtg
gagatatgtt ggtgagaagc ctgaggcagg aagcagagaa 600cagcaagtcc
atcaacttga aagatttctt tggggcctac accatggatg taatcactgg
660cacattattt ggagtgaact tggattctct caacaatcca caagatccct
ttctgaaaaa 720tatgaagaag cttttaaaat tggatttttt ggatcccttt
ttactcttaa tatcactctt 780tccatttctt accccagttt ttgaagccct
aaatatcggt ttgtttccaa aagatgttac 840ccatttttta aaaaattcca
ttgaaaggat gaaagaaagt cgcctcaaag ataaacaaaa 900gcatcgagta
gatttctttc aacagatgat cgactcccag aattccaaag aaacaaagtc
960ccataaagct ctgtctgatc tggagcttgt ggcccagtca attatcatca
tttttgctgc 1020ctatgacaca actagcacca ctctcccctt cattatgtat
gaactggcca ctcaccctga 1080tgtccagcag aaactgcagg aggagattga
cgcagtttta cccaataagg cacctgtcac 1140ctacgatgcc ctggtacaga
tggagtacct tgacatggtg gtgaatgaaa cgctcagatt 1200attcccagtt
gttagtagag ttacgagagt ctgcaagaaa gatattgaaa tcaatggagt
1260gttcattccc aaagggttag cagtgatggt tccaatctat gctcttcacc
atgacccaaa 1320gtactggaca gagcctgaga agttctgccc tgaaaggttc
agtaagaaga acaaggacag 1380catagatctt tacagataca taccttttgg
agctggaccc cgaaactgca ttggcatgag 1440gtttgctctc acaaacataa
aacttgctgt cattagagca ctgcagaact tctccttcaa 1500accttgtaaa
gagactcaga tcccactgaa attagacaat ctaccaattc ttcaaccaga
1560aaaacctatt gttctaaaag tgcacttaag agatgggatt acaagtggac
cctgactttc 1620cctaaggact tccactttgt tcaagaaagc tgtatcccag
aacactagac acttcaaatt 1680gttttgtgaa taaaactcag aaatgaagat
gagcttaatt aacctagtat actgggtgaa 1740taattagaaa ttctctacat
tcattgagct ctcattgtct gggtagagta ttacacgttg 1800catactacaa
agcaggtgac aaatcaatgc caaataagta cagtcatctt ctctagttct
1860cataagacta tctccccgcc acctatagtt agtaccctca agtcctcctg
agctgtgatc 1920agagaataaa catttctcaa caattttacc aacaattttt
aatgaaaagg aaaattatac 1980ttgtgattct cgtagtgaca tttatattac
atgttccatt tgtgatattc tataataagt 2040attatattga gaaagtcaac
aagcacctct ttacaaaact gttatctgat gtcttcctgc 2100atattaagga
tgaatctaca gaattagatc aataaggatc aacaaataaa tatttttggt 2160catt
2164444380DNAHomo sapiens 44gtggcggctt cgcccgcgag tccagaggca
ggcgagcagc tcggtcgccc ccaccggccc 60catggcagcc cccggcgccc cagctgagta
cggctacatc cggaccgtcc tgggccagca 120gatcctggga caactggaca
gctccagcct ggcgctgccc tccgaggcca agctgaagct 180ggcggggagc
agcggccgcg gcggccagac agtcaagagc ctgcggatcc aggagcaggt
240gcagcagacc ctcgcccgga agggccgcag ctccgtgggc aacggaaatc
ttcaccgaac 300cagcagtgtt cctgagtatg tctacaacct acacttggtt
gaaaatgatt ttgttggagg 360ccgttcccct gttcctaaaa cctatgacat
gctaaaggct ggcacaactg ccacttatga 420aggtcgctgg ggaagaggaa
cagcacagta cagctcccag aagtccgtgg aagaaaggtc 480cttgaggcat
cctctgagga gactggagat ttctcctgac agcagcccgg agagggctca
540ctacacgcac agcgattacc agtacagcca gagaagccag gctgggcaca
ccctgcacca 600ccaagaaagc aggcgggccg ccctcctagt gccaccgaga
tatgctcgtt ccgagatcgt 660gggggtcagc cgtgctggca ccacaagcag
gcagcgccac tttgacacat accacagaca 720gtaccagcat ggctctgtta
gcgacaccgt ttttgacagc atccctgcca acccggccct 780gctcacgtac
cccaggccag ggaccagccg cagcatgggc aacctcttgg agaaggagaa
840ctacctgacg gcagggctca ctgtcgggca ggtcaggccg ctggtgcccc
tgcagcccgt 900cactcagaac agggcttcca ggtcctcctg gcatcagagc
tccttccaca gcacccgcac 960gctgagggaa gctgggccca gtgtcgccgt
ggattccagc gggaggagag cgcacttgac 1020tgtcggccag gcggccgcag
ggggaagtgg gaatctgctc actgagagaa gcactttcac 1080tgactcccag
ctggggaatg cagacatgga gatgactctg gagcgagcag tgagtatgct
1140cgaggcagac cacatgccgc catccaggat ttctgctgca gctactttca
tacagcacga 1200gtgcttccag aaatctgaag ctcggaagag ggttaaccag
cttcgtggca tcctcaagct 1260tctgcagctc ctaaaagttc agaatgaaga
cgttcagcga gctgtgtgtg gggccttgag 1320aaacttagta tttgaagaca
atgacaacaa attggaggtg gctgaactaa atggggtacc 1380tcggctgctc
caggtgctga agcaaaccag agacttggag actaaaaaac aaataacaga
1440ccatacagtc aatttaagaa gtaggaatgg ctggccgggc gcggtggctc
acgcctgtaa 1500tcccagcact ttgggaggcc aaggcgggcg gatcacgagg
tcaggagttc gagaccagcc 1560tgaccaacat ggtttgctgt ggaatttgtc
atctaatgac aaactcaaga atctcatgat 1620aacagaagca ttgcttacgc
tgacggagaa tatcatcatc cccttttctg ggtggcctga 1680aggagactac
ccaaaagcaa atggtttgct cgattttgac atattctaca acgtcactgg
1740atgcctaaga aacatgagtt ctgctggcgc tgatgggaga aaagcgatga
gaagatgtga 1800cggactcatt gactcactgg tccattatgt cagaggaacc
attgcagatt accagccaga 1860tgacaaggcc acggagaatt gtgtgtgcat
tcttcataac ctctcctacc agctggaggc 1920agagctccca gagaaatatt
cccagaatat ctatattcaa aaccggaata tccagactga 1980caacaacaaa
agtattggat gttttggcag tcgaagcagg aaagtaaaag agcaatacca
2040ggacgtgccg atgccggagg aaaagagcaa ccccaagggc gtggagtggc
tgtggcattc 2100cattgttata aggatgtatc tgtccttgat cgccaaaagt
gtccgcaact acacacaaga 2160agcatcctta ggagctctgc agaacctcac
ggccggaagt ggaccaatgc cgacatcagt 2220ggctcagaca gttgtccaga
aggaaagtgg cctgcagcac acccgaaaga tgctgcatgt 2280tggtgaccca
agtgtgaaaa agacagccat ctcgctgctg aggaatctgt cccggaatct
2340ttctctgcag aatgaaattg ccaaagaaac tctccctgat ttggtttcca
tcattcctga 2400cacagtcccg agtactgacc ttctcattga aactacagcc
tctgcctgtt acacattgaa 2460caacataatc caaaacagtt accagaatgc
acgcgacctt ctaaacaccg ggggcatcca 2520gaaaattatg gccattagtg
caggcgatgc ctatgcctcc aacaaagcaa gtaaagctgc 2580ttccgtcctt
ctgtattctc tgtgggcaca cacggaactg catcatgcct acaagaaggc
2640tcagtttaag aagacagatt ttgtcaacag ccggactgcc aaagcctacc
actcccttaa 2700agactgagga aaatgacaaa gtattctcgg ctgcaaaaat
ccccaaagga aaacacctat 2760ttttctacta cccagcccaa gaaacctcaa
aagcatgcct tgtttctatc cttctctatt 2820tccgtggtcc cctgaatcca
gaaaacaaat agaacataat tttatgagtc ttccagaaga 2880cctttgcaag
tttgccacca gtagataccg gccacaggct cgacaaatag tggtctttgt
2940tattagggct tatggtacat ggcttcctgg aatcaaaatg tgaattcatg
tggaagggac 3000attaatccaa taaataagga aagaagctgt tgcattactg
ggattttaaa agtttgattt 3060acatttatat tccttttctg gttcccatgt
tttgtcactc atgtgcacat tgcttcgcca 3120ttgggcctcc agtgtattgt
tctgcagtgt tgaaacagaa tggaaatgac aagaaatatc 3180tgcagttatc
caggagaaag tataatggca aaattattgg tttctttctt tactttgtgc
3240ttgtttttat ccccttgggt tgtttttctc tgatttttaa ataaacttaa
gaaatttaga 3300ttacagagta tgcatgactg taagaaaaag aaattgagag
gaagtgatca tagcaaatta 3360aagaagtctt ttcctcccag aacttaaagt
aaaataaaaa ataaataaat aaataaaatc 3420ttttccacag agaaaggcaa
ctgtgatgat aaaatttaac gttcccccaa acactgagtc 3480aatgagattt
ttctcaggag atactttacc tataacaacg ccgttaaatc caaatctctt
3540ctaaacgatg gcattctatg taatgccttt cctggacttt tttggccact
gccctggact 3600agtgaaagaa tggactctat ctttatctgc aagaggaact
aaggccttct atcagactgc 3660ctggccagcc tggggcactg aaaatacggc
tcatgttaat gagttacatt atcagccagc 3720ccagccttgc ccaccattta
agaaatatca cagagccact agatctcata tgatcttctt 3780caagccatta
ttttaactca agaaaactct agagaagaaa agtgaagaag tcatgttgaa
3840gaagatgtaa gaatgtgtca agaccatcca gaaatgatat gagaaatact
gatattttaa 3900atggttgaca tcatccagcg aaatgaatct acattaaatg
ttgttttaac tgcgctatga 3960ttaaaaccat tcatatagag ttagtcttta
caactactat tctgttattt ttttttttaa 4020tctgacaaca tttgtcctaa
gtaagataag caaaaaaatt cttcaactcc ttttggcaag 4080aaaactgtaa
cagaaaataa attttgaatg tgtacttaag tctttattat atttgaagca
4140attttttttc aattttaaaa gctgaatgaa gacaacttag gttgctaacc
tagttcaaaa 4200tgaaattatt tagataccaa tttttaaaat actggagaga
atttatatgt ctttttccag 4260agttctgatg ataagcattt ggagtgcatt
tattcctcca gataataaat gtgtgttcag 4320aactttttgt gttttttaag
gcattaataa agccttcgat aatattaaat acaaaatgaa 4380
* * * * *