Note: Descriptions are shown in the official language in which they were submitted.
DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 5
CONTENANT LES PAGES 1 A 191
NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME
THIS IS VOLUME 1 OF 5
CONTAINING PAGES 1 TO 191
NOTE: For additional volumes, please contact the Canadian Patent Office
NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
PRIMARY RAT HEPATOCYTE TOXICITY MODELING
INVENTORS: Donna MENDRICK, Mark PORTER, Kory JOHNSON, Brandon
HIGGS, Arthur CASTLE, Michael ORR and Michael ELASHOFF
RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. ~119(e) to U.S.
Provisional
Applications 60/353,171, filed February 4, 2002; 60/363,534, filed March 13,
2002;
60/371,135, filed April 10, 2002; 60/371,134, filed April 10, 2002;
60/370,248, filed April 8,
2002; 60/371,150, filed April 10, 2002; 60/371,413, filed April 11, 2002;
60/373,601, filed
April 19, 2002; 60/374,139, filed April 22, 2002; 60/394,253, filed July 9,
2002; 60/378,652,
filed May 9, 2002; 60/373,602, filed April 19, 2002; 60/378,653, filed May 9,
2002;
60/378,665, filed May 9, 2002; 60/378,370, filed May 8, 2002; 60/394,230,
filed July 9,
2002; and 60/407,688, filed September 4, 2002, all of wluch are herein
incorporated by
reference in their entirety.
[0002] This application is also related to pending U.S. Applications
09/917,800, filed July
31, 2001, 10/060,087, filed January 31, 2002, and PCT/LJS03/ , entitled
"Molecular
Hepatotoxicology Modeling," filed January 31, 2003, as well as to PCT
Application
PCT/USOl/23872, filed July 31, 2001, all of which are herein incorporated by
reference in
their entirety.
SEQUENCE LISTING SUBMISSION ON COMPACT DISC
[0003] The Sequence Listing submitted concurrently herewith on compact disc
under 37
C.F.R. ~ ~ 1.821 (c) and 1.821 (e) is herein incorporated by reference in its
entirety. Four
copies of the Sequence Listing, one on each of four compact discs are
provided. Copy 1,
Copy 2 and Copy 3 are identical. Copies 1, 2 and 3 are also identical to the
CRF. Each
electronic copy of the Sequence Listing was created on February 3, 2003 with a
file size of
6321 I~B. The file names are as follows: Copy 1- g15113wo.txt; Copy 2-
g15113wo.txt;
Copy 3- g15113wo.txt; CRF- g15113wo.txt.
BACKGROUND OF THE INVENTION
[0004] The need for methods of assessing the toxic impact of a compound,
pharmaceutical
agent or environmental pollutant on a cell or living organism has led to the
development of
procedures which utilize living organisms as biological monitors. The simplest
and most
convenient of these systems utilize unicellular microorganisms such as yeast
and bacteria,
since they are most easily maintained and manipulated. Unicellular screening
systems also
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-2-
often use easily detectable changes in phenotype to monitor the effect of test
compounds on
the cell. Unicellular organisms, however, are inadequate models for estimating
the potential
effects of many compounds on complex multicellular animals, as they do not
have the ability
to carry out biotransformations to the extent or at levels found in higher
organisms.
[0005] The biotransformation of chemical compounds by multicellular organisms
is a
significant factor in determining the overall toxicity of agents to which they
are exposed.
Accordingly, multicellular screening systems or screening systems using
isolated eukaryotic
cells may be preferred or required to detect the toxic effects of compounds.
The use of
multicellular organisms as toxicology screening tools has been significantly
hampered,
however, by the lack of convenient screening mechanisms or endpoints, such as
those
available in yeast or bacterial systems. In addition, previous attempts to
produce toxicology
prediction systems have failed to provide the necessary modeling data and
statistical
information to accurately predict toxic responses (e.g., WO 00/12760, WO
00/47761, WO
00/63435, WO 01/32928, WO 01/38579).
SUMMARY OF THE INVENTION
[0006] The present invention is based on the elucidation of the global changes
in gene
expression in primary hepatocytes exposed to known toxins in particular
hepatotoxins, as
compared to unexposed cells as well as the identification of individual genes
that are
differentially expressed upon toxin exposure.
[0007] In various aspects, the invention includes methods of predicting at
least one toxic
effect of a compound, predicting the progression of a toxic effect of a
compound, and
predicting the hepatoxicity of a compound. The invention also includes methods
of
identifying agents that modulate the onset or progression of a toxic response.
Also provided
are methods of predicting the general pathology classes and cellular pathways
that a
compound modulates in a cell. The invention includes methods of identifying
agents that
modulate protein activities.
[0008] In a further aspect, the invention provides probes comprising sequences
that
specifically hybridize to genes in Tables 1-SXX. Also provided are solid
supports
comprising at least two of the previously mentioned probes. The invention also
includes a
computer system that has a database containing information identifying the
expression level
in a tissue or cell sample exposed to a hepatotoxin of a set of genes
comprising at least two
genes in Tables 1-SXX.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-3-
DETAILED DESCRIPTION
[0009] Many biological functions are accomplished by altering the expression
of various
genes through transcriptional (e.g. through control of initiation, provision
of RNA precursors,
RNA processing, etc.) and/or translational control. For example, fundamental
biological
processes such as cell cycle, cell differentiation and cell death are often
characterized by the
variations in the expression levels of groups of genes.
[0010] Changes in gene expression are also associated with the effects of
various
chemicals, drugs, toxins, pharmaceutical agents and pollutants on an organism
or cells. For
example, the lack of sufficient expression of functional tumor suppressor
genes and/or the
over expression of oncogene/protooncogenes after exposure to an agent could
lead to
tumorgenesis or hyperplastic growth of cells (Marshall, Cell, 64: 313-326
(1991); Weinberg,
Science, 254:1138-1146 (1991)). Thus, changes in the expression levels of
particular genes
(e.g. oncogenes or tumor suppressors) may serve as signposts for the presence
and
progression of toxicity or other cellular responses to exposure to a
particular compound.
[0011] Monitoring changes in gene expression may also provide certain
advantages during
drug screening and development. Often drugs are screened for the ability to
interact with a
major target without regard to other effects the drugs have on cells. These
cellular effects
may cause toxicity in the whole animal, which prevents the development and
clinical use of
the potential drug.
[0012] The present inventors have examined primary rat hepatocytes exposed to
the known
hepatotoxins which induce detrimental liver effects, to identify global and
individual changes
in gene expression induced by these compounds. These global changes in gene
expression,
which can be detected by the production of expression profiles, as well as the
individual
genes, provide useful toxicity markers that can be used to monitor toxicity
and/or toxicity
progression by a test compound. Expression profiles, as well as the individual
markers, may
also be used to monitor or detect various disease or physiological states,
disease progression,
drug efficacy and drug metabolism.
Identification of Toxicity Markers
[0013] To evaluate and identify gene expression changes that are predictive of
toxicity,
studies using selected compounds with well characterized toxicity have been
conducted by
the present inventors to catalogue altered gene expression during exposure in
vivo and ih
vitro. In the present study, amiodarone, alpha-naphthylisothiocyante (ANIT),
acetaminophen
(APAP), AY-25329, carbamazepine, carbon tetrachloride, chlorpromazine, CI-
1000,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-4-
clofibrate, CPA, diclofenac, diflunisal, dimethylnitrosamine (DMl~, 17a-
ethinylestradiol,
gemfibrozil (Lopid~), hydrazine, imipramine (Janimine), indomethacin,
lipopolysaccharide,
lovastatin (Mevacor~), methotrexate, phenobarbital, tacrine, tamoxifen,
tetracycline,
valproate and Wy-14643 were selected as a known hepatotoxins.
[0014] Amiodarone (Cordarone~) is an anti-arrhythmic agent whose chemical
structure
contains a benzofuran ring (ring A) coupled to a p-OH-benzene structure
substituted with 2
iodines and a diethyl-ethanolamine side chain (ring B). This drug is known to
cause damage
to the liver and has been shown to adversely effect the mitochondria by
uncoupling oxidative
phosphorylation and inhibiting beta-oxidation and respiration. Inhibition of
respiration
decreases ATP and increases production of reactive oxygen species, which in
turn cause lipid
peroxidation. The steatosis and hepatitis observed following treatment with
amiodarone are
believed to be due, at least in part, to lipid peroxidation products (Spaniol
et al., JHepatol
35(5):628-636 (2001); Berson et al., GastYOenterology 114:764-774, (1998)).
[0015] Aromatic and aliphatic isothiocyanates are commonly used soil fumigants
and
pesticides (Shaaya et al., Pesticide Science 44(3):249-253 (1995); Cairns et
al., JAssoc
O~cial Analytical Chemists 71(3):547-550 (1988)). These compounds are also
environmental hazards, because they remain as toxic residues in plants (Cerny
et al., J
Ag~icultunal and Food Chemistry 44(12):3835-3839 (1996)) and because they are
released
from the soil into the surrounding air (Gar et al., JAgricutu~al and Food
Chemistry
46(3):986-990 (1998)).
[0016] Exposure to a-naphthylisothiocyanate (ANIT) has been shown to increase
serum
levels of total bilirubin, alkaline phosphatase, serum glutamic oxaloacetic
transaminase and
serum glutamic pyruvic transaminase, while total bile flow was reduced, all of
which are
indications of severe biliary dysfunction. ANIT also induces j aundice and
cholestatis (the
condition caused by failure to secrete bile, resulting in plasma accumulation
of bile
substances, liver cell necrosis and bile duct obstruction) (Tanaka et al.,
Clinical and
Expe~imeyatal Pharmacology and Physiology 20:543-547 (1993)). ANIT fails to
produce
extensive necrosis, but was found to produce inflammation and edema in the
portal tract of
the liver (Maziasa et al., Toxicol Appl Pha~macol 110:365-373 (1991)). AI~IIT-
induced
hepatotoxicity may also characterized by cholangiolitic hepatitis and bile
duct damage.
Acute hepatotoxicity caused by Al~IT in rats is manifested as neutrophil-
dependent necrosis
of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. These
changes mirror
the cholangiolitic hepatitis found in humans (Hill, Toxicol Sci 47:118-125
(1999)).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-5-
[0017] Histological changes include an infiltration of polymorphonuclear
neutrophils and
elevated number of apoptotic hepatocytes (Calvo et al., J Cell Biochem
80(4):461-470
(2001)). Other known hepatotoxic effects of exposure to ANIT include a damaged
antioxidant defense system, decreased activities of superoxide dismutase and
catalase (Ohta
et al., Toxicology 139(3):265-275 (1999)), and the release of proteases from
the infiltrated
neutrophils, alanine aminotransferase, cathepsin G, elastase, which mediate
hepatocyte
killing (Hill et al., Toxicol Appl Pharmacol 148(1):169-175 (1998)).
[0018] Acetominophen (APAP) is a widely used analgesic and antipyretic agent
that is an
effective substitute for aspirin. Although acetaminophen does not have anti-
inflammatory
properties, it is preferably given to patients with ulcers or patients in whom
prolonged
clotting times would not be desirable. It also preferably taken by people who
do not tolerate
aspirin well.
[0019] Acetominophen is metabolized to N acetyl p-benzoquinoneimine (NAPQI) by
N-
hydroxylation in a cytochrome P450-mediated process. This highly reactive
intermediate,
which reacts with sulfhydryl ,groups in glutathione, and in other liver
proteins following the
depletion of glutathione, can cause centrilobular hepatic necrosis
(particularly in zone 3),
renal tubular necrosis, and hepatic and renal failure (Goodman and Gilinan's
The
Pharmacological Basis of Therapeutics, Ninth Ed., Hardman et al., eds., pp.
631-633,
McGraw-Hill, New York, 1996; Chanda et al., Hepatology 21(2):477-486 (1995)).
Less
serious side effects include skin rashes (erythemas and urticarias) and
allergic reactions.
[0020] Upon treatment of rats with acetaminophen, hepatotoxicity can be
observed 24 hours
after dosing, as determined by statistically significant elevations of ALT and
AST in the
serum and by hepatocellular necrosis visualized at the light microscopic level
(Hessel et al.,
B~az JMed Biol Res 29(6):793-796 (1996); Bruck et al., Dig Dis Sci 44(6):1228-
1235
(1999)). High, but non-lethal, doses of acetaminophen given to rats also
produced elevated
levels of genes involved in hepatic acute phase response and liver cell
maintenance and
repair: arginase, beta-fibrinogen, alpha 1-acid glycoprotein, alpha-tubulin,
histone 3, TGF
beta and cyclin d. Expression levels of genes regulated by the cell cycle were
decreased
(Tygstrup et al., JHepatol 25(2):183-190 (1996); Tygstrup et al., JHepatol
27(1):156-162
(1997)). In mice, expression levels of genes that encode growth arrest and
cell cycle
regulatory proteins were increased, along with expression levels of stress-
induced genes,
transcription factor LRG-21, SOCS-2 (cytokine signaling repressor) and PAI-1
(plasminogen
activator inhibitor-1) (Reilly et al., Biochem Biophys Res Comm 282(1):321-328
(2001)).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-6-
[0021] AY-25329 is a phenothiazine that has been shown to be toxic in liver
and in kidney
tissue, where it can cause nephrosis. Phenothiazines are a class of
psychoactive drugs that
are used to treat schizophrenia, paranoia, mania, hyperactivity in children,
some forms of
senility, and anxiety (http://www.encyclopedia.com/articlesnew/ 36591.html).
Side effects
associated with prolonged use of these drugs are reduced blood pressure,
Parkinsonism,
reduction of motor activity, and visual impairment.
[0022] The present inventors have noted indications of liver and renal effects
of AY-25329
by changes in serum chemistry. As early as 6 hours after the first dose,
statistically
significant increases in serum levels of creatinine, BUN, ALT, triglycerides
and cholesterol
were observed. Most of these markers of renal and liver dysfunction remained
altered
throughout the 14 day study period. Light microscopic analysis revealed
effects in the liver
as early as 6 and 24 hours, as evidenced by an increased number of hepatocytic
mitotic
figures and decreased glycogen content. Following 14 days of repeated dosing,
nephrosis
and alterations in the peripheral lobes of the liver and in the cytoplasm of
hepatocytes were
evident in rats dosed with 250 mg/kg/day of AY-25329.
[0023] Carbamazepine (Tegretol~) is an anti-epieleptic agent. In rats, it has
been shown to
induce a number of cytochrome P450 enzymes, in particular CYP2B, and the drug
may also
cause steatohepatitis in humans (Tateishi et al., Chem Biol Interact 117:257-
268 (1999);
Grieco et al., Eur J Gastroenterol 13(8):973-975 (2001)).
[0024] The pathogenesis of acute carbon tetrachloride (CC14)-induced
hepatotoxicity
follows a well-characterized course in humans and experimental animals
resulting in
centrilobular necrosis and steatosis, followed by hepatic regeneration and
tissue repair.
Severity of the hepatocellular injury is also dose-dependent and may be
affected by species,
age, gender and diet.
[0025] Differences in susceptibility to CC14 hepatotoxicity are primarily
related to the
ability of the animal.model to metabolize CC14 to reactive intermediates. CCl4
induced
hepatotoxicity is dependent on CCl4 bioactivation to trichloromethyl free
radicals by
cytochrome P450 enzymes (CYP2E1), localized primarily in centrizonal
hepatocytes.
Formation of the free radicals leads to membrane lipid peroxidation and
protein denaturation
resulting in hepatocellular damage or death.
[0026] The onset of hepatic injury is rapid following acute administration of
CCl4 to male
rats. Morphologic studies have shown cytoplasmic accumulation of lipids in
hepatocytes
within 1 to 3 hours of dosing, and by 5 to 6 hours, focal necrosis and
hydropic swelling of
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
_7_
hepatocytes are evident. Centrilobular necrosis and inflammatory infiltration
peak by 24 to
48 hours post dose. The onset of recovery is also evident within this time
frame by increased
DNA synthesis and the appearance of mitotic figures. Removal of necrotic
debris begins by
48 hours and is usually completed by one week, with full restoration of the
liver by 14 days.
[0027] Increases in serum transaminase levels also parallel CCl4 induced
hepatic
histopathology. In male Sprague Dawley (SD) rats, alanine aminotrasferase
(ALT) and
aspartate aminotransferase (AST) levels increase within 3 hours of CC14
administration (0.1,
1,2, 3, 4 mL/kg, ip; 2.5 mL/kg, po) and reach peak levels (approximately 5-10
fold increases)
within 48 hours post dose. Significant increases in serum -glutathione s-
transferase (-GST)
levels have also been detected as early as 2 hours after CC14 administration
(25 L/kg, po) to
male SD rats.
[0028] At the molecular level, induction of the growth-related proto-
oncogenes, c-fos and
c jun, is reportedly the earliest event detected in an acute model of CCl4
induced
hepatotoxicity (Schiaffonato et al., Liver 17:183-191 (1997)). Expression of
these early-
immediate response genes has been detected within 30 minutes of a single dose
of CC14 to
mice (0.05 -1.5 mL/kg, ip) and by 1 to 2 hours post dose in rats (2 mL/kg, po;
5 mL/kg, po)
(Schiaffonato et al., supra, and Hong et al., Yohsei Medical J 38:167-177
(1997)). Similarly,
hepatic c-myc gene expression is increased by 1 hour following an acute dose
of CC14 to
male SD rats (5 mL/kg, po) (Hong et al., supra). Expression of these genes
following
exposure to CCl4 is rapid and transient. Peak hepatic mRNA levels for c-fos, c
jun, and c-
myc, after acute administration of CC14 have been reported at 1 to 2 hours, 3
hours, and 1
hour post dose, respectively.
[0029] The expression of tumor necrosis factor-cc (TNF-a).is also increased in
the livers of
rodents exposed to CC14, and TNF-a has been implicated in initiation of the
hepatic repair
process. Pre-treatment with anti-TNF-a antibodies has been shown to prevent
CC14 -
mediated increases in c-jun and c-fos gene expression, whereas administration
of TNF-a
induced rapid expression of these genes (Bruccoleri et al., Hepatol 25:133-141
(1997)). Up-
regulation of transforming growth factor-~i (TGF-Vii) and transforming growth
factor
receptors (TBRI-III) later in the repair process (24 and 48 hours after CCl4
administration)
suggests that TGF-~i may play a role in limiting the regenerative response by
induction of
apoptosis (Grasl-Kraupp et al., Hepatol 28:717-7126 (1998)).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
_g_
[0030] Chlorpromazine (Thorazine~) is a central nervous system depressant that
is used as a
sedative and also as an anti-nausea or anti-itching medication. The mechanism
of action is
not known. The drug induces canalicular cholestasis, a condition characterized
by a decrease
in the volume of bile formed and impaired secretion of solutes into bile,
resulting in elevated
serum levels of bile salts and bilirubin. Chlorpromazine has also been shown
to inhibit bile
acid uptake and canalicular contractility. Bile plugs can form in the bile
ducts and canaliculi.
Drug-induced cholestasis is also associated with cell swelling, inflammation
and cell death
(Casarett and Doull's Toxicolo~~The Basic Science of Poisons, 6th Ed.,
Klaassen et al. eds.,
pp. 476-486, McGraw-Hill Medical Pub. Div., New York, 2001).
[0031] CI-1000 (4H-pyrrolo:3,2-d:pyrimidin-4-one, 2-amino-3,5-dihydro-7-(3-
thienyhnethyl)-monohydrochloride monohydrate) is a compound with anti-
inflammatory
properties. After treatment with CI-1000, increased serum ALT levels, a
standard marker of
liver toxicity, were observed in dogs.
[0032] Clofibrate, a halogenated phenoxypropanoic acid derivative (ethyl ester
of clofibric
acid), is an antilipemic agent. The exact mechanism by which clofibrate lowers
serum
concentrations of triglycerides and low-density lipoprotein (LDL) cholesterol,
as well as
raising high-density lipoprotein (HDL) cholesterol is uncertain. The drug has
several
antilipidemic actions, including activating lipoprotein lipase, which enhances
the clearance of
triglycerides and very-low-density lipoprotein (VLDL) cholesterol, inhibition
of cholesterol
and triglyceride biosynthesis, mobilization of cholesterol from tissues,
increasing fecal
excretion of neutral steroids, decreasing hepatic lipoprotein synthesis and
secretion, and
decreasing free fatty acid release.
[0033] Clofibrate has a number of effects on the rat liver, including
hepatocellular
hypertrophy, cellular proliferation, hepatomegaly, induction of CYP450
isozymes, and
induction of palmitoyl CoA oxidation. Long term administration of clofibrate
causes
increased incidence of hepatocellular carcinoma, benign testicular Leydig cell
tumors, and
pancreatic acinar adenomas in rats. Clofibrate induces proliferation of
peroxisomes in
rodents and this effect, rather than genotoxic damage, is believed to be the
causative event in
rodent carcinogenesis (AHFS Drub Information Handbook 2001, McEvoy, ed.,
pp.1735-
1738; Electronic Physicians' Desk Reference- Atromid-S (clofibrate) at
www.pdr.net; Brown
and Goldstein, "Drugs used in the treatment of hyperliproteinemias," in
Goodman and
Gilman's The Pharmacological Basis of Therapeutics, Eighth ed., Goodman et
al., eds., pp.
874-896, Pergamon Press, New York, 1990).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-9-
[0034] Clofibrate also increases hepatic lipid content and alters its normal
composition by
significantly increasing levels of phosphatidylcholine and phosphatidyl-
ethanolamine
(Adinehzadeh et al., Clzem Res Toxicol 11(5):428-440 (1998)). A rat study of
liver
hyperplasia and liver tumors induced by peroxisome proliferators revealed that
administration of clofibrate increased levels of copper and altered copper-
related gene
expression in the neoplastic liver tissues. Down-regulation of the
ceruloplasmin gene and of
the Wilson's Disease gene (which encodes P-type ATPase), along with up-
regulation of the
metallothionein gene, were noted in these tissues (Eagon et al.,
Ca~cinogehesis 20(6):1091-
1096 (1999)). Clofibrate-induced peroxisome proliferation and carcinogenicity
are believed
to be rodent-specific, and have not been demonstrated in humans.
[0035] Cyproterone acetate (CPA) is a potent androgen antagonist and has been
used to
treat acne, male pattern baldness, precocious puberty, and prostatic
hyperplasia and
carcinoma (Goodman ~z Gilinan's The Pharmacological Basis of Therapeutics 9th
ed., p.
1453, J.G. Hardman et al., Eds., McGraw Hill, New York, 1996). Additionally,
CPA has
been used clinically in hormone replacement therapy to protect the endometrium
and
decrease menopausal symptoms and the risk of osteoporotic fracture (Schneider,
"The role of
antiandrogens in hormone replacement therapy," Climacteric 3 (Suppl. 2): 21-27
(2000)).
[0036] In experiments with rats, CPA was shown to induce unscheduled DNA
synthesis in
vitro. After a single oral dose, continuous DNA repair activity was observed
after 16 hours.
CPA also increased the occurrence of S phase cells, which corroborated the
mitogenic
potential of CPA in rat liver (I~asper et al., Caf~cinogefzesis 17(10): 2271-
2274 (1996)). CPA
has also been shown to produce cirrhosis in humans (Gamy et al., EuY JPediat~
158(5): 367-
370 (1999)).
[0037] Diclofenac, a non-steroidal anti-inflammatory drug, has been frequently
administered to patients suffering from rheumatoid arthritis, osteoarthritis,
and ankylosing
spondylitis. Following oral administration, diclofenac is rapidly absorbed and
then
metabolized in the liver by cytochrome P450 isozyme of the CYC2C subfamily
(Goodman &
Gilinan's The Pharmacological Basis of Therapeutics 9th ed., p. 637, J.G.
Hardman et al.,
eds., McGraw Hill, New York, 1996). In addition, diclofenac has been applied
topically to
treat pain due to corneal damage (Jayamanne et al., Eye 11(Pt. 1): 79-83
(1997); Dornic et
al., Am JOplathalrnol 125(5): 719-721 (1998)).
[0038] Although diclofenac has numerous clinical applications, adverse side-
effects have
been associated with the drug, such as corneal complications, including
corneal melts,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-10-
ulceration, and severe keratopathy (Guidera et al., Ophthalmology 108(5): 936-
944 (2001)).
Another study investigated 180 cases of patients who had reported adverse
reactions to
diclofenac to the Food and Drug Administration (Banks et al., Hepatology
22(3): 820-827
(1995)). Of the 180 reported cases, the most common symptom was jaundice (75%
of the
symptomatic patients). Liver sections were taken and analyzed, and hepatic
injury was
apparent one month after drug treatment. An additional report showed that a
patient
developed severe hepatitis five weeks after begimung diclofenac treatment for
osteoarthritis
(Bhogaraju et al., South Med J92(7): 711-713 (1999)).
[0039] In one study on diclofenac-treated Wistar rats (Ebong et al., Afi~ JMed
Sci 27(3-4):
243-246 (1998)), diclofenac treatment induced an increase in serum chemistry
levels of
alanine aminotransferase, aspartate aminotransferase, methaemoglobin, and
total and
conjugated bilirubin. Additionally, diclofenac enhanced the activity of
alkaline phosphatase
and 5'nucleotidase. A study on humans revealed elevated levels of hepatic
transaminases and
serum creatine when compared to the control group (McI~enna et al., Scaud
JRheumatol
30(1): 11-18 (2001)).
[0040] Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a
difluorophenyl
derivative of salicylic acid (Goodman ~ Gilman's The Pharmacological Basis of
Therapeutics 9th ed., p. 631, J.G. Hardman et al., Eds., McGraw Hill, New
York, 1996). It is
most frequently used in the treatment of osteoarthritis and musculoskeletal
strains. NSAIDs
have analgesic, antipyretic and anti-inflammatory actions, however,
hepatotoxicity is known
to be an adverse side effect of NSAID treatment (Masubuchi et al., JPharmacol
Exp Then
287:208-213 (1998)). Diflunisal has been shown to be less toxic than other
NSAIDs, but it
can eventually have deleterious effects on platelet or kidney function
(Bergamo et al., Am J
Neph~ol 9:460-463 (1989)). Other side effects that have been associated with
diflunisal
treatment are diarrhea, dizziness, drowsiness, gas or heartburn, headache,
nausea, vomiting,
and insomnia (http:/larthritisinsight.com/medical/ meds/dolobid.html).
[0041] In a comparative hepatotoxicity study of 18 acidic NSAIDs, diflunisal
was shown to
increase LDH leakage in rat hepatocytes, a marker for cell injury, when
compared to control
samples. Additionally, treatment with diflunisal led to decreased
intracellular ATP
concentrations. In a study comparing the effects of diflunisal and ibuprofen,
both drugs
appeared to cause abdominal cramping, even during short-term usage. Because
the toxic
dosages were selected to be below the level at which gastric ulceration
occurs, more severe
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-11-
gastrointestinal effects were not detected. But, increased serum levels of
creatinine, a sign of
renal injury, were also observed (Muncie et al., Clih Ther 11:539-544 (1989)).
[0042] Another model compound, dimethyhiitrosamine (DMN), is a known
carcinogen and
inducer of liver fibrosis and lipid peroxidation. DMN causes oxidative stress
in liver cells,
which may be the link between chronic liver damage and liver fibrosis. Rats
treated with
DMN showed diffuse fibronectin deposition, elevated hydroxyproline levels (an
indicator of
fibrosis), increased levels of collagens, fibrous septa, and impaired
oxidative balance. Serum
levels of ALT and malondialdehyde (MDA) were increased, while serum levels of
SOD were
decreased (Vendemiale et al., Toxicol Appl Pharfzaacol 175(2):130-139 (2001);
Liu et al.,
Zho~ghua Gah Zang Bing Za Zhi 9 Supp1:18-20 (2001)). Other studies in rats
have noted
severe centrilobular congestion and haemorrhagic necrosis several days after a
three-day
period of DMN administration. Following additional periods of DMN treatment,
the rats
developed centrilobular necrosis and intense neutrophilic infiltration, which
progressed to
severe centrilobular necrosis, fiber deposition, focal fatty deposits, bile
duct proliferation,
bridging necrosis and fibrosis around the central veins (cirrhosis-like
symptoms). A decrease
in total protein and increase in DNA were also observed (George et al. (2001)
Toxicology
156(2-3):129-138).
[0043] 17a-ethinylestradiol, a synthetic estrogen, is a component of oral
contraceptives,
often combined with the progestational compound norethindrone. It is also used
in post-
menopausal estrogen replacement therapy (PDR 47th Ed., pp. 2415-2420, Medical
Economics
Co., Inc., Montvale, NJ, 1993; Goodmaiz & Gilman's The Pharmalo~ical Basis of
Therapeutics 9th Ed., pp. 1419-1422, J.G. Hardman et al. Eds., McGraw Hill,
New York,
1996).
[0044] The most frequent adverse effects of 17a-ethinylestradiol usage are
increased risks
of cardiovascular disease: myocardial infarction, thromboembolism, vascular
disease and
high blood pressure, and of changes in carbohydrate metabolism, in particular,
glucose
intolerance and impaired insulin secretion. There is also an increased risk of
developing
benign hepatic neoplasia. Because this drug decreases the rate of liver
metabolism, it is
cleared slowly from the liver, and carcinogenic effects, such as tumor growth,
may result.
[0045] 17a-ethinylestradiol has been shown to cause a reversible intrahepatic
cholestasis in
male rats, mainly by reducing the bile-salt-independent fraction of bile flow
(BSIF) (Koopen
et al., Hepatology 27:537-545 (1998)). Plasma levels of bilirubin, bile salts,
aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) in this study were
not changed.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-12-
This study also showed that 17a-ethinylestradiol produced a decrease in plasma
cholesterol
and plasma triglyceride levels, but an increase in the weight of the liver
after 3 days of drug
administration, along with a decrease in bile flow. Further results from this
study are as
follows. The activities of the liver enzymes leucine aminopeptidase and
alkaline phosphatase
initially showed significant increases, but enzyme levels decreased after 3
days. Bilirubin
output increased, although glutathione (GSH) output decreased. The increased
secretion of
bilirubin into the bile without affecting the plasma level suggests that the
increased bilirubin
production must be related to an increased degradation of heme from heme-
containing
proteins. Similar results were obtained in another experiment (Bouchard et
al., Lives 13:193-
202 (1993)) in which the livers were also examined by light and electron
microscopy. Daily
doses of 17a-ethinylestradiol have been shown to cause cholestasis as well,
although,
following drug treatment, bile flow rates gradually returned to normal (Hamada
et al.,
Hepatology 21:1455-1464 (1995)). Liver hyperplasia, possibly in response to
the effects of
tumor promoters, has also been observed (Mayol, Carcihogeaesis 13:2381-2388
(1992)).
[0046] The lipid-lowering drug gemfibrozil (Lopid~) is a know peroxisome
proliferator in
liver tissue, causing both hyperplasia and enlargement of liver cells. Upon
exposure to
gemfibrozil, hepatocarcinogenesis has been observed in rats and mice, and a
decrease in
alpha-tocopherol and an increase in DT-diaphorase activity have been observed
in rats and
hamsters (impaired antioxidant capability). Peroxisome proliferators increase
the activities of
enzymes involved in peroxisomal beta-oxidation and omega-hydroxylation of
fatty acids,
which results in oxidative stress (O'Brien et al., Toxicol Sci 60(2):271-278
(2001); Carthew
et al., JAppl Toxicol 17(1):47-51 (1997)).
[0047] Hydrazine (NHZ=NHa), is a component of many industrial chemicals, such
as
aerospace and airplane fuels, corrosion inhibitors, dyes and photographic
chemicals. Its
derivatives axe used in pharmaceuticals such as hydrazine sulphate, used to
treat cachexia in
cancer patients, isoniazid, an anti-tuberculosis drug, and hydralazine, an
anti-hypertensive.
These drugs are metabolized in vivo to produce hydrazine, among other by-
products.
Consequently, exposure to hydrazine is by direct contact, e.g., among military
and airline
personnel, or the result of its production in the body, e.g., in patients with
cancer or high
blood pressure.
[0048] Studies on rat hepatocytes have shown that hydrazine causes a dose-
dependent loss
of viability, leakage of LDH, depletion of GSH and ATP and a decreased rate of
protein
synthesis (Delaney et al., ~enobiotica 25(12):1399-1410 (1995)). When
administered to rats,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-13-
hepatotoxic changes, characterized by GSH and ATP depletion and induction of
fatty liver
(increases in liver weight and triglycerides, with the appearance of fatty
droplets, swelling of
mitochondria and appearance of microbodies) were also found to be dose-
dependent (Jenner
et al., Arch Toxicol 68(6):349-357 (1994); Scales et al., JToxicol Ehvi~oyz
Health 10(6):941-
953 (1982)). The hepatoxicity, as well as renal toxicity, associated with
hydrazine exposure
has been linked to free radical damage resulting from oxidative metabolism by
cytochrome
P4502E1 (CYP2E1), which catalyzes the conjugation of free radicals with
reduced
glutathione. Although exposure to hydrazine and several hydrazine derivatives
increased
enzyme levels in kidney tissue, increased enzyme levels were not detected in
liver tissue
(Range-Morns et al., Drug Metab Dispos 24(7):734-737 (1996)).
[0049] The mutagenic and hepatocarcinogenic effects of hydrazine were examined
in
hamster livers. Ih vivo, hydrazine reacts with formaldehyde to form
formaldehyde hydrazone
(CHZ N-NH2), an alkylating intermediate that methylates guanine in DNA. Upon
treatment
with hydrazine, liver DNA showed the presence of methylated guanine, DNA
adducts and the
impairment of maintenance methylation (impaired methylation of deoxycytosine).
Hepatic
adenomas and carcinomas also developed in a dose-dependent mamier and could be
correlated with decreased maintenance methylation (FitzGerald et al.,
Carcinogeyiesis
17(12):2703-2709 (1996)).
[0050] Imipramine, a dibenzazepine derivative, is a tricyclic anti-depressant
agent commonly
used for the treatment of major depression. Experiments in rats have shown
that the drug
induces cytochrome P450-mediated formation of reactive metabolites, which
cause acute cell
injury. Decreased levels of glutathione and protein thiols, as well as lactate
dehydrogenase
leakage, all standard measures of liver toxicity, were also noted (Masubuchi
et al., Arch
Toxicol 73(3):147-151 (1999). On rare occasions, imipramine has induced
cholestasis and
hepatitis in humans (Moskovitz et al., J Clin Psychiatry 43(4):165-066 (1982);
Horst et al.,
Gastroenterology 79(3):550-544 (1980)).
[0051] Indomethacin is a non-steroidal antiinflamrnatory, antipyretic and
analgesic drug
commonly used to treat rheumatoid arthritis, osteoarthritis, ankylosing
spondylitis, gout and a
type of severe, chronic cluster headache characterized by many daily
occurrences and jabbing
pain. This drug acts as a potent inhibitor of prostaglandin synthesis; it
inhibits the
cyclooxygenase enzyme necessary for the conversion of arachidonic acid to
prostaglandins
(PDR 47th Ed., Medical Economics Co., Inc., Montvale, NJ, 1993; Goodman &
Gilman's The
Pharmalo~ical Basis of Therapeutics 9th Ed., J.G. Hardman et al. eds., pp.
1074-1075, 1089-
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-14-
1095, McGraw Hill, New York, 1996; Cecil Textbook of Medicine, 20th Ed., part
XII, pp.
772-773, 805-808, J. C. Bennett and F. Plum Eds., W. B. Saunders Co.,
Philadelphia, 1996).
[0052] The most frequent adverse effects of indomethacin treatment are
gastrointestinal
disturbances, usually mild dyspepsia, although more severe conditions, such as
bleeding,
ulcers and perforations can occur. Hepatic involvement is uncommon, although
some fatal
cases of hepatitis and jaundice have been reported. Renal toxicity can also
result, particularly
after long-term administration. Renal papillary necrosis has been observed in
rats, and
interstitial nephritis with hematuria, proteinuria and nephrotic syndrome have
been reported
in humans. Patients suffering from renal dysfunction risk developing a
reduction in renal
blood flow, because renal prostaglandins play an important role in renal
perfusion.
[0053] In rats, although indomethacin produces more adverse effects in the
gastrointestinal
tract than in the liver, it has been shown to induce changes in hepatocytic
cytochrome P450.
In one study, no widespread changes in the liver were observed, but a mild,
focal,
centrilobular response was noted. Serum levels of albumin and total protein
were
significantly reduced, while the serum level of urea was increased. No changes
in creatinine
or aspartate aminotransferase (AST) levels were observed (Falzon et al., Br J
exp Path
66:527-534 (1985)). In another rat study, a single dose of indomethacin was
shown to reduce
liver and renal microsomal enzymes, including CYP450, and cause lesions in the
GI tract
(Fracasso et al., Agents Actions 31:313-316 (1990)).
[0054] LPS (lipopolysaccharide) is an endotoxin released by gram-negative
bacteria upon
breakage or rupture of the cells that induces an acute inflammatory response
in mammals and
that can cause septic shock. LPS is also a research tool used to initiate
liver injury in rats
through an inflammatory mechanism. Typically, the membrane components of LPS
are lipid-
A, KDO (2-lceto-3-deoxy-octulosonic acid), core polysaccharides and O-antigen
polysaccharides, the polysaccharide units differing from one bacterium to
another (Zinsser
Microbiolo~y 20th Ed., Joklik et al., eds., pp. 82-87, Appleton ~ Lange,
Norwalk, CT, 1992).
[0055] Primary rat hepatocytes derived from liver parenchyma) cells and
sinusoidal cells of
rats that have been exposed to LPS in vivo can directly respond to LPS in cell
culture.
Numerous effects of LPS-induced endotoxemia can be detected, including
elevated levels of
nitric oxide synthetase (NOS) with increased nitric oxide and nitrite
production, cellular
hypertrophy, vacuolization, chromosomal emargination, cytoplasmic DNA
fragmentation and
necrosis (Pittner et al., Bioclaem Biophys Res Commun 185(1):430-435 (1992);
Laskin et al.,
Hepatology 22(1):223-234 (1995); Wang et al., Am JPhysiol 269(2 Pt 1):G297-304
(1995)).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-15-
Other studies have indicated that the presence of Kupffer cells with primary
rat hepatocytes is
essential for the induction of hepatocyte apoptosis by LPS (Hamada et al.,
JHepatol
30(5):807-818 (1999)).
[0056] Exposure of rats or primary hepatocytes to LPS induces the expression
of a number
of acute-phase proteins in the liver. Recent evidence has indicated that rat
hepatocytes
express soluble CD14 protein, and LPS is capable of markedly increasing levels
of CD14 at
both the gene expression and protein expression levels (Liu et al., Infect
Immun 66(11):5089-
5098 (1998)). Soluble CD14 is believed to be a critical LPS recognition
protein required for
the activation of a variety of cells to toxic levels of LPS, even in
endothelial and epithelial
cells (Pugin et al., P~oc Natl Acad Sci USA 90(7):2744-2748 (1993)). Another
key
component of the LPS recognition system is lipopolysaccharide-binding protein
(LBP),
which binds to LPS. The LPS-LBP complex interacts with the CD14 receptor,
inducing LPS
sensitive genes. LBP can be induced in hepatocytes isolated from rats that
have not been
primed with LPS, indicating that this key regulatory pathway is intact in
primary rat
hepatocytes (Wan et al., Infect Immura 63(7):2435-2442 (1995)).
[0057] Lovastatin (Mevacor~) is a cholesterol-lowering agent belonging to a
class of
compounds, the statins, that are potent inhibitors of HMG-CoA reductase. This
enzyme
catalyzes the conversion of HMG-CoA to mevalonate, the rate-controlling enzyme
in
cholesterol biosynthesis. HMG-CoA reductase inhibitors block the production of
cholesterol
in the liver leading to a reduction of LDL particles in the plasma. Lovastatin
has additional
effects on lipid metabolism, including depletion of intracellular pools of
sterols and increased
synthesis of LDL receptors, leading to enhanced removal of LDL and LDL
precursors from
plasma. Upon treatment with lovastatin, plasma levels of VLDL, IDL and
triglycerides also
decrease. Oral doses of lovastatin are extensively absorbed by the liver, and
the drug is
excreted primarily via the liver; less than 13% of its metabolites are
excreted in the urine
(Goodman and Gilman's The Pharmacological Basis of Therapeutics, Ninth Ed.,
Hardman et
al., eds., pp. 884-888, McGraw-Hill, New York, 1996).
[0058] The most frequent side effects are liver damage, characterized by
elevated levels of
hepatic transaminases (e.g., AST and ALT), creatinine phosphokinase and
alkaline
phosphatase, and myopathy, characterized by muscle pain and destruction of
skeletal muscle
cells. Cases of drug-induced hepatitis, accompanied by j aundice and elevated
levels of liver
enzymes, have also been reported, although the symptoms were reversible
following
withdrawal of the drug (Huchzermeyer et al., Deutsch Med Wochenschr 120(8):252-
256
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-16-
(1995); Heuer et al., Med Kliyz 95(11):642-644 (2000)). Histologic examination
of affected
liver tissue showed centrilobular necrosis, centrilobular cholestasis, and
infiltrates with
mononuclear and polymorphonuclear cells, including eosinophils (Grimbert et
al., Dig Dis
Sci 39(9):2032-2033 (1994)).
[0059] Experiments by the present inventors have found that when rats were
dosed with
lovastatin, at 9 or 90 mg/kg twice a day, no effects were noted in liver
tissue after 6 or after
24 hours. After 14 days of treatment at the higher dosage, however, liver
cells showed
abnormal vacuolization of the cytoplasm. Hepatoxicity data from other studies
of laboratory
animals treated with lovastatin have not been widely reported. Therefore, in
order to
establish a more sensitive model for examining the changes in liver tissue
caused by
lovastatin, as well as to have a means of examining changes in expression
level of individual
genes as a result of exposure to lovastatin, experiments in cultured
hepatocytes were
undertaken.
[0060] Methotrexate is a widely used antineoplastic drug that is also
frequently prescribed
for the treatment of psoriasis (a disease characterized by abnormal
proliferation of epidermal
cells), juvenile lymphoblastic leukemia, rheumatoid arthritis, and a number of
other
cancerous diseases, such as leukemic meningitis and choriocarcinoma. Although
generally
not metabolized, at high dosages, metabolites such as 7-hydroxy-methotrexate,
a nephrotoxin,
do accumulate. Methotrexate polyglutamates are retained in the kidneys for
weeks and in the
liver for months ((Goodman and Gilman's The Pharmacological Basis of
Therapeutics, Ninth
Ed., Hardman et al., eds., pp. 1243-1247, McGraw-Hill, New York, 1996).
[0061] Methotrexate acts to prevent DNA synthesis and cell replication by
inhibiting the
rate-limiting enzyme in purine and thymidine synthesis, dihydrofolate
reductase (DHFR)
(Goodman and Gilinan's, supra; Schwartz et al., P>"oc Nat Acad Sci USA
89(2):594-598
(1992)). It also acts as an suppressant of cell-mediated immune responses. The
biochemical
toxicology of methotrexate has been well characterized in man, where long-term
administration produces hepatic fibrosis or cirrhosis, especially in heavy
drinkers, which is
linked to persistent, mild-to-moderate, increases in serum transaminases,
alkaline
phosphatases and bilirubin (Reynolds et al., South Med J 79(5):536-539 (1986);
Tolman et
al., JRheumatol 12 (Suppl 12):29-34 (1985)). Methotrexate is a rather long-
acting, rapidly
reversible DHFR inhibitor, despite its high affinity for the target enzymes in
many cell types,
which may be due to the formation of methotrexate polyglutamates that reduce
the ability of
DHFR to pass through cell membranes. The toxic effects of methotrexate may be
due to the
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-17-
depletion of tetrahydrofolate cofactors that are required for purine and
thymidylate synthesis
(methylation reactions in hepatic 1-carbon metabolism) and to the iuubition of
folate-
dependent enzymes involved in the metabolism of purines and thymidylate, the
inhibition
caused by the accumulation of methotrexate polyglutamates and dihydrofolate
polyglutamates.
[0062] The mechanism of methotrexate-induced hepatotoxicity is not yet fully
elucidated,
partly because the pathological changes in humans are rather difficult to
reproduce in animal
models, although experiments in rats have shown that, in a dose-dependent
fashion,
methotrexate produces liver damage ranging from focal to confluent necrosis of
zone 3
hepatocytes, with eaxly stage fibrosis (Hall et al., Hepatology 14(5):906-10
(1991)). Other
studies in rats have demonstrated that treatment with methotrexate produces
intrahepatocytic
fat deposits, along with fatty accumulations in hepatocytes that range from
fine droplets to
large vacuoles. The areas of necrosis showed signs of the hypoxia associated
with congestive
failure, as well as anemic infarcts, fibrotic foci of the collapse type,
atrophy of the hepatic
cords, and hemosiderosis (Custer et al., ,I Natl Cancer Inst 58(4):1011-1015
(1977)).
Hepatotoxicity probably involves interference with triglyceride and other
lipid biosynthetic
pathways in the liver. For example, studies on rats have shown that
methotrexate inhibits the
biosynthesis of lipotropic substances such as methionine and choline through
its interference
with hepatic 1-carbon metabolism. The drug also inhibits the activity of
vitamin B12,
another lipotropic factor (Tuma et al., Biochem Pha~macol 24:1327-1331 (1975)
and impairs
RNA and protein synthesis, triglyceride secretion and total triglyceride
esterification
(Deboyser et al., Toxic ira Vitro 6(2):129-132 (1992).
[0063] Methotrexate does not appear to be cytotoxic to cultured primary
hepatocytes
following short-term exposures (up to 3.5 hr), but significant effects on
HepG2 growth curves
have been observed at low concentrations during the course of 7-day exposures
(Wu et al.,
P~oc Natl Acad Sci USA 80(10):3078-3080 (1983)). Additionally, it has been
demonstrated
that methotrexate increases hepatic glycogenolysis, oxygen consumption and
calcium efflux
and decreases glutathione levels (Yamamoto et al., Biochem Pharmacol 44(4):761-
767,
(1992); de Oliveira et al., Res Commun Claem Pathol Pharmacol 53(2):173-181
(1986);
Lindenthal et al., EuY JPlaaYmacol 228(5-6):289-298 (1993)). Experiments on
cultured rat
hepatocytes have shown that methotrexate also inhibits the activity of hepatic
N-
acetyltransferase 2 (NAT2), although the drug has only a slight inhibitory
effect on rat NAT1,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-18-
enzymes that catalyze the acetylation of a variety of therapeutic arylamines
(Zaher et al.,
Toxicol in hit~o 11:271-283 (1997)).
[0064] Phenobarbital, a barbiturate, is used as an anti-epileptic, sedative or
hypnotic drug
and can also be used to treat neuroses with related tension states, such as
hypertension,
coronary artery disease, gastrointestinal disturbances and preoperative
apprehension.
Phenobarbital is also found in medications to treat insomnia and headaches
(Remington: The
Science and Practice of Pharmacy, 19th Ed., A. R. Gennaro ed., pp. 1164-1165,
Mack
Publishing Co., Easton, Pennsylvania, 1995).
[0065] Phenobarbital induces a variety of drug metabolizing enzymes such as
cytochrome
P450 oxidoreductase, aldehyde dehydrogenases, UDP-glucuronyltransferase, GSTs,
epoxide
hydrolase, and an assortment of cytochrome P450 monooxygenases (Waxman et al.,
Biochem
J 1281(Pt 3):577-592 (1992); Kaplowitz et al., Biochem J 146(2):351-356
(1975); Tank et
al., Biochem Pha~macol 35(24):4563-4569 (1986). The induction of liver enzymes
is usually
accompanied by liver enlargement, proliferation of smooth endoplasmic
reticulum, and tumor
promotion (Waxman et al., supra; Rice et al., Carcihogehesis 15(2):395-402
(1994); Nims et
al., Ca~cihogenesis 8(1):67-71, (1987). Incidences of cholestasis and
hepatocellular injury
have also been found (Selim et al., Hepatology 29(5):1347-1351 (1999); Gut et
al., Envi~of~
Health Perspect 104(Suppl 6):1211-1218 (1999)). Phenobarbital has been
classified as
nongenotoxic hepatocarcinogen as it induces liver tumors in rodents but lacks
detectable
signs of genotoxicity using short term iya vivo or ih vitro assays (Whysner et
al., Pharmacol
They 71(1-2):153-191 (1996)).
[0066] The effects of phenobarbital on phospholipid metabolism in rat liver
have been
studied. In one study, phenobarbital, administered intraperitonially (i.p.),
was found to cause
an increase in the microsomal phosphatidylcholine content. Additionally,
levels of
glycerophosphate acyltransferase (GAT), phosphatidate cytidylyltransferase
(PCT),
phosphatidate phosphohydrolase (PPH) and choline phosphotransferase (CPT) were
significantly increased (Hoshi et al., Claem Phaf~m Bull 38:3446-3448 (1990)).
[0067] Tacrine (1,2,3,4-tetrahydro-9-aminoacridine-hydrochloride), a strong
acetylcholinesterase (AChE) inhibitor, is used in the treatment of mild to
moderate cases
Alzheimer's dimentias. Alzheimer's patients have synaptic loss, neuronal
atrophy and
degeneration of cholinergic nuclei in the forebrain, which are associated with
reduced
oxidative metabolism of glucose and decreased levels of ATP and acetyl CoA.
Administration of AChE inhibitors, such as tacrine, is designed to increase
cholinergic
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-19-
activity to combat this loss (Weinstock, Neurodegeneration 4(4):349-356
(1995)). The effect
seen in the patients is a reversal of the cognitive and functional decline,
but the drug does not
appear to change the neurodegenerative process (Goodman & Gilinan's The
Pharmacolo igLcal
Basis of Therapeutics 9th Ed., Hardman et al. eds., p. 174, McGraw Hill, New
York, 1996).
[0068] Hepatotoxicty caused by tacrine is typically reversible, although cases
of severe
hepatotoxicity have been seen (Blackard et al., J Clin Gastnoentenol 26:57-59
(1998)). The
toxicity is characterized by decreased levels of protein synthesis and the
release of lactate
dehydrogenase, as well as by increased transaminase levels and decreased
levels of ATP,
glycogen and glutathione. The decrease in protein synthesis may represent a
signal leading to
cell death (Lagadic-Gossmann et al., Cell Biol Toxicol 14(5):361-373 (1998)).
[0069] Preclinical studies have failed to detect adverse hepatic events,
although tacrine
displayed cytotoxicity to human hepatoma cell lines and primary rat
hepatocytes (Viau et al.,
Drug Clzem Toxicol 16:227-239 (1993)). While hepatotoxicity has been found in
humans, in
vivo rat studies have not shown a correlation between tacrine exposure and
hepatotoxicity,
and the mechanism of action is not completely understood. An in vitno study
comparing the
reaction of human and rat liver microsomal preparations to tacrine showed that
the two
species reacted differently to the drug, suggesting that the rat may not be
the best model for
monitoring tacrine-induced elevations in liver marker enzymes (Woolf et al.,
Dnug Metab
Dispos 21:874-882 (1993)).
[0070] While tacrine does not reveal classic signs of hepatotoxicity in rats,
gene expression
changes due to tacrine administration can be used to predict that the drug
will be a liver toxin
in humans. This suggests that toxicogenomics might be able to detect drugs
that prove to be
toxic in the clinic even when classical but more crude measures in preclinical
screening fail
to detect toxicity.
[0071] Tamoxifen is a nonsteroidal anti-estrogen used for breast cancer in
males and
females. Tamoxifen has been associated with changes in liver enzyme levels,
disruption of
mitochondrial metabolism and, occasionally, with a spectrum of more severe
liver
abnormalities including fatty liver, cholestasis, hepatic necrosis and NASH
(nonalcoholic
steatohepatitis) (Duthie et al., Xenobiotica 25(10):1151-1164 (1995); Cardoso
et al., Toxicol
Appl Phanrnacol 176(3):145-152 (2001); Pinol et al., Gastnoentenol Hepatol
23(2):57-61
(2000); and Farrell, Semin Liven Dis 22(2):185-194 (2002)). A few of these
serious cases
included fatalities. A few cases of liver cancer have also been reported.
Additionally, studies
in mice and rats have shown that tamoxifen significantly alters the activities
of liver enzymes
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-20-
and can induce hepatic carcinomas (Caballero et al., Irat JBioche~a Cell Biol
33(7):681-690
(2001); Guzelian, Semin Oncol 24(1 Suppl 1):S1-105-121 (1997)).
[0072] Tetracycline is a broad spectrum antibiotic whose main mechanism of
action is the
inhibition of bacterial protein synthesis. Hepatic toxicity, principally
steatosis, has been
observed in patients receiving high doses of tetracycline. In rats and dogs,
exposure to
tetracycline has been shown to increase levels of total lipids and
triglycerides in liver cells
due to inhibition of mitochondrial lipid metabolism and beta-oxidation (Lewis
et al., Am J
Dig Dis 12:429-438, (1967); Amacher et al., Fundam Appl Toxicol 40(2):256-263
(1997).
[0073] Valproate (n-dipropylacetic acid, Depakene~) is routinely used to treat
several types
of epileptic seizures- absence seizures, myoclonic seizures and tonic-clonic
seizures. Most
other anti-epileptics are effective against only one type. Valproate acts on
neurons to inhibit
the sustained repetitive firing caused by depolarization of cortical or spinal
cord neurons, and
a prolonged recovery of inactivated voltage-activated Na channels follows. The
drug also
acts by reducing the low-threshold Caz+ current and its multiple mechanisms
contribute to its
use in multiple types of seizures. Although valproate does not affect neuronal
responses to
GABA, it does increase the activity of the GABA synthetic enzyme, glutamic
acid
decarboxylase, and it inhibits enzymes that degrade GABA, GABA transaminase
and
succinic semialdehyde dehydrogenase (Goodman and Gilman's The Pharmacological
Basis
of Therapeutics, 9th Ed., Hardman et al., eds., pp. 462, 476 and 477, McGraw-
Hill, New
York, 1996).
[0074] The most common side effects are gastrointestinal symptoms, including
anorexia,
nausea and vomiting. Effects on the CNS include sedation, ataxia and tremor.
Rash, hair
loss, increased appetite and teratogenic effects have also been observed
(Briggs et al., A
Reference Guide to Fetal and Neonatal Risk. Drugs in Pre~y and Lactation, 4th
ed., p.
869, Williams & Wilkins, Baltimore, 1994). With respect to liver toxicity,
valproate
produces elevated levels of hepatic enzymes in about 40% of patients, which
may be an
asymptomatic condition, and elevated levels of hepatic lipids. Fulininant
hepatitis,
microvesicular steatosis (fatty degeneration), hepatocyte necrosis and hepatic
failure can also
result. It is believed that hepatoxicity is caused by an accumulation of
unsaturated
metabolites of valproate, in particular 4-en-valproate, which is structurally
similar to two
known hepatotoxins, 4-en-pentanoate and methylenecyclopropylacetic acid (Eadie
et al., Med
Toxicol Adverse Drug Exp 3(2):85-106 (1988)).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-21-
[0075] In a study on rats, microvesicular steatosis caused by valproate was
found to be
accompanied by myeloid bodies, lipid vacuoles and mitochondria) abnormalities
(Kesterson
et al., Flepatology 4(6):1143-1152 (1984)). Experiments on cultured rat
hepatocytes have
shown that valproate produces a dose-dependent leakage of lactic acid
dehydrogenase and
increased amounts of acyl-CoA esters, compounds that interfere with the beta-
oxidation of
fatty acids (Vance et al., Epilepsia 35(5):1016-1022 (1994)). Administration
of valproate to
rats has also been shown to cause enhanced excretion of dicarboxylic acids, a
sign of
impaired mitochondria) beta-oxidation. Other metabolic effects include
hypoglycemia,
hyperammonemia, decreased levels of beta-hydroxybutyrate and carnitine and
decreased
activities of acyl-CoA dehydrogenases, enzymes involved in fatty acid
oxidation. mRNA
levels of genes involved in fatty acid oxidation, however, such as the short-,
medium- and
long-chain acyl-CoA dehydrogenases, were found to have increased (Kibayashi et
al.,
Pediaty~ Ifzt 41(1):52-60 (1999)).
[0076] Wy-14643, a tumor-inducing compound that acts in the liver, has been
used to study
the genetic profile of cells during the various stages of carcinogenic
development, with a
view toward developing strategies for detecting, diagnosing and treating
cancers (Rockett et
al., Toxicology 144(1-3):13-29 (2000)). In contrast to other carcinogens, Wy-
14643 does not
mutate DNA directly. Instead, it acts on the peroxisome proliferator activated
receptor-alpha
(PPARalpha), as well as on other signaling pathways that regulate growth
(Johnson et al., J
Steroid Biochem Mol Biol 77(1):59-71 (2001)). The effect is elevated and
sustained cell
replication, accompanied by a decrease in apoptosis (Rusyn et al.,
Ca~ciraogehesis
21(12):2141-2145 (2000)). These authors (Rusyn et al.) noted an increase in
the expression
of enzymes that repair DNA by base excision, but no increased expression of
enzymes that do
not repair oxidative damage to DNA. In a study on rodents, Johnson et al.
noted that Wy-
14643 inhibited liver-X-receptor-mediated transcription in a dose-dependent
manner, as well
as de novo sterol synthesis.
[0077] In experiments with mouse liver cells (Peters et al., CaYCinoge~esis
19(11):1989-
1994 (1998)), exposure to Wy-14643 produced increased levels of acyl CoA
oxidase and
proteins involved in cell proliferation: CDK-1, 2 and 4, PCNA and c-myc.
Elevated levels
may be caused by accelerated transcription that is mediated directly or
indirectly by
PPARalpha. It is likely that the carcinogenic properties of peroxisome
proliferators are due
to the PPARalpha-dependent changes in levels of cell cycle regulatory
proteins.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-22-
[0078] Another study on rodents (Keller et al., Bioclaim Biophys Acta
1102(2):237-244
(1992)) showed that Wy-14643 was capable of uncoupling oxidative
phosphorylation in rat
liver mitochondria. Rates of urea synthesis from ammonia and bile flow, two
energy-
dependent processes, were reduced, indicating that the energy supply for these
processes was
disrupted as a result of cellular exposure to the toxin. Wy-14643 has also
been shown to
activate nuclear factor kappaB, NADPH oxidase and superoxide production in
Kupffer cells
(Rusyn et al., Cancer Res 60(17):4798-4803 (2000)). NADPH oxidase is known to
induce
mitogens, which cause proliferation of liver cells.
Toxicity Identification, Prediction and Modeling
[0079] The genes and gene expression information, as well as the portfolios
and subsets of
the genes provided in Tables 1-SXX may be used to predict or identify at least
one toxic
effect, including the hepatotoxicity of a test or unknown compound. As used,
herein, at least
one toxic effect includes, but is not limited to, a detrimental change in the
physiological
status of a cell or organism. The response may be, but is not required to be,
associated with a
particular pathology, such as tissue necrosis. Accordingly, the toxic effect
includes effects at
the molecular and cellular level. Hepatotoxicity is an effect as used herein
and includes, but
is not limited to, genotoxic and non-genotoxic carcinogenesis, cholestasis,
hepatitis, liver
enlargement, inflammation, necrosis, necrosis with steatosis, peroxisome
proliferation,
steatosis, and steatosis with hepatitis. In addition, hepatoxicity includes
the effect of direct-
acting agents (such as metformin, rosiglitazone and dexamethasone), which are
pharmaceuticals that act in the liver, but are not considered toxic to the
liver. Exposure to
these agents results in altered gene expression profiles. As used herein, a
gene expression
profile comprises any quantitative representation of the expression of at
least one mRNA
species in a cell sample or population and includes profiles made by various
methods such as
differential display, PCR, hybridization analysis, etc.
[0080] In general, assays to predict the toxicity or hepatotoxicity of a test
agent (or
compound or multi-component composition) comprise the steps of exposing a cell
population
to the test compound, assaying or measuring the level of relative or absolute
gene expression
of one or more of the genes in Tables SA-SXX and comparing the identified
expression
levels) to the expression levels disclosed in the Tables and databases)
disclosed herein.
Assays may include the measurement of the expression levels of about 2, 3, 4,
5, 6, 7, 8, 9,
10, 15, 20, 25, 30, 50, 75, 100, 200, 300, 400, 500, 1000 or more genes from
Tables SA-SXX
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-23-
to create multi-gene expression profiles. In some embodiments, all or
substantially all of the
genes of Tables SA-5XX may be used to predict toxicity, etc. In other
embodiments, the
genes or subsets of the genes for each individual toxin model, for instance,
the genes of Table
SA, may be used. An "adequate amount" of the data of Tables SA-SXX refers to
an amount
of information that allows toxicity identification or prediction (typically 2
or more genes).
"Substantially" or nearly all of the data in the tables refers to at least
about 80% of the data
for an individual model.
[0081] In the methods of the invention, the gene expression level for a gene
or genes
induced by the test agent, compound or compositions may be comparable to the
levels found
in the Tables or databases disclosed herein if the expression level varies
within a factor of
about 2, about 1.5 or about 1.0 fold. In some cases, the expression levels are
comparable if
the agent induces a change in the expression of a gene in the same direction
(e.g., up or
down) as a reference toxin. "Comparing" may comprise determinng the
relationship of the
database information to the sample gene expression profile with or without
application of an
algorithm to the results, differences or similarities between the two.
[0082] The cell population that is exposed to the test agent, compound or
composition may
be exposed iyz vitro or ih vivo. For instance, cultured or freshly isolated
hepatocytes, in
particular rat hepatocytes, may be exposed to the agent under standard
laboratory and cell
culture conditions. In another assay format, in vivo exposure may be
accomplished by
administration of the agent to a living animal, for instance a laboratory rat.
[0083] Procedures for designing and conducting toxicity tests in in vitro and
ih vivo systems
are well known, and are described in many texts on the subject, such as Loomis
et al.,
Loomis's Esstentials of Toxicology, 4th Ed., Academic Press, New York, 1996;
Echobichon,
The Basics of Toxici Testing, CRC Press, Boca Raton, 1992; Frazier, editor, Ih
Yitro
Toxici Testing, Marcel Dekker, New York, 1992; and the like.
[0084] In in vitro toxicity testing, two groups of test organisms are usually
employed: One
group serves as a control and the other group receives the test compound in a
single dose (for
acute toxicity tests) or a regimen of doses (for prolonged or chronic toxicity
tests). Because,
in some cases, the extraction of tissue as called for in the methods of the
invention requires
sacrificing the test animal, both the control group and the group receiving
compound must be
large enough to permit removal of animals for sampling tissues, if it is
desired to observe the
dynamics of gene expression through the duration of an experiment.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-24-
[0085] In setting up a toxicity study, extensive guidance is provided iil the
literature for
selecting the appropriate test organism for the compound being tested, route
of
administration. dose ranges, and the like. Water or physiological saline (0.9%
NaCl in water)
is the solute of choice for the test compound since these solvents permit
administration by a
variety of routes. When this is not possible because of solubility
limitations, vegetable oils
such as corn oil or organic solvents such as propylene glycol may be used.
[0086] Regardless of the route of achninistration, the volume required to
administer a given
dose is limited by the size of the animal that is used. It is desirable to
keep the volume of
each dose uniform within and between groups of animals. When rats or mice are
used, the
volume administered by the oral route generally should not exceed about 0.005
ml per gram
of animal. Even when aqueous or physiological saline solutions are used for
parenteral
inj ection the volumes that are tolerated are limited, although such solutions
are ordinarily
thought of as being innocuous. The intravenous LDso of distilled water in the
mouse is
approximately 0.044 ml per gram and that of isotonic saline is 0.068 ml per
gram of mouse.
In some instances, the route of administration to the test animal should be
the same as, or as
similar as possible to, the route of administration of the compound to man for
therapeutic
purposes.
[0087] When a compound is to be administered by inhalation, special techniques
for
generating test atmospheres are necessary. The methods usually involve
aerosolization or
nebulization of fluids containing the compound. If the agent to be tested is a
fluid that has an
appreciable vapor pressure, it may be administered by passing air through the
solution under
controlled temperature conditions. Under these conditions, dose is estimated
from the
volume of air inhaled per unit time, the temperature of the solution, and the
vapor pressure of
the agent involved. Gases are metered from reservoirs. When particles of a
solution are to be
administered, unless the particle size is less than about 2 ~,m the particles
will not reach the
terminal alveolar sacs in the lungs. A variety of apparatuses and chambers are
available to
perform studies for detecting effects of irritant or other toxic endpoints
when they are
administered by inhalation. The preferred method of administering an agent to
animals is via
the oral route, either by intubation or by incorporating the agent in the
feed.
[0088] When the agent is exposed to cells in vitYO or in cell culture, the
cell population to be
exposed to the agent may be divided into two or more subpopulations, for
instance, by
dividing the population into two or more identical aliquots. In some preferred
embodiments
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-25-
of the methods of the invention, the cells to be exposed to the agent are
derived from liver
tissue. For instance, cultured or freshly isolated rat hepatocytes may be
used.
[0089] The methods of the invention may be used generally to predict at least
one toxic
response, and, as described in the Examples, may be used to predict the
likelihood that a
compound or test agent will induce various specific liver pathologies, such as
genotoxic and
non-genotoxic carcinogenesis, cholestasis, direct action toxicity, hepatitis,
liver enlargement,
inflammation, necrosis, necrosis with steatosis, peroxisome proliferation,
steatosis, steatosis
with hepatitis, or other pathologies associated with at least one of the
toxins herein described.
The methods of the invention may also be used to determine the similarity of a
toxic response
to one or more individual compounds. In addition, the methods of the invention
may be used
to predict or elucidate the potential cellular pathways influenced, induced or
modulated by
the compound or test agent due to the similarity of the expression profile
compared to the
profile induced by a known toxin (see Tables SA-SG, SJ, SK, SM-SS, SU-SY, SAA-
SEE,
SHH-SJJ, SMM, 500, SPP and SSS-SXX). Further, the link between a specific
liver
pathology that is the result of exposure to a toxin and a specific gene
expression profile
allows for distinction of the genes in Tables SA-SXX as markers of liver
toxicity.
Diagnostic Uses for the Toxicity Markers
[0090] As described above, the genes and gene expression information or
portfolios of the
genes with their expression information as provided in Tables SA-SXX may be
used as
diagnostic markers for the prediction or identification of the physiological
state of tissue or
cell sample that has been exposed to a compound or to identify or predict the
toxic effects of
a compound or agent. For instance, a tissue sample such as a sample of
peripheral blood cells
or some other easily obtainable tissue sample may be assayed by any of the
methods
described above, and the expression levels from a gene or genes from Tables SA-
5XX may
be compared to the expression levels found in tissues or cells exposed to the
toxins described
herein. These methods may result in the diagnosis of a physiological state in
the cell or may
be used to identify the potential toxicity of a compound, for instance a new
or unknown
compound or agent. The comparison of expression data, as well as available
sequence or
other information may be done by researcher or diagnostician or may be done
with the aid of
a computer and databases as described below.
[0091] In another format, the levels of a genes) of Tables SA-SXX, its encoded
protein(s),
or any metabolite produced by the encoded protein may be monitored or detected
in a sample,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-26-
such as a bodily tissue or fluid sample to identify or diagnose a
physiological state of an
organism. Such samples may include any tissue or fluid sample, including
urine, blood and
easily obtainable cells such as peripheral lymphocytes.
Use of the Markers for Monitoring Toxicity Progression
[0092] As described above, the genes and gene expression information provided
in Tables
SA-SXX may also be used as markers for the monitoring of toxicity progression,
such as that
found after initial exposure to a drug, drug candidate, toxin, pollutant, etc.
For instance, a
tissue or cell sample may be assayed by any of the methods described above,
and the
expression levels from a gene or genes from Tables SA-SXX may be compared to
the
expression levels found in tissue or cells exposed to the hepatotoxins
described herein. The
comparison of the expression data, as well as available sequence or other
information may be
done by researcher or diagnostician or may be done with the aid of a computer
and databases.
Use of the Toxicity Markers for Drug Screening
[0093] According to the present invention, the genes identified in Tables SA-
SXX may be
used as markers or drug targets to evaluate the effects of a candidate drug,
chemical
compound or other agent on a cell or tissue sample. The genes may also be used
as drug
targets to screen for agents that modulate their expression and/or activity.
In various formats,
a candidate drug or agent can be screened for the ability to simulate the
transcription or
expression of a given marker or markers or to down-regulate or counteract the
transcription
or expression of a marker or markers. According to the present invention, one
can also
compare the specificity of a drug's effects by looking at the number of
markers which the
drug induces and comparing them. More specific drugs will have less
transcriptional targets.
Similar sets of markers identified for two drugs may indicate a similarity of
effects. As used
herein, an agent is said to modulate the expression of a nucleic acid of the
invention if it is
capable of up- or down-regulating expression of the nucleic acid in a cell.
[0094] Assays to monitor the expression of a marker or markers as defined in
Tables SA-
SXX may utilize any available means of monitoring for changes in the
expression level of the
nucleic acids of the invention.
[0095] ~ In one assay format, microarrays containing probes to one, two or
more genes from
Tables SA-SXX may be used to directly monitor or detect changes in gene
expression in the
treated or exposed cell. Cell lines, tissues or other samples are first
exposed to a test agent
and in some instances, a known toxin, and the detected expression levels of
one or more, or
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
_27_
preferably 2 or more of the genes of Tables SA-SXX are compared to the
expression levels of
those same genes exposed to a known toxin alone. Compounds that modulate the
expression
patterns of the known toxins) would be expected to modulate potential toxic
physiological
effects ih vivo. The genes in Tables SA-SXX are particularly appropriate marks
in these
assays as they are differentially expressed in cells upon exposure to a known
hepatotoxin.
[0096] In another format, cell lines that contain reporter gene fusions
between the open
reading frame and/or the transcriptional regulatory regions of a gene in
Tables SA-SXX and
any assayable fusion partner may be prepared. Numerous assayable fusion
partners are
known and readily available including the firefly luciferase gene and the gene
encoding
chloramphenicol acetyltransferase (Alam et al., Ahal Biochem 188:245-254
(1990)). Cell
lines containing the reporter gene fusions are then exposed to the agent to be
tested under
appropriate conditions and time. Differential expression of the reporter gene
between
samples exposed to the agent and control samples identifies agents which
modulate the
expression of the nucleic acid.
[0097] Additional assay formats may be used to monitor the ability of the
agent to modulate
the expression of a gene identified in Tables SA-SXX. For instance, as
described above,
mRNA expression may be monitored directly by hybridization of probes to the
nucleic acids
of the invention. Cell lines are exposed to the agent to be tested under
appropriate conditions
and time and total RNA or mRNA is isolated by standard procedures such those
disclosed in
Sambrook et al. (Molecular Cloning: A Laboratory Manual, 3d Ed., Cold Spring
Harbor
Laboratory Press, Cold Spring Harbor, New York, 2001).
[0098] In another assay format, cells or cell lines are first identified which
express the gene
products of the invention physiologically. Cell and/or cell lines so
identified would be
expected to comprise the necessary cellular machinery such that the fidelity
of modulation of
the transcriptional apparatus is maintained with regard to exogenous contact
of agent with
appropriate surface transduction mechanisms and/or the cytosolic cascades.
Further, such
cells or cell lines may be transduced or transfected with an expression
vehicle (e.g., a plasmid
or viral vector) construct comprising an operable non-translated 5'-promoter
containing end
of the structural gene encoding the gene products of Tables SA-SXX fused to
one or more
antigenic fragments or other detectable markers, which are peculiar to the
instant gene
products, wherein said fragments are under the transcriptional control of said
promoter and
are expressed as polypeptides whose molecular weight can be distinguished from
the
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
naturally occurring polypeptides or may further comprise an immunologically
distinct or
other detectable tag. Such a process is well known in the art (see Sambrook et
al., supra).
[0099] Cells or cell lines transduced or transfected as outlined above are
then contacted
with agents under appropriate conditions; for example, the agent comprises a
pharmaceutically acceptable excipient and is contacted with cells comprised in
an aqueous
physiological buffer such as phosphate buffered saline (PBS) at physiological
pH, Eagles
balanced salt solution (BSS) at physiological pH, PBS or BSS comprising serum
or
conditioned media comprising PBS or BSS and/or serum incubated at 37°C.
Said conditions
may be modulated as deemed necessary by one of skill in the art. Subsequent to
contacting
the cells with the agent, said cells are disrupted and the polypeptides of the
lysate are
fractionated such that a polypeptide fraction is pooled and contacted with an
antibody to be
further processed by immunological assay (e.g., ELISA, immunoprecipitation or
Western
blot). The pool of proteins isolated from the agent-contacted sample is then
compared with
the control samples (no exposure and exposure to a known toxin) where only the
excipient is
contacted with the cells and an increase or decrease in the immunologically
generated signal
from the agent-contacted sample compared to the control is used to distinguish
the
effectiveness and/or toxic effects of the agent.
[00100] Another embodiment of the present invention provides methods for
identifying
agents that modulate at least one activity of a proteins) encoded by the genes
in Tables SA-
SXX. Such methods or assays may utilize any means of monitoring or detecting
the desired
activity.
[00101] In one format, the relative amounts of a protein (Tables SA-SXX)
between a cell
population that has been exposed to the agent to be tested compared to an un-
exposed control
cell population and a cell population exposed to a known toxin may be assayed.
In this
format, probes such as specific antibodies are used to monitor the
differential expression of
the protein in the different cell populations. Cell lines or populations are
exposed to the agent
to be tested under appropriate conditions and time. Cellular lysates may be
prepared from the
exposed cell line or population and a control, unexposed cell line or
population. The cellular
lysates are then analyzed with the probe, such as a specific antibody.
[00102] Agents that are assayed in the above methods can be randomly selected
or rationally
selected or designed. As used herein, an agent is said to be randomly selected
when the agent
is chosen randomly without considering the specific sequences involved in the
association of
the a protein of the invention alone or with its associated substrates,
binding partners, etc. An
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-29-
example of randomly selected agents is the use a chemical library or a peptide
combinatorial
library, or a growth broth of an organism.
[00103] As used herein, an agent is said to be rationally selected or designed
when the agent
is chosen on a nonrandom basis which takes into account the sequence of the
target site
and/or its conformation in connection with the agent's action. Agents can be
rationally
selected or rationally designed by utilizing the peptide sequences that make
up these sites.
For example, a rationally selected peptide agent can be a peptide whose amino
acid sequence
is identical to or a derivative of any functional consensus site.
(00104] The agents of the present invention can be, as examples, peptides,
small molecules,
vitamin derivatives, as well as carbohydrates. Dominant negative proteins,
DNAs encoding
these proteins, antibodies to these proteins, peptide fragments of these
proteins or mimics of
these proteins may be introduced into cells to affect function. "Mimic" used
herein refers to
the modification of a region or several regions of a peptide molecule to
provide a structure
chemically different from the parent peptide but topographically and
functionally similar to
the parent peptide (see G.A. Grant in: Molecular Biolo~;y and Biotechnolo~y,
Meyers, ed.,
pp. 659-664, VCH Publishers, New York, 1995). A skilled artisan can readily
recognize that
there is no limit as to the structural nature of the agents of the present
invention.
Nucleic Acid Assay Formats
[00105] The genes identified as being differentially expressed upon exposure
to a known
hepatotoxin (Tables SA-SXX) may be used in a variety of nucleic acid detection
assays to
detect or quantititate the expression level of a gene or multiple genes in a
given sample. The
genes described in Tables SA-SXX may also be used in combination with one or
more
additional genes whose differential expression is associate with toxicity in a
cell or tissue. In
preferred embodiments, the genes in Tables SA-SXX may be combined with one or
more of
the genes described in prior and related applications 60/353,171; 60/363,534;
60/371,135;
60/371,134; 60/370,248; 60/371,150; 60/371,413; 60/373,601; 60/374,139;
60/394,253;
60/378,652; 60/373,602; 60/378,653; 60/378,665; 60/378,370; 60/394,230;
60/407,688;
09/917,800; 10/060,087; PCT/LJS03/ , entitled "Molecular Hepatotoxicology
Modeling," filed January 31, 2003; and PCT/USO1/23872, all of which are
incorporated by
reference on page 1 of this application.
[00106] Any assay format to detect gene expression may be used. For example,
traditional
Northern blotting, dot or slot blot, nuclease protection, primer directed
amplification, RT-
PCR, semi- or quantitative PCR, branched-chain DNA and differential display
methods may
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-30-
be used for detecting gene expression levels. Those methods are useful for
some
embodiments of the invention. In cases where smaller numbers of genes are
detected,
amplification based assays may be most efficient. Methods and assays of the
invention,
however, may be most efficiently designed with hybridization-based methods for
detecting
the expression of a large number of genes.
[00107] Any hybridization assay format may be used, including solution-based
and solid
support-based assay formats. Solid supports containing oligonucleotide probes
for
differentially expressed genes of the invention can be filters, polyvinyl
chloride dishes,
particles, beads, microparticles or silicon or glass based chips, etc. Such
chips, wafers and
hybridization methods are widely available, for example, those disclosed by
Beattie (WO
95/11755).
[00108] Any solid surface to which oligonucleotides can be bound, either
directly or
indirectly, either covalently or non-covalently, can be used. A preferred
solid support is a
high density array or DNA chip. These contain a particular oligonucleotide
probe in a
predetermined location on the array. Each predetermined location may contain
more than
one molecule of the probe, but each molecule within the predetermined location
has an
identical sequence. Such predetermined locations are termed features. There
may be, for
example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 or more of such
features on a
single solid support. The solid support, or the area within which the probes
are attached may
be on the order of about a square centimeter. Probes corresponding to the
genes of Tables
SA-SXX or from the related applications described above may be attached to
single or
multiple solid support structures, e.g., the probes may be attached to a
single chip or to
multiple chips to comprise a chip set.
(00109] Oligonucleotide probe arrays for expression monitoring can be made and
used
according to any techniques known in the art (see for example, Lockhart et
al., Nat
Biotech~.ol 14:1675-1680 (1996); McGall et al., Proc Nat Acad Sci USA 93:13555-
13460
(1996)). Such probe arrays may contain at least two or more oligonucleotides
that are
complementary to or hybridize to two or more of the genes described in Tables
SA-SXX. For
instance, such arrays may contain oligonucleotides that are complementary or
hybridize to at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70, 100 or more the genes
described herein.
Preferred arrays contain all or nearly all of the genes listed in Tables SA-
SXX, "or
individually, the gene sets of Tables SA-SXX. In a preferred embodiment,
arrays are
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-31-
constructed that contain oligonucleotides to detect all or nearly all of the
genes in any one of
or all of Tables SA-SXX on a single solid support substrate, such as a chip.
[00110] The sequences of the expression marker genes of Tables SA-SXX are in
the public
databases. Table 1 provides the GenBank Accession Number, SEQ m NO: and GLGC m
No. (Gene Logic reference no.) for each of the sequences (see
www.hcbi.hlm.~cih.gov~, while
Table 2 provides identification information for the human homologues of the
genes of Tables
1 and SA-SXX. Table 3 identifies the metabolic pathways in which the genes of
Tables 1 and
SA-SXX are believed to function. Table 4 defines the model codes used in
Tables 1, 2, 3 and
SA-SXX. The sequences of the genes in GenBank are expressly herein
incorporated by
reference in their entirety as of the filing date of this application, as are
related sequences, for
instance, sequences from the same gene of different lengths, variant
sequences, polymorphic
sequences, genomic sequences of the genes and related sequences from different
species,
including the human counterparts, where appropriate. These sequences may be
used in the
methods of the invention or may be used to produce the probes and arrays of
the invention.
In some embodiments, the genes in Tables SA-SXX that correspond to the genes
or fragments
previously associated with a toxic response may be excluded from the Tables.
[00111] As described above, in addition to the sequences of the GenBank
Accession Nos.
and GLGC m Nos. disclosed in the Tables SA-SXX, sequences such as naturally
occurring
variant or polymorphic sequences may be used in the methods and compositions
of the
invention. For instance, expression levels of various allelic or homologous
forms of a gene
disclosed in the Tables SA-SXX may be assayed. Any and all nucleotide
variations that do
not alter the functional activity of a gene listed in the Tables SA-SXX ,
including all naturally
occurring allelic variants of the genes herein disclosed, may be used in the
methods and to
make the compositions (e.g., arrays) of the invention.
[00112] Probes based on the sequences of the genes described above may be
prepared by any
commonly available method. Oligonucleotide probes for screening or assaying a
tissue or
cell sample are preferably of sufficient length to specifically hybridize only
to appropriate,
complementary genes or transcripts. Typically the oligonucleotide probes will
be at least
about 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some cases,
longer probes of at
least 30, 40, or 50 nucleotides will be desirable.
[00113] As used herein, oligonucleotide sequences that are complementary to
one or more of
the genes described in Tables SA-SXX refer to oligonucleotides that are
capable of
hybridizing under stringent conditions to at least part of the nucleotide
sequences of said
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-32-
genes. Such hybridizable oligonucleotides will typically exhibit at least
about 75% sequence
identity at the nucleotide level to said genes, preferably about 80% or 85%
sequence identity
or more preferably about 90% or 95% or more sequence identity to said genes.
[00114] "Bind(s) substantially" refers to complementary hybridization between
a probe
nucleic acid and a target nucleic acid and embraces minor mismatches that can
be
accommodated by reducing the stringency of the hybridization media to achieve
the desired
detection of the target polynucleotide sequence.
[00115] The terms "background" or "background signal intensity" refer to
hybridization
signals resulting from non-specific binding, or other interactions, between
the labeled target
nucleic acids and components of the oligonucleotide array (e.g., the
oligonucleotide probes,
control probes, the array substrate, etc.). Baclcground signals may also be
produced by
intrinsic fluorescence of the array components themselves. A single background
signal can
be calculated for the entire array, or a different background signal may be
calculated for each
target nucleic acid. In a preferred embodiment, background is calculated as
the average
hybridization signal intensity for the lowest 5% to 10% of the probes in the
array, or, where a
different background signal is calculated for each target gene, for the lowest
5% to 10% of
the probes for each gene. Of course, one of skill in the art will appreciate
that where the
probes to a particular gene hybridize well and thus appear to be specifically
binding to a
target sequence, they should not be used in a background signal calculation.
Alternatively,
background may be calculated as the average hybridization signal intensity
produced by
hybridization to probes that are not complementary to any sequence found in
the sample (e.g.
probes directed to nucleic acids of the opposite sense or to genes not found
in the sample
such as bacterial genes where the sample is mammalian nucleic acids).
Background can also
be calculated as the average signal intensity produced by regions of the array
that lack any .
probes at all.
[00116] The phrase "hybridizing specifically to" refers to the binding,
duplexing, or
hybridizing of a molecule substantially to or only to a particular nucleotide
sequence or
sequences under stringent conditions when that sequence is present in a
complex mixture
(e.g., total cellular) DNA or RNA.
[00117] Assays and methods of the invention may utilize available formats to
simultaneously
screen at least about 100, preferably about 1000, more preferably about 10,000
and most
preferably about 1,000,000 different nucleic acid hybridizations.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-33-
[00118] As used herein a "probe" is defined as a nucleic acid, capable of
binding to a target
nucleic acid of complementary sequence through one or more types of chemical
bonds,
usually through complementary base pairing, usually through hydrogen bond
formation. As
used herein, a probe may include natural (i. e., A, G, U, C, or T) or modified
bases (7-
deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined
by a linkage
other than a phosphodiester bond, so long as it does not interfere with
hybridization. Thus,
probes may be peptide nucleic acids in which the constituent bases are joined
by peptide
bonds rather than phosphodiester linkages.
[00119] The term "perfect match probe" refers to a probe that has a sequence
that is perfectly
complementary to a particular target sequence. The test probe is typically
perfectly
complementary to a portion (subsequence) of the target sequence. The perfect
match (PM)
probe can be a "test probe", a "normalization~control" probe, an expression
level control
probe and the like. A perfect match control or perfect match probe is,
however, distinguished
from a "mismatch control" or "mismatch probe."
[00120] The terms "mismatch control" or "mismatch probe" refer to a probe
whose sequence
is deliberately selected not to be perfectly complementary to a particular
target sequence. For
each mismatch (MM) control in a high-density array there typically exists a
corresponding
perfect match (PM) probe that is perfectly complementary to the same
particular target
sequence. The mismatch may comprise one or more bases.
[00121] While the mismatch(s) may be located anywhere in the mismatch probe,
terminal
mismatches are less desirable as a terminal mismatch is less likely to prevent
hybridization of
the target sequence. In a particularly preferred embodiment, the mismatch is
located at or
near the center of the probe such that the mismatch is most likely to
destabilize the duplex
with the target sequence under the test hybridization conditions.
[00122] The term "stringent conditions" refers to conditions under which a
probe will
hybridize to its target subsequence, but with only insubstantial hybridization
to other
sequences or to other sequences such that the difference may be identified.
Stringent
conditions are sequence-dependent and will be different in different
circumstances. Longer
sequences hybridize specifically at higher temperatures. Generally, stringent
conditions are
selected to be about 5°C lower than the thermal melting point (Tm) for
the specific sequence
at a defined ionic strength and pH.
[00123] Typically, stringent conditions will be those in which the salt
concentration is at
least about 0.01 to 1.0 M Na~ ion concentration (or other salts) at pH 7.0 to
8.3 and the
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-34-
temperature is at least about 30°C for short probes (e.g., 10 to 50
nucleotides). Stringent
conditions may also be achieved with the addition of destabilizing agents such
as formamide.
[00124] The "percentage of sequence identity" or "sequence identity" is
determined by
comparing two optimally aligned sequences or subsequences over a comparison
window or
span, wherein the portion of the polynucleotide sequence in the comparison
window may
optionally comprise additions or deletions (i.e., gaps) as compared to the
reference sequence
(which does not comprise additions or deletions) for optimal alignment of the
two sequences.
The percentage is calculated by determining the number of positions at which
the identical
submit (e.g. nucleic acid base or amino acid residue) occurs in both sequences
to yield the
number of matched positions, dividing the number of matched positions by the
total number
of positions in the window of comparison and multiplying the result by 100 to
yield the
percentage of sequence identity. Percentage sequence identity when calculated
using the
programs GAP or BESTFIT (see below) is calculated using default gap weights.
Probe design
[00125] One of skill in the art will appreciate that an enormous number of
array designs are
suitable for the practice of this invention. The high density array will
typically include a
number of test probes that specifically hybridize to the sequences of
interest. Probes may be
produced from any region of the genes identified in the Tables and the
attached representative
sequence listing. In instances where the gene reference in the Tables is an
EST, probes may
be designed from that sequence or from other regions of the corresponding full-
length
transcript that may be available in any of the sequence databases, such as
those herein
described. See WO 99/32660 for methods of producing probes for a given gene or
genes. In
addition, any available software may be used to produce specific probe
sequences, including,
for instance, software available from Molecular Biology Insights, Olympus
Optical Co. and
Biosoft International. In a preferred embodiment, the array will also include
one or more
control probes.
[00126] High density array chips of the invention include "test probes." Test
probes may be
oligonucleotides that range from about 5 to about 500, or about 7 to about 50
nucleotides,
more preferably from about 10 to about 40 nucleotides and most preferably from
about 15 to
about 35 nucleotides in length. In other particularly preferred embodiments,
the probes are
20 or 25 nucleotides in length. In another preferred embodiment, test probes
are double or
single strand DNA sequences. DNA sequences are isolated or cloned from natural
sources or
amplified from natural sources using native nucleic acid as templates. These
probes have
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-35-
sequences complementary to particular subsequences of the genes whose
expression they are
designed to detect. Thus, the test probes are capable of specifically
hybridizing to the target
nucleic acid they are to detect.
[00127] In addition to test probes that bind the target nucleic acids) of
interest, the high
density array can contain a number of control probes. The control probes may
fall into three
categories referred to herein as 1) normalization controls; 2) expression
level controls; and 3)
mismatch controls.
[00128] Normalization controls are oligonucleotide or other nucleic acid
probes that are
complementary to labeled reference oligonucleotides or other nucleic acid
sequences that are
added to the nucleic acid sample to be screened. The signals obtained from the
normalization
controls after hybridization provide a control for variations in hybridization
conditions, label
intensity, "reading" efficiency and other factors that may cause the signal of
a perfect
hybridization to vary between arrays. In a preferred embodiment, signals
(e.g., fluorescence
intensity) read from all other probes in the array are divided by the signal
(e.g., fluorescence
intensity) from the control probes thereby normalizing the measurements.
[00129] Virtually any probe may serve as a normalization control. However, it
is recognized
that hybridization efficiency varies with base composition and probe length.
Preferred
normalization probes are selected to reflect the average length of the other
probes present in
the axray, however, they can be selected to cover a range of lengths. The
normalization
controls) can also be selected to reflect the (average) base composition of
the other probes in
the array, however in a preferred embodiment, only one or a few probes are
used and they axe
selected such that they hybridize well (i.e., no secondary structure) and do
not match any
target-specific probes.
[00130] Expression level controls axe probes that hybridize specifically with
constitutively
expressed genes in the biological sample. Virtually any constitutively
expressed gene
provides a suitable target for expression level controls. Typically expression
level control
probes have sequences complementary to subsequences of constitutively
expressed
"housekeeping genes" including, but not limited to the (3-actin gene, the
glyceraldehyde-3-
phosphate dehydrogenase (GADPH) gene, the transferrin receptor gene and the
like.
[00131] Mismatch controls may also be provided for the probes to the target
genes, for
expression level controls or for normalization controls. Mismatch controls are
oligonucleotide probes or other nucleic acid probes identical to their
corresponding test or
control probes except for the presence of one or more mismatched bases. A
mismatched
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-3 6-
base is a base selected so that it is not complementary to the corresponding
base in the target
sequence to which the probe would otherwise specifically hybridize. One or
more
mismatches are selected such that under appropriate hybridization conditions
(e.g., stringent
conditions) the test or control probe would be expected to hybridize with its
target sequence,
but the mismatch probe would not hybridize (or would hybridize to a
significantly lesser
extent) Preferred mismatch probes contain a central mismatch. Thus, for
example, where a
probe is a 20 mer, a corresponding mismatch probe will have the identical
sequence except
for a single base mismatch (e.g., substituting a G, a C or a T for an A) at
any of positions 6
through 14 (the central mismatch).
[00132] Mismatch probes thus provide a control for non-specific binding or
cross
hybridization to a nucleic acid in the sample other than the target to which
the probe is
directed. For example, if the target is present the perfect match probes
should be consistently
brighter than the mismatch probes. In addition, if all central mismatches are
present, the
mismatch probes can be used to detect a mutation, for instance, a mutation of
a gene in the
accompanying Tables SA-SXX. The difference in intensity between the perfect
match and
the mismatch probe provides a good measure of the concentration of the
hybridized material.
Nucleic Acid Samples
[00133] Cell or tissue samples may be exposed to the test agent ih vitro or ih
vivo. When
cultured cells or tissues are used, appropriate mammalian liver extracts may
also be added
with the test agent to evaluate agents that may require biotransformation to
exlubit toxicity.
In a preferred format, primary isolates of animal or human hepatocytes which
already express
the appropriate complement of drug-metabolizing enzymes may be exposed to the
test agent
without the addition of mammalian liver extracts.
[00134] The genes which are assayed according to the present invention are
typically in the
form of mRNA or reverse transcribed mRNA. The genes may be cloned or not. The
genes
may be amplified or not. The cloning and/or amplification do not appear to
bias the
representation of genes within a population. In some assays, it may be
preferable, however,
to use polyA+ RNA as a source, as it can be used with less processing steps.
[00135] As is apparent to one of ordinary skill in the art, nucleic acid
samples used in the
methods and assays of the invention may be prepared by any available method or
process.
Methods of isolating total mRNA are well known to those of skill in the art.
For example,
methods of isolation and purification of nucleic acids are described in detail
in Chapter 3 of
Laboratory Technicmes in Biochemistry and Molecular Biolo~y. Vol. 24,
Hybridization With
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-37-
Nucleic Acid Probes: Theory and Nucleic Acid Probes, P. Tijssen, Ed., Elsevier
Press, New
York, 1993. Such samples include RNA samples, but also include cDNA
synthesized from a
mRNA sample isolated from a cell or tissue of interest. Such samples also
include DNA
amplified from the cDNA, and RNA transcribed from the amplified DNA. One of
skill in the
art would appreciate that it is desirable to inhibit or destroy RNase present
in homogenates
before homogenates are used.
[00136] Biological samples may be of any biological tissue or fluid or cells
from any
organism as well as cells raised in vitro, such as cell lines and tissue
culture cells. Frequently
the sample will be a tissue or cell sample that has been exposed to a
compound, agent, drug,
pharmaceutical composition, potential environmental pollutant or other
composition. In
some formats, the sample will be a "clinical sample" which is a sample derived
from a
patient. Typical clinical samples include, but are not limited to, sputum,
blood, blood-cells
(e.g., white cells), tissue or fine needle biopsy samples, urine, peritoneal
fluid, and pleural
fluid, or cells therefrom.
[00137] Biological samples may also include sections of tissues, such as
frozen sections or
formalin fixed sections taken for histological purposes.
Forming High Density Arrays
[00138] Methods of forming high density arrays of oligonucleotides with a
minimal number
of synthetic steps axe known. The oligonucleotide analogue array can be
synthesized on a
single or on multiple solid substrates by a variety of methods, including, but
not limited to,
light-directed chemical coupling, and mechanically directed coupling (see
Pirrung, U.S.
Patent No. 5,143,854).
[00139] In brief, the light-directed combinatorial synthesis of
oligonucleotide arrays on a
glass surface proceeds using automated phosphoramidite chemistry and chip
masking
techniques. In one specific implementation, a glass surface is derivatized
with a silane
reagent containing a functional group, e.g., a hydroxyl or amine group blocked
by a
photolabile protecting group. Photolysis through a photolithogaphic mask is
used selectively
to expose functional groups which are then ready to react with incoming 5'
photoprotected
nucleoside phosphoramidites. The phosphoramidites react only with those sites
which are
illuminated (and thus exposed by removal of the photolabile blocking group).
Thus, the
phosphoramidites only add to those areas selectively exposed from the
preceding step. These
steps are repeated until the desired array of sequences have been synthesized
on the solid
surface. Combinatorial synthesis of different oligonucleotide analogues at
different locations
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-38-
on the array is determined by the pattern of illumination during synthesis and
the order of
addition of coupling reagents.
[00140] In addition to the foregoing, additional methods which can be used to
generate an
array of oligonucleotides on a single substrate are described in PCT
Publication Nos. WO
93/09668 and WO 01/23614. High density nucleic acid arrays can also be
fabricated by
depositing pre-made or natural nucleic acids in predetermined positions.
Synthesized or
natural nucleic acids are deposited on specific locations of a substrate by
light directed
targeting and oligonucleotide directed targeting. Another embodiment uses a
dispenser that
moves from region to region to deposit nucleic acids in specific spots.
Hybridization
[00141] Nucleic acid hybridization simply involves contacting a probe and
target nucleic
acid under conditions where the probe and its complementary target can form
stable hybrid
duplexes through complementary base pairing. See WO 99132660. The nucleic
acids that do
not form hybrid duplexes are then washed away leaving the hybridized nucleic
acids to be
detected, typically through detection of an attached detectable label. It is
generally
recognized that nucleic acids are denatured by increasing the temperature or
decreasing the
salt concentration of the buffer containing the nucleic acids. Under low
stringency conditions
(e.g., low temperature andlor high salt) hybrid duplexes (e.g., DNA:DNA,
RNA:RNA, or
RNA:DNA) will form even where the annealed sequences are not perfectly
complementary.
Thus, specificity of hybridization is reduced at lower stringency. Conversely,
at higher
stringency (e.g., higher temperature or lower salt) successful hybridization
tolerates fewer
mismatches. One of skill in the art will appreciate that hybridization
conditions may be
selected to provide any degree of stringency.
[00142] In a preferred embodiment, hybridization is performed at low
stringency, in this case
in 6X SSPET at 37°C (0.005% Triton X-100), to ensure hybridization and
then subsequent
washes are performed at higher stringency (e.g., I X SSPET at 37°C) to
eliminate mismatched
hybrid duplexes. Successive washes may be performed at increasingly higher
stringency
(e.g., down to as low as 0.25 X SSPET at 37°C to 50°C) until a
desired level of hybridization
specificity is obtained. Stringency can also be increased by addition of
agents such as
formamide. Hybridization specificity may be evaluated by comparison of
hybridization to
the test probes with hybridization to the various controls that can be present
(e.g., expression
level control, normalization control, mismatch controls, etc.).
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-39-
[00143] In general, there is a tradeoff between hybridization specificity
(stringency) and
signal intensity. Thus, in a preferred embodiment, the wash is performed at
the highest
stringency that produces consistent results and that provides a signal
intensity greater than
approximately 10% of the background intensity. Thus, in a preferred
embodiment, the
hybridized array may be washed at successively higher stringency solutions and
read between
each wash. Analysis of the data sets thus produced will reveal a wash
stringency above
which the hybridization pattern is not appreciably altered and which provides
adequate signal
for the particular oligonucleotide probes of interest.
Signal Detection
[00144] The hybridized nucleic acids are typically detected by detecting one
or more labels
attached to the sample nucleic acids. The labels may be incorporated by any of
a number of
means well known to those of skill in the art. See WO 99/32660.
Databases
[00145] The present invention includes relational databases containing
sequence
information, for instance, for the genes of Tables SA-SXX, as well as gene
expression
information from tissue or cells exposed to various standard toxins, such as
those herein
described (see Tables SA-SXX). Databases may also contain information
associated with a
given sequence or tissue sample such as descriptive information about the gene
associated
with the sequence information (see Tables 1, 2 and 3), or descriptive
information concerning
the clinical status of the tissue sample, or the animal from which the sample
was derived.
The database may be designed to include different parts, for instance a
sequence database and
a gene expression database. Methods for the configuration and construction of
such
databases and computer-readable media to which such databases are saved are
widely
available, for instance, see U.S. Patent No. 5,953,727, which is herein
incorporated by
reference in its entirety.
[00146] The databases of the invention may be linked to an outside or external
database such
as GenBank (www.ncbi.nlna.nih.govlentYez.index.latml); I~EGG (www.genorne.ad
jplkegg);
SPAD (www.grt.kyushu-u.ac jplspadlindex.latml); HUGO
(www.gene.ucl.ac.uklhugo); Swiss-
Prot (www. expasy. ch.sprot); Prosite (www. expasy. chltoolslscyapsitl. html);
OMIM
(www.ncbi.nlnZ.nih.govlomina); LocusLink (www.ncbi.nlm.nih.govlLocusLink~;
RefSeq
(www.ncbi.rZlm.nih.govlLocusLinklnefseq.html) and GDB (www.gdb.org). In
apreferred
embodiment, as described in Tables 1-3, the external database is GenBank and
the associated
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-40-
databases maintained by the National Center for Biotechnology Information
(NCBI)
(www. ~ccbi. nlm. hih.gov).
[00147] Any appropriate computer platform, user interface, etc. may be used to
perform the
necessary comparisons between sequence information, gene expression
information and any
other information in the database or information provided as an input. 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 appropriate platforms for the databases
of the
invention.
[00148] The databases of the invention may be used to produce, among other
things,
electronic Northerns that allow the user to determine the cell type or tissue
in which a given
gene is expressed and to allow determination of the abundance or expression
level of a given
gene in a particular tissue or cell.
[00149] The databases of the invention may also be used to present information
identifying
the expression level in a tissue or cell of a set of genes comprising one or
more of the genes
in Tables SA-5~, comprising the step of comparing the expression level of at
least one gene
in Tables SA-5~ in a cell or tissue exposed to a test agent to the level of
expression of the
gene in the database. Such methods may be used to predict the toxic potential
of a given
compound by comparing the level of expression of a gene or genes in Tables SA-
SX~i from a
tissue or cell sample exposed to the test agent to the expression levels found
in a control
tissue or cell samples exposed to a standard toxin or hepatotoxin such as
those herein
described. Such methods may also be used in the drug or agent screening assays
as described
herein.
Kits
[00150] The invention further includes kits combining, in different
combinations, high-
density oligonucleotide arrays, reagents for use with the arrays, protein
reagents encoded by
the genes of the Tables, signal detection and array-processing instruments,
gene expression
databases and analysis and database management software described above. The
kits may be
used, for example, to predict or model the toxic response of a test compound,
to monitor the
progression of hepatic disease states, to identify genes that show promise as
new drug targets
and to screen known and newly designed drugs as discussed above.
[00151] The databases packaged with the kits are a compilation of expression
patterns from
human or laboratory animal genes and gene fragments (corresponding to the
genes of Tables
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-41-
SA-SXX). In particular, the database software and packaged information that
may contain
the databases saved to a computer-readable medium include the expression
results of Tables
SA-SXX that can be used to predict toxicity of a test agent by comparing the
expression
levels of the genes of Tables SA-SXX induced by the test agent to the
expression levels
presented in Tables SA-SXX. In another format, database and software
information may be
provided in a remote electronic format, such as a website, the address of
which may be
packaged in the kit.
[00152] The kits may used in the pharmaceutical industry, where the need for
early drug
testing is strong due to the high costs associated with drug development, but
where
bioinformatics, in particular gene expression informatics, is still lacking.
These kits will
reduce the costs, time and risks associated with traditional new drug
screening using cell
cultures and laboratory animals. The results of large-scale drug screening of
pre-grouped
patient populations, pharmacogenomics testing, can also be applied to select
drugs with
greater efficacy and fewer side-effects. The kits may also be used by smaller
biotechnology
companies and research institutes who do not have the facilities for
performing such large-
scale testing themselves.
[00153] Databases and software designed for use with use with microarrays is
discussed in
Balaban et al., U.S. Patent Nos. 6,229,911, a computer-implemented method for
managing
information, stored as indexed tables, collected from small or large numbers
of microarrays,
and 6,185,561, a computer-based method with data mining capability for
collecting gene
expression level data, adding additional attributes and reformatting the data
to produce
answers to various queries. Chee et al., U.S. Patent No. 5,974,164, discloses
a software-
based method for identifying mutations in a nucleic acid sequence based on
differences in
probe fluorescence intensities between wild type and mutant sequences that
hybridize to
reference sequences.
[00154] Without further description, it is believed that one of ordinary skill
in the art can,
using the preceding description and the following illustrative examples, make
and utilize the
compounds of the present invention and practice the claimed methods. The
following
working examples therefore, specifically point out the preferred embodiments
of the present
invention, and are not to be construed as limiting in any way the remainder of
the disclosure.
EXAMPLES
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-42-
Example 1: Identification of Toxicity Markers in Rat Hepatocytes
[00155] To evaluate their toxicity, the hepatotoxins alpha-
naphthylisothiocyante (ANIT),
acetaminophen (APAP), AY-25329, carbon tetrachloride, clofibrate, diclofenac,
17a-
ethinylestradiol, hydrazine, indomethacin, lipopolysaccharide, lovastatin,
methotrexate,
tacrine, valproate and control compositions were administered to cultures of
primary rat
hepatocytes from male Sprague-Dawley rats at various time points using
administration
diluents, protocols and dosing regimes as previously described in the art and
in the prior
applications discussed above, as well as in Table 6. Laboratory protocols for
the
administration of the hepatotoxins amiodarone, carbamazepine, chlorpromazine,
CI-1000,
CPA, diflunisal, DMN, gemfibrozil, imipramine, phenobarbital, tamoxifen,
tetracycline and
Wy-14643 also appear in Table 6. Identification of toxicity markers was
performed by
microarray analysis and by the AlamarBlue~ assay, a classical measure of
cytotoxicity. The
AlamarBlue~ assay was performed in triplicate.
[00156] The source of the primary rat hepatocytes was Sprague Dawley Outbred
CD~ Rats
(CRL:CD~[SD] IGS BR, Charles River Laboratories). Hepatocyte cultures were
obtained in
24-well matrigel coated plates for the AlamarBlue~ assay (175,000 cells/cmz)
or in T-75cm2
matrigel coated flasks for RNA isolation for microarray analysis (187,000
cells/cm2) .
Primary rat hepatocytes were received the day after the cells were removed
from the animals.
After arrival, the cells, the cells were incubated overnight (~l5hrs) before
the toxin was
added to the cultures. The vehicle used in the toxicity experiments was HIM
culture medium
(Hepatocyte Incubation Medium, In Vitro Technologies Cat. No. 290009)
containing 0.2%
DMSO (Sigma Cat. No. D-5879). Toxin or vehicle was administered to hepatocyte
cultures
as follows. For each treatment, i.e., vehicle alone, vehicle + toxin at low
dose, or vehicle +
toxin at high dose, cells were harvested after 3, 6 and 24-hour incubations
with the toxin
solution or with the vehicle.
[00157] The AlamarBlue~ assay was performed as follows, using only the 24-hour
time
point samples.
1. Primary rat hepatocyte cultures were prepared as described above in a
matrigel-coated
plates at 175,000 cells/cm2.
2. The culture medium (HIM) was removed from each well and replaced with 500
~.1 of
fresh HIM following arnval of the cells, and the cells were incubated
overnight
(approximately l5hrs) at 37°C, 5% C02.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-43-
3. The next day, the HIM was removed and 500 ~,1 of the medium containing
either vehicle
or a dose of toxin was added.
4. Lysis solution was used as a negative control. 450 ~,l medium + 50 X19%
Triton X100
were added to each of 3 wells containing cells, for a final Triton
concentration of 1%.
5. The cells in all wells were incubated for 24 hours at 37°C, 5% COa.
6. HIM medium was removed, and a solution containing 500 ~,1 of fresh HIM
medium + 50
~,1 AlamarBlue~ (BioSource International, Inc., Cat. No. DAL1100) was added to
each
well.
7. The cells were incubated at 37°C, 5% C02 for 2 hours.
8. 100 ~,1 medium was removed from each well of the 24-well plate and added to
a well of a
96-well plate. The fluorescence was measured using 544 nm as the excitation
and 590
nm as the emission on a Molecular Devices, SpectraMax Gemini, Softmax pro
2.6.1.
Alternatively, two absorbance readings can be measured for the oxidized
(600nm) and the
reduced (570nm) form of AlamarBlue~. After obtaining absorbance readings,
results
were calculated according to the manufacturer's protocol provided in the
product
description.
9. The data were evaluated to determine whether or not the toxin reduced cell
viability. If
so, the dose of the toxin that reduced cell viability by ~ 10-20% was
determined.
Collection of RNA from Rat Hepatocytes
[00158] More than 107 cells are typically prepared for each sample. RNA was
collected at 3,
6~ and 24 hours following addition of the toxin according to the following
procedure.
[00159] The medium from the flasks was discarded, and the cells were washed
once with 20
ml of warm (37°C) RPMI-1640 + l OmM HEPES medium (Life Technologies,
Cat. No.
22400-089). 12 ml of Trizol (Life Technologies, Cat. No. 15596-018) was placed
immediately into each T-75 flask. Each flask contained ~10-20 million cells.
The contents
of each flask were mixed vigorously for one minute with a vortex mixer and
then aspirated up
and down 5 times with a pipette. The contents of each flask (~12 ml each) was
collected into
a 50 ml conical polypropylene tissue culture tube (Falcon), snap frozen in
liquid nitrogen and
stored at < -86° C.
[00160] Microarray sample preparation was conducted with minor modifications,
following
the protocols set forth in the Affymetrix GeneChip~ Expression Analysis
Manual. Frozen
cells were ground to a powder using a Spex Certiprep 6800 Freezer Mill. Total
RNA was
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-44-
extracted with Trizol (GibcoBRL) utilizing the manufacturer's protocol. The
total RNA yield
for each sample was 200-500 ~g per 300 mg cells. mRNA was isolated using the
Oligotex
mRNA Midi kit (Qiagen) followed by ethanol precipitation. Double stranded cDNA
was
generated from mRNA using the Superscript Choice system (GibcoBRL). First
strand
cDNA synthesis was primed with a T7-(dT24) oligonucleotide. The cDNA was
phenol-
chloroform extracted and ethanol precipitated to a final concentration of 1
~.g/ml. From 2 ~,g
of cDNA, cRNA was synthesized using Ambion's T7 MegaScript in vitro
Transcription Kit.
[00161] To biotin label the cRNA, nucleotides Bio-11-CTP and Bio-16-UTP (Enzo
Diagnostics) were added to the reaction. Following a 37°C incubation
for six hours,
impurities were removed from the labeled cRNA following the RNeasy Mini kit
protocol
(Qiagen). cRNA was fragmented (fragmentation buffer consisting of 200 mM Tris-
acetate,
pH 8.1, 500 mM KOAc, 150 mM MgOAc) for thirty-five minutes at 94°C.
Following the
Affymetrix protocol, 55 ~,g of fragmented cRNA was hybridized on the
Affymetrix rat array
set for twenty-four hours at 60 rpm in a 45°C hybridization oven. The
chips were washed
and stained with Streptavidin Phycoerythrin (SAPE) (Molecular Probes) in
Affymetrix
fluidics stations. To amplify staining, SAPE solution was added twice with an
anti-streptavidin biotinylated antibody (Vector Laboratories) staining step in
between.
Hybridization to the probe arrays was detected by fluorometric scanning
(Hewlett Packard
Gene Array Scanner). Data was analyzed using Affymetrix GeneChip~ version 3.0
and
Expression Data Mining Tool (EDMT) software (version 1.0), S-Plus, and the
GeneExpress~
software system.
[00162] Differential expression of genes between the toxin-exposed and control
samples
corresponding to patterns indicative of toxicity was determined using the
following criteria.
[00163] Table 1 discloses those genes that are differentially expressed upon
exposure to the
named toxins with their corresponding SEQ ID NOS:, GenBank Accession or Refseq
ID
Nos., GLGC ID Nos. (internal Gene Logic identification nos.), gene names and
Unigene
Sequence Cluster titles. The metabolic pathways in which the genes of Table 1
function are
indicated in Table 3, and the corresponding human homologues are given in
Table 2. The
model codes, identified in Table 4, represent the various toxicity or liver
pathology states
associated with differential expression of each gene, as well as the
individual toxin types
associated with differential expression of each gene.
[00164] Tables SA-SXX disclose the summary statistics for each of the
comparisons
performed. Each of these tables contains a set of predictive genes and creates
a model for
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-45-
predicting the hepatoxicity of an unknown, i.e., untested compound. Each gene
is identified
by its Gene Logic identification number and can be cross-referenced to a gene
name and
representative SEQ m NO. in Table 1. For each comparison of gene expression
levels
between samples in the toxicity group ("Tox" samples, i.e., samples affected
by exposure to a
specific toxin) and samples in the non-toxicity group ("Non-tox" samples,
i.e., samples not
affected by exposure to that same specific toxin), the group mean for Tox
samples is the
mean signal intensity, as normalized for the various chip parameters that are
being assayed.
The Non-tox mean represents the mean signal intensity, as normalized for the
various chip
parameters that are being assayed, in samples other than those treated with
the high dose of
the specific toxin. These samples were treated with a low dose of the specific
toxin, or with
vehicle alone, or with a different toxin. Tox samples were obtained from
treated cells
processed at the timepoint(s) indicated in the tables, while Non-tox samples
were obtained
from control cells processed at all time points in the experiments. For
individual genes, an
increase in the Tox group mean compared to the Non-tox group mean indicates up-
regulation
upon exposure to a toxin. Conversely, a decrease in the Tox group mean
compared to the
Non-tox group mean indicates down-regulation.
[00165] The mean values are derived from Average Difference (AveDiff) values
for a
particular gene, averaged across the corresponding samples. Each individual
Average
Difference value is calculated by integrating the intensity information from
multiple probe
pairs that are tiled for a particular fragment. The normalization multiplies
each expression
intensity for a given experiment (chip) by a global scaling factor. The intent
of this
normalization is to make comparisons of individual genes between chips
possible. The
scaling factor is calculated as follows:
1. From all the unnormalized expression values in the experiment, delete the
largest 2%
and smallest 2% of the values. That is, if the experiment yields 10,000
expression values,
order the values and delete the smallest 200 and the largest 200.
2. Compute the trimmed mean, which is equal to the mean of the remaining
values.
3. Compute the scale factor SF =100/(trimmed mean)
[00166] The value of 100 used here is the standard target. value used. Some
AveDiff values
may be negative due to the general noise involved in nucleic acid
hybridization experiments.
Although many conclusions can be made corresponding to a negative value on the
GeneChip
platform, it is difficult to assess the meaning behind the negative value for
individual
fragments. Our observations show that, although negative values are observed
at times
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-46-
within the predictive gene set, these values reflect a real biological
phenomenon that is highly
reproducible across all the samples from which the measurement was taken. For
this reason,
those genes that exhibit a negative value are included in the predictive set.
It should be noted
that other platforms of gene expression measurement may be able to resolve the
negative
numbers for the corresponding genes. The predictive ability of each of those
genes should
extend across platforms, however. Each mean value is accompanied by the
standard
deviation for the mean.
[00167] The linear discriminant analysis score (discriminant score), as
disclosed in the
tables, measures the ability of each gene to predict whether or not a sample
is toxic. The
discriminant score is calculated by the following steps:
Calculation of a discriminant score
[00168] Let X; represent the AveDiff values for a given gene across the Group
1 samples,
i=l...n.
[00169] Let Y; represent the AveDiff values for a given gene across the Group
2 samples,
i=l...t.
[00170] The calculations proceed as follows:
[00171] Calculate mean and standard deviation for X;'s and Y;'s, and denote
these by mx,
mY, sx,sY.
[00172] For all X;'s and Y;'s, evaluate the function f(z) _ ((1/sy)*exp( -.5*(
(z-mY)/sY)2)) /
(((1/sY)*exp( -.5*( (z-mY)/sY)2)) +((1/sx)*exp( -.5*( (z-mx)/sx)a))),
[00173] The number of correct predictions, say P, is then the number of Yi's
such that
f(Y;)>.5 plus the number of X;'s such that f(X;)<.5.
[00174] The discriminant score is then P/(n+t).
[00175] Linear discriminant analysis uses both the individual measurements of
each gene
and the calculated measurements of all combinations of genes to classify
samples. For each
gene, a weight is derived from the mean and standard deviation of the Tox and
Non-tox
sample groups. Every gene is multiplied by a weight and the sum of these
values results in a
collective discriminate score. This discriminant score is then compared
against collective
centroids of the Tox and Non-tox groups. These centroids are the average of
all tox and
nontox samples respectively. Therefore, each gene contributes to the overall
prediction. This
contribution is dependent on weights that are large positive or negative
numbers if the
relative distances between the Tox and Non-tox samples for that gene are large
and small
numbers if the relative distances are small. The discriminant score for each
unknown sample
1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-47-
and centroid values can be used to calculate a probability between zero and
one as to the
group in which the unknown sample belongs.
Example 2: General Toxicity Modeling
[00176] Samples were selected for grouping into Tox and Non-tox groups by
examining
each study individually with Principal Components Analysis (PCA) to determine
which
treatments had an observable response. Only sample groups where confidence of
the tox-
responding or non-tox-responding status (expression level affected by exposure
to a specific
toxin or expression level not affected by exposure to a specific toxin,
respectively) was
established were included in building a general toxicity prediction model.
[00177] Linear discriminant models were generated to describe Tox and Non-tox
samples.
The top discriminant genes and/or EST's were used to determine toxicity by
calculating each
gene's contribution with homo and heteroscedastic treatment of variance and
inclusion or
exclusion of mutual information between genes. Prediction of samples within
the database
exceeded ~0% true positives with a false positive rate of less than 5%. It was
determined that
combinations of genes and/or EST's generally provided a better prediction than
individual
genes and that the more genes and/or EST used, the better the prediction.
Although the
preferred embodiment includes fifty or more genes, many pairings or larger
combinations of
genes andlor EST can work better than individual genes. All combinations of
two or more
genes from the selected list could be used to predict toxicity. These
combinations could be
selected by pairing in an agglomerate, divisive, or random approach. Further,
as yet
undetermined genes and/or EST's could be combined with individual or a set of
genes and/or
EST's described here to increase predictive ability. However, the genes and/or
EST's
described here would contribute most of the predictive ability to any such
undetermined
combinations.
[00178] Other variations on the above method can provide adequate predictive
ability.
These include selective inclusion of components via agglomerate, divisive, or
random
approaches or extraction of loading and combining them in agglomerate,
divisive, or random
approaches. Also the use of composite variables in logistic regression to
determine
classification of samples can also be accomplished with linear discriminate
analysis, neural or
Bayesian networks, or other forms of regression and classification based on
categorical or
continual dependent and independent variables.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-48-
Example 3: Modeling Methods
[00179] The above modeling methods provide broad approaches of combining the
expression of genes to predict sample toxicity. One could also provide no
weight in a simple
voting method or determine weights in a supervised or unsupervised method
using
agglomerate, divisive, or random approaches. All or selected combinations of
genes may be
combined in ordered, agglomerate, or divisive, supervised or unsupervised
clustering
algorithms with unknown samples for classification. Any form of correlation
matrix may
also be used to classify unknown samples. The spread of the group distribution
and ,
discriminate score alone provide enough information to enable a skilled person
to generate all
of the above types of models with accuracy that can exceed the discriminate
ability of
individual genes. Some examples of methods that could be used individually or
in
combination after transformation of data types include but are not limited to:
Discriminant
Analysis, Multiple Discriminant Analysis, logistic regression, multiple
regression analysis,
linear regression analysis, conjoint analysis, canonical correlation,
hierarchical cluster
analysis, k-means cluster analysis, self organizing maps, multidimensional
scaling, structural
equation modeling, support vector machine determined boundaries, factor
analysis, neural
networks, bayesian classifications, and resampling methods.
Example 4: Grouping of Individual compound and Pathology Classes
[00180] Samples were grouped into individual pathology classes based on known
toxicological responses and observed clinical chemical and pathology
measurements or into
observable toxicity produced by a compound (Tables SA-S~X). The top 10, 25,
50, 100
genes based on individual discriminate scores were used in a model to ensure
that a
combination of genes provided a better prediction than individual genes. As
described above,
all combinations of two or more genes from this list could potentially provide
better
prediction than individual genes when selected in any order or by ordered,
agglomerate,
divisive, or random approaches. In addition, combining these genes with other
genes could
provide better predictive ability, but most of this predictive ability would
come from the
genes listed herein.
[00181] A sample may be considered a Tox sample if it scores positive in any
pathological
or individual compound class represented here, or in any modeling method
mentioned under
general toxicology models, based on a combination of the sample's time point
and dosage
group in a study using an individual compound (with known or potentially toxic
properties)
by comparisons obtainable from the data. The pathological groupings and early
and late
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
-49-
phase models are preferred examples of all obtainable combinations of sample
time and dose
points. Most logical groupings with one or more genes and one or more sample
dose and
time points should produce better predictions of general toxicity,
pathological specific
toxicity, or similarity to a known toxin than individual genes.
[00182] Although the present invention has been described in detail with
reference to
examples above, it is understood that various modifications can be made
without departing
from the spirit of the invention. Accordingly, the invention is limited only
by the following
claims. All cited patents, patent applications and publications referred to in
this application
axe herein incorporated by reference in their entirety.
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~n
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No,19262713
SEQ GLGGGenBank Model Known Gene Name nigene Sequence Cluster
~ _ U Title .
ID D Acc.or _
I N0. C ode
NQ~ RefSeq
ID ,
No.
29 6901AA799479 HHs:NADH dehydrogenaseESTs, Highly similar
1 r to NUIM HUMAN
( ubiquinone) Fe-S NADH-ubiquinone oxidoreductase
protein 8 23 kDa
( 23kD) (NADH-coenzymesubunit, mitochondria)
Q precursor (Complex
I-
reductase) 23KD) (CI-23KD) (TYKY
subunit)
f H.sapiensl
196 16756AA818089q, HHs:glycyl-tRNA ESTs, Highly similar
z synthetase to SYG_HUMAN Glycyl-
tRNA synthetase (Glycine--tRNA
ligase)
(GIyRS) (H.sapiensl
231 5331AA818996i, HHs:glutaminyl-tRNAESTs, Moderately similar
i rr to SYQ_HUMAN
synthetase Glutaminyl-tRNA synthetase
(Glutamine--
tRNA liqase) (GLNRS)
(H.sapiens~
735 12031AA893860GeneralHHsahreonyl-tRNA ESTs, Moderately similar
synthetase to SYTC_HUMAN
Threonyl-tRNA synthetase,
cytoplasmic
(Threonine--tRNA ligase)
(ThrRS)
fH.sapiensl
913 10569AA942681n, HHs:ATPase, H+ ESTs, Highly similar
z, transporting, to VATH HUMAN
Generallysosomal 50I57kDVacuolar ATP synthase
V1 subunit subunit H (V-
H ATPase H subunit) (Vacuolar
proton pump H
subunit) (V-ATPase 50157
kDa subunits)
(Vacuolar proton pump
subunit SFD) (CGI-
11) fH.saoiensl
991 22283AA945172mm HHs:leucine aminopeptidaseESTs, Highly similar
3 to AMPL_HUMAN
Cytosol aminopeptidase
(Leucine
aminopeptidase) (LAP)
(Leucyl
aminopeptidase) (Proline
aminopeptidase)
(Prolvl aminoaeotidasel
fH.saoiensl
120216625AA998062j HHs:AlgS, S. cerevisiae,ESTs, Highly similar
to T51776 dolichyl-
homolog of phosphate beta-glucosyltransferase
(EC
2.4.1.117) (imported)
- human (H.sapiens~
130522056A1008066p, HHs:ubiquinol-cytochromeESTs, Moderately similar
mm c to UCRH HUMAN
reductase hinge Ubiquinol-cytochrome
protein C reductase complex
11 kDa protein, mitochondria)
precursor
(Mitochondria) hinge
protein) (Cytochrome
C1, nonheme 11 kDa protein)
(Complex III
subunit VIII) [H.sapiensj
166710138A1059048m HHs:Sp3 transcriptionEST, Highly similar
factor to SP3_HUMAN
TRANSCRIPTION FACTOR
SP3 (SPR-2)
[H.sapiensl
175316058A1071490General,HHsaerine ESTs, Highly similar
to JC5180 serine C-
vv palmitoyltransferase,palmitoyltransferase
long chain (EC 2.3.1.50) Lcb2
base subunit 2 chain - mouse [M.musculusl
195718278AI105080m HHs:3-oxoacid ESTs, Highly similar
CoA transferase to SCOT_HUMAN
Succinyl-CoA:3-ketoacid-coenzyme
A
transferase, mitochondria)
precursor
(Succinyl CoA:3-oxoacid
CoA-transferase)
H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Attorney
Docket
No.
44921-5113W0
_
Documeht
No.1926271.2
SE GLGCGenBank Model Known Gene Name Unigene Sequence-Cluster
Q Title
ID D Acc: Code
I N0: or
N0:- RefSeq
ID
No.=:
214397027AI170679xx HHs:UDP-glucose ESTs, Highly similar
to UDP-glucose
pyrophosphorylasepyrophosphorylase 2;
2 UTP-glucose-1-
phosphate uridyltransferase;
UDP-glucose
diphosphorylase; UGPase
2 [Homo sapiens]
fH.saaiensl
24343376AI179755w HHs:Rho guanine ESTs, Highly similar
nucleotide to Rho guanine
exchange factor nucleotide exchange
(GEF) 5 factor 5; oncogene
TIM; transforming immortalized
mammary
oncogene; guanine nucleotide
regulatory
protein TIM (Homo sapiensl
fH.saoiensl
28654714AI639518k, HHs:polymerase ESTs, Highly similar
ww, (RNA) II (DNA to S55370 RNA
xx
directed) polypeptidepolymerase II chain
H hRPB17 - human
(H.sapiensl
352423424NM 021680x, HHs:alanyl-tRNA ESTs, Highly similar
z synthetase to SYA_HUMAN Alanyl-
tRNA synthetase (Alanine--tRNA
ligase)
(AIaRS) (H.sapiensl
4301242 NM_145683a HHs:protein tyrosineRattus norvegicus cytosolic
protein tyrosine
phosphatase, non-receptorphosphatase HePTPILC-PTP
type mRNA,
7 complete cds
885 16945AA925541c heterogeneous heterogeneous nuclear
nuclear ribonucleoprotein L
ribonucleoprotein
L
886 17513AA925554h, succinate dehydrogenasesuccinate dehydrogenase
a complex, subunit
complex, subunit A, flavoprotein (Fp)
A, flavoprotein
(Fp)
135422748A1009786g , ribosomal proteinribosomal protein L41
hh L41
287918456D00688 bb monoamine oxidaseESTs, Highly similar
A to 1903159A
monoamine oxidase A
[Rattus norvegicus]
[R.norvepicusl
294324513J02705 v Oncomodulin Oncomodulin
307824504NM 012574k Glutamate receptor,Glutamate receptor,
ionotropic, ionotropic, N-methyl
D-
N-meth I D-aspartateaspartate 2B
2B
308424735NM 012596pp Leptin receptor Leptin receptor (fatty)
(fatty)
32881561NM 016995d, Complement componentComplement component
v, 4 4 binding protein,
uu
binding protein, beta
beta
32966598NM 017020j, Interleukin 6 Interleukin 6 receptor
n, receptor
xx
3485235 NM 019347ii Urea transporter,Urea transporter
solute carrier
f amily 14, member
2
368022282NM_024394h, 5-Hydroxytryptamine5-Hydroxytryptamine
m, (serotonin) (serotonin) receptor
3A
General,receptor 3A
uu
3728301 NM 031049jj 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol
lanosterol cyclase
cyclase
3728302 NM 031049jj 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol
lanosterol cyclase
cyclase
3728303 NM 031049k, 2,3-oxidosqualene:2,3-oxidosqualene: lanosterol
jj lanosterol cyclase
c clase
388013186NM 031755n carcinoembryonic carcinoembryonic antigen-related
antigen- cell
related cell adhesionadhesion molecule
molecule
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Aftocney
Docket
Ho.
44921-5113W0
'
271.2
Document
No.1926
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster.Title
lD D Acc. Code
I NO. or
NO~ RefSeq
1D
No.
414313424NM 080899ww nhibitor of kappanhibitor of kappa light
i light i polypeptide enhancer
polypeptide enhancern B-cells, kinase complex-associated
in B-cells,
i
kinase complex-associatedprotein
protein
414524604NM 080906r, HIF-1 responsiveHIF-1 responsive RTP801
pp RTP801
415317512NM_130428w succinate dehydrogenasesuccinate dehydrogenase
complex, subunit
complex, subunitA, flavoprotein (Fp)
A, flavoprotein
(Fp)
43961359U78977 mm ATPase, Class ATPase, Class II, type
II, type 9A 9A
344518362NM 019187n, Coenzyme Q (ubiquinone)Coenzyme Q (ubiquinone)
ff
370925476NM 031009xx angiotensin II angiotensin II type-1
type-1 receptor receptor
12 21815AA686423o ESTs, Highly similar
to T46390 hypothetical
protein DKFZp434C1920.1-
human
(fragment) fH.sapiensl
18 3636AA799336qq ESTs, Moderately similar
to T00741 NADH
dehydrogenase (ubiquinone)
(EC 1.6.5.3)
acyl carrier chain, mitochondrial
- human
(fragment) fH.sapiensl
23 20957AA799440fP ESTs, Moderately similar
to L13 protein
[Homo sapiens] [H.sapiens]
28 19675AA799475s, ESTs, Weakly similar
oo to T08700 hypothetical
protein DKFZp564G013.1
- human
(fragment) (H.sapiensl
42 16576AA799570c, ESTs, Highly similar
a to hypothetical protein
FLJ13725; KIAA1930 protein
[Homo
sapiensl (H.sapiensl
44 20973AA799581v, ESTs, Moderately similar
General to Y218_HUMAN
Putative deoxyribonuclease
KIAA0218
[H.sapiensl
50 19472AA799616c, ESTs, Moderately similar
f, to PTTG_HUMAN
p, -
General, Pituitary tumor-transforming
gene 1 protein-
kk interacting protein (Pituitary
tumor-
transforming gene protein
binding factor)
(PTTG-binding factor)
(PBF) [H.sapiens]
51 20980AA799633dd, ESTs, Moderately similar
oo to hypothetical
protein MGC13016 [Homo
sapiens]
(H.sapiensl
69 16730AA799766I ESTs, Moderately similar
to JTV1;
hypothetical protein
PR00992 [Homo
sapiensl fH.sapiensl
71 11531AA799773d ESTs, Weakly similar
to A37098 gelation
factor ABP-280, long
form - human
[H.sapiensl
91 20811AA799899ee ESTs, Highly similar
to R5RT18 ribosomal
protein L18a, cytosolic
[validated] - rat
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
5R
TABLE
1
Attorney
Docket
No.
44921=5113W0
Document'No.19262712
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
Title
ID D Acc. Code
' NQ. or
I
NO." RefSeq
ID
No. _ _ ,
103 9202AA800053c ESTs, Highly similar
to T08775 hypothetical
protein DKFZp586C1620.1-
human
(fragment) fH.sapiensl
105 23329AA800126t ESTs, Highly similar
t to 155595 splicing
factor
- human [H.sapiens]
115 22918AA8002430, ESTs, Highly similar
p, to CIDA_MOUSE Cell
w,
ii,
rr death activator CIDE-A
(Cell death-inducing
DFFA-like effector A)
[M.musculus]
120 17206AA800296a ESTs, Highly similar
to PAP_HUMAN
Poly(A) polymerase alpha
(PAP)
(Polynucleotide adenylyltransferase
alpha)
[H.sapiensl
136 17997AA800671h, ESTs, Moderately similar
p, to A54854 Ras
w,
General GTPase activating protein-related
protein -
human fH.sapiensl
149 21379AA800738II ESTs, Highly similar
to TI60_HUMAN 60
kDa Tat interactive
protein (HIV-1 Tat
interactive protein)
[H.sapiensl
155 19102AA800794ww ESTs, Highly similar
to HT2A_HUMAN Zinc-
finger protein HT2A
(72 kDa Tat-interacting
protein) (Tripartite
motif containing protein
32) IH.sapiensl
160 10320AA800855k ESTs, ESTs, Highly similar
to
MLF2_MOUSE Myeloid leukemia
factor 2
(Myelodysplasia-myeloid
leukemia factor 2)
fM.musculusl
160 17775AA800855cc ESTs, Highly similar
to MLF2_MOUSE
Myeloid leukemia factor
2 (Myelodysplasia-
myeloid leukemia factor
2) [M.musculusl
164 19440AA800946II EST, Moderately similar
to B Chain B,
Crystal Structure Of
The D1d2 Sub-Complex
From The Human Snrnp
Core Domain
(H.sapiensl
170 21437AA801230z ESTs, Highly similar
to hypothetical protein
MGC19606 [Homo sapiens]
[H.sapiens]
208 6332AA818406a ESTs, Highly similar
to LSM6_HUMAN U6
snRNA-associated Sm-like
protein LSm6
(H.sapiensl
232 5527AA819027gg, ESTs, Highly similar
hh to GLYC_MOUSE
Serine hydroxymethyltransferase,
cytosolic
(Serine methylase) (Glycine
hydroxymethyltransferase)
(SHMT)
fM.musculusl
240 7208AA819337t, ESTs, Highly similar
mm, to T47140 hypothetical
qq
protein DKFZp761 K1115.1-
human
fra ment H.sa lens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
.5d
TABLE
1.
=
Attorney
Docket
No.
44921-51'I3WQ
Document
No,19262T1.2
$EQ GLGCGenBank Model;Known Gene Name Upigene Sequence Cluster
Title
ID: I~NO.Acc.or Code
I 4
N0 RefSeq
ID
No.
241 17024AA819356 ESTs, Moderately similar
j to hypothetical
protein MGC15677 [Homo
sapiens]
[H.sapiens]
287 19412AA849222j ESTs, Weakly similar
j to T46904 hypothetical
protein DKFZp761 D081.1-
human
[H.sapiens]
295 22933AA849763y ESTs, Moderately similar
to Y188_HUMAN
Hypothetical protein
KIAA0188 [H.sapiens]
299 18876AA849790a ESTs, Highly similar
to hypothetical protein
FLJ11773 [Homo sapiens]
[H.sapiens]
301 14608AA849805j, ESTs, Highly similar
ss to HLA-B associated
transcript-5; BAT5 protein
[Homo sapiens]
[H.sapiens]
303 22071AA849843uu, ESTs, Highly similar
ww to T08661 anti-silencing
protein ASF1 homolog
DKFZp547E2110.1 -
human [H.sapiens]
331 14963AA851161ii ESTs, Highly similar
to DYNC_HUMAN
Dynactin complex 50
kDa subunit (50 kDa
dynein-associated polypeptide)
(Dynamitin)
(DCTN-50) iH.sapiens
333 12769AA851192a, ESTs, Highly similar
cc, to T46254 hypothetical
jj
protein DKFZp761 H171.1-
human
[H.sapiens]
336 19187AA851230General, ESTs, Moderately similar
to hypothetical
pp protein MGC11102 [Homo
sapiens]
[H.sapiens]
341 3833AA851255ss ESTs, Highly similar
to T14743 hypothetical
protein DKFZp586F1524.1-
human
(fragment) [H.sapiens]
347 11221AA851352II ESTs, Highly similar
to A24050
ribonucleoside-diphosphate
reductase (EC
1.17.4.1) chain M1 -
mouse [M.musculusl
357 19269AA851785General ESTs, Highly similar
to eukaryotic
translation initiation
factor 3, subunit 8
(110kD) [Homo Sapiens]
[H.sapiens]
363 16409AA852027pp ESTs, Weakly similar
to DIA1 HUMAN
Diaphanous protein homolog
1 (Diaphanous-
related formin 1) (DRF1)
[H.sapiens]
368 10517AA858600nn ~ ESTs, Highly similar
to 154388 LZTR-1 -
human [H.sapiens]
392 15148AA859325w ESTs, Highly similar
to hypothetical protein
MGC14151 [Homo sapiens]
[H.sapiens]
403 23340AA859519jj ESTs, Highly similar
to JC6127 RNA-binding
protein type 1 - human
[H.sapiens]
403 23341AA859519bb ESTs, Highly similar
to JC6127 RNA-binding
rotein t a 1 - human
H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Aftorney
Docket
No.
44921-5113W0
Document
No.19262712
SEQ GLGCGenBank Model Known Gerie Name Unigene Sequence~ClusterTitle
-
~
ID D Acc. Code
I N0. or :,
NO: RefSeq
ID
No. ''
423 19486AA859870, nn ESTs, Weakly similar
I to Y063_HUMAN
Hypothetical protein
KIAA0063 (HA1234)
[ H.sapiensl
436 23346AA859983c ESTs, Weakly similar
to T50607 hypothetical
protein DKFZp43411016.1
- human
(fragment) [H.sapiensl
440 23347AA860015c ESTs, Weakly similar
to T50607 hypothetical
protein DKFZp43411016.1-
human
(fragment) [H.sapiensl
462 16042AA874827cc ESTs, Weakly similar
to Y008_HUMAN
Hypothetical protein
KIAA0008 [H.sapiensl
463 15182AA874832ff ESTs, Moderately similar
to anaphase-
promoting complex subunit
5 [Homo
sapiensl [H.sapiensl
469 15115AA874928r, ESTs, Highly similar
v to SNX4_HUMAN
Sorting nexin 4 [H.sapiensl
474 16215AA874999j ESTs, Highly similar
to protein translocation
complex beta; protein
transport protein
SEC61 beta subunit [Homo
sapiensj
[H.sapiensl
493 7875AA875127x ESTs, Highly similar
to cell division cycle
2-
like 5, isoform 1; cholinesterase-related
cell
division controller;
CDC2-related protein
kinase 5 [Homo sapiensl
fH.sapiensl
498 15371AA875205xx ESTs, Highly similar
to IF39_HUMAN
Eukaryotic translation
initiation factor 3
subunit 9 (eIF-3 eta)
(eIF3 p116) (eIF3
p110) [H.sapiensl
498 15372AA875205y, ESTs, Highly similar
General, to IF39_HUMAN
gg, Eukaryotic translation
hh, initiation factor 3
II
subunit 9 (eIF-3 eta)
(eIF3 p116) (eIF3
p110) [H.sapiensl
505 15410AA875268r ESTs, Highly similar
to NUKM HUMAN
-
NADH-ubiquinone oxidoreductase
20 kDa
subunit, mitochondria)
precursor (Complex
I-
20KD) (CI-20KD) (PSST
subunit)
IH.saoiensl
513 17314AA875509r ESTs, Moderately similar
to S15349 mdm2
rotein - mouse [M.musculusl
522 11889AA875641k ESTs, Highly similar
to A Chain A, The Sh3
Domain Of Eps8 Exists
As A Novel
Intertwined Dimer [M.musculusl
523 18152AA875661x ESTs, Highly similar
to S58284 BCL7B
protein - human [H.sapiensl
537 16037AA891441j ESTs, Moderately similar
to MPL3_RAT
Microtubule-associated
proteins 1A11B light
chain 3 (MAP1AIMAP1B
LC3)
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
.5F
TABLE
1
Attorney
Docket
No.
44921-5113WQ
Document
No.1=9262713
SEQ GLGGGenBank Model Known Gene Name Unigene Sequence ClusterT~tle
ID D Acc: Code
, NO. or
I
NO.. RefSeq
ID
No.
540 21952AA891537t ESTs, Weakly similar
t to protein predicted
by
clone 23733 [Homo sapiens]
[H.sapiens]
561 17271AA891759a, ESTs, Moderately similar
s to hypothetical
protein MGC4308 [Homo
sapiens]
[H.sapiensl
566 11966AA891800w ESTs, Weakly similar
to F22G12.,5.p
[Caenorhabditis elegans]
[C.elegans], ESTs,
Weakly similar to IPYR_HUMAN
Inorganic
pyrophosphatase (Pyrophosphate
phospho-
hydrolase) (PPase) [H.sapiens]
579 17779AA891914w ESTs, Moderately similar
to A47488
aminoacylase (EC 3.5.1.14)
- human
[H.sapiensl
582 23862AA891933g ESTs, Moderately similar
to A Chain A,
Crystal Structure Of
SmacDIABLO
[H.sapiensl
605 8317AA892234b, ESTs, Moderately similar
s, to microsomal
z,
General glutathione S-transferase
3; microsomal
glutathione S-transferase
III [Homo sapiens]
fH.sapiensl
609 22903AA892250h, ESTs, Highly similar
q, to SYK_HUMAN Lysyl-
dd
tRNA synthetase (Lysine--tRNA
ligase)
(LysRS) [H.sapiensl
616 4373AA892310v ESTs, Highly similar
to T08783 hypothetical
protein DKFZp58600120.1
- human
(fragment) [H.sapiensl
617 17405AA892313ii, ESTs, Moderately similar
rr to beta-tubulin
cofactor E [Homo sapiens]
[H.sapiens]
630 16469AA892462j, ESTs, Moderately similar
mm to UCRY_HUMAN
Ubiquinol-cytochrome
C reductase complex
6.4 kDa protein (Complex
III subunit XI)
fH.sapiensl
637 11994AA892507h ESTs, Moderately similar
to S63540 protein
DS 1, 24K - human [H.sapiens]
673 22872AA892859g, ESTs, Weakly similar
rr to PL01 RAT
Procollagen-lysine,2-oxoglutarate
5-
dioxygenase 1 precursor
(Lysyl hydroxylase
1) (LH1) [R.norveaicusl
686 3439AA893000o ESTs, Moderately similar
to T00335
hypothetical protein
KIAA0564 - human
(fragment) [H.sapiensl
694 13856AA893183gg, ESTs, Weakly similar
hh to S57447 HPBRII-7
protein - human [H.sapiens]
694 13857AA893183bb ESTs, Weakly similar
to S57447 HPBRII-7
rotein - human H.sa
lens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~7
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271:2
SEG1GLGCGenBank Model Known Gene Name Unigene Sequence Clusfer
' Title
ID D Acc. Code
I NO. or .
N0~ RefSeq
ID '
No. - -
699 3877AA893224d ESTs, Highly similar
to UBPJ_HUMAN
Ubiquitin carboxyl-terminal
hydrolase 19
(Ubiquitin thiolesterase
19) (Ubiquitin-
specific processing
protease 19)
(Deubiauitinatina enzyme
191 IH.sapiensl
702 3879AA893237t, ESTs, Moderately similar
cc, to hypothetical
xx
protein MBC3205 [Homo
sapiens]
[H.sapiens]
728 19411AA893667r ESTs, Weakly similar
to T46904 hypothetical
protein DKFZp761 D081.1-
human
[H.sapiens]
731 24185AA893708y ESTs, Highly similar
to T00333 hypothetical
protein KIAA0560 - human
[H.sapiens]
732 17858AA893741c, ESTs, Moderately similar
d, to T46305
oo
hypothetical protein
DKFZp434D1411.1 -
human (fra ment) [H.sapiens]
772 22490AA899289ii ESTs, Moderately similar
to KIAA1049
protein [Homo sapiens]
[H.sapiens]
775 4636AA899491m ESTs, Highly similar
to SYW_MOUSE
Tryptophanyl-tRNA synthetase
(Tryptophan--
tRNA ligase) (TrpRS)
[M.musculus]
785 21213AA899991f, ESTs, ESTs, Highly similar
General to T46254
hypothetical protein
DKFZp761H171.1 -
human [H.sapiens]
786 15373AA900018x ESTs, Highly similar
to IF39_HUMAN
Eukaryotic translation
initiation factor 3
subunit 9 (eIF-3 eta)
(eIF3 p116) (eIF3
p110) fH.sapiensl
797 16754AA900474d ESTs, Moderately similar
to T50619
hypothetical protein
DKFZp762M136.1-
human (fragment) [H.sapiensl
810 12335AA901065k, ESTs, Highly similar
cc to T17225 hypothetical
protein DKFZp564C246.1-
human
[H.sapiens]
816 17096AA901343g ESTs, Moderately similar
to suppressor of
G2 allele of SKP1 [Homo
sapiens]
[H.sapiens]
823 12354AA923957a, ESTs, Weakly similar
k, to UDP-N-
cc,
tt
acteylglucosamine pyrophosphorylase
1;
AgX; sperm associated
antigen 2; UDP-N-
acteylglucosamine pyrophosphorylase
1;
Sperm associated antigen
2 [Homo sapiensJ
IH.saoiensl
830 4917AA924140p ESTs, Weakly similar
to Y193_HUMAN
Hypothetical protein
KIAA0193 [H.sapiens]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
5ft
TABLE
1
Attorney
Docket
No:
A~4921-51'13W0
Document'No.19262712
SEQ GLGCGenBank Modeh Known Genie NameUni~ene Sequence Cluster
Title
ID D Acc. Code
I N0. or
N0.- RefSeq
ID _
No.
834 4931AA9242610o ESTs, Weakly similar
to PRS4_MOUSE 26S
PROTEASE REGULATORY SUBUNIT
4
(P26S4) fR.norvegicusl
852 5009AA924737qq ESTs, Highly similar
to T17237 hypothetical
protein DKFZp434P106.1-
human
(fragment) [H.sapiensl
860 2462AA924913d ESTs, Moderately similar
to T50619
hypothetical protein
DKFZp762M136.1 -
human (fragment) [H.sapiensl
906 16468AA926137p, ESTs, Moderately similar
t, to UCRY_HUMAN
y,
mm
Ubiquinol-cytochrome
C reductase complex
6.4 kDa protein (Complex
III subunit XI)
fH.sapiensl
915 9942AA942697y ESTs, Highly similar
to hypothetical protein
MGC3133 [Homo Sapiens]
[H.sapiens]
921 22102AA942845m ESTs, Weakly similar
to Y218 HUMAN
-
Putative deoxyribonuclease
KIAA0218
[H.sapiens]
931 21993AA943149t, ESTs, Weakly similar
ff to T00084 hypothetical
protein KIAA0512 - human
[H.sapiens]
939 21911AA943610s ESTs, Highly similar
to T08795 hypothetical
protein DKFZp586J1822.1-
human
(fragment) [H.sapiensl
968 17948AA944581f ESTs, Moderately similar
to A57088
nucleoporin-like protein
Rab - human
[H.sapiensl
969 22471AA944617bb ESTs, Highly similar
to CU02_HUMAN
Protein C21orf2 (C21orf-HUMF09G8.5)
(YF5/A2) [H.sapiensl
972 22492AA944741dd ESTs, Moderately similar
to KIAA1049
protein [Homo sapiens]
[H.sapiens]
980 23423AA944912dd ESTs, Moderately similar
to ERC6_HUMAN
Excision repair protein
ERCC-6 (Cockayne
syndrome protein CSB)
[H.sapiens]
100722636AA945724v ESTs, Weakly similar
to T12543 hypothetical
protein DKFZp434M154.1-
human
(fragment) [H.sapiens]
10099657AA945739a ESTs, Moderately similar
to Y391 HUMAN
Hypothetical protein
KIAA0391 [H.sapiens]
101121334AA945753pp ESTs, Moderately similar
to ANM2_HUMAN
Protein arginine N-methyltransferase
2
[H.sapiens]
103421410AA946408c ESTs, Moderately similar
to MCA3_HUMAN
Multisynthetase complex
auxiliary
com onent 18 H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
59
TABLE
1
Attorney
Docket
No.-44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc: Code .
_ N0. or
.
Nb: RefSeq
ID
-'
No.
103818383AA946421m ESTs, Highly similar
to S59641 transcription
f actor TFEB - mouse (fragment)
[ M.musculusl
105417191AA955382c ESTs, Highly similar
to T46457 hypothetical
protein DKFZp434L032.1
- human
(fragment) (H.sapiensl
106223278AA955553I ESTs, Moderately similar
to hypothetical
protein IMAGE3455200
[Homo sapiens]
~H.sapiensl
106423637AA955587pp ESTs, Highly similar
to A45142 cleavage
stimulation factor 50K
chain - human
(H.sapiensl
108024046AA956185a ESTs, Moderately similar
to COQ6_HUMAN
Putative ubiquinone
biosynthesis
monooxgenase COQ6 (CGI-10)
[H.sapiens]
108518669AA956453w ESTs, Highly similar
to OBRG_MOUSE
Leptin receptor gene-related
protein (OB-R
gene related protein)
(OB-RGRP)
fM.musculusl
108723800AA956534j ESTs, Weakly similar
to RNG1 HUMAN
Polycomb complex protein
RING1 (RNF1)
(H.sapiensl
108923852AA956746p ESTs, Highly similar
to CHD4_HUMAN
Chromodomain helicase-DNA-binding
protein 4 (CHD-4) (Mi-2
autoantigen 218
kDa protein) (Mi2-beta)
fH.sapiensl
110418413AA957763ff ESTs, Highly similar
to UBPJ_HUMAN
Ubiquitin carboxyl-terminal
hydrolase 19
(Ubiquitin thiolesterase
19) (Ubiquitin-
specific processing
protease 19)
(Deubiquitinatina enzyme
19) IH.saoiensl
111115183AA963036I ESTs, Moderately similar
to anaphase-
promoting complex subunit
5 [Homo
sapiens fH.sapiensl
11125952 AA963102r amino acid transporteramino acid transporter
system system A2
A2
11252270 AA964116s ESTs, Moderately similar
to tripartite motif-
containing 37; RING-B-box-coiled-coil
protein; MUL protein;
Mulibrey nanism
(Homo sapiensl IH.sapiensl
113624166AA964630d, ESTs, Moderately similar
n to T02345
hypothetical protein
KIAA0324 - human
(fragment) [H.sapiensl
11532583 AA965166u, ESTs, Moderately similar
mm to IPYR_HUMAN
Inorganic pyrophosphatase
(Pyrophosphate
phospho-hydrolase) (PPase)
[H.sapiens]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~n
TABLE
1
Aftorney
Docket
No.
44921-5113W0
Document
No.192627~:2
SEQ GLGGGenBank Mode) Known Gene Name- Unigene Sequence:Cluster
= Title
ID D Acc..or Code
- N0.
:
I
NO: RefSeq
ID
No.::
11612809AA996471p ESTs, Moderately similar
to JM11 protein
. Homo sapiens] [H.sapiens]
116711928AA996829gg, ESTs, Moderately similar
hh to T46305
hypothetical protein
DKFZp434D1411.1 -
human (fragment) [H.sapiensl
12073367AA998110xx ESTs, Weakly similar
to YCE3_HUMAN
Hypothetical protein
CGI-143 [H.sapiens]
120812628AA998123General ESTs, Moderately similar
to JC5707 HYA22
protein - human [H.sapiens]
121926118AA998471d ESTs, Highly similar
to 149668 binding
protein - mouse [M.musculus]
122323648AA998547mm ESTs, Highly similar
to Y144_HUMAN
Hypothetical protein
KIAA0144 [H.sapiens]
122526120AA998619s ESTs, Weakly similar
to T51776 dolichyl-
phosphate beta-glucosyltransferase
(EC
2.4.1.117) [imported]
- human [H.sapiensl
12313660AA998833j ESTs, Weakly similar
to T46908 hypothetical
protein DKFZp76162423.1-
human
[H.sapiens]
12352526AA998979bb ESTs, Moderately similar
to T00051
hypothetical protein
KIAA0404 - human
(fragment) [H.sapiens]
12383710AA999064s, ESTs, Highly similar
t to T47142 hypothetical
protein DKFZp761 P0724.1-
human
(fragment) [H.sapiens]
125423417AB022209I, ribonucleoproteinribonucleoprotein F
General,F
kk
127213464AF047707f, UDP-glucose:ceramideUDP-glucose:ceramide
ss glycosyltransferase
glycosyltransferase
130317359A1007981mm ESTs, Moderately similar
to UCRX_HUMAN
-
Ubiquinol-cytochrome
C reductase complex
7.2 kDa protein (Cytochrome
C1, nonheme 7
kDa protein) (Complex
III subunit X) (7.2
kDa cytochrome c1-associated
protein
subunit) (HSPC119) [H.sapiens]
132522801A1009197a ESTs, Moderately similar
to hypothetical
protein IMAGE3455200
[Homo sapiens]
[H.sapiens]
133216956A1009390ee ESTs, Moderately similar
to NIPM_HUMAN
NADH-ubiquinone oxidoreductase
15 kDa
subunit (Complex I-15
kDa) (CI-15 kDa)
[H.sapiensl
133711322A1009492j ESTs, Highly similar
to hypothetical protein
Homo sa iens H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
R1
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.19262712
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster.Title
ID D Acc: Code
I N0. or ~
N0 RefSeq
ID
No:
13638047A1010100a ESTs, Highly similar
to vacuolar protein
sorting 18 (yeast),
isoform 1; vacuolar
protein sorting protein
18 [Homo sapiens]
f H.sapiensl
140223768A1011709ii ESTs, Moderately similar
to S21977 Pm5
protein - human [H.sapiens]
140618684A1011812pp ESTs, Highly similar
to T12468 hypothetical
protein DKFZp5640123.1
- human
[H.sapiensl
14325528A1012631bb, Rattus norvegicus mRNA
qq for Vps54-like
protein
143312475A1012632c ESTs, Weakly similar
to hypothetical protein
FLJ14775 [Homo sapiens]
[H.sapiens]
14399386A1012785c ESTs, Weakly similar
to T47142 hypothetical
protein DKFZp761 P0724.1-
human
(fragment) [H.sapiensl
14432937A1012951pp ESTs, Moderately similar
to PEXD HUMAN
Peroxisomal membrane
protein PEX13
(Peroxin-13) [H.sapiensl
145511969A1013273rr ESTs, Highly similar
to B27496 proteinase
inhibitor nexin 1 precursor
- rat (fragment)
[R.norvegicusl
146012794A1013442ee ESTs, Highly similar
to T12539 hypothetical
protein DKFZp434J154.1
- human
[H.sapiensl
146123444A1013448rr ESTs, Highly similar
to chromosome 20
open reading frame 30;
HSPC274 protein
[Homo sapiensl fH.sapiensl
146312795A1013482y ESTs, Highly similar
to T17303 hypothetical
protein DKFZp566F2124.1-
human
(fragment) [H.sapiensl
14862909A1013946m ESTs, Weakly similar
to A34581 oxysterol-
binding protein - human
[H.sapiens]
149415247A10141690, upregulated by upregulated by 1,25-dihydroxyvitamin
ii, 1,25- D-3
II,
pp,
xx dihydroxyvitamin
D-3
15047420A1029291I ESTs, Highly similar
to CLPX_MOUSE ATP-
dependent CLP protease
ATP-binding
subunit CIpX-like, mitochondria)
precursor
fM.musculusl
15087451A1029450I, ESTs, Moderately similar
z, to SYEP_HUMAN
General Bifunctional aminoacyl-tRNA
synthetase
[Includes: Glutamyl-tRNA
synthetase
(Glutamate--tRNA ligase);
Prolyl-tRNA
synthetase (Proline--tRNA
ligase)]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
R~
TABLE
1
'
Attorney
Docket
No.
449215113W0
Document
No.1926271.2
SEQ GLGGGenBank Model Known Gene Name Unigene Sequence Cluster
:; Title
ID D=NO.Acc~ Code
I or
N0. RefSeq
ID
No. .
15505346A1043601gg, ESTs, Weakly similar
hh to T08680 hypothetical
protein DKFZp564P0622.1-
human
(fragment) fH.sapiensl
15837136A1044604s ESTs, Weakly similar
to T12528 hypothetical
protein DKFZp434N093.1
- human
(fragment) [H.sapiensl
15855556A1044638ii ESTs, Moderately similar
to Y127_HUMAN
Hypothetical protein
KIAA0127 [H.sapiens]
16035715A1045158v ESTs, Moderately similar
to hypothetical
protein MGC4675 [Homo
sapiens]
[H.sapiensl
160511763A1045196tt ESTs, Weakly similar
to A47328 natural
killer cell tumor-recognition
protein - human
[H.sapiensl
16136609A1045458ii, ESTs, Highly similar
tt to 155595 splicing
factor
- human [H.sapiens]
16236808A1045600a ESTs, Highly similar
to S30034 translocating
chain-associating membrane
protein -
human [H.sapiensl
16315866A1045751y ESTs, Moderately similar
to SYN_HUMAN
Asparaginyl-tRNA synthetase,
cytoplasmic
(Asparagine--tRNA ligase)
(AsnRS)
[H.sapiensl
165010080A1058639General EST, Weakly similar
to PRTZ_HUMAN
Vitamin K-dependent
protein Z precursor
[H.sapiensl
17008496A1059974tt ESTs, Moderately similar
to T17285
hypothetical protein
DKFZp434N0535.1 -
human (fragment) [H.sapiensl
17038132A1060050p, ESTs, Highly similar
bb to NGP1 HUMAN
Autoanti en NGP-1 [H.sapiens]
170610304A1060149b ESTs, Weakly similar
to T48687 hypothetical
protein DKFZp76161923.1
- human
(fragment) fH.sapiensl
17104337A1060281II ESTs, Weakly similar
to T50633 hypothetical
protein DKFZp762F1811.1
- human
(fragment) [H.sapiensl
174211596A1071194pp ESTs, Weakly similar
to S16506 hypothetical
protein - human [H.sapiens]
17499615A1071289I, ESTs, Highly similar
z to Y779_HUMAN
Hypothetical protein
KIAA0779 [H.sapiens]
17619259A1071606q ESTs, Highly similar
to UBP1 HUMAN
Ubiquitin carboxyl-terminal
hydrolase 1
(Ubiquitin thiolesterase
1) (Ubiquitin-specific
processing protease
1) (Deubiquitinating
enzyme 1) (hUBP) [H.sapiens]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Attorney
Docket
No.
44921-5913W0
'Document
No:1926271:2
SEQ GLGC GenBankModef Known Gene Name Unigene SequenceCluster
~ Title
ID D Acc_or Code
-- N0.
I
N0 RefSeq
ID
--
No.
177317673A1071895i EST, Moderately similar
i to 138937 DNAIRNA
binding protein - human
(fragment)
fH.sapiensl
17758665 A1071965ee ESTs, Moderately similar
to T17342
hypothetical protein
DKFZp586K1924.1 -
human (fragment) [H.sapiens],
R.norvegicus
hsp70.2 mRNA for heat
shock protein 70
184016814AI101462jj ESTs, Highly similar
to cisplatin resistance
related protein CRR9p
[Homo sapiens]
[H.sapiensl
18692972 AI102606ss ESTs, Moderately similar
to NADH
dehydrogenase (ubiquinone)
1 alpha
subcomplex, 10 (42kD)
[Homo Sapiens]
IH.sapiensl
18717379 A1102643d, ESTs, Moderately similar
dd, to 2105233A
rr
transcription factor
ISGF3gamma [Mus
musculusl ~M.musculusl
19123940 AI103718qq ESTs, Highly similar
to 139383 angio-
associated migratory
cell protein - human
[H.sapiensl
193718395AI104388nn heat shock 27kD heat shook 27kD protein
protein 1 1
195322957AI104897u, ESTs, Moderately similar
w to MEA6_HUMAN
Meningioma-expressed
antigen 6111 (MEA6)
(MEA11) [H.sapiens]
195524375AI104979q, ESTs, Moderately similar
z, to EBNA1 binding
dd,
ee
protein 2; nucleolar
protein p40; homolog
of
yeast EBNA1-binding protein;
nuclear FGF3
binding protein; EBNA1-binding
protein 2
[Homo sapiens] [H.sapiens]
197518466AI1118280o ESTs, Highly similar
to Y196_HUMAN
Hypothetical protein
KIAA0196 [H.sapiens]
197611339AI111840jj ESTs, Moderately similar
to PMVK_HUMAN
PHOSPHOMEVALONATE KINASE
(PMKASE) [H.sapiens]
200815196AI136610ee ESTs, Highly similar
to RRP5 HUMAN
-
RRP5 protein homolog
(Fragment)
[H.sapiensl
20176552 AI137062d ESTs, Highly similar
to OM07_HUMAN
Probable mitochondria)
import receptor
subunit TOM7 homolog
(Translocase of
outer membrane 7 kDa
subunit homology
Protein AD-014 H.sa lens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
Fd
TABLE
1
-
Attorney
Docket
No.
44921-5113W0
Document
No.192627~1:2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
4 Title
ID D Acc~.or Code
- N0.
l
N0. RefSeq
ID
No.
20327414AI137586n, ESTs, Highly similar
p, to IMB3_HUMAN
z,
GeneralI mportin beta-3 subunit
(Karyopherin beta-3
subunit) (Ran-binding
protein 5) [H.sapiens]
203314396AI137689s Rattus norvegicus mRNA
for Vps54-like
protein
20426898AI144623p ESTs, Moderately similar
to TRI3_HUMAN
Thyroid receptor interacting
protein 3 (TRIP-
3) [H.sapiensl
205112482AI144965p ESTs, Highly similar
to SN24_HUMAN
Possible global transcription
activator
SNF2L4 (SNF2-beta) (BRG-1
protein)
(Mitotic growth and
transcription activator)
(Brahma protein homoloa
1) fH.saoiensl
206115399AI14545100 ' ESTs, Highly similar
to RR41 HUMAN
Exosome complex exonuclease
RRP41
(Ribosomal RNA processing
protein 41)
fH.sapiensl
210016727AI169287z, ESTs, Highly similar
General, to T47146 hypothetical
kk protein DKFZp761 C169.1-
human
(fragment) fH.sapiensl
210711550AI169591a ESTs, Highly similar
to S57447 HPBRII-7
protein - human [H.sapiens]
213624048AI170570qq ESTs, Moderately similar
to COQ6_HUMAN
Putative ubiquinone
biosynthesis
monooxgenase COQ6 (CGI-10)
[H.sapiens]
21422750AI170666n, ESTs, Highly similar
q, to ARGR_HUMAN
dd
Arginine-rich protein
[H.sapiens]
21461923AI170754r, ESTs, Highly similar
z, to T50836 Yippee
ee
protein [imported] -
human (fragment)
[H.sapiensl
215914941AI171196pp ESTs, Highly similar
to MAN1 HUMAN Inner
nuclear membrane protein
Man1 [H.sapiens]
21625953AI171231r, amino acid transporteramino acid transporter
y, system system A2
z,
tt
A2
216611518A1171272a ESTs, Highly similar
to similar to S.
cerevisiae RER1 [Homo
sapiens]
[H.sapiensl
217817746AI171615ss ESTs, Moderately similar
to 139166 cellular
apoptosis susceptibility
protein CAS - human
[H.sapiensl
21926085AI171990ww ESTs, Highly similar
to T50620 hypothetical
protein DKFZp762M186.1
- human
(fragment) [H.sapiensl
219422876AI172041r, ESTs, Moderately similar
w, to CGD7_HUMAN
z,
ee
Protein CGI-137 (Protein
AD-004)
H.sa lens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
-
Attorney
Docket
No.
44921-5113W0
Document
No.1926271~2
SEQ GLGCGenBank Model Kriown Gene NameUnigene Sequence Cluster
Title
ID D Acc.or Code
I N0.
NO. RefSeq
ID
No.
21996057AI172102dd ESTs, Highly similar
to STXH_HUMAN
Syntaxin 18 [H.sapiensl
220511416AI172185t, ESTs, Highly similar
ff to mitochondria)
ribosomal protein L49;
chromosome 11 open
reading frame 4 [Homo
sapiensj [H.sapiens]
221311525AI172286p ESTs, Moderately similar
to LPRC_HUMAN
130 kDa leucine-rich
protein (LRP 130)
(GP130) (Leucine-rich
PPR-motif containing
protein) fH.sapiensl
22297740AI175011vv ESTs, Moderately similar
to COF1 RAT
COFILIN, NON-MUSCLE ISOFORM
[R.norveaicusl
22366454AI175342p, ESTs, Weakly similar
kk to T31067 BIR repeat
containing ubiquitin-conjugating
enzyme
BRUCE - mouse [M.musculusl
224218562AI175515s ESTs, Moderately similar
to PRTP_MOUSE
Lysosomal protective
protein precursor
(Cathepsin A) (Carboxypeptidase
C) (M054)
[M.musculusj
22571587AI176063ii Rat general mitochondria)
matrix processing
protease (MPP) mRNA,
3' end
22617711AI176125a ESTs, Moderately similar
to T14773
hypothetical protein
DKFZp564B0482.1 -
human [H.sapiensl
226812999AI176276General ESTs, Highly similar
to UAP1 HUMAN UDP-
N-acetylhexosamine pyrophosphorylase
(Antigen X) (AGX) (Sperm-associated
antigen 2) [Includes:
UDP-N-
acetylgalactosamine pyrophosphorylase
(AGX-1); UDP-N-acetylglucosamine
pyrophosphorylase (AGX-2)]
[H.sapiens]
227717920AI176422n, ESTs, Highly similar
kk, to S41115 probable
pp
flavoprotein-ubiquinone
oxidoreductase (EC
1.6.5.-) - human [H.sapiensl
227717921AI176422p, ESTs, Highly similar
kk to S41115 probable
flavoprotein-ubiquinone
oxidoreductase (EC
1.6.5.-) - human [H.sapiensl
228213678AI176490a ~ ESTs, Weakly similar
to T00065 hypothetical
protein KIAA0442 - human
(fragment)
[H.sapiensl
22903619AI176588vv ESTs, Weakly similar
to tumor protein p53-
binding protein; topoisomerase
I binding
protein [Homo sapiensl
[H.sapiensl
23144190AI177016z, ESTs, Highly similar
ee to LSMB_HUMAN U6
snRNA-associated Sm-like
protein LSm8
H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
FR
TABLE
1
_
Attorney
Docket
No.
44921-5113W0
Document'No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence.ClusterTitle
~
ID D Acc: Code
' N0. or
I
N0 RefSeq
ID
No:
232823162AI177353a, ESTs, Highly similar
q, to A47220
x,
dd
dermatopontin precursor
- human
[H.sapiens]
23386315AI177645bb ESTs, Weakly similar
to S69890 mitogen
i nducible gene mig-2
- human [H.sapiens]
235716739AI178151cc ESTs, Highly similar
to T46366 hypothetical
protein DKFZp434C0118.1-
human
(fragment) fH.sapiens]
236023248AI178267b, ESTs, Weakly similar
f, to JC7185
p,
q,
General, chromosome 1 C1orf9
protein - human
dd [H.sapiensl
23718418AI178566a ESTs, Highly similar
to T00260 hypothetical
protein KIAA0605 - human
[H.sapiens]
237423456AI178665p ESTs, Moderately similar
to T08719
hypothetical protein
DKFZp566B183.1 -
human [H.sapiens
237511374AI178672k ESTs, Weakly similar
to 601614 zinc finger
protein 127 - human
[H.sapiens]
23911924AI178902r, ESTs, Highly similar
z to T50836 Yippee
protein [imported] -
human (fragment)
[H.sapiensl
24004587AI179092ff ESTs, Moderately similar
to RL22_RAT 60S
-
RIBOSOMAL PROTEIN L22
[R.norvegicus]
240213055AI179100General, ESTs, Highly similar
jj to CN01 HUMAN
-
Protein C14orf1 (HSPC288)
(Protein AD-
011) (x0006) [H.sapiens]
240421631AI179125s ESTs, Highly similar
to eukaryotic
translation initiation
factor 3, subunit 3
(gamma, 40kD) [Homo
sapiens] [H.sapiens]
240617358AI179147b, ESTs, Highly similar
ii, to B Chain B, Three-
pp
Dimensional Structure
Of Human Electron
Transfer Flavoprotein
To 2.1 A Resolution
fH.sapiens
241013606AI179289j ESTs, Weakly similar
to S65464 pregnancy-
associated plasma protein
A precursor-
human [H.sapiens]
243823989AI179953ii, ESTs, Highly similar
ss to 1604368A gap
junction protein Cx26
[Rattus norvegicus]
(R.norvegicusl
244617365AI180249m ESTs, Highly similar
to colon cancer-
associated protein Mic1
[Homo sapiens]
[H.sapiens]
24537460AI180413r ESTs, Highly similar
to NBRT apolipoprotein
H precursor - rat [R.norvegicus]
248921822AI2286420o ESTs, Highly similar
to hypothetical protein
MGC1936 Homo sa iens
H.sa iens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
R7
TABLE
1
Attorney
Docket
No.
44921'-5113W0
Document
No.1926271.2
SEQ GLGCGenBa~k Model Known Gene Name Uriigene Sequence ClusterTitle
-
ID D Acc. Code
I N0. or
~
N0. RefSeq
tD
No.
250223955AI229178a ESTs, Highly similar
to S51635 fibroblast
growth factor receptor
2b, keratinocyte
growth factor receptor
- rat [R.norvegicusl
250811527AI229307rr, ESTs, Highly similar
uu to S27958 transcription
factor BTF2 62K chain
- human [H.sapiens]
251119138AI229413s ESTs, Moderately similar
to T00054
hypothetical protein
KIAA0415 - human
(fragment) [H.sapiensl
251323563AI229421pp ESTs, Moderately similar
to S78100 MAPK-
activated protein kinase
(EC 2.7.1.-) 2 -
mouse (fragment) [M.musculus]
25232688AI229793k, ESTs, Weakly similar
s to hypothetical protein
FLJ20010 [Homo sapiens]
[H.sapiens]
252713879AI2300040o ESTs, Moderately similar
to T00374
hypothetical protein
KIAA0648 - human
(fragment) f H.sa lens]
25284722AI230038c, ESTs, Moderately similar
II to T08811
hypothetical protein
DKFZp586M1523.1 -
human (fragment) [H.sapiensl
25354662AI230215II ESTs, Moderately similar
to hypothetical
protein FLJ10468 [Homo
sapiens]
[H.sapiensl
253615862AI230228m, ESTs, Weakly similar
n, to SERC_HUMAN
a -
Phosphoserine aminotransferase
(PSAT)
[H.sapiens]
255524270AI230758rr ESTs, Moderately similar
to cargo selection
protein (mannose 6 phosphate
receptor
binding pr; cargo selection
protein (mannose
6 phosphate receptor
binding protein) [Homo
sapiensl fH.saaiensl
25578036AI230884c, ESTs, Highly similar
tt to HMBA-inducible
[Homo sapiens] [H.sapiens]
256514303AI231159y ESTs, Highly similar
to KIAA1049 protein
[Homo sapiens] [H.sapiens]
257619271AI231566f, ESTs, Highly similar
q, to MAX_RAT MAX
pp,
ww protein [R.norvegicus]
258824501AI232006m translation elongationtranslation elongation
factor 1- factor 1-delta subunit
delta subunit
260615122AI232303g, ESTs, Weakly similar
General, to JC5393 zinc finger
dd proteinKF-1 precursor-mouse
[M.musculusl
261914051AI232489w, ESTs, Weakly similar
z, to dual specificity
dd,
ee phosphatase 11; RNAIRNP
complex-
interacting phosphatase;
serinelthreonine
specific protein phosphatase
[Homo sapiens]
H.sa i ns
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
RR
TABLE~1.
-
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
Title
ID D Acc. Code
I NO. or
NO: RefSeq
. ID
No.
26203662AI232506o ESTs, Weakly similar
to T46908 hypothetical
protein DKFZp76162423.1-
human
[H.sapiensl
262813645AI232694tt ESTs, Weakly similar
to S24C_HUMAN
Protein transport protein
Sec24C (SEC24-
related protein C) [H.sapiensl
263817240AI233054mm ESTs, Weakly similar
to UCRC~HUMAN
Ubiquinol-cytochrome
C reductase complex
ubiquinone-binding protein
QP-C (Ubiquinol-
cytochrome C reductase
complex 9.5 kDa
protein) (Complex III
subunit VII) [H.sapiens]
264611507AI233222ee ESTs, Highly similar
to hypothetical protein
MGC2803 [Homo sapiens]
[H.sapiens]
266118900AI233570ee ESTs, Highly similar
to PSD8 HUMAN 26S
-
proteasome non-ATPase
regulatory subunit
8 (26S proteasome regulatory
subunit S14)
(p31)[H.sapiensl
26637888A1233583n, ESTs, Highly similar
kk to SYR_HUMAN
ARGINYL-TRNA SYNTHETASE
(ARGININE
-TRNA LIGASE) (ARGRS)
[H.sapiens],
ESTs, Moderately similar
to JC4365 arginine
-tRNA ligase (EC 6.1.1.19)
- human
IH.saoiensl
26697243AI233717z, ESTs, Moderately similar
ee to ERHUAH
coatomer complex alpha
chain homolog -
human [H.sapiens]
267017210AI233746pp ESTs, Weakly similar
to SC14_HUMAN
SEC14-like protein 1
[H.sapiens]
269514745AI234919bb, ESTs, Moderately similar
mm to SYHUQT
multifunctional aminoacyl-tRNA
ligase -
human [H.sapiens]
26983875AI235047q ESTs, Highly similar
to S50082 nuclear cap
bindin protein - human
[H.sapiens]
271720140AI235566g ESTs, Moderately similar
to SYEP_HUMAN
Bifunctional aminoacyl-tRNA
synthetase
[Includes: Glutamyl-tRNA
synthetase
(Glutamate--tRNA ligase);
Prolyl-tRNA
synthetase (Proline--tRNA
ligase)]
IH.saoiensl
272224373AI235748I, ESTs, Moderately similar
y, to Y110_HUMAN
ee,
rr
Hypothetical protein
KIAA0110 (HA0666)
[H.sapiens]
272514768AI235912f ESTs, Weakly similar
to highly charged
protein [Homo sapiens]
[H.sapiens]
27326976AI236072qq , ESTs, Weakly similar
to T08680 hypothetical
protein DKFZp564P0622.1
- human
fra ment H.sa lens
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
RA
TABLE
1
.:
Attorney
Docket
No.
44921-5113W0
Document
No.19262'T1.2
SEQ GLGCGeriBankModel.:Known Gene Name Unigene=Sequenae Cluster
. Title
ID D Accor Code
= N0.
I
N0 RefSeq
ID
No;
273814879AI236200ee ESTs, Moderately similar
to M1A1 MOUSE
Mannosyl-oligosaccharide
1,2-alpha-
mannosidase IA (Processing
alpha-1,2-
mannosidase IA) (Alpha-1,2-mannosidase
I A) (Mannosidase alpha
class 1A member 1)
(Man(9)-alpha-mannosidase)
[M.musculus]
274615398AI236566s ESTs, Moderately similar
to T12473
hypothetical protein
DKFZp564G1762.1 -
human (fragment) [H.sapiensl
274823249AI236597p, ESTs, Weakly similar
ff to JC7185
chromosome 1 C1 orf9
protein - human
f H.sapiensl
278121653AI237535I, LPS-induced TNF-alphaLPS-induced TNF-alpha
qq factor factor
278915248AI237654nn, upregulated by upregulated by 1,25-dihydroxyvitamin
xx 1,25- D-3
dihydroxyvitamin
D-3
283218533AI639231g ESTs, Highly similar
to T46480 hypothetical
protein DKFZp434L1850.1-
human
(fragment) [H.sapiensl
283925942AI639291cc ESTs, Weakly similar
to S38783 integrin
alpha chain - rat (fragment)
[R.norvegicus]
284314606AI639342d ESTs, Highly similar
to YS64 HUMAN
_
Hypothetical protein
S164 [H.sapiens]
286120468AI639494m ESTs, Weakly similar
to 601614 zinc finger
protein 127 - human
[H.sapiensl
290721864H31144 pp ESTs, Moderately similar
to 1914275A non-
receptor Tyr kinase
[Homo sapiens]
[H.sapiensl
290720456H31144 II, ESTs, Moderately similar
pp to 1914275A non-
receptor Tyr kinase
[Homo sapiens]
[H.sapiensl
291717913H31707 I, ESTs, Moderately similar
x, to T50621
General, hypothetical protein
DKFZp7620076.1 -
dd, human fragment) [H.sapiensl
uu
29184360H31813 z, ESTs, Moderately similar
General to T14781
hypothetical protein
DKFZp586B1621.1 -
human (fragment) [H.sapiensl
30104224M31322 ff, sperm membrane sperm membrane protein
mm protein (YWK- (YWK-II)
II)
30104225M31322 nn, sperm membrane sperm membrane protein
uu protein (YWK- (YWK-II)
II)
30201586M57728 00, Rat general mitochondria)
pp matrix processing
protease (MPP) mRNA,
3' end
313515174NM_012756j, Insulin-like growthInsulin-like growth
ss factor 2 factor 2 receptor
rece for
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7(1
TABLE
1
Attorney
Docket
No.
44921'-5113W0
Document
No.=1926271.2
SEQ GLGC GenBankModel;Known Gene Name Unigene Sequetlce Cluster
Title
ID D Acc.-orCode
I N0. _
N0~ RefSeq
ID
No.
340320583NM 017306k, ESTs, Highly similar
nn to D3D2_RAT 3,2-
TRANS-ENOYL-COA ISOMERASE,
MITOCHONDRIAL PRECURSOR
(DODECENOYL-COA DELTA-ISOMERASE)
IR.norveaicusl
35791867 NM 022510ee ribosomal proteinribosomal protein L4
L4
37131024 NM 031016k muscarinic receptormuscarinic receptor
m2 m2
37251336 NM 031042k general transcriptiongeneral transcription
factor IIF, factor IIF, polypeptide
2
polypeptide 2 (30kD subunit)
(30kD subunit)
38831105 NM_031758nn somatostatin receptor-likesomatostatin receptor-like
protein
protein
399822919NM 053556uu, maternal G10 transcriptmaternal G10 transcript
ww
407420939NM 053884I, ATPase, vacuolar,14ATPase, vacuolar, 14
m, kD kD
s,
General,
bb,
qq,
uu
414918027NM_130407a UDP glycosyltransferaseUDP glycosyltransferase
1 1 family,
family, polypeptidepolypeptide A7
A7
414918028NM_130407a UDP glycosyltransferaseUDP glycosyltransferase
1 1 family,
family, polype polypeptide A7
tide A7
418321703NM 1335250o putative c-Myc-responsiveputative c-Myc-responsive
420515655NM_133621nn global ischemia global ischemia induced
induced protein protein GIIG15B
GIIG15B
421212719NM 134373I, Esau Esau
uu
422114697NM_134419dd protein associatingprotein associating
with small with small stress protein
stress protein PASS1
PASS1
423413563NM 138530m, MAWD binding proteinMAWD binding protein
fP
42581049 NM_138901g phosphatidylinositolphosphatidylinositol
glycan, glycan, class L
class L
426616176NM_139087a cell growth regulatorycell growth regulatory
with EF- with EF-hand domain
hand domain
428022595NM_139253d stem cell derivedstem cell derived neuronal
neuronal survival protein
survival protein precursor
precursor
42847859 NM_139328kk liver regeneration-relatedliver regeneration-related
protein
protein
429417277NM_145082g Rattus norvegicus glycine-,
glutamate-,
thienylcyclohexylpiperidine-binding
protein
mRNA, complete cds
42976731 NM_145096c Rattus norvegicus small
rec (srec) mRNA,
complete cds
43106824 NM_147138II, Rattus norvegicus SNAP25
ss interacting
protein 30 (Sip30) mRNA,
complete cds
434024351S74257 ii, ESTs, Weakly similar
kk, to ABD4_MOUSE ATP
II,
ww
binding cassette, sub-family
D, member 4
(Peroxisomal membrane
protein 69)
(PMP69) (Peroxisomal
membrane protein 1-
like) (PXMP1-L) (P70R)
[M.muscqlus]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
71
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271:2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
Title
lD D Acc:: Code
I N0. or
NO'. RefSeq
ID . a:
No.
438221654U53184 f, LPS-induced TNF-alphaLPS-induced TNF-alpha
I, factor factor
y,
General,
ee
439923282U90725 q, ipoprotein-bindinipoprotein-binding protein
ff, protein l
tt
l
441520810X14181 I ESTs, Highly similar
to R5RT18 ribosomal
protein L18a, cytosolic
[validated] - rat
[R.norveqicusl
44207459X15551 a, ESTs, Highly similar
j, to NBRT apolipoprotein
n,
r
H precursor- rat [R.norvegicus]
442323987X51615 w, ESTs, Highly similar
gg, to 1604368A gap
hh
j unction protein Cx26
[Rattus norvegicus]
[R.norvegicusl
44634223X77934 mm sperm membrane sperm membrane protein
protein (YWK- (YWK-II)
II)
73 13683AA799788s HHs:cell divisionESTs, Moderately similar
cycle 34 to 154552
hypothetical serine
proteinase - rat
[R.norveqicusl
82 16346AA799824a, HHs:ATPase, H+ ESTs, Highly similar
e, transporting, to VATC_MOUSE
f,
s,
General,lysosomal 42kD, Vacuolar ATP synthase
V1 subunit C, subunit C (V-
kk, isoform 1 ATPase C subunit) (Vacuolar
oo proton pump C
subunit) IM.musculusl
107 4832AA8001900o HHs:phosphorylase,ESTs, Highly similar
glycogen; to S37300 glycogen
brain phosphorylase (EC 2.4.1.1
), brain - rat
[R.norvegicusl
12063364AA998097GeneralHHsaelenium donorESTs, Moderately similar
protein to SPS2_MOUSE
_
Selenide,water dikinase
2 (Selenophosphate
synthetase 2) (Selenium
donor protein 2)
(M.musculusl
171517506A1070068n, HHs:growth arrestESTs, Weakly similar
kk and DNA- to 2104282A Gadd45
damage-inducible,gene [Rattus norvegicus]
beta [R.norvegicus]
191323829AI103754h HHs:UDP-Gal:betaGIcNAcESTs, Weakly similar
beta to glycoprotein
1,4- galactosyltransferase,galactosyltransferase
beta 1, 4; beta-1,4-
polypeptide 2 GaIT; galactosyltransferase
2 beta 1, 4; B-
1,4-GaIT1; beta-1,4-GaIT1
[Mus musculus]
IM.musculusl
191915050AI103911r HHs:ubiquinol-cytochromeESTs, Highly similar
c to A32296 ubiquinol--
reductase, Rieskecytochrome-c reductase
iron-sulfur (EC 1.10.2.2)
polypeptide 1 Rieske iron-sulfur protein
precursor - rat
(fragment) [R.norveaicusl
196723596AI105435uu, HHs:glutaryl-CoenzymeESTs, Highly similar
vv A to GCDH_MOUSE
dehydrogenase Glutaryl-CoA dehydrogenase,
mitochondrial
precursor (GCD) [M.musculus]
209023152AI169170xx HHs:eukaryotic ESTs, Highly similar
translation to S00985 translation
initiation factorinitiation factor eIF-4A
4A, isoform 2 II - mouse
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7?
TABLE
1
Attorney-Docket
No.
44929-5113W0
Document
No.19262712
SEQ GLGCGenBank Model Known Gene-Name Unigene Sequence Cluster
Title
ID D Acc. Code
I N0. or '
NO: RefSeq
ID
No.
297913682L38482 p HHs:cell divisionESTs, Moderately similar
cycle 34 to 154552
hypothetical serine
proteinase - rat
fR.norveaicus~
13 1599AA686470GeneralDNA-damage inducibleDNA-damage inducible
transcript 3
transcript 3
13 1600AA686470pp DNA-damage inducibleDNA-damage inducible
transcript 3
transcript 3
65 14250AA799729qq, PhosphodiesteraseESTs, Phosphodiesterase
vv 4B, cAMP- 4B, cAMP-specific
specific (dunce (dunce (Drosophila)-homolog
(Drosophila)-
homolog phosphodiesterasephosphodiesterase E4)
E4)
66 18060AA799735c, RuvB-like proteinRuvB-like protein 1
j, 1
q,
x
66 18061AA799735dd, RuvB-like proteinRuvB-like protein 1
oo 1
74 1680AA799792, hh Carboxyl ester Carboxyl ester lipase
lipase
163 15852AA800942g, Complement componentComplement component
hh 4 4
166 11901AA801058I, aldehyde dehydrogenasealdehyde dehydrogenase
nn family family 9, subfamily
9, subfamily A1 A1
216 6054AA818658ww Diphtheria toxin Diphtheria toxin receptor
receptor (heparin binding
(heparin binding epidermal growth factor
epidermal - like growth factor)
growth factor
- like growth
factor)
217 4230AA818669I, RAB7, member RAS RAB7, member RAS oncogene
ss oncogene family
family '
234 576 AA819118vv S - adenosylmethionineS - adenosylmethionine
synthetase
synthetase
236 6018AA819140x carbonic anhydrasecarbonic anhydrase 3
3
252 6288AA819554ww brain-specific brain-specific angiogenesis
angiogenesis inhibitor 1-
inhibitor 1-associatedassociated protein 2
protein 2
449 17742AA866302ss 4-hydroxyphenylpyruvic4-hydroxyphenylpyruvic
acid acid dioxygenase
dioxy enase
455 16333AA866414k Solute carrier Solute carrier family
family 4, member 4, member 1, anion
1, anion exchangeexchange protein 1 (kidney
protein 1 band 3)
(kidney band 3)
484 1190AA875089II Calpastatin Calpastatin
549 19321AA891666t melanoma antigen,melanoma antigen, family
family D,1 D,1
572 21674AA891828jj procolla en, typeprocollagen, type I,
I, alpha 2 alpha 2
624 820 AA892395a, Aldolase B, fructose-Aldolase B, fructose-biphosphate
s,
ss,
uu
biphosphate
778 4661AA899709a receptor activityreceptor activity modifying
modifying protein 3
protein 3
805 23038AA900881t, branched chain branched chain aminotransferase
mm 1,
aminotransferase cytosolic
1, cytosolic
835 20711AA924267o Cytochrome P450, Cytochrome P450, subfamily
subfamily IVB,
IVB, polypeptide polypeptide 1
1
869 23451AA925243j restin (Reed-Steinbergrestin (Reed-Steinberg
cell- cell-espressed
espressed intermediate- intermediate filament-associated
filament protein)
associated rotein
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7R
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1v926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
_, _ Title
ID D Acc~ Code
I N0. or
NO. Ref$eq
ID
No.
108323700AA956382f Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase,
f 3- 3-oxo acyl-CoA
oxo acyl-CoA thiolasehiolase A 1, peroxisomal
A 1, t
peroxisomal
119420712AA997806b, Cytochrome P450, Cytochrome P450, subfamily
uu subfamily IVB,
IVB, polypeptide polypeptide 1
1
12413081 AA999171GeneralSignal transducerSignal transducer and
and activator activator of
of transcription transcription 1
1
125222567AB017544u, peroxisomal membraneperoxisomal membrane
kk anchor anchor protein
protein
125619702AF008587p hemochromatosis hemochromatosis
127122602AF044574o putative peroxisomalputative peroxisomal
2,4-dienoyl~ 2,4-dienoyl-CoA
CoA reductase reductase
127122603AF0445740, putative peroxisomalputative peroxisomal
kk 2,4-dienoyl~ 2,4-dienoyl-CoA
CoA reductase reductase
129910108A1007857b, HGF-regulated HGF-regulated tyrosine
General,tyrosine kinase kinase substrate
dd substrate
137617524A1010568ss Growth hormone Growth hormone receptor
receptor
142824411A1012577h, Insulin-like growthInsulin-like growth
z factor II factor II (somatomedin
A)
(somatomedin A)
14541332 A1013222mm Platelet-derived ESTs, Platelet-derived
growth factor growth factor A chain
A
chain
149617957A1028975d Adaptor protein Adaptor protein complex
complex AP-1, AP-1, beta 1
beta 1 subunit subunit
15665648 A1044035ss protein phosphataseprotein phosphatase
4, 4, regulatory subunit
1
re ulatory subunit
1
162624336A1045621r Myristoylated Myristoylated alanine-rich
alanine-rich protein kinase C
protein kinase substrate
C substrate
166619835A1058964II transporter protein;transporter protein;
system N1 system N1 Na+ and H+-
Na+ and H+-coupledcoupled glutamine transporter
glutamine
transporter
190218679AI103496bb GDP-dissociation GDP-dissociation inhibitor
inhibitor 1 1
21054091 AI169417I, Phosphoglycerate Phosphoglycerate mutase
rr, mutase 1 1
tt
216423465AI171243ww erythrocyte proteinerythrocyte protein
band 4.1-like band 4.1-like 3
3
216814960AI171319gg, guanine nucleotideESTs, Highly similar
hh binding to SWI/SNF related,
protein (G protein),matrix associated, actin
beta dependent regulator
polypeptide 2-likeof chromatin, subfamily
1 b, member 1;
integrase interactor
1 [Mus musculus]
[M.musculus], guanine
nucleotide binding
protein (G protein),
beta polypeptide 2-like
1
22197579 AI172453v proteasome (prosome,proteasome (prosome,
macropain) 26S
macropain) 26S subunit, non-ATPase,
subunit, non- 10
ATPase, 10
226410182AI176185tt FBJ murine osteosarcomaFBJ murine osteosarcoma
viral viral (v-fos)
(v-fos) oncogene oncogene homolo
homolog
229916477AI176701jj Fatty acid bindingFatty acid binding protein
protein 3, 3, muscle and
muscle and heart heart
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
74
TABLE
1
Attorney
Docket
Ho.'44921-5113WQ
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluste~
. Title...::
ID D Acc. Code
I N0. or
NO: RefSeq
ID
No.
230617235AI176815n Tissue inhibitor Tissue inhibitor of
of metalloproteinase 3
metalloproteinase
3
233014989AI177366b Integrin, beta ntegrin, beta 1
1 I
234713558AI177901k Adrener is receptorAdrener is receptor
beta 1 beta 1
234815315AI177911x cal actin I heavycalpactin I heavy chain
chain
242716081AI179610s, Heme oxygenase Heme oxygenase
rr
25374280 AI230247c, selenoprotein selenoprotein P, plasma,1
v, P, plasma,1
General
25461378 AI230602m Retinoblastoma-relatedRetinoblastoma-related
gene gene
256118778AI230982ww Eph receptor B2 Eph receptor B2 (ELK-related
(ELK-related protein
protein tyrosine tyrosine kinase)
kinase)
257024326AI231292a, Cystatin C (cysteineCystatin C (cysteine
I, proteinase proteinase inhibitor)
General,inhibitor)
cc,
qq
257024327AI231292h, Cystatin C (cysteineCystatin C (cysteine
I, proteinase proteinase inhibitor)
rr
inhibitor)
257119288AI231305a Platelet-derived Platelet-derived growth
growth factor factor receptor alpha
receptor alpha
264717907AI233224t Epidermal growth Epidermal growth factor
factor receptor, formerly
receptor, formerlyavian erythroblastic
avian leukemia viral (v-erbB)
erythroblastic oncogene homolog (Erbb1)
leukemia viral
(v-
erbB) oncogene
homolog
(Erbb1)
270619995A1235320p, mitochondrial mitochondrial aconitase
t aconitase (nuclear(nuclear aco2 gene)
aco2 gene)
27122241 A1235500ss cofilin 1, non-musclecofilin 1, non-muscle
288018686D00729 0, dodecenoyl-CoenzymeRat mRNA for delta3,
ff, A delta delta2-enoyl-CoA
jj
isomerase (3,2 isomerase, dodecenoyl-Coenzyme
trans-enoyl- A delta
Coenyme A isomerase)isomerase (3,2 trans-enoyl-Coenyme
A
isomerase)
2889536 D25290 Cadherin 6 (K-cadherin)Cadherin 6 (K-cadherin)
289016610D28557 n, cold shock domaincold shock domain protein
General,protein A A
oo,
rr
2897935 D49434 bb, Arylsulfatase Arylsulfatase B (MPS
ww B (MPS VI) VI)
294620429J05035 t, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase,
xx alpha
alpha polypeptidepolypeptide 1 (3-oxo-5
1 (3-oxo-5 alpha-steroid delta
4-
alpha-steroid dehydrogenase alpha
delta 4- 1 )
dehydroaenase
alpha 1)
294620430J05035 bb, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase,
qq alpha
alpha polypeptidepolypeptide 1 (3-oxo-5
1 (3-oxo-5 alpha-steroid delta
4-
alpha-steroid dehydrogenase alpha
delta 4- 1)
dehvdroaenase
alpha 1)
29471247 J05181 vv Glutamylcysteine Glutamylcysteine gamma
gamma synthetase light
s nthetase light chain
chain
294920549K01701 y OxytocinlneurophysinOxytacin/neurophysin
295620865L00117 g, Elastase 1 Elastase 1
w,
rr
29575616 L00191 j Fibronectin 1 Fibronectin 1
295924425L08812 k transcri tion transcri tion factor
factor EC EC
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE~1
Attorney
Docket
No.
44921-5113W0
Documenfi
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence,ClusterTitle
ID D Acc~ Code
I N0. or
'
NQ-. RefSeq
ID
No.
297415073L22761 ww GATA-binding proteinGATA-binding protein
4 4
297512058L25387 phosphofructokinase,ESTs, Highly similar
t platelet to A53047 6-
phosphofructokinase (EC
2.7.1.11) - rat
fR.norveqicusl
29806406 L38615 v Glutathione synthetaseGlutathione synthetase
ene ene
298521097M12112 s Angiotensinogen Angiotensinogen
299120714M14972 0, Cytochrome P450, Cytochrome P450, subfamily
r subfamily IVB,
IVB, polypeptide polypeptide 1
1
299524407M17960 v Insulin-like growthInsulin-like growth factor
factor II II (somatomedin A)
(somatomedin A)
30046626 M24353 I, mannosidase 2, ESTs, Highly similar
k, alpha 1 to M2A1 RAT Alpha-
General, mannosidase II (Mannosyl-oligosaccharide
II
1,3-1,6-alpha-mannosidase)
(MAN II) (Golgi
alpha-mannosidase II)
(Mannosidase alpha
class 2A member 1) [R.norvegicus]
3005668 M25823 jj Protein tyrosine Protein tyrosine phosphatase,
phosphatase, receptor-type,
receptor-type, c polypeptide (antigen
c polypeptide Cd45, leukocyte-
(antigen Cd45, common antigenlT200 glycoprotein)
leukocyte- also
common antigenlT200RT7
qlvcooroteinl
also RT7
300716930M27440 h, Apolipoprotein Apolipoprotein B
o, B
ss,
vv
301123610M32754 I Inhibin, alpha Inhibin, alpha
301920713M57718 0, Cytochrome P450, Cytochrome P450, subfamily
r, subfamily IVB,
xx
IVB, polypeptide polypeptide 1
1
30222465 M59814 ee, Eph receptor B2 Eph receptor B2 (ELK-related
ww (ELK-related protein
protein tyrosine tyrosine kinase)
kinase)
3023457 M60666 c, Tropomyosin 1 Tropomyosin 1 (alpha)
nn (alpha)
302424253M61142 s Thimet oli opeptidaseThimet oli opeptidase
304317991M96626 g ATPase, Ca++ transporting,ATPase, Ca++ transporting,
plasma
plasma membrane membrane 3
3
30441678 M96674 I, glucagon receptorglucagon receptor
General,
nn,
pp
304623698NM 0124890, Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase,
xx 3- 3-oxo acyl-CoA
oxo acyl-CoA thiolasethiolase A 1, peroxisomal
A 1,
peroxisomal
304623699NM 0124890, Acetyl-CoA acyltransferase,Acetyl-CoA acyltransferase,
u, 3- 3-oxo acyl-CoA
v,
ss
oxo acyl-CoA thiolasethiolase A 1, peroxisomal
A 1,
peroxisomal
3047265 NM 012494, hh, Angiotensin receptorAn iotensin receptor
jj 2 2
30487062 NM 012495t, Aldolase A, fructose-Aldolase A, fructose-bisphosphate
bb,
mm
bisphosphate
30487064 NM 012495s Aldolase A, fructose-Aldolase A, fructose-bisphosphate
bisphosphate
30491655 NM 012497n Aldolase C, fructose-Aldolase C, fructose-biphosphate
bi hos hate
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7R
TABLE
1
Aftorney
Docket
No44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
'' Title
ID D Acc. Code
I N0. or.
'
NO RefSeq
ID .
N o. ''
30501421 NM 012500 N-acylaminoacyl-peptideN-acylaminoacyl-peptide
f hydrolase
hydrolase
305117787NM 012501ee Apolipoprotein Apolipoprotein C-III
C-III
305315675NM 012504GeneralATPase, Na+K+ ATPase, Na+K+ transporting,
transporting, alpha 1
alpha 1 polypeptidepolypeptide
305315677NM_012504General,ATPase, Na+K+ ATPase, Na+K+ transporting,
transporting, alpha 1
mm alpha 1 polypeptidepolypeptide
3054855 NM 012507II ATPase, Na+K+ ATPase, Na+K+ transporting,
transporting, beta
beta polypeptide polypeptide 2
2
30567427 NM 012515II Benzodiazepin Benzodiazepin receptor
receptor (peripheral)
(peripheral)
305820518NM 012518e, CalmOdulin III Calmodulin III
nn
305915740NM 012520p Catalase Catalase
305915741NM 0125200, Catalase Catalase
General,
bb
306024865NM 012521ss Calcium-binding Calcium-binding protein,
protein, intestinal, vitamin
D
intestinal, vitamindependent (9-kDa CaBP)
D-dependent
(9-kDa CaBP)
306111115NM 012531I, Catecholamine-0- Catecholamine-0-methyltransferase
nn
methyltransferase
306111116NM 012531nn Catecholamine-0- Catecholamine-0-methyltransferase
methyltransferase
306320357NM 012534p, Crystallin, alphaCrystallin, alpha polypeptide
bb polypeptide A A
3064488 NM 012540j, Cytochrome P450, Cytochrome P450, subfamily
w subfamily I I (aromatic
(aromatic compound-inducible),compound-inducible),
member A1 (C6, form
member A1 (C6, c)
form c)
3064489 NM 012540e, Cytochrome P450, Cytochrome P450, subfamily
tt subfamily I I (aromatic
(aromatic compound-inducible),compound-inducible),
member A1 (C6, form
member A1 (C6, c)
form c)
306420705NM 012540j Cytochrome P450, Cytochrome P450, subfamily
subfamily I I (aromatic
(aromatic compound-inducible),compound-inducible),
member A2 (Q42,
member A2 (Q42, form d)
form d)
306520703NM 012541xx Cytochrome P450, Cytochrome P450, subfamily
subfamily I I (aromatic
(aromatic compound-inducible),compound-inducible),
member A2 (Q42,
member A2 (Q42, form d)
form d)
3066225 NM 012544j Angiotensin I-convertingAngiotensin I-converting
enzyme (Dipeptidyl
enzyme (Dipeptidylcarboxypeptidase 1)
carboxypeptidase
1)
306723868NM 012551dd, Early rowth responseEarly rowth response
oo, 1 1
tt
306723869NM 01255100, Early growth responseEarly growth response
tt 1 1
306723871NM 012551tt, Early growth responseEarly growth response
vv 1 1
306723872NM 012551dd, Early growth responseEarly growth response
tt 1 1
306917676NM 012556g, Fatty acid bindingFatty acid binding protein
j protein 1, liver 1, liver
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
77
TABLE
1
Afto~ney
Docket
Ho~
44921-5113W0
Document
No.-1926271:2
SEQ GLGC GenBank'Model Known Gene Name Jnigene'Sequence Cluster
l Title
ID D Acc: Code
' NO. or
I
N0. Ref$eq
ID
No.f.
30721732 NM 012561p Follistatin Follistatin
1
307420717NM 012569c Glutaminase Glutaminase
30754573 NM 012570, GeneralGlutamate dehydroGlutamate dehydrogenase
I enase
30754574 NM 012570h, Glutamate dehydrogenaseGlutamate dehydrogenase
I,
p,
General,
dd,
ii,
uu
307785 NM 012572c Glutamate receptor,Glutamate receptor,
ionotropic, ionotropic, kainate
4
kainate 4
307916024NM 012578m Histone H1-0 Histone H1-0
307916025NM 012578m, Histone H1-0 Histone H1-0
ww
307916026NM 012578m, Histone H1-0 Histone H1-0
ww
308120313NM 012585k 5-Hydroxytryptamine5-Hydroxytryptamine
(serotonin) (serotonin) receptor
1A
rece for 1A
308221162NM 012591d, Interferon re Interferon regulatory
a ulatory factor factor 1
1
30834449 NM 012592z, Isovaleryl CoenzymeIsovaleryl Coenzyme
GeneralA A dehydrogenase
dehydro enase
30834450 NM 012592p Isovaleryl CoenzymeIsovaleryl Coenzyme
A A dehydrogenase
dehydrogenase
30852505 NM 012597w Lipase, hepatic Lipase, hepatic
30882628 NM_012603f, Avian myelocytomatosisAvian myelocytomatosis
I, viral (v- viral (v-myc)
y,
z,
Generalmyc) oncogene onco ene homolo
homolog
30882629 NM 012603f, Avian myelocytomatosisAvian myelocytomatosis
I, viral (v- viral (v-myc)
I,
z,
General,myc) oncogene oncogene homolog
homolog
nn
308916850NM_012608k Membrane metallo-Membrane metallo-endopeptidase
(neutral
endopeptidase endopeptidase/enkephalinase)
(neutral
endopeptidase/enkephalinase)
309124506NM 012614d, Neuropeptide Y Neuropeptide Y
v
309223522NM 012615c, Ornitine decarboxylaseOrnitine decarboxylase
g,
I,
m,
n,
w,
General,
kk
309223523NM 012615I, Ornitine decarboxylaseOrnitine decarboxylase
v
30936055 NM 012619b, Phenylalanine Phenylalanine hydroxylase
I, hydroxylase
General,
uu
309524568NM 012630g Prolactin receptorProlactin receptor
309618553NM 012631b, Prion protein, Prion protein, structural
c, structural
qq,
vv
309820798NM 012639II Murine leukemia Murine leukemia viral
viral (v-raf-1) (v-raf-1) oncogene
oncogene homolog homolog 1 (3611-MSV)
1 (3611-
MSV)
309820799NM 012639p Murine leukemia Murine leukemia viral
viral (v-raf-1) (v-raf-1) oncogene
oncogene homolog homolog 1 (3611-MSV)
1 (3611-
MSV)
310016220NM 012656c, Secreted acidic Secreted acidic cystein-rich
cc cystein-rich glycoprotein
glycoprotein (osteonectin)(osteonectin)
310324825NM 012668x, T rosine aminotransferaseT rosine aminotransferase
ee,
ss
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7A
TABLE
1
Attorney,Docket
No.
44921~51131NQ
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name nigene Sequence Cluster
U Title
ID- ID Acc: Code
N0. or
NO. RefSeq
w ID''
No
310424427NM 012669pp Transcription Transcription factor
factor 1, hepatic;1, hepatic; LF-B1,
LF-B1, hepatic hepatic nuclear factor
nuclear factor (HNF1): albumin
(HNF1): albumin proximal factor, also
proximal TCF1
factor, also TCF1
310617117NM 012673w Thymus cell surfaceThymus cell surface
anti en antigen
31104185 NM_012681ee, Transthyretin Transthyretin (prealbumin,
gg, (prealbumin, amyloidosis type
hh
amyloidosis type I)
I)
31104186 NM 012681n, Transthyretin Transthyretin (prealbumin,
ee (prealbumin, myloidosis type
a
am loidosis type I)
I)
31115850 NM 012687g ThromboxA ane ThromboxA ane s nthase
synthase 1 1
311224453NM 012690a, ATP-binding cassette,ATP-binding cassette,
s sub- sub-family B
family B (MDRITAP),(MDRITAP), member 4
member 4 (P-glycoprotein 3I
(P-glycoprotein multidrug resistance
3/ multidrug 2
resistance 2
31161850 NM 012696a T-kininogen, see T-kininogen, see also
also D11EIh1 D11EIh1 and D11Mit8
and D11Mit8
31161854 NM 012696a T-kininogen, see T-kininogen, see also
also D11EIh1 11EIh1 and D11Mit8
D
and D11Mit8
31204002 NM 012708p, Low molecular Low molecular mass polypeptide
General,mass 2
nn polypeptide 2
31204003 NM 012708p Low molecular Low molecular mass polypeptide
mass 2
polypeptide 2
31204004 NM 012708nn Low molecular Low molecular mass polypeptide
mass 2
polypeptide 2
31204005 NM 012708GeneralLow molecular Low molecular mass
mass olypeptide 2
p
polypeptide 2
3122322 NM 012715p, Adrenomedullin Adrenomedullin
t,
ff,
ii,
pp,
xx
31231632 NM 012717d, Calcitonin receptor-likeCalcitonin receptor-like
y receptor receptor
31271372 NM 012734xx Hexokinase 1 Hexokinase 1
31371348 NM 012776m adrenergic receptoradrenergic receptor
kinase, beta inase, beta 1
k
1
31371349 NM 012776i, adrenergic receptoradrenergic receptor
i rr kinase, beta kinase, beta 1
1
313911938NM 012783x Basigin (0x47 Basigin (0x47 antigen
antigen or CE-9) or
C E-9) (EMMPRIN
( EMMPRIN in human)n human) (neurothelin,
i HT7 or 5A11 in
( neurothelin, HT7 avian)
or 5A11 in
avian)
314216947NM 012793a, Guanidinoacetate Guanidinoacetate methyltransferase
b,
e,
m,
s, methyltransferase
z,
General,
aa,
uu,
vv
314216948NM 012793qq, Guanidinoacetate Guanidinoacetate
uu m ethyltransferase
methyltransferase
3143961 NM 012796p g lutathione S-transferase,lutathione S-
theta g ransferase, theta 2
t
2
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
7A
TABLE
1
..
Attorney:Docket
No.
44921-5113WC1
Document
No.1926271
~2
SEQ GLGC GenBankModel'Known Gene Name Unigene SequencevCluster
Title
ID D Acc: Code
' N0. or
I
N0: RefSeq
ID
No.
.
314715032NM_012816 alpha-methylacyl-CoAalpha-methylacyl-CoA
t racemase
racemase
3148326 NM_012818ss Arylalkylamine Arylalkylamine N - acetyltransferase
N -
acetyltransferase(Serotonin N - acetyltransferase)
(Serotonin N
-
acetyltransferase)
31496780 NM 012819n Acyl Coenzyme Acyl Coenzyme A dehydrogenase,
A long
dehydrogenase, chain
long chain
315120586NM 012826a, Zn - alpha2 - Zn - alpha2 - glycoprotein
m, lycoprotein
vv
315120587NM 012826v, Zn - alpha2 - Zn - alpha2 - glycoprotein
vv lycoprotein
315215035NM 012836nn Carboxypeptidase Carboxypeptidase D precursor
D precursor
31532853 NM 012838j, Cystatin beta Cystatin beta
I,
qq
31532854 NM 012838j, Cystatin beta Cystatin beta
I,
General,
cc,
rr
31532855 NM 012838I, Cystatin beta Cystatin beta
cc
3155338 NM 012843t, Epithelial membraneEpithelial membrane
ff, protein 1 protein 1
mm
315617541NM_012844I, Epoxide hydrolaseEpoxide hydrolase 1
s, 1 (microsomal xenobiotic
General,(microsomal xenobiotichydrolase)
ff,
II, hydrolase)
ww
3157644 NM 012846kk Fibroblast growthFibroblast growth factor
factor 1 1 (heparin binding)
( heparin binding)
315820819NM 012847vv Farnesyltransferase,Farnesyltransferase,
subunit subunit alpha
alpha
316515872NM 012879bb Solute carrier Solute carrier family
family 2 A2 2 A2 (gkucose
( kucose transporter,transporter, type 2)
ty a 2)
316616301NM 012883g, Estrogen sulfotransferaseEstro en sulfotransferase
w,
rr
31664282 NM 012883rr Estrogen sulfotransferase,Estrogen sulfotransferase,
selenoprotein P,
selenoprotein plasma, 1
P, plasma, 1
316716870NM 012887v Thymopoietin (laminaThymopoietin (lamina
associated
associated polypeptidepolypeptide 2)
2)
316716871NM 012887r, Thymopoietin (laminaThymopoietin (lamina
z, associated
ee,
oo
associated polypeptidepolypeptide 2)
2)
316716872NM 012887pp Thymopoietin (laminaThymopoietin (lamina
associated
associated polypeptidepolypeptide 2)
2)
316916708NM 012895a, Adenosin kinase Adenosin kinase
b,
h,
w
317116273NM 012898k alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein
317116274NM 012898r alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein
317116275NM 012898r, alpha-2-HS-glycoproteinalpha-2-HS-glycoprotein
ee
317218564NM 012899k, aminolevulinate,delta-aminolevulinate,delta-
,dehydratase
w
,dehydratase
31737897 NM 012901a Alpha-1 micro Alpha-1 microglobulinlbikunin
lobulinlbikunin
31737898 NM 012901e, Alpha-1 microglobulinlbikuninAlpha-1
microglobulinlbikunin
r
31737899 NM 012901a Alpha-1 micro Alpha-1 micro lobulinlbikunin
lobulinlbikunin
317620590NM 012913n, ATPase, Na+K+ ATPase, Na+K+ transporting,
kk transporting, beta
beta polypeptide polypeptide 3
3
317724783NM 012914p ATPase, Ca++ transporting,ATPase, Ca++ transporting,
ubiquitous
ubi uitous
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
.
Attorney
DockefNo.
44921-5113W0
Document
No.1926271.2
SEQGL.GCGenBankModel Known Gene Name IJnlgene Sequence Cluster
_ Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No:
3179776 NM 012922a Caspase 3, apoptosisCaspase 3, apoptosis
related related cysteine
cysteine proteaseprotease (ICE-like cysteine
(ICE-like protease)
cysteine protease)
3179777 NM 012922z Caspase 3, apoptosisCaspase 3, apoptosis
related related cysteine
cysteine proteaseprotease (ICE-like cysteine
(ICE-like protease)
cysteine protease)
31821977 NM 0129300, Carnitine palmitoyltransferaseCarnitine
palmitoyltransferase
p, 2 2
y,
ff,
xx
3186190 NM 012940a Cytochrome P4501b1Cytochrome P4501b1
3186191 NM 012940a Cytochrome P4501 Cytochrome P4501 b1
b1
3186192 NM 012940a Cytochrome P4501b1Cytochrome P4501b1
3186193 NM 012940e, Cytochrome P4501b1Cytochrome P4501b1
v
318720928NM 012941ee Cytochrom P450 Cytochrom P450 Lanosterol
Lanosterol 14 14 alpha-
alpha-demethylasedemethylase
318720929NM 012941jj Cytochrom P450 Cytochrom P450 Lanosterol
Lanosterol 14 14 alpha-
alpha-demethylasedemethylase
318720931NM 012941uu Cytochrom P450 Cytochrom P450 Lanosterol
Lanosterol 14 14 alpha-
alpha-demethylasedemethylase
31891285 NM 012948r, Emerin Emerin
x
31901813 NM_012953I, Fos-like antigen Fos-like antigen 1
p, 1
y,
z,
ee
31925034 NM 012966v Heat shock 10 Heat shock 10 kD protein
kD protein 1 1 (chaperonin 10)
(chaperonin 10)
31932554 NM_012967vv Intercellular Intercellular adhesion
adhesion moleculemolecule 1
1
31932555 NM_012967vv Intercellular Intercellular adhesion
adhesion moleculemolecule 1
1
319524528NM 012973g Potassium (K+) Potassium (K+) channel
channel protein, protein, slowly
slowly activatin activating (Isk)
(Isk)
320024492NM 012987jj Nestin Nestin
3201764 NM 012988c, Nuclear Factor Nuclear Factor IA
p, IA
r,
z,
General
3201765 NM_012988h, Nuclear Factor Nuclear Factor IA
q, IA
z,
General
320216417NM 012991I, Nucleoprotein Nucleoprotein 50kD
x, 50kD
General,
VV
320317393NM 012992b, Nucleoplasmin-relatedNucleoplasmin-related
I, protein protein (Nuclear
j,
General,(Nuclear protein protein B23
B23
aq
320317394NM 012992GeneralNucleoplasmin-relatedNucleoplasmin-related
protein protein (Nuclear
(Nuclear protein protein B23
B23
32061640 NM 013000pp Peptidylglycine Peptidylglycine alpha-amidating
alpha-amidating
monooxygenase monooxygenase
32061649 NM 013000n Peptidylglycine Peptidylglycine alpha-amidating
alpha-amidating
monoox enase monoox enase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
R1
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
fD D Act: Code:
= N'0. or
I
N0. Ref$eq
ID
No:
320825279NM 013011bb Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan
5-
monooxygenase/tryptophanmonooxygenase activation
5- protein, zeta
monooxygenase polypeptide
activation
protein, zeta
polVpeptide
32083405 NM_013011ss Tyrosine 3- Tyrosine 3-monooxygenaseltryptophan
5-
monooxygenase/tryptophanmonooxygenase activation
5- protein, zeta
monooxygenase polypeptide
activation
protein, zeta
polVpeptide
321011905NM 013016s, Protein tyrosine Protein tyrosine phosphatase,
x phosphatase, non-receptor
non-receptor typetype substrate 1 (SHP
substrate 1 substrate 1 )
(SHP substrate
1)
32121588 NM_013026j, Syndecan 1 Syndecan 1
t,
mm,
ww
32121589 NM 013026mm Syndecan 1 Syndecan 1
321317894NM 013027v Selenoprotein Selenoprotein W muscle
W muscle 1 1
32141734 NM 0130280o Short stature Short stature homeobox
homeobox 2 2
3216313 NM 013033g Solute carrier Solute carrier family
family 5, member 5, member alpha 1
alpha 1 (Na+Iglucose(Na+/glucose cotransporter)
cotransporter)
321724809NM 013036g Somatostatin receptorSomatostatin receptor
subtype 4 subtype 4 Rattus
R attus norvegicus norvegicus Sprague-Dawley
Sprague- major
Dawley major hippocampalhippocampal somatostatin
receptor (SSTR4)
somatostatin receptormRNA
(SSTR4)
mRNA
3218115 NM 013037a Interleukin 1 Interleukin 1 receptor-like
receptor-like 1 (Fos-responsive
1 (Fos~
responsive ene gene 1)
1)
322112013NM 013050I, Ubiquitin conjugatingUbiquitin conjugating
nn enzyme enzyme E21
E21
322112014NM_013050I, Ubiquitin conjugatingUbiquitin conjugating
j, enzyme enzyme E21
y
E21
322216683NM 013052r Tyrosine 3- Tyrosine 3-monooxygenaseltryptophan
5-
monooxygenaseltryptophanmonooxygenase activation
5- protein, eta
monooxygenase polypeptide
activation
protein, eta polypeptide
322216684NM 013052pp Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan
5-
monooxygenaseltryptophanmonooxygenase activation
5- protein, eta
monooxygenase polypeptide
activation
protein, eta polVpeptide
322412370NM 013055a Mitogen activatedMitogen activated protein
protein kinase kinase 12 (Zipper
12 (Zipper (leucine)(leucine) protein kinase)
protein
kinase)
323213282NM 013078n, Ornithine carbamoyltransferaseOrnithine
carbamoyltransferase
jj
323213283NM 013078h, Ornithine carbamoyltransferaseOrnithine
carbamoyltransferase
I,
m,
s,
General,
cc,
uu
323915296NM 013102k FK506 binding FK506-binding protein
protein 2 (13 1 (12kD)
kDa), FK508-binding
protein 1
12kD
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
82
TABLE
1;
_
Aftorney
DocketNo.
44921=5113W0
Document
No.1.926271:2
SEQGLGC GertBankModel Knowrt:Gene Name Unigene'Sequence ClusterTitle
ID ID_N0.Acc, Code
or
NO. RefSeq
ID
No.
32401885 NM 013103I, Transcription Transcription factor
u, factor 2, hepatic;2, hepatic; LF-B3;
z
LF-B3; variant variant hepatic nuclear
hepatic nuclear factor
factor
324224195NM 013111f, Solute carrier Solute carrier family
q family 7 member 7 member A1 (amino
A1 (amino acid acid transporter cationic
transporter 1)
cationic 1)
324224196NM 013111f, S0lute carrier Solute carrier family
I, family 7 member 7 member A1 (amino
q,
z,
General,A1 (amino acid acid transporter cationic
transporter 1)
dd cationic 1)
324614300NM 013129pp Interleukin 15 Interleukin 15
3248650 NM_013134vv 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-
Coenzyme
A
Coenzyme A reductasereductase
3248651 NM_013134t 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-
Coenzyme
A
Coenz me A reductasereductase
3248652 NM_013134n, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-
Coenzyme
t A
Coenzyme A reductasereductase
32501712 NM_013138nn Inositol 1, 4, Inositol 1, 4, 5-triphosphate
5-triphosphate receptor 3
receptor 3
32515837 NM 013143s Meprin 1 alpha Meprin 1 alpha
325421683NM 013154d, CCAAT/enhancerbinding,CCAAT/enhancerbinding,
g protein (C/EBP)
protein (CIEBP) delta
delta
32563430 NM 013156g, Cathepsin L Cathepsin L
General,
oo,
pp,
uu
32563431 NM 013156z, Cathepsin L Cathepsin L
cc
3260447 NM 013165tt Cholecystokinin Cholecystokinin B receptor
B receptor
326124750NM 013167cc Uncoupling proteinUncoupling protein 3,
3, mitochondria)
mitochondria)
327320854NM 013200j, Carnitine palmitoyltransferaseCarnitine
palmitoyltransferase
nn 1 1 beta,
beta, muscle isoformmuscle isoform
327320856NM_0132000, Carnitine palmitoyltransferaseCarnitine
palmitoyltransferase
jj 1 1 beta,
beta, muscle isoformmuscle isoform
327523361NM 013216r Ras homolog enrichedRas homolo enriched
in brain in brain
328221078NM_016986I, Acyl-Coenzyme Acyl-Coenzyme A dehydrogenase,
o, A C-4 to C-
ss
dehydrogenase, 12 straight-chain
C-4 to C-12
straight-chain
328315612NM 016987ee ATP citrate lyaseATP citrate lyase
328315613NM 016987ii, ATP citrate lyaseATP citrate lyase
II,
ww
328524868NM 016992nn Arginine vasopressinArginine vasopressin
(Diabetes (Diabetes insipidus)
insipidus)
328524869NM 016992g Arginine vasopressinArginine vasopressin
(Diabetes (Diabetes insipidus)
insipidus)
329015620NM 017005p Fumarate hydrataseFumarate hydratase
32918417 NM 017008I Glyceraldehyde-3-phosphateGlyceraldehyde-3-phosphate
dehydrogenase dehydrogenase
329417815NM 017015p, Glucuronidase, Glucuronidase, beta
r, beta
w,
z
3295649 NM 017017cc Hepatocyte growthHepatocyte growth factor
factor (scatter factor)
scatter factor
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
83
TABLE
1
-
Attorney
Docket
No~'44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankMode Known Gene Name Unigene'Sequence Cluster
I Title
1D ID Ace. _
NO. or Code
N0. RefSeq
ID
No.
329811836NM 017023g Potassium inwardly-rectifyingPotassium inwardly-
rectifying
channel,
channel, subfamilysubfamily J
J
3299670 NM 017024a, Lecithin-cholesterolLecithin-cholesterol
m, acyltransferase
v,
cc,
uu, acyltransferase
vv
33014500 NM 017037m, Peripheral myelinPeripheral myelin protein
protein
General,
ii,
qq,
uu,
vv
33023202 NM 017039 Protein phosphataseProtein phosphatase
t 2 (formerly 2 (formerly 2A),
2A), catalytic catalytic subunit, alpha
subunit, alpha isoform
isoform
33023203 NM 0170390o Protein phosphataseProtein phosphatase
2 (formerly 2 (formerly 2A),
2A), catalytic catalytic subunit, alpha
subunit, alpha isoform
isoform
330324697NM 017048rr S0lute carrier Solute carrier family
family 4, member 4, member 2, anion
2, anion exchangeexchange protein 2
protein 2
330420876NM 017050k, Superoxide dismutaseSuperoxide dismutase
tt 1, 1, soluble
soluble
33051877 NM 017052w Sorbitol dehydrogenaseSorbitol dehydrogenase
33096653 NM 017068tt Lysosomal-associatedLysosomal-associated
membrane protein 2
membrane protein .
2
331020649NM 017072b, Carboamyl-phosphateCarboamyl-phosphate
General, synthetase 1
kk, synthetase 1
vv
331020650NM 017072b, Carboamyl-phosphateCarboamyl-phosphate
c, synthetase 1
General,synthetase 1
cc,
kk,
uu,
vv
331218957NM 0170750, Acetyl-CO A acetyltransferaseAcetyl-Co A
acetyltransferase
xx 1, 1,
mitochondria) mitochondria)
331218958NM 0170750, Acetyl-CO A acetyltransferaseAcetyl-Co A
acetyltransferase
jj 1, 1,
mitochondria) mitochondria)
33171550 NM 017084uu Glycine methyltransferaseGlycine methyltransferase
33171551 NM 017084uu Glycine methyltransferaseGlycine methyltransferase
33171552 NM 017084g, Glycine methyltransferaseGlycine methyltransferase
uu
33181383 NM 017088GeneralGDP-dissociation GDP-dissociation inhibitor
inhibitor 1 1
33206013 NM 017096e, C-reactive proteinC-reactive protein
w,
rr,
vv
332420745NM 017113a, granulin granulin
k,
I,
cc,
tt,
uu
332420746NM 017113a, granulin granulin
j,
I,
cc,
ss,
uu,
vv
332521538NM 017116, hh calpain 2 calpain 2
332721663NM 017126I, ferredoxin 1 ferredoxin 1
p
33281305 NM 0171270o Choline kinase Choline kinase
33281306 NM 017127f, Choline kinase Choline kinase
I,
General,
kk
vv
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
84
TABLE
1
Attorney
Docket
No:
4492-5113W0
Document
No:1926271-.2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster-Title
ID ID r- Code a
N0.NO. Acc.
or
RefSeq
ID
No.
333024693NM 017134a, arginase 1, liverarginase 1, liver
b,
I,
General,
cc
333116681NM 017136r, squalene epoxidasesqualene epoxidase
w,
jj
333116682NM 017136t, squalene epoxidasesqualene epoxidase
mm
333224885NM 017138q, laminin receptor laminin receptor 1
II 1
333224886NM 017138I, laminin receptor laminin receptor 1
II 1
3333492 NM 017140I dopamine receptordopamine receptor 3
3
333424105NM 017141a DNA polymerase DNA polymerase beta
beta
333424107NM 017141d, DNA polymerase DNA polymerase beta
g beta
333715364NM 017147j cofilin 1, non-musclecofilin 1, non-muscle
333916953NM 017151h, ribosomal proteinribosomal protein S15
II S15
333916954NM 017151bb, ribosomal proteinribosomal protein S15
gg, S15
hh
333916955NM 017151a ribosomal proteinribosomal protein S15
S15
334021643NM_017152u, ribosomal proteinribosomal protein S17
General,S17
ee,
II
33411694 NM 017153h, ribosomal proteinribosomal protein S3a
z, S3a
General,
ee
334470 NM 017159b, histidine ammoniahistidine ammonia lyase
c, lyase
y
334517105NM 017160ee ribosomal proteinribosomal protein S6
S6
3346595 NM 017161bb, Adenosine A2b Adenosine A2b receptor
mm receptor
335624670NM 017189a, asialoglycoproteinasialo lycoprotein receptor
n receptor 2 2
335920779NM_017201a S-adenosylhomocysteineS-adenosylhomocysteine
hydrolase hydrolase
336014694NM 017202ff cytochrome c oxidase,cytochrome c oxidase,
subunit subunit IVa
IVa
33631703 NM 017210mm deiodinase, iodothyroninedeiodinase, iodothyronine
type type III
III
33631704 NM 017210mm, deiodinase, iodothyroninedeiodinase, iodothyronine
xx type type III
III
3365317 NM 017218h, avian erythroblastosisavian erythroblastosis
General,oncogene oncogene B 3
bb, B 3
pp
336818147NM_017226cc peptidyl argininepeptidyl arginine deiminase,
deiminase, type II
type II
3369442 NM_017229y phosphodiesterasephosphodiesterase 3B,
3B, cGMP- cGMP-inhibited
inhibited
337020192NM 017232s prostaglandin-endoperoxideprostaglandin-endoperoxide
synthase 2 synthase 2
337020193NM 017232qq, prostaglandin-endoperoxideprostaglandin-endoperoxide
vv synthase 2 synthase 2
337117740NM 017233ss 4-hydroxyphenylpyruvic4-hydroxyphenylpyruvic
acid acid dioxygenase
dioxygenase
337315598NM 017236rr phosphatidylethanolaminephosphatidylethanolamine
binding protein binding protein
337624582NM_017243kk, phosphoribosyl phosphoribosyl pyrophosphate
pp pyrophosphate synthetase 1
s nthetase 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Aftorney
Docket
No:
44921'-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
N0. or
NO'. RefSeq
ID
No,.
33781418 NM 017246u, mitogen activatedmitogen activated protein
cc protein kinase kinase kinase 5
kinase 5
3380614 NM 017251General,gap junction membranegap junction membrane
channel channel protein beta
rr, protein beta 1 1
uu
338123037NM_017253, mm branched chain branched chain aminotransferase
t 1,
aminotransferase cytosolic
1, cytosolic
33821496 NM 017255qq, purinergic receptorpurinergic receptor
vv P2Y, G- P2Y, G-protein coupled
2
protein coupled
2
338415300NM 017259n, Early induced Early induced gene,
p, gene, B-cell B-cell translocation
rr
t ranslocation genegene 2
2
338415301NM 017259n, Early induced Early induced gene,
p, gene, B-cell B-cell translocation
ss,
tt
t ranslocation ene ene 2
2
338415299NM_017259p Early induced Early induced gene,
gene, B-cell B-cell translocation
translocation gene 2
gene 2
338515224NM_017264f protease (prosome,protease (prosome, macropain)
macropain) 28 subunit,
28 subunit, alphaalpha
338620600NM 017268q, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-
Coenzyme
w, A
jj
Coenzyme A synthasesynthase 1
1
338620601NM_017268q, 3-hydroxy-3-methylglutaryl-3-hydroxy-3-methylglutaryl-
Coenzyme
w, A
jj
Coenzyme A synthasesynthase 1
1
3387570 NM 017271a, nuclear distributionnuclear distribution
I, gene C gene C homolog
v,
General,homolog (Aspergillus)(Aspergillus)
dd,
00
339017959NM 017277w Adaptor protein Adaptor protein complex
complex AP-1, AP-1, beta 1
beta 1 subunit subunit
339115141NM 017278gg, proteasome (prosome,proteasome (prosome,
hh macropain) subunit,
macropain) subunit,alpha type 1
alpha type
1
33925747 NM 017279p proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,alpha type 2
alpha type
2
33925748 NM 017279xx proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,alpha type 2
alpha type
2
33931447 NM_017281t proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,alpha type 4
alpha type
4
33943254 NM 017282e, proteasome (prosome,proteasome (prosome,
kk, macropain) subunit,
mm,
nn macropain) subunit,alpha type 5
alpha type
5
33943256 NM 017282I, proteasome (prosome,proteasome (prosome,
j, macropain) subunit,
xx
macropain) subunit,alpha type 5
alpha type
5
340015819NM_017298a calcium channel, calcium channel, voltage-dependent,
voltage- L type,
dependent, L type,alpha 1 D sutiunit
alpha 1 D
subunit
34011531 NM 017300General,bile acid-Coenzymebile acid-Coenzyme A
ff, A dehydrogenase:
rr, dehydrogenase: amino acid n-acyltransferase
uu amino acid n-
ac Itransferase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
86
TABLE
1
Aftorney
Docket
No:
44921-5113WQ
Document
No.:1926271.2
SEQGLGC GenBankModel Known-Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
N0. or
N~.. RefSeq
ID
No.
340214002NM 017305qq glutamate-cysteineglutamate-cysteine ligase
ligase , , modifier subunit
modifier subunit
340214003NM 017305qq, glutamate-cysteineglutamate-cysteine ligase
vv ligase , , modifier subunit
modifier subunit
340318685NM 017306o dodecenoyl-Coenzymedodecenoyl-Coenzyme
A delta A delta isomerase
isomerase (3,2 (3,2 trans-enoyl-Coenyme
trans-enoyl- A isomerase)
Coenyme A isomerase)
340318687NM 0173060, dodecenoyl-CoenzymeRat mRNA for delta3,
ff, A delta delta2-enoyl-CoA
rr
isomerase (3,2 isomerase, dodecenoyl-Coenzyme
traps-enoyl- A delta
Coenyme A isomerase)isomerase (3,2 traps-enoyl-Coenyme
A
isomerase)
340519671NM_017309k, protein phospataseprotein phospatase 3,
mm 3, regulatory regulatory subunit
B,
subunit B, alpha alpha isoform (calcineurin
isoform B, type I)
(calcineurin B,
type p
340616844NM 017311r ATP synthase, ATP synthase; H+ transporting,
N+ transporting,
mitochondria) mitochondria) FO complex,
FO complex, subunit c (subunit
subunit c (subunit9), isoform 1
9), isoform 1
342021846NM 017355gg, ras-related GTP-bindingras-related GTP-binding
hh protein protein 4b
4b
342220417NM 017359Generalras-related proteinras-related protein
rab10 rab10
3427455 NM_019131k, Tropomyosin 1 Tropomyosin 1 (alpha)
bb, (alpha)
II,
mm,
nn
342916227NM 019137gg, Zinc-finger transcriptionZinc-finger transcription
hh factor factor NGFI-C (early
NGFI-C (early response gene)
response gene)
343013715NM 019139gg, Glial cell line ESTs, Glial cell line
hh derived neutrophicderived neutrophic
factor
factor
343114971NM 019140n, Protein tyrosine Protein tyrosine phosphatase,
bb phosphatase, receptor type,
receptor type, D
D
343114975NM 019140dd Protein tyrosine Protein tyrosine phosphatase,
phosphatase, receptor type,
receptor type, D
D
34335617 NM 019143k Fibronectin 1 Fibronectin 1
34335618 NM 019143k Fibronectin 1 Fibronectin 1
34335619 NM 019143GeneralFibronectin 1 Fibronectin 1
34335622 NM 019143I, Fibronectin 1 Fibronectin 1
ii
343520863NM 019152g calpain 1 calpain 1
343721090NM 019158General,aquaporin 8 aquaporin 8
dd,
fP,
nn
343820256NM 019163ii presenilin 1 presenilin 1
34407489 NM 019169 synuclein, alpha synuclein, alpha
344424019NM 019186ss, ADP-ribosylation-likeADP-ribosylation-like
tt 4 4
344615242NM 019191f, MAD homolog 2 MAD homolog 2 (Drosophila)
General,(Drosophila)
11
344722065NM 019195bb, integrin-associatedintegrin-associated
nn protein protein
344818572NM 019201pp, C-terminal bindingC-terminal binding protein
tt protein 1 1
345019241NM 019206I, Serinelthreonine Serine/threonine kinase
y, kinase 10 10
General,
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
R7
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SE GLGC GenBankModel Known Gene Name Unigene Sequerice-Cluster
': Q Title
lD D Ace. Code
I N0. or
NO RefSeq
1D
.
No.
34522078 NM 019220p, amino-terminal amino-terminal enhancer
s, enhancer of splitof split
pp
34522079 NM_019220z amino-terminal amino-terminal enhancer
enhancer of splitof split
345420938NM 019223t NADH dehydrogenaseNADH dehydrogenase Fe-S
Fe-S protein 6
protein 6
345816449NM 019238j farnesyl diphosphatefarnesyl diphosphate
j farnesyl farnesyl transferase
1
transferase 1
345816450NM 019238j, farnesyl diphosphatefarnesyl diphosphate
j oo, farnesyl farnesyl transferase
ss 1
transferase 1
345816451NM 019238bb, farnesyl diphosphatefarnesyl diphosphate
jj farnesyl farnesyl transferase
1
transferase 1
345816452NM_019238jj farnesyl diphosphatefarnesyl diphosphate
farnesyl farnesyl transferase
1
transferase 1
346121109NM_019243r prostaglandin prostaglandin F2 receptor
F2 receptor negative regulator
ne ative regulator
3462888 NM_019246n proprotein convertaseproprotein convertase
subtilisinlkexin type
7
subtilisinlkexin
type 7
346324849NM_019248e, neurotrophic tyrosineneurotrophic tyrosine
a kinase, kinase, receptor, type
receptor, type 3
3
34651450 NM 019251x blocked early blocked early in transport
in transport 1 homolog
1
homolog (S.cerevisiae)(S.cerevisiae)
346610340NM 019252d, dolichol-phosphatedolichol-phosphate (beta-D)
j, (beta-D)
tt
mannosyltransferasemannosyltransferase
2 2
34687693 NM 019258g cystatin 8 (cystatin-relatedcystatin 8 (cystatin-
related
epididymal
epididymal spermatogenic)spermato enic)
346915259NM 019259rr complement componentcomplement component
1, q 1, q subcomponent
subcomponent bindingbinding protein
protein
347115763NM 019265k sodium channel, sodium channel, voltage-gated,
voltage-gated, type XI,
type XI, alpha alpha polypeptide
polypeptide
347223625NM 0192690 solute carrier solute carrier family
family 22 (organic22 (organic cation
cation transporter),transporter), member
member 5 5
34731412 NM 019271ww stress 70 proteinstress 70 protein chaperone,
chaperone, microsome-
microsome-associated,associated, 60kD human
60kD homolog
human homolog
34741129 NM_019274nn collagen-like collagen-like tail subunit
tail subunit (single strand of
(single
strand of homotrimer)homotrimer) of asymmetric
of
asymmetric acetylcholinesterase
acetvlcholinesterase
347620734NM_019283q, solute carrier solute carrier family
z, family 3 (activators3 (activators of dibasic
General,of dibasic and and neutral amino acid
jj neutral amino transport), member
2
acid transport),
member 2
347620735NM 019283I, solute carrier solute carrier family
I, family 3 (activators3 (activators of dibasic
q,
z,
Generalof dibasic and and neutral amino acid
neutral amino transport), member
2
acid transport),
member 2
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
88
TABLE
1
Attorney
Docket
No.
44921=5113W0
Documerit
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence;Clustee
~ Title
ID ID Acc. Code'
NO. or
N0 RefSeq-ID
No.
347722219NM 019286c, Alcohol dehydrogenaseAlcohol dehydrogenase
vv (class (class I), alpha
I ), alpha polypeptidepolypeptide
34871389 NM 019350g synaptotagmin synaptotagmin 5
5
348923491NM 019359k, calponin 3, acidiccalponin 3, acidic
v
349118819NM 019367gg, palmitoyl-proteinpalmitoyl-protein thioesterase
hh, thioesterase 2
ii 2
349820443NM_019379n, vesicle docking vesicle docking protein,115
q, protein,115 kDa kDa
dd,
00
350024626NM 019381h, Testis enhanced Testis enhanced gene
x, gene transcript transcript
General
350918714NM 020075y eukaryotic initiationeukaryotic initiation
factor 5 (eIF- factor 5 (eIF-5)
5)
350918715NM 020075I eukaryotic initiationeukaryotic initiation
factor 5 (eIF- factor 5 (eIF-5)
5)
350918716NM_020075p, eukaryotic initiationeukaryotic initiation
gg, factor 5 (eIF- factor 5 (eIF-5)
hh
5
351020493NM 020076b, 3-hydroxyanthranilate3-hydroxyanthranilate
k, 3,4- 3,4-dioxygenase
I,
General,dioxygenase
bb,
ff,
qq,
tt,
uu
351020494NM 020076cc, 3-hydroxyanthranilate3-hydroxyanthranilate
ii, 3,4- 3,4-dioxygenase
ss
dioxy enase
352622916NM 021740ff prothymosin alphaprothymosin alpha
352719709NM 021742d nuclear receptor nuclear receptor subfamily
subfamily 5, 5, group A,
group A, member member 2
2
352919712NM 021745t, nuclear receptor nuclear receptor subfamily
General,subfamily 1, 1, group H,
ff, group H, member member 4
kk, 4
oo
353220090NM 021757v, pleiotropic regulatorpleiotropic regulator
ww 1 1
353417936NM_021766qq progesterone receptorprogesterone receptor
membrane
membrane componentcomponent 1
1
353520162NM 021835u, Avian sarcoma Avian sarcoma virus
tt virus 17 (v-jun) 17 (v-jun) oncogene
oncogene homolog homolog
353522350NM 021835tt Avian sarcoma Avian sarcoma virus
virus 17 (v-jun) 17 (v-jun) oncogene
onco ene homolo homolog
353522351NM 021835kk, Avian sarcoma Avian sarcoma virus
tt virus 17 (v-jun) 17 (v-jun) oncogene
oncogene homolog homolog
353522352NM_021835y, Avian sarcoma Avian sarcoma virus
kk, virus 17 (v-jun) 17 (v-jun) oncogene
ss,
tt
oncogene homolog homolog
3539243 NM 021989ii, tissue inhibitor ESTs, tissue inhibitor
rr of of metalloproteinase
2
metalloproteinase
2
354325699NM 022180General,Hepatic nuclear Hepatic nuclear factor
tt factor 4 (alpha 4 (alpha transcription
transcription factor 4)
factor 4)
354320257NM 022180GeneralHepatic nuclear Hepatic nuclear factor
factor 4 (alpha 4 (alpha transcription
transcription factor 4)
factor 4)
355020312NM 022224bb phosphotriesterasephosphotriesterase related
related
355310509NM 022268p, liver glycogen liver glycogen phosphorylase
Generalphosphorylase
355325814NM 022268I liver I co en liver I co en hos ho
hos ho lase lase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
89
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel'Known Gene Name Unigene Sequence.Cluster
= w Title
ID D Acc:-orCode
I N0.
NO. RefSeq
ID
':
No.
35581914 NM 022380g signal transducersignal transducer and
and activator activator of
of transcription transcription 5b
5b
355911454NM_022381c, Proliferating Proliferating cell nuclear
f, cell nuclear antigen
kk, antigen
tt
355911455NM 022381c, Proliferating Proliferating cell nuclear
f, cell nuclear antigen
jj, antigen
kk,
nn
3569402 NM 022403c, tryptophan-2,3-dioxygenasetryptophan-2,3-dioxygenase
I,
vv,
xx
357020915NM_022407b, Aldehyde dehydrogenaseAldehyde dehydrogenase
ff 1, 1, subfamily A1
subfamily A1
35714647 NM_022498h, Protein phosphataseProtein phosphatase
r, 1, catalytic 1, catalytic subunit,
w,
rr
subunit, gamma gamma isoform 1
isoform 1
35729183 NM 022499s, Parvalbumin (calciumParvalbumin (calcium
nn binding binding protein)
protein)
35742515 NM 022501ww cysteine-rich cysteine-rich protein
protein 2 2
35761347 NM 022506h, ribosomal proteinribosomal protein L31
I L31
35813027 NM 022514h, ribosomal proteinribosomal protein L27
w, L27
ee,
II,
as
35822696 NM 022515z, ribosomal proteinribosomal protein L24
General,L24
ee
35822697 NM 022515ee, ribosomal proteinribosomal protein L24
II L24
35938984 NM 022539ww methionine aminopeptidasemethionine aminopeptidase
2 2
359621062NM 022585c, ornithine decarboxylaseornithine decarboxylase
kk, antizyme inhibitor
tt,
ww antizyme inhibitor
359621063NM_022585ff ornithine decarboxylaseornithine decarboxylase
antizyme inhibitor
antizyme inhibitor
361117567NM 022672h, ribosomal proteinribosomal protein S14
gg, S14
hh
361324564NM 022676bb protein phosphataseprotein phosphatase
1, 1, regulatory (inhibitor)
regulatory (inhibitor)subunit 1A
subunit 1A
361717729NM 022697h, ribosomal proteinribosomal protein L28
v, L28
x
362124344NM 022701pp flotillin 1 flotillin 1
363024838NM 022924tt coagulation factorcoagulation factor II
II
363519669NM 022944x SH2-containing SH2-containing inositol
inositol phosphatase 2
phosphatase 2
364115727NM 022953g SIit1 SIit1
36474228 NM 023950a RAB7, member RAS RAB7, member RAS oncogene
oncogene family
family
364921238NM 024125t, Liver activating Liver activating protein
ff protein (LAP, (LAP, also NF-IL6,
also NF-IL6, nuclearnuclear factor-IL6,
factor-IL6, previously designated
previously designatedTCFS)
TCFS)
364921239NM 024125d, Liver activating Liver activating protein
I, protein (LAP, (LAP, also NF-IL6,
z
also NF-IL6, nuclearnuclear factor-IL6,
factor-IL6, previously designated
previously designatedTCFS)
TCFS)
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Attorney
Docket
No._44921-51137N0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc: Code
Nb. or
N0. RefSeq
ID
No. _ : .
3650352 NM_024127s, DNA-damage-inducibleDNA-damage-inducible
General transcript 1
transcript 1
3650353 NM 024127n, DNA-damage-inducibleDNA-damage-inducible
z, transcript 1
General,transcript 1
ee,
kk,
qq,
ww
3650354 NM 024127n, DNA-damage-inducibleDNA-damage-inducible
r, transcript 1
General,transcript 1
qq,
vv
365217226NM 024131b, D-dopachrome tautomeraseD-dopachrome tautomerase
ff,
vv
365217227NM 024131b, D-dopachrome tautomeraseD-dopachrome tautomerase
f,
ff,
vv
3653851 NM 024132c, fatty acid amide fatty acid amide hydrolase
kk hydrolase
36541598 NM 024134f, DNA-damage inducibleDNA-damage inducible
I, transcript 3
o,
p,
q,
General,transcript 3
cc,
dd,
kk,
II,
qq
36561878 NM 024138cc guanine nucleotideguanine nucleotide binding
binding protein (G
protein (G protein),protein), gamma 7 subunit
gamma 7
subunit
365720801NM 024148m, apuriniclapyrimidinicapuriniclapyrimidinic
cc, endonuclease 1
oo,
uu, endonuclease 1
ww
3661561 NM 024156nn annexin VI annexin VI
366222079NM 024157a, complement factorcomplement factor I
General,I
uu,
vv
36644655 NM 024346a Scgn101ike-proteinSc n101ike-protein
366517764NM 024351h, heat shock 70kD heat shock 70kD protein
I, protein 8 8
w,
uu
366517765NM 024351I heat shock 70kD heat shock 70kD protein
protein 8 8
366715350NM 024356p GTP cyclohydrolaseGTP cyclohydrolase 1
1
36681146 NM 024359a, hypoxia induciblehypoxia inducible factor
m factor 1, alpha 1, alpha subunit
subunit
36681148 NM 024359a hypoxia induciblehypoxia inducible factor
factor 1, alpha 1, alpha subunit
subunit
367020772NM_024363c, heterogeneous heterogeneous nuclear
v, nuclear ribonucleoproteins
oo
ribonucleoproteinsmethyltransferase-like
2 (S. cerevisiae)
methyltransferase-like
2 (S.
cerevisiae)
367320380NM 024381o Glycerol kinase Glycerol kinase
368119993NM 0243980, mitochondria) mitochondria) aconitase
xx aconitase (nuclear(nuclear aco2 gene)
aco2 ene)
36851835 NM 024483a adrenergic receptor,adrenergic receptor,
alpha 1d alpha 1d
368621039NM 024484ii aminolevulinic aminolevulinic acid
acid synthase synthase 1
1
36971928 NM 030872z, pyruvate dehydrogenasepyruvate dehydrogenase
General,kinase kinase 2 subunit
ee, 2 subunit p45 p45 (PDK2)
kk (PDK2)
369917377NM 030989jj Tumor protein Tumor protein p53 (Li-Fraumeni
p53 (Li-Fraumeni syndrome)
s ndrome
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
91
TABLE
1
-
Attorney
Docket
No.
44921-5113W0
Document
No.
X926271.:2
SE4 GLGCGenBank Model Known Gene Name Unigene $equenee Cluster
Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No.
370691 NM 031006II adenosine deaminaseadenosine deaminase RNA-specific
RNA-
specific
371015682NM 031011a S-AdenosylmethionineS-Adenosylmethionine
decarboxylase 1
decarboxylase
1
371015683NM 031011kk, S-AdenosylmethionineS-Adenosylmethionine
oo decarboxylase 1
decarboxylase
1
371215700NM 031013k l iver multidrug liver multidrug resistance-associated
resistance- protein
associated protein6
6
3721626 NM_031032b, glia maturation glia maturation factor
h, factor beta beta
m,
s,
x,
General,
dd,
00
37337351NM 031059g homeo box, msh-likehomeo box, msh-like 1
1
3734400 NM 031062jj, mevalonate pyrophosphatemevalonate pyrophosphate
ww decarboxylase
decarboxylase
373521701NM 031063jj mevalonate kinasemevalonate kinase
373611849NM 031065j, ribosomal proteinribosomal protein L10a
z, L10a
General,
II
37441376NM 031094a Retinoblastoma-relatedRetinoblastoma-related
gene gene
374920462NM 031102h, ribosomal proteinribosomal protein L18
m L18
375119268NM 031104gg, ribosomal proteinribosomal protein L22
hh L22
375724615NM 031112Generalribosomal proteinribosomal protein S24
S24
37591579NM_031117c, SNRPN upstream small nuclear ribonucleoparticle-
associated
oo, reading
ww
frame, small protein (snRNP) mRNA,
nuclear clone Sm51
ribonucleoparticle-associated
protein (snRNP)
mRNA, clone
Sm51
377516157NM 0312350o three-PDZ containingthree-PDZ containing
protein protein similar to C.
similar to C. elegans PAR3 (partitioning
elegans PAR3 defect)
(partitioning
defect)
37791857NM 0313150, acyl-C0A thioesteraseacyl-CoA thioesterase
xx 1, 1, cytosolic
cytosolic
378015661NM 031318a, t-complex testist-complex testis expressed
b, expressed 1 1
m,
uu,
vv
378015662NM 031318m, t-complex testist-complex testis expressed
Generalexpressed 1 1
378015663NM 031318m t-complex testist-complex testis expressed
expressed 1 1
37834234NM_031330m, argininosuccinateheterogeneous nuclear
ff lyase, ribonucleoprotein
heterogeneous AIB
nuclear
ribonucleoprotein
AIB
379315608NM 031355n mitochondria) mitochondria) voltage
voltage dependent anion
dependent anion channel 3
channel 3
379524645NM 031502a, Amylase 1 Amylase 1
d,
k,
I,
dd,
uu
379824410NM 031511g Insulin-like Insulin-like growth factor
growth factor II (somatomedin A)
II
(somatomedin
Aj
38011783NM 0315210o Cell adhesion Cell adhesion molecule,
molecule, neuralneural (CD56)
CD56
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
92
TABLE
1
Attorney
Docket
No.
44927-5113W0
Document
No.19262712
SEQGLGC GenBankModel Knowri: Gene NameJnigene Sequence Cluster
Title
ID ID Acc. Code
NO. or
N0. RefSeq
ID
No.
380616047NM 031541j, CD36 antigen (collagenCD36 antigen (collagen
General,type I type I receptor,
II receptor, thrombospondinthrombospondin receptor)-like
1 (scavanger
receptor)-like receptor class B type
1 (scavanger 1 )
receptor class
B tvpe 1)
38081504 NM 031544a, Adenosine monophosphateAdenosine
I, m onophosphate deaminase
3
General,deaminase 3
uu
380918389NM 031545gg, Brain natriureticBrain natriuretic factor
hh factor
381028 NM 031546v, Regucalcin Regucalcin
rr
381315411NM 0315590, Carnitine palmitoyltransferaseCarnitine
y, 1 almitoyltransferase 1
ff p alpha, liver
alpha, liver isoformisoform
381418315NM 031561o CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinthrombospondin receptor)
receptor)
381418316NM_031561o CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinthrombospondin receptor)
receptor)
381418317NM_031561o CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinthrombosp0ndin receptor)
receptor)
381418318NM_031561j CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinhrombospondin receptor)
t
receptor)
381418319NM 031561o CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinhrombospondin receptor)
t
receptor)
381425139NM 031561o CD36 antigen (collagenCD36 antigen (collagen
type I type I receptor,
receptor, thrombospondinhrombospondin receptor)
t
receptor)
381516164NM 031563h, nuclease sensitivenuclease sensitive element
m, element binding protein 1
n,
Generalbindin protein
1
382024219NM 031579n, protein tyrosine protein tyrosine phosphatase
Generalphosphatase 4a1
4a1
38211444 NM 031583ww chondroitin sulfatechondroitin sulfate proteoglycan
proteoglycan 6
6
3822405 NM_031587f, peroxisomal membraneperoxisomal membrane
k, protein protein 2, 22 kDa
w,
cc
2, 22 kDa
38245496 NM 031589e, glucose-6-phosphatase,glucose-6-phosphatase,
k, transport protein 1
I,
m,
General,transport protein
1
dd,
qq,
ss
38245497 NM 031589a, glucose-6-phosphatase,lucose-6-phosphatase,
k, g transport protein 1
I,
qq
transport protein
1
382621843NM_031594e, purinergic receptorpurinergic receptor P2X,
ee, P2X, ligand- ligand-gated ion
tt,
ww gated ion channelhannel 4
4 c
382919344NM 031603ee tyrosine 3- t yrosine 3-monooxygenase/tryptophan
5-
monooxygenaseltryptophanmonooxygenase activatioprotein,
5- epsilon
monooxygenase olypeptide
p
activatioprotein,
epsilon
of a tide
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
AR
TABLE
1
Attorney
Docket
No.=44921-5113W0
Document
No.1926271.2
SE GLGC GenBankModel-Known Gene Name Un(gene Sequence Cluster=Title
- Q
ID D _ Code
I N0. Acc~
or
N0. RefSeq
ID
No.
383211296NM_031606b, phosphatase and phosphatase and tensin
m, tensin homolog (mutated
General,homolog (mutated n multiple advanced cancers
in multiple i 1)
oo, advanced cancers
ww, 1)
xx
383211297NM 031606ss phosphatase and phosphatase and tensin
tensin homolog (mutated
homolog (mutated n multiple advanced cancers
in multiple i 1)
advanced cancers
1)
383319023NM 031609cc Neuroblastoma, Neuroblastoma, suppression
suppression of of
tumorigenicity tumorigenicity 1 (DNA
1 (DNA segment segment human
human D1S1733E) D1S1733E)
383412132NM 031612ss apelin apelin
383524235NM 031614uu thioredoxin reductasethioredoxin reductase
1 1
38361925 NM 031616a, zinc fin er proteinzinc fin er protein 265
265
384015767NM 031623n, growth factor growth factor receptor
y, receptor bound bound protein 14
z,
General,protein 14
dd
384220940NM 031629y, proteasome (prosome,proteasome (prosome,
nn macropain) subunit,
macropain) subunit,beta type, 4 ,
beta type, 4
384220941NM 031629bb proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type, 4
beta type, 4
384220942NM 031629mm proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type, 4
beta type, 4
38446554 NM 031640f plasma glutamate plasma glutamate carboxypeptidase
carboxypeptidase
384718368NM 031648k FXYD domain-containingFXYD domain-containing
ion ion transport
transport regulatorregulator 1
1
384718369NM 031648s FXYD domain-containingFXYD domain-containing
ion ion transport
transport re ulatorregulator 1
1
3849866 NM_031657gg, G protein-coupledG protein-coupled receptor
hh, receptor kinase 6
pp
kinase 6
385124881NM_031663pp solute carrier solute carrier family
family 18 18 (vesicular
(vesicular monoamine),monoamine), member 3
member
3
38535358 NM 031675t, Actinin, alpha Actinin, alpha 4
ee, 4
mm
385515823NM 031680g pyrimidinergic pyrimidinergic receptor
receptor P2Y, P2Y, G-protein
G-
protein coupled, coupled, 4
4
38581004 NM 031685m, golgi SNAP receptorgolgi SNAP receptor complex
x, complex member 2
dd
member 2
386121575NM 031698xx ribophorin II ribophorin II
386320404NM 031700Generalclaudin 3 claudin 3
386320405NM 031700a, claudin 3 claudin 3
I,
General,
cc,
ss
3865811 NM 031705c, dihydropyrimidinasedihydropyrimidinase
s,
General,
II
3865812 NM 031705s, dih dro rimidinasedih dro rimidinase
oo
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
94
TABLE
1
Attorney
Docket
No44921-5113W0
Document
No.1926271.2
SEQGLGC CenBankMode) Known Gene Name UntgeneSequence Cluster
Title -
ID ID Ace. Code
N0. or
~
N0. RefSeq
1D
No.
386616204NM 031706, x, ibosomal proteinribosomal protein S8
I r S8
General
386718055NM 031707nn RuvB-like proteinRuvB-like protein 1
1
386718056NM 031707c RuvB-like proteinRuvB-like protein 1
1
386921693NM 031714p, tt heat-responsive heat-responsive protein
protein 12 12
38701339 NM 031715e, bb phosphofructokinase,phosphofructokinase,
muscle muscle
387119049NM_031719a chloride channel,chloride channel, nucleotide-
sensitive,
nucleotide- 1A
sensitive,1A
387119050NM 031719e, p chloride channel,chloride channel, nucleotide-
sensitive,1A
nucleotide-
sensitive,1A
387323883NM_031731n, General,alcohol dehydrogenasealcohol dehydrogenase
family 3, family 3, subfamily
ee subfamily A2 A2
387323884NM 031731ii alcohol dehydrogenasealcohol dehydrogenase
family 3, family 3, subfamily
subfamily A2 A2
38761214 NM 031741z, jj nuclear receptorsolute carrier family
subfamily 1, 2 (facilitated glucose
group H, member transporter), member
4, solute 5
carrier family
2 (facilitated
glucose transporter),
member 5,
synaptojanin
2 binding protein
388111611NM 031756w gamma-glutamyl gamma- lutamyl carboxylase
carboxylase
388716115NM 031775bb caspase 6 caspase 6
389515864NM_031797x Kangai 1 (suppressionESTs, Kangai 1 (suppression
of of
tumorigenicity tumorigenicity 6, prostate;
6, prostate; CD82 antigen (R2
CD82
antigen (R2 leukocyteleukocyte antigen, antigen
antigen, detected by
antigen detectedmonoclonal and antibody
by monoclonal IA4))
and antibody
IA4))
390322321NM 031832f, j, lectin, galactoselectin, galactose binding,
binding, solublesoluble 3
General,3
ss
391316726NM 031855General,Ketohexokinase Ketohexokinase
dd
391519190NM 031969s Calmodulin 1 Calmodulin 1 (phosphorylase
(phosphorylase kinase, delta)
kinase, delta)
391519193NM_031969I, dd Calmodulin 1 Calmodulin 1 (phosphorylase
(phosphorylase kinase, delta)
kinase, delta)
391519195NM 031969c Calmodulin 1 Calmodulin 1 (phosphorylase
(phosphorylase kinase, delta)
kinase, delta) i
391519196NM_031969rr Calmodulin 1 Calmodulin 1 (phosphorylase
(phosphorylase kinase, delta)
kinase, delta)
391525802NM 031969c, x Calmodulin 1 Calmodulin 1 (phosphorylase
(phosphorylase kinase, delta)
kinase, delta)
391716865NM 031973a, cc, dipeptidyl peptidasedipeptidyl peptidase
uu 7 7
391817075NM 031974I, General,clathrin light clathrin light chain
chain
kk,
II,
ss
392017601NM_031976ww 5'-AMP-activated5'-AMP-activated protein
protein kinase, kinase, beta
beta subunit subunit
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
TABLE
1
Attorney
Docket
No.?44921-5113W0
Document
No.1926271:2
SEQ GL:GCGenBank Model Known Gene Name:Unigene Sequence Cluster
. Title
ID D Acc..or Code
-. NO. '
I
N0. RefSeq
- ID
No.
39215470NM 031978u, 26S proteasome, 26S proteasome, subunit
1 mm subunit p112 p112
392418501NM 031984s, cerebellar Ca-bindingcerebellar Ca-binding
v, protein, protein, spot 35
mm,
xx spot 35 protein protein
392720554NM 031987o carnitine 0-octanoyltransferasecarnitine 0-
octanoyltransferase
392720555NM 031987o carnitine 0-octanoyltransferasecarnitine 0-
octanoyltransferase
392818640NM 032057p, Inositol (myo)-1Inositol (myo)-1 (or
ee (or 4)- 4)-monophosphatase 1
monophosphatase
1
3932590 NM 032080b, glycogen synthaseglycogen synthase kinase
c, kinase 3 3 beta
m,
kk
b eta
3932591 NM 032080b, glycogen synthaseglycogen synthase kinase
c, kinase 3 3 beta
I,
z,
General,beta
tt,
vv
393517474NM 032614a thioredoxin-likethioredoxin-like 2
2
393720490NM_032617II RAB11 B, member RAB11 B, member RAS oncogene
RAS family
oncogene family
39431409NM 033349t, Hydroxyacyl glutathioneHydroxyacyl glutathione
jj hydrolase
hydrolase
394412363NM 0333510o Fc fragment immunoglobulinFc fragment immunoglobulin
G G receptor
receptor
394412364NM_033351o Fc fragment immunoglobulinFc fragment immunoglobulin
G G receptor
receptor
394623895NM 033485tt Prostate apoptosisProstate apoptosis response
response protein 4
protein 4
39481423NM 052801mm von Hippel-Lindauvon Hippel-Lindau syndrome
syndrome
39481424NM 052801ww von Hippel-Lindauvon Hippel-Lindau syndrome
syndrome
395025024NM 052809b, cytosolic cysteinecytosolic cysteine dioxygenase
o, dioxygenase 1
vv 1
395015028NM 052809b, cytosolic cysteinecytosolic cysteine dioxygenase
qq, dioxygenase 1
vv 1
3951412 NM 053288y Orosomucoid 1 Orosomucoid 1
39531524NM 053293GeneralGlutathione S-transferaseGlutathione S-transferase
1 1 (theta)
(theta) '
39541187NM 053295t Calpastatin Calpastatin
395615749NM_053309cc homer, neuronal homer, neuronal immediate
immediate early gene, 2
early ene, 2
395615750NM 053309a homer, neuronal homer, neuronal immediate
immediate early gene, 2
early gene, 2
395615751NM 053309x homer, neuronal homer, neuronal immediate
immediate early gene, 2
early ene, 2
395717473NM_053319pp, dynein, cytoplasmic,dynein, cytoplasmic,
tt light chain light chain 1
1
395925480NM 053329x insulin-like insulin-like growth factor
growth factor binding protein,
binding
protein, acid acid labile subunit
labile subunit
396214934NM 053337m, Msx-interacting-zincMsx-interacting-zinc
x, finger finger
II,
ww
396418949NM 053345f general transcriptiongeneral transcription
factor Ila, factor Ila, 2 (12kD
2
(12kD subunit) subunit)
3968623 NM 053369' transcri tion transcri tion factor
factor 4 4
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
96
TABLE
1
Attorney
Docket
No.
44921-5113WQ
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
' Title ; '~
ID;:fD' Acc, Code:
NO. or
NO _ RefSeq
ID
No.
39703844 NM 053371j fractured callus fractured callus expressed
expressed transcript 1
transcript 1
398222586NM 053469a, hepcidin antimicrobialhepcidin antimicrobial
n, peptide peptide
y
398321866NM 053472s cytochrome c oxidase,cytochrome c oxidase,
subunit subunit IVb
IVb
39902016 NM 053527d CDC5 (cell divisionCDC5 (cell division
cycle 5, S. cycle 5, S. pombe,
pombe, homology-likehomology-like
400110986NM 053571c, regucalcin gene regucalcin gene promotor
I, promotor region region related
m,
Generalrelated protein protein
400219252NM 053576x peroxiredoxin peroxiredoxin 5
5
400421154NM 053584m, golgi SNAP receptorgolgi SNAP receptor
z, complex complex member 1
dd,
ee member 1
401615925NM_053607m long-chain fatty long-chain fatty acid
acid coenzyme coenzyme A ligase 5
A ligase 5
401720243NM 053615ff casein kinase casein kinase 1, alpha
1, alpha 1 1
40183062 NM 053617a, carboxypeptidase carboxypeptidase B2
cc B2 (plasma) (plasma)
4019926 NM 053619g complement componentcomplement component
5, 5, receptor 1
receptor 1
4021659 NM 053622q nuclear pore membranenuclear pore membrane
glycoprotein 121 kD
glycoprotein 121
kD
402523305NM 053638jj isocitrate dehydrogenaseisocitrate dehydrogenase
3 3 (NAD+) alpha
(NAD+) alpha
40291120 NM 053655g, dynamin 1-like dynamin 1-like
n
403813369NM 053742v phosphotidylinositolphosphotidylinositol
transfer transfer protein, beta
protein, beta
403910512NM 053743k, CDC37 (cell divisionCDC37 (cell division
mm cycle 37, S. cycle 37, S. cerevisiae,
cerevisiae, homologyhomology
404115376NM 053747x, ubiquilin 1 ubiquilin 1
General,
kk
40447927 NM 053765e, UDP-N-acetylglucosamine-2-UDP-N-acetylglucosamine-2-
epimerase/N-
t
epimerase/N- acetylmannosamine kinase
acetylmannosamine
kinase
404615995NM_053769r, protein tyrosine protein tyrosine phosphatase,
ff phosphatase, non-receptor
non-receptor typetype 16
16
404615996NM 053769n, protein tyrosine protein tyrosine phosphatase,
ff, phosphatase, non-receptor
kk
non-receptor typetype 16
16
404615997NM 053769d, protein tyrosine protein tyrosine phosphatase,
n, phosphatase, non-receptor
r,
w,
y
non-receptor typetype 16
16
4080794 NM 053902I kynureninase(L-kynureninekynureninase (L-kynurenine
hydrolase)
hydrolase)
408217937NM 053911ss, pleckstrin homology,pleckstrin homology,
uu Sec7 and Sec7 and coiledlcoil
coiledlcoil domainsdomains 2
2
408515857NM 053948b, polymerase (RNA) polymerase (RNA) II
e, II (DNA (DNA
bb,
oo, directed)polypeptidedirected)polypeptide
ww G G
409019991NM 053961cc mitochondria) mitochondria) aconitase
aconitase (nuclear(nuclear aco2 gene)
aco2 ene
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
97
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigepe Sequence Cluster
: Title '
lD ID Acc. Code
N0. or
NO: RefSeq
ID
No.
410822849NM 057099c proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type 6
beta type 6
41119527 NM 057104c, ectonucleotide ectonucleotide
q,
General,jjpyrophosphataselphosphodiestpyrophosphataselphosphodiesterase
2
erase 2
41125492 NM 057105a UDP glycosyltransferaseESTs, UDP glycosyltransferase
1 1 family,
family, polypeptidepolypeptide A6
A6
41125493 NM 057105a UDP glycosyltransferaseESTs, UDP glycosyltransferase
1 1 family,
family, polypeptidepolypeptide A6
A6
411215124NM_057105jj UDP glycosyltransferaseUDP glycosyltransferase
1 1 family,
family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase
1
glycosyltransferasefamily, polypeptide
1 family, A7, UDP-
polypeptide A7, glucuronosyltransferase
UDP- 1 family, member 1
glucuronosyltransferase
1
family. member
1
411215126NM_057105t, UDP glycosyltransferaseUDP glycosyltransferase
jj 1 1 family,
family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase
1
glycosyltransferasefamily, polypeptide
1 family, A7, UDP-
polypeptide A7, glucuronosyltransferase
UDP- 1 family, member 1
glucuronosyltransferase
1
family. member
1
411215127NM 057105k, UDP glycosyltransferaseUDP glycosyltransferase
t, 1 1 family,
General,family, polypeptidepolypeptide A6, UDP
A6, UDP glycosyltransferase
1
mm glycosyltransferasefamily, polypeptide
1 family, A7, UDP-
polypeptide A7, glucuronosyltransferase
UDP- 1 family, member 1
glucuronosyltransferase
1
family. member
1
41133743 NM 057107nn fatty acid Coenzymefatty acid Coenzyme
A ligase, A ligase, long chain
3
long chain 3
412119834NM_057139v transporter protein;transporter protein;
system N1 system N1 Na+ and H+-
Na+ and H+-coupledcoupled glutamine transporter
glutamine
transporter
412615408NM 057197rr 2,4-dienoyl CoA 2,4-dienoyl CoA reductase
reductase 1, 1, mitochondria)
mitochondria)
412615409NM 057197ff, 2,4-dienoyl CoA 2,4-dienoyl CoA reductase
ii, reductase 1, 1, mitochondria)
jj
mitochondria)
413224653NM 080580a RAB3D, member RAB3D, member RAS oncogene
RAS family
oncogene family
413317956NM_080583m, adaptor-related adaptor-related protein
vv protein complex complex 2, beta 1
2, beta 1 subunitsubunit
413317958NM 080583ff, adaptor-related adaptor-related protein
xx protein complex complex 2, beta 1
2, beta 1 subunitsubunit
413416108NM 080585d, N-ethylmaleimide N-ethylmaleimide sensitive
q, sensitive fusion protein
gg,
hh fusion protein attachment protein alpha
attachment
protein alpha
413416109NM 080585e, N-ethylmaleimide N-ethylmaleimide sensitive
q sensitive fusion protein
fusion protein attachment protein alpha
attachment
rotein al ha
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
QR
TABLE
1
Attorney
Docket
No.
44921=5113W0
"Document
No.1926271.2
SEQ GLGCGenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
N0. or
N0. RefSeq
~ ID
No
~
4136 19831NM_080781b, coatomer protein coatomer protein complex,
q, complex, subunit beta 1
x,
dd
subunit beta 1
4138 25693NM 080783jj, alactose-4-epimerase,galactose-4-epimerase,
xx UDP UDP
4139 25799NM 080886a, sterol-C4-methyl sterol-C4-methyl oxidase-like
f, oxidase-like
n,
x,
cc,
ff,
jj,
uu
4139 21842NM 080886a, sterol-C4-methyl~oxidase-likesterol-C4-methyl oxidase-
like
f,
jj,
pp
4148 8167NM 130406q, Fas-associated Fas-associated factor
II factor 1 1
4154 13515NM_130430y proteasome (prosome,proteasome (prosome,
macropain) 26S
macropain) 26S subunit, non-ATPase,
subunit, non- 9
ATPase, 9
4156 14959NM_130734h, guanine nucleotideguanine nucleotide binding
x, binding protein (G
General,protein (G protein),protein), beta polypeptide
beta 2-like 1
dd, polypeptide 2-like
ee 1
4159 22220NM_130780vv Alcohol dehydrogenaseAlcohol dehydrogenase
(class (class I), alpha
I), alpha polypeptidepolypeptide
4165 25730NM 133290r, zinc finger proteinzinc finger protein
t 36 36
4166 20879NM 133295j carboxylesterase carboxylesterase 3
3
4167 19456NM_133298I, glycoprotein (transmembrane)glycoprotein
(transmembrane)
cc, nmb
qq,
uu nmb
4167 4048NM_133298I, glycoprotein (transmembrane)glycoprotein
(transmembrane)
cc, nmb
qq,
uu nmb
4167 4049NM 133298, cc, glycoprotein (transmembrane)lycoprotein
(transmembrane)
I tt, g nmb
uu
nmb
4184 2788NM 133528z, preimplantation preimplantation protein
ee protein 3 3
4222 21098NM 134432qq Angiotensinogen An iotensino en
4226 12215NM 138502o monoglyceride monoglyceride lipase
lipase
4228 16179NM 138508xx Sterol carrier Sterol carrier protein
protein 2, liver 2, liver
4228 16180NM_138508h, Sterol carrier Sterol carrier protein
I, protein 2, liver 2, liver
General,
dd,
jj,
00
4238 4822NM_138708m, Rab geranylgeranylRab geranylgeranyl transferase
1 s transferase
c omponenet, subunitcomponenet, subunit
beta beta
4240 6248NM_138827, mm Solute carrier Solute carrier family
1 t family 2 a 1 2 a 1 (facilitated
glucose
( facilitated glucosetransporter) brain
transporter)
b rain
4240 6249NM 138827p, Solute carrier Solute carrier family
1 ff family 2 a 1 2 a 1 (facilitated
glucose
( facilitated glucosetransporter) brain
transporter)
b rain
4240 6250M 138827mm olute carrier Solute carrier family
1 N S family 2 a 1 2 a 1 (facilitated
glucose
( facilitated glucosetransporter) brain
transporter)
b rain
4240 6251M 138827mm olute carrier Solute carrier family
1 N S family 2 a 1 2 a 1 (facilitated
glucose
( facilitated glucoseransporter) brain
transporter)
t
b rain
4241 6400M 138828m, polipoprotein Apolipoprotein E,
1 N x E,
A
4271 7203M_139099p A TP synthase, H+ ATP synthase, H+ transporting,
1 N p transporting,
mitochondrial mitochondrial F1 complex,
F1 complex, epsilon subunit
a silon subunit
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
AA
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document:
No.1926271.2
SEQ GLGCGeriBankModel Known Gene Name Unigene Sequence Cluster
Title
ID D:NO.Accor Code
I
NO. RefSeq
ID
No.
427117204NM_139099p, ATP synthase, ATP synthase, H+ transporting,
x, H+ transporting,
mm
mitochondria) mitochondria) F1 complex,
F1 complex, epsilon subunit
epsilon subunit
427217549NM_139100m, solute carrier solute carrier family
ee family 25 25 (mitochondria)
(mitochondria) carrier; adenine nucleotide
carrier; adenine translocator),
nucleotide translocator),member 3
member 3
43111382NM 147177c, RuvB-like proteinRuvB-like protein 1
e, 1
dd
43265624847122 bb, Fibronectin 1 Fibronectin 1
cc
43351471S68809 a S100 calcium bindingESTs, Highly similar
protein A1 to S10A RAT S-100
-
protein, alpha chain
[R.norvegicus]
435120431S81448 qq, Steroid-5-alpha-reductase,Steroid-5-alpha-reductase,
xx alpha
alpha polypeptidepolypeptide 1 (3-oxo-5
1 (3-oxo-5 alpha-steroid delta
4-
alpha-steroid dehydrogenase alpha
delta 4- 1)
dehvdroaenase
alpha 1)
436316675017565 ww mini chromosome mini chromosome maintenance
maintenance deficient 6
deficient 6 (S. (S. cerevisiae)
cerevisiae)
437715851042719 vv Complement componentComplement component
4 4
437819543044948 ww cysteine-rich cysteine-rich protein
protein 2 2
43901715072660 0, Ninjurin Ninjurin
mm
4404818 X02291 a, Aldolase B, fructose-Aldolase B, fructose-biphosphate
s,
ff,
qq,
tt, biphosphate
uu
440820715X07259 0, Cytochrome P450, Cytochrome P450, subfamily
xx subfamily IVB,
IVB, polypeptide polypeptide 1
1
441220597X12459 b, Ar inosuccinate Arginosuccinate synthetase
ff synthetase 1 1
4421575 X15734 a, S - adenosylmethionineS - adenosylmethionine
I synthetase
synthetase
442920427X53378 General,ribosomal proteinribosomal protein S13
II S13
443925702X58465 I Ribosomal proteinRibosomal protein S5
S5
443910109X58465 h, Ribosomal proteinRibosomal protein S5
I, S5
ee,
II
448319694248444 ee A disintegrin A disintegrin and metalloprotease
and domain
metalloprotease (ADAM) 10
domain
(ADAM) 10
448415569278279 bb procollagen, typeprocollagen, type I,
I, alpha 1 alpha 1
63 20995AA799724GeneralHMm:RNA polymeraseESTs, Highly similar
1-3 (16 to RPA9_MOUSE DNA-
kDa subunit) directed RNA polymerase
I 16 kDa
polypeptide (RPA16)
[M.musculus]
63 20996AA799724b, HMm:RNA polymeraseESTs, Highly similar
f, 1-3 (16 to RPA9_MOUSE DNA-
General,kDa subunit) directed RNA polymerase
I 16 kDa
kk, polypeptide (RPA16)
nn, [M.musculus]
qq
416 14138AA859700p, HMm:protoporphyrinogenESTs, Highly similar
General to PPOX_MOUSE
oxidase PROTOPORPHYRINOGEN OXIDASE
PPO M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1 (1(1
TABLE
1
Aftorraey
Docket
No.
44921-5113W0
Document
No.19262712
SE GLGCGenl3ankModel Known Gene Name Unigerie Sequence Cluster
_ Title
Q
ID D Accaor Code
= N0. '
I
NO. RefSeq
ID
No.
464 16074AA874874t HMm:alcohol dehydrogenaseESTs, Highly similar
5 to ADHX_RAT
ALCOHOL DEHYDROGENASE
CLASS III
(ALCOHOL DEHYDROGENASE
2)
(GLUTATHIONE-DEPENDENT
FORMALDEHYDE DEHYDROGENASE)
(FDH) (FALDH) (ALCOHOL
DEHYDROG NASE-B21 fR.norveai
sl
480 20389AA87504500 HMm:phosphodiesteraseESTs, Highly similar
6D, to CNRD_MOUSE
cGMP-specific, Retinal rod rhodopsin-sensitive
rod, delta cGMP 3',5'-
cyclic phosphodiesterase
delta-subunit
(GMP-PDE delta) fM.musculusl
483 21589AA875084y, HMmaransducin-likeESTs, Highly similar
nn enhancer to TLE4_RAT
of split 1, homologTransducin-like enhancer
of Drosophila protein 4 (ESP2
E(spp protein) fR.norveqicusl
552 9090AA891690h, HMmaumor necrosisESTs, Highly similar
s factor to tumor necrosis
(ligand) superfamily,factor (ligand) superfamily,
member 13 member 13 [Mus
musculusl f M.musculusl
668 11997AA892828II HMm:pyruvate dehydrogenaseESTs, Highly similar
to S15892 pyruvate
(lipoamide) beta dehydrogenase (lipoamide)
(EC 1.2.4.1)
beta chain - rat [R.norveqicusl
705 17754AA893246a, HMm:ATPase, H+ ESTs, Highly similar
w transporting, to VATD_MOUSE
lysosomal 34kD, Vacuolar ATP synthase
V1 subunit D subunit D (V-
ATPase D subunit) (Vacuolar
proton pump D
subunit) (V-ATPase 28
kDa accessory
protein) fM.musculusl
107624289AA955986t HMm:galactokinaseESTs, Highly similar
to GAL1 MOUSE
-
Galactokinase (Galactose
kinase)
[M.musculusl
109812000AA957319bb HMm:pyruvate dehydrogenaseESTs, Highly similar
to S15892 pyruvate
(lipoamide) beta dehydrogenase (lipoamide)
(EC 1.2.4.1)
beta chain - rat (R.norveqicusl
11262308AA964227I, HMm:methylenetetrahydrofolateESTs, Highly similar
General to A33267
dehydrogenase methylenetetrahydrofolate
(NAD+ dehydrogenase
dependent), (NAD+) (EC 1.5.1.15)
/
methenyltetrahydrofolatemethenyltetrahydrofolate
cyclohydrolase (EC
cyclohydrolase 3.5.4.9) precursor-
mouse [M.musculus]
128420214AF091567xx olfactory receptorolfactory receptor 41
41
128520236AF091570cc olfactory receptorolfactory receptor 41
41
128625222AF091574g olfactory receptorolfactory receptor 41
41
133615452A1009484s HMm:gelsolin ESTs, Highly similar
to GELS_MOUSE
Gelsolin (Actin-depolymerizing
factor) (ADF)
(Brevin) [M.musculusl
145621302A1013297o HMm:NADH dehydrogenaseESTs, Moderately similar
to NADH
(ubiquinone) Fe-Sdehydrogenase (ubiquinone)
protein 4 Fe-S protein 4;
NADH dehydrogenase (ubiquinone)
Fe-S
protein 4 (18 kDa) [Mus
musculus]
M.mu ulu
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1f11
TABLE
1
'
Attorriey
Docket
No.
44921-5113W0
Document
No.1926271,2
SEQ GLGC GenBankModel Known Gene Name- Unigene Sequence Cluster
Title
ID D Acc. Code
I NO, or- -'
N0. RefSeq
== ID
No.
15657935 A1043945GeneralHMm:ferrochelataseESTs, Highly similar
to A37972
ferrochelatase (EC 4.99.1.1)
precursor-
mouse fM.musculusl
18099421 A1072885pp HMm:inositol polyphosphate-1-ESTs, Moderately similar
to INPP_MOUSE
phosphatase Inositol polyphosphate
1-phosphatase
(IPPase) (IPP) [M.musculusl
202023788AI137176ss HMm:alpha-N- ESTs, Moderately similar
to alpha-N-
acetylglucosaminidaseacetylglucosaminidase
(Sanfilippo disease
(Sanfilippo diseaseIIIB); alpha-N-acetylglucosaminidase,
IIIB)
Ivsosomal [Mus musculusl
fM.musculusl
22595876 AI1761170o HMm:pyruvate dehydrogenaseESTs, ESTs, Highly similar
to S15892
(lipoamide) beta pyruvate dehydrogenase
(lipoamide) (EC
1.2.4.1) beta chain -
rat R.norvegicusl
23874279 AI178808k HMm:interleukin ESTs, Highly similar
2 receptor, to 149280 interleukin-2
gamma chain receptor gamma chain
precursor - mouse
[M.musculusl
268916781AI234527II, HMm:glutathione ESTs, Highly similar
qq S-transferase, to S23433 glutathione
alpha 4 transferase (EC 2.5.1.18)
8 - rat
[R.norvegicusl
286020082AI639488h, HMmaransformed ESTs, Highly similar
r, mouse 3T3 to A42772 mdm2
General,cell double minuteprotein - rat (fragments)
ii 2 [R.norvegicus]
287814882D00362 w, Esterase 2 Esterase 2
II,
rr
29284378 H32966 y HMm:Tnf receptor-associatedESTs, Highly similar
to 161512 TNF receptor
factor 2 associated factor 2 -
mouse [M.musculus]
299714881M20629 j, Esterase 2 Esterase 2
dd,
II
30341379 M83676 qq, RAB12, member RAB12, member RAS oncogene
vv RAS oncogene family
family
318318694NM_012931mm v-crk-associated v-crk-associated tyrosine
tyrosine kinase kinase substrate
substrate
3194709 NM 012968h Interleukin 1 Interleukin 1 receptor
receptor accessoryaccessory protein
protein
32049917 NM 012993qq N-arginine dibasicN-arginine dibasic convertase
convertase 1 1
32049918 NM 012993II N-arginine dibasicN-arginine dibasic convertase
convertase 1 1
320724718NM_013003tt PhosphatidylethanolaminePhosphatidylethanolamine
N- N-
methyltransferasemethyltransferase
322314421NM 013053o Tyrosine 3- Tyrosine 3-monooxygenase/tryptophan
5-
monooxygenaseltryptophanmonooxygenase activation
5- protein, theta
monooxygenase polypeptide
activation
protein, theta
polvpeptide
3313923 NM 017076f, Tumor-associated Tumor-associated glycoprotein
I, glycoprotein pE4
n,
p,
kk, pE4
xx
336118050NM 017204nn microtubule-associatedmicrotubule-associated
protein protein 6
6
3399707 NM 017293b kinase interacting- kinase interacting
with leukemia with leukemia-associated
associated ene ene stathmin
stathmin
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
Ana
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document:No.1926271.2
SEQ GLGGGenBank Model Kriowri Gene Namenigene Sequence Cluster
U Title
ID D. Acc: Code
> N0. or =
I
N0.- RefSeq
ID
No. __
34752439NM 019277m, SEC15 homolog SEC15 homolog (S. cerevisiae)
ss (S. cerevisiae)
3562695 NM 022388y corticosteroid-inducedcorticosteroid-induced
protein protein
36698879NM_024360a hairy and enhancerhairy and enhancer of
of split 1, split 1, (Drosophila)
( Drosophila)
383167 NM 031605cc cytochrome P450, cytochrome P450, 4a10
4a10
386016664NM 031695v sialyltransferasesialyltransferase 5
5
386816918NM 031709x, ribosomal proteinribosomal protein S12
z, S12
ee,
gg,
hh,
II
395520235NM_053302bb adrenomedullin ESTs, Weakly similar
receptor to dual-specificity
phosphatase [Mus musculus]
[M.musculus]
41171888NM 057130n, BH3 interacting BH3 interacting (with
bb (with BCL2 BCL2 family) domain,
f amily) domain, apoptosis agonist
apoptosis
agonist
41851394NM_133536I, RAB3C, member RAB3C, member RAS oncogene
v, RAS family
xx
oncogene family
43051448NM_1457830o HMm:cytochrome Rat CoxVa mRNA for mitochondria)
c oxidase,
subunit Va cytochrome c oxidase
subunit Va
435313520S87522 c HMm:leukotriene ESTs, Highly similar
A4 hydrolase to S20444 leukotriene-
A4 hydrolase (EC 3.3.2.6)
- rat
[R.norvegicus]
444916780X62660 b, HMm:glutathione ESTs, Highly similar
m, S-transferase, to S23433 glutathione
qq,
vv alpha 4 transferase (EC 2.5.1.18)
8 - rat
[R.norvegicus]
6 6049AA685178a, ESTs, Highly similar
General, to T30827 nascent
cc, polypeptide-associated
rr complex alpha chain,
non-muscle splice form
- mouse
f M.musculusl
16 22646AA799301r ESTs, Highly similar
to LIGA_MOUSE
Ligatin [M.musculus]
22 6581AA799412v ESTs, Weakly similar
to 167424 hERR-2
homolo - rat (fra ment)
(R.norvegicus]
32 6505AA799499p ESTs, Moderately similar
to RIKEN cDNA
2700033116 [Mus musculus]
[M.musculus]
34 16942AA799520ee ESTs, Highly similar
to ITMB_MOUSE
Integral membrane protein
2B (E25B
protein) [M.musculus]
35 21120AA799526pp ~ ESTs, Highly similar
to RIKEN cDNA
1700043E15 Mus musculus]
[M.musculus]
40 16959AA799550a ESTs, Moderately similar
to RIKEN cDNA
9130413122 [Mus musculus]
[M.musculus]
52 20093AA799637a ESTs, Weakly similar
to A55071 hydrogen
peroxide-inducible protein
hic-5 - mouse
(M.musculus]
53 18226AA799641u, ESTs, Moderately similar
rr, to 153063 testicular
ss
tumor overexpressed
protein - mouse
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~n~
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document-No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence: Cluster
Title
ID D Acc. Code
I N0. or
NO. RefSeq
ID
_ No. .
76 18880AA799801bb, ESTs, Moderately similar
ii to predicted gene
I CRFP703B1614Q5.6;
I CRFP703N2430Q5.6; C11orf17
[Mus
musculusl ~M.musculusl
87 18378AA799888bb ESTs, Highly similar
to nuclear localization
signal protein absent
in veto-cardio-facial
patients [Mus musculus]
[M.musculusl
90 15011AA799893I, ESTs, Highly similar
s, to DDRT helix-
z,
kk,
nn destabilizin protein
- rat [R.norve icus]
95 18881AA799992a, ESTs, Moderately similar
d to predicted gene
ICRFP703B1614Q5.6;
ICRFP703N2430Q5.6; C11orf17
[Mus
musculusl [M.musculusl
95 18883AA799992a ESTs, ESTs, Moderately
similar to predicted
gene ICRFP703B1614Q5.6;
ICRFP703N2430Q5.6; C11orf17
[Mus
musculusl [M.musculusl
96 2098AA799995I ribosomal proteinribosomal protein L14
L14
106 21064AA800175m, ESTs, Highly similar
ww to JC7136 peptidylprolyl
isomerase (EC 5.2.1.8)
- mouse
[M.musculus]
110 15659AA800199ss ESTs, Weakly similar
to 839066 proline-rich
protein 15 - rat [R.norve
icus]
116 18442AA800258f, ESTs, Moderately similar
pp, to low density
ww
lipoprotein B [Mus musculus]
[M.musculus]
133 16463AA800663k ESTs, Highly similar
to RAN binding protein
16 [Mus musculus] [M.musculus]
158 22025AA800849ss ESTs, Moderately similar
to 0806162L
protein URF5 [Mus musculus]
[M.musculus]
168 23115AA801165d Testis-specific Testis-specific histone
histone 2a 2a
175 1397AA817787s, ESTs, Highly similar
General to potassium channel
modulatory factor DEBT-91;
clone DEBT-91
[Mus musculus [M.musculus]
188 2431AA817945ff ESTs, Highly similar
to TBCA_MOUSE
TUBULIN-SPECIFIC CHAPERONE
A
(TUBULIN-FOLDING COFACTOR
A) (CFA)
(TCP1-CHAPERONIN COFACTOR
A)
IM.musculusl
193 2845AA818026h ESTs, Weakly similar
to PSD7_MOUSE 26S
proteasome non-ATPase
regulatory subunit
7 (26S proteasome regulatory
subunit S12)
(Proteasome subunit
p40) (Mov34 protein)
IM.musculusl
198 3275AA818112f, ESTs, Weakly similar
uu to neugrin; neurite
outgrowth associated
protein [Mus
musculusl [M.musculus]
213 14123AA818554g R.norvegicus mRNA for
tropomyosin isoform
6
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
104
TX~BLE
1
Attorriey
Docket
No.
4492~Ir5113WQ
Document
No:1926271:2
SEQGLGC GenBankModel Known Gene Name tJnigene Sequence Cluster
Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No. .
2254491 AA818798xx Rattus norvegicus mRNA
for cathepsin Y,
partial cds
23511978AA819129b ESTs, Moderately similar
to S27161
glutathione transferase
(EC 2.5.1.18) 5 - rat
fR.norvegicusl
2376329 AA819259j, ESTs, Moderately similar
p to S31799
apolipoprotein C2 precursor-
mouse
[M.musculusl
2399000 AA819318r ESTs, Highly similar
to JC4141 YL-1 protein
mouse [M.musculus]
2485169 AA819488I, ESTs, Weakly similar
General to 834488 calpain (EC
3.4.22.17) large chain
3 - rat [R.norvegicus]
26019451AA819788II ESTs, Weakly similar
to 28kD interferon
alpha responsive protein
[Mus musculusJ
M.musculusl
264230 AA819870uu Rattus norvegicus complement
C8 beta
(C8b) mRNA, partial cds
26519566AA819879c ESTs, Weakly similar
to phosducin-like
protein 2; protein B
[Mus musculusJ
[M.musculusl
266320 AA819905ee stearoyl-Coenzymestearoyl-Coenzyme A desaturase
A 1
desaturase 1
27123759AA848402a ESTs, Weakly similar
to A57284 spermatid
perinuclear RNA-binding
protein Spnr-
mouse [M.musculusl
2827749 AA848804jj ESTs, Highly similar
to BTF3_MOUSE
Transcription factor
BTF3 (RNA polymerase
B transcription factor
3) [M.musculus]
30618696AA849965q, ESTs, Highly similar
nn, to M025_MOUSE
qq,
xx M025 protein [M.musculus]
31519042AA850378t ESTs, Moderately similar
to methyl-CpG
binding domain protein
2 [Mus musculusJ
[M.musculusl
31713975AA850450xx Rattus norvegicus mRNA
for class I beta-
tubulin, complete cds
32316132AA850885ee unknown Glu-Pro unknown Glu-Pro dipeptide
dipeptide repeat protein
repeat protein
3272847 AA850919cc ESTs, Weakly similar
to FAS_RAT FATTY
ACID SYNTHASE [INCLUDES:
EC 2.3.1.38;
EC 2.3.1.39; EC 2.3.1.41;
EC 1.1.1.100; EC
4.2.1.61; EC 1.3.1.10;
EC 3.1.2.14]
IR.norveoicusl
3283924 AA851017ff ESTs, Highly similar
to molybdenum
cofactor synthesis 2
[Mus musculusJ
[M.musculusl
3324490 AA851184ii Rattus norvegicus mRNA
for cathepsin Y,
artial cds
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~n5
TABLE
1;
Attorney
Docket
No.
44921-5113W0
Documerit
No.1926271
~2
SEQ GLGC GenBankMode[ Known Gene Name Unigene Sequence Cluster
_ Title
ID_ D Acc. Code-
I N0. or
NO. RefSeq
ID
No:
335 17823AA851214y ESTs, Highly similar
to hypothetical protein
MGC7474 [Mus musculus]
[M.musculus]
338 19189AA851237dd ESTs, Highly similar
to UBPI MOUSE
_
Ubiquitin carboxyl-terminal
hydrolase 18
(Ubiquitin thiolesterase
18) (Ubiquitin-
specific processing
protease 18)
(Deubiquitinating enzyme
18) (43 kDa
ubiauitin-specific protease)
fM.musculusl
346 883 AA851347t ESTs, Highly similar
to SNXS_MOUSE
Sortin nexin 5 M.musculus]
349 21489AA851443a ESTs, Weakly similar
to 149523 tumor
necrosis factor alpha-induced
protein 2 -
mouse [M.musculus]
355 6687 AA851739General ESTs, Highly similar
to tousled-like kinase
2
(Arabidopsis); protein
kinase U-alpha;
Tousled-like kinase
(Arabidopsis) [Mus
musculusl IM.musculusl
356 18697AA851776j ESTs, Highly similar
to M025 MOUSE
_
M025 protein [M.musculus]
358 14292AA851791c ESTs, Weakly similar
to CBP_MOUSE
CREB-binding protein
[M.musculus]
365 18001AA858573x, spp-24 precursor spp-24 precursor
bb,
gg,
hh
375 6380 AA858758o ESTs, Weakly similar
to RIKEN cDNA
1500031019 [Mus musculus]
[M.musculus]
379 6403 AA858879y ESTs, Highly similar
to proteasome
(prosome, macropain)
26S subunit, non-
ATPase,13; 26S proteasome
subunit p40.5
fMus musculusl IM.musculusl
381 14589AA858982p, ESTs, Highly similar
y to LIM only 4 [Mus
musculus] [M.musculus]
382 16985AA858990rr ESTs, Highly similar
to EF1 G_MOUSE
Elongation factor 1-gamma
(EF-1-gamma)
(eEF-1 B gamma) [M.musculus]
383 17559AA858994II parathymosin parathymosin
388 6440 AA859130w, ESTs, Weakly similar
pp to JC2524
phosphoprotein phosphatase
(EC 3.1.3.16)
1A-beta - rat [R.norvegicus]
396 15172AA859362p ESTs, Highly similar
to BAG3_MOUSE BAG-
family molecular chaperone
regulator-3 (BCL
2 binding athanogene-3)
(BAG-3) (Bcl-2-
bindinq protein Bis)
[M.musculusl
408 17142AA859612gg, EST, Moderately similar
hh to 0806162) protein
URF4 [Mus musculus]
[M.musculus]
434 22593AA859977tt ESTs, Highly similar
to HS9B_RAT Heat
_
shock protein HSP 90-beta
(HSP 84)
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
106
TABLE
1
Attorney
Docket
Nor
44921-5113W0
Document
No.19262712
_ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
SEQ Title
~
ID ID Acc: Code
~ N0. or
NO:. RefSeq
ID.
No.
441 4222 AA860024I, ESTs, Highly similar
I rr to EF1 G_MOUSE
Elongation factor 1-gamma
(EF-1-gamma)
( eEF-1B gamma) [M.musculus]
442 13974AA860030n, Rattus norvegicus mRNA
qq, for class I beta-
ss
t ubulin, complete cds
460 16013AA866482r, ESTs, Highly similar
x to FGD1 MOUSE
Putative Rho/Rac guanine
nucleotide
exchange factor (Rho/Rac
GEF)
(Faciogenital dysplasia
protein homology
IM.musculusl
461 16029AA874803ss ESTs, Moderately similar
to 0806162L
protein URF5 [Mus musculus]
[M.musculus]
470 16146AA874934y ESTs, Moderately similar
to A Chain A, The
C2b-Domain Of Rabphilin:
Structural
Variations In A Janus-Faced
Domain
fR.norveaicusl
471 17303AA874990a ESTs, Weakly similar
to RIKEN cDNA
6330407611 [Mus musculus]
[M.musculus]
481 16319AA875047tt ESTs, Highly similar
to TCPZ_MOUSE T-
complex protein 1, zeta
subunit (TCP-1-zeta)
(CCT-zeta) (CCT-zeta-1)
[M.musculus]
504 15205AA875263m ESTs, Highly similar
to microspherule
protein 1; nucleolar
protein [Mus musculus]
[M.musculusl
514 24470AA875523jj ESTs, Highly similar
to MLES_RAT Myosin
light chain alkali,
smooth-muscle isoform
(MLC3SM) [R.norvegicus]
514 24471AA875523y ESTs, Highly similar
to MLES_RAT Myosin
light chain alkali,
smooth-muscle isoform
(MLC3SM) [R.norvegicus]
518 18911AA875615s, ESTs, Highly similar
qq to PMC1 MOUSE
Polymyositis/scleroderma
autoantigen 1
(Autoantigen PM/Scl
1)
(Polymyositislscleroderma
autoantigen 75
kDa) (PMIScI-75) (P75
polymyositis-
scleroderma overlap
syndrome associated
a t antiaenl fM.musculusl
521 2846 AA875639bb, ESTs, Weakly similar
ll, to FAS RAT FATTY
rr _
ACID SYNTHASE [INCLUDES:
EC 2.3.1.38;
EC 2.3.1.39; EC 2.3.1.41;
EC 1.1.1.100; EC
4.2.1.61; EC 1.3.1.10;
EC 3.1.2.14]
fR.norveaicusl
525 5384 AA891041vv jun B proto-onco jun B proto-onco ene
ene
539 21951AA891535f, ESTs, Highly similar
s, to hippocampus
pp
abundant gene transcript
1 [Mus musculus]
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
107
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGCGeriBankModel Known Gene Name Unigene Sequence Gluster'Title
ID D Accor Code
_ N0.--
I
NO RefSeq
ID
No:
542 17225AA891553I, ESTs, Moderately similar
nn to IF37_MOUSE
Eukaryotic translation
initiation factor 3
subunit 7 (eIF-3 zeta)
(eIF3 p66)
f M.musculusl
548 22858AA891591w programmed cell programmed cell death
death 8 8 (apoptosis-
(apoptosis-inducingnducin factor)
factor) i
559 6535AA891746r ESTs, Highly similar
to endothelial
differentiation-related
factor 1; hypothetical
rotein 1-9 [Mus musculusl
[M.musculusl
567 6967AA891810pp ESTs, Moderately similar
to g1-related zinc
finger protein [Mus
musculus] [M.musculus]
567 6968AA891810q, ESTs, Moderately similar
x, to g1-related zinc
ss
fin er protein [Mus
musculus] [M.musculus]
575 16023AA891872w ESTs, Highly similar
to NNTM_MOUSE
NAD(P) transhydrogenase,
mitochondrial
precursor (Pyridine
nucleotide
transhydrogenase) (Nicotinamide
nucleotide
transhydrogenase) [M.musculus]
588 17088AA891998General, ESTs, Highly similar
to JC4978 oxidative
cc, stress protein A170
oo, - mouse [M.musculus]
uu
589 16836AA892005r ESTs, Weakly similar
to PGC1 RAT
Membrane associated
progesterone
receptor component 1
(Acidic 25 kDa
protein) (25-DX) fR.norveaicusl
599 19469AA892112r ESTs, Weakly similar
to PROD MOUSE
_
PROLINE OXIDASE, MITOCHONDRIAL
PRECURSOR (PROLINE
DEHYDROGENASE) (M.musculusl
607 3427AA892246nn ESTs, Weakly similar
to serine/threonine
kinase 25 (yeast); Ste20-like
kinase;
serinelthreonine kinase
25 (Ste20, yeast
homology; Yeast Sps1/Ste20-related
kinase
1 fMus musculusl fM.musculusl
618 18208AA892318gg, ESTs, Highly similar
hh to JC7219 nuclear
protein SR-25 - mouse
[M.musculus]
618 18209AA892318r, ESTs, Highly similar
bb to JC7219 nuclear
protein SR-25 - mouse
[M.musculus]
627 23194AA892417c ephrin A1 ephrin A1
639 _ AA892531f, ESTs, Weakly similar
13160 pp to 839066 proline-rich
protein 15 - rat [R.norvegicus]
640 15154AA892532q, R.norvegicus (Wistar)
x, CaBP1 mRNA
dd,
tt
641 _ AA892545General ESTs, Moderately similar
17468 to organic cationic
transporter-like 2 [Mus
musculus]
fM.musculusl
655 20065AA892647c germinal histone erminal histone H4 ene
H4 gene
660 4524AA892759f, synaptosomal-associatedsynaptosomal-associated
s, protein, 23 kD
ff,
pp,
vv rotein 23 kD
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
108
TABLE~1
Attorney
Docket
No:44921-5113W0
Document
No.1926271.2
S~Q GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID._-D Acc. Code'
I NO. or
N0. RefSeq
ID
No.'
670 17581AA892835f ESTs, Moderately similar
to BTF3_MOUSE
Transcription factor
BTF3 (RNA polymerase
B transcription factor
3) [M.musculus]
685 3381 AA892993j ESTs, Moderately similar
j to high mobility
group protein 20 B;
BRCA2-associated
factor 35 [Mus musculus
[M.musculusl
689 3865 AA893065k, ESTs, Weakly similar
p to THDE_RAT
_
Thyrotropin-releasing
hormone degrading
ectoenzyme (TRH-degrading
ectoenzyme)
(TRH-DE) (TRH-specific
aminopeptidase)
(Thyroliberinase) (Pyroglutamyl-peptidase
II)
(PAP-Ill iR.norveaicusl
693 14859AA893173a ESTs, Highly similar
to vacuolar protein
sorting 29 (S. pombe);
vacuolar protein
sorting 29 (yeast);
vacuolar sorting protein
29 fMus musculusl fM.musculusl
706 16168AA893280z, ESTs, Moderately similar
nn to ADFP_MOUSE
ADIPOPHILIN (ADIPOSE
DIFFERENTIATION-RELATED
PROTEIN)
(ADRP) fM.musculusl
708 17900AA893353gg, ESTs, Highly similar
hh, to DNPE_MOUSE
rr _
Aspartyl aminopeptidase
[M.musculus]
710 4678 AA893384v ESTs, Moderately similar
to IRF3_MOUSE
Interferon regulatory
factor 3 (IRF-3)
[M.musculusl
715 13088AA893495x ESTs, Highly similar
to A40066
corticosteroid-binding
globulin precursor
- rat
[R.norveaicusl
750 24473AA894200y ESTs, Highly similar
to MLES_RAT Myosin
light chain alkali,
smooth-muscle isoform
(MLC3SM) [R.norvegicusl
751 22783AA894207cc ESTs, Weakly similar
to dual-specificity
phosphatase [Mus musculus]
[M.musculus]
766 15009AA899106pp cyclin D2 cyclin D2
792 21649AA900351I, ESTs, Weakly similar
uu to RIKEN cDNA
3930402F23 [Mus musculus]
[M.musculus]
803 3944 AA900688ww ESTs, Weakly similar
to A45988 dentin
matrix acidic phosphoprotein
AG1 - rat
[R.norvegicus]
808 18379AA900993a ESTs, Highly similar
to nuclear localization
signal protein absent
in velo-cardio-facial
patients [Mus musculus]
[M.musculus]
813 4857 AA901237mm ESTs, Weakly similar
to CYCK_MOUSE
Cyclin K [M.musculus]
839 4944 AA924405h ESTs, Weakly similar
to NFH_MOUSE
Neurofilament triplet
H protein (200 kDa
neurofilament protein)
(Neurofilament heavy
of a tide NF-H M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
109
TABLE
1
Attorney
Docket
No44921-5113W0
Document
No:1926271-.2
SEQ-GLGC'GenBankModel Knowri Gene Name Upigene Sequence Clusfer
: Title a
ID:ID=N0._Acc. Code
or
N0.. RefSeq
ID
No.
84616806AA924591r, Rat Cyp4a locus, encoding
nn cytochrome
P450 (IVA3) mRNA, complete
cds
8514994 AA924658k ESTs, Moderately similar
to PIN21TRF1-
interacting protein
[Mus musculus]
[M.musculus]
87423159AA925318I, I-kappa-B-beta I-kap a-B-beta
q,
x,
dd
88222125AA925503ss ribosomal proteinribosomal protein S27
S27
90811691AA926193t, sulfotransferase sulfotransferase family,
mm family, cytosolic,1 C,
cytosolic,1 C, member 2
member 2
91114223AA926352h ESTs, Highly similar
to Trk-fused gene;
TFG
[Mus musculus] [M.musculus]
91420910AA942693x ESTs, Highly similar
to RIKEN cDNA
5730406115 [Mus musculus]
[M.musculus]
91922677AA942718t, B cell lymphoma B cell lymphoma 2 like
ff, 2 like
pp
94421600AA943997r ESTs, Highly similar
to C184L-22 [Mus
musculus] [M.musculus]
9462762 AA944165c ESTs, Highly similar
to C10_MOUSE
Putative C10 protein
(B-cell receptor-
associated protein 37)
M.musculus]
94922017AA944209d ESTs, Moderately similar
to PIM1 RAT
Proto-oncogene serinelthreonine-protein
kinase pim-1 [R.norveqicusl
96219480AA9444420o ESTs, Weakly similar
to SLI3_RAT
SKELETAL MUSCLE LIM-PROTEIN
3
(SLIM 3) (LIM-DOMAIN
PROTEIN DRAL)
(FOUR AND A HALF LIM
DOMAINS
PROTEIN 2) (FHL-21 fR.norveaicusl
9652175 AA944528ii ESTs, Weakly similar
to T9S2_MOUSE
Transmembrane 9 superfamily
protein
member 2 precursor [M.musculus]
98823813AA945149b, ESTs, Moderately similar
vv to S27161
glutathione transferase
(EC 2.5.1.18) 5 - rat
[R.norveqicus]
99016635AA945171k ESTs, Highly similar
to APC4_RAT
APOLIPOPROTEIN C-IV
PRECURSOR
(APO-CIV) (APOLIPOPROTEIN
E-LINKED)
(ECL) [R.norveaicusl
99522029AA945284dd ESTs, Moderately similar
to 0806162L
protein URF5 [Mus musculus]
[M.musculus]
9967683 AA945320a ESTs, Highly similar
to IMA3_MOUSE
Importin alpha-3 subunit
(Karyopherin alpha-
3 subunit) (Importin
alpha Q2) [M.musculus]
100513751AA945699kk synaptosomal-associatedsynaptosomal-associated
protein, 23 kD
protein, 23 kD
101022639AA945746t ESTs, Highly similar
to SPT4_HUMAN
Transcription initiation
protein SPT4
homolo 1 M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~~n
TABLE
1
.
Attorney
Docket
No.
44921-5113WQ
Document
No.19262T1.3
SEQ GLGC GenBankModel Known Gene Name. Unigene Sequence
= C lusterTitle
ID_ ID Acc, Code
NO: or
N0. RefSeq
ID
-
No:
102018110AA945932a Annexin A3 Annexin A3, ESTs, ESTs,
Weakly similar to
LURT3 annexin III -
rat [R.norve icus]
102821157AA946189I ESTs, Moderately similar
to RGP1 MOUSE
Ran-GTPase activating
protein 1
[M.musculus]
103218280AA946361c ESTs, Weakly similar
to CBP_MOUSE
CREB-bindin protein
[M.musculus]
107217540AA955914f EST, EST, Moderately
PP similar to
FBRL_MOUSE Fibrillarin
(Nucleolar protein
1 ) [M.musculus], ESTs,
Highly similar to
S38342 fibrillarin -
mouse [M.musculus]
107522576AA955983m, ESTs, Weakly similar
dd to FLAP RAT 5-
lipoxygenase activating
protein (FLAP) (MK-
886-binding protein)
[R.norveqicus]
109316578AA957143d ESTs, Highly similar
to DP30 MOUSE Dpy-
30-like protein [M.musculus]
109316579AA957143bb ESTs, Highly similar
to DP30_MOUSE Dpy-
30-like protein [M.musculus]
109522357AA957264k Rattus norvegicus hypothetical
RNA binding
protein RDA288 mRNA,
complete cds
110624156AA957803k ESTs, Moderately similar
to RNP_RAT
Ribonuclease pancreatic
precursor (RNase
1) (RNaseA) (RL1) [R.norvegicus]
11202205 AA963808t ESTs, Highly similar
to zinc finger RNA
binding protein [Mus
musculus]
f M.musculus]
11228430 AA964033t Rattus norvegicus NonOlp54nrb
homolog
mRNA, partial cds
113312563AA964533m ESTs, Highly similar
to RIKEN cDNA
1 500003K04 [Mus musculus]
[M.musculus]
11452326 AA964892ii E STs, Highly similar
to CA14 MOUSE
C OLLAGEN ALPHA 1(IV)
CHAIN
P RECURSOR [M.musculusl
11692939 AA996885II E STs, Moderately similar
to SY19_MOUSE
S mall inducible cytokine
A19 precursor
( CCL19) (Epstein-Barr
virus induced
m olecule 1 ligand chemokine)
(EB11-ligand
c hemokine) IELC) fM.musculusl
11703054 AA996899, hh spermato enesis permatogenesis associated
associated 2 2
s
11732958 AA996944ee E STs, Weakly similar
to ring finger protein
2 3; RING-B box-coiled
coil-830.2 [Mus
m usculus] [M.musculus]
118516883AA997345dd E STs, Highly similar
to RIKEN cDNA
1 190017819 [Mus musculus]
[M.musculus]
11913250 AA997765n f ibrillin-1 fi brillin-1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
111
TABLE
1
Attorney
Docket
No.
44921-5113WQ
Document
No.1926271.2
SE GLGC GenBankModel':Known Gene Name Jnigene SequencevCluster
Q t Title
lD' D Accor Code
I N0.
NO: RefSeq
ID
No.
121014149AA998172y platelet-activatingplatelet-activating
factor factor acetylhydrolase
acetylhydrolase alpha 2 subunit (PAF-AH
alpha 2 subunit alpha 2)
(PAF-AH alpha
2)
12183558 AA9984610o ESTs, Moderately similar
to gene trap
ROSA 26 antisense, Philippe
Soriano; gene
trap ROSA 26 antisense
[Mus musculus]
[M.musculusl
12216965 AA998523h ESTs, Moderately similar
to C54354
calnexin precursor -
rat [R.norvegicus]
122822210AA998690p ESTs, Highly similar
to IF6_MOUSE
Eukaryotic translation
initiation factor 6
(eIF-
6) (B4 integrin interactor)
(CAB) (p27(BBP))
fM.musculusl
122920271AA998747cc, procollagen-lysine,procollagen-lysine,
mm 2- 2-oxoglutarate 5-
oxoglutarate 5-dioxygenasedioxygenase (lysine
hydroxylase, Ehlers-
(lysine hydroxylase,Danlos syndrome type
Ehlers- VI)
Danlos syndrome
type VI)
124516304ABOO8424e, Rat cytochrome P-450
j IID3 mRNA, complete
cds
124813973AB011679y, Rattus norvegicus mRNA
ee for class I beta-
tubulin, complete cds
12664292 AF034896e, Rattus norvegicus olfactory
h receptor-like
protein (SCR D-8) mRNA,
complete cds
12698426 AF036335pp Rattus norvegicus Non01p54nrb
homolog
mRNA, partial cds
12698427 AF036335pp Rattus norvegicus NonO/p54nrb
homolog
mRNA, partial cds
127317597AF0519430o nucleoside diphosphatenucleoside diphosphate
kinase kinase type 6
type 6
127317598AF0519430o nucleoside diphosphatenucleoside diphosphate
kinase kinase type 6
type 6
127615801AF061443p Rattus norvegicus G
protein-coupled
receptor LGR4 (LGR4)
mRNA, complete cds
13104233 A1008409h unknown Glu-Pro unknown Glu-Pro dipeptide
dipeptide repeat protein
repeat protein
131524151A1008793a ESTs, Highly similar
to T2D5_RAT
Transcription initiation
factor TFIID 70 kDa
subunit (TAFII-70) (TAFII-80)
(TAF1180)
(p80) iR.norveaicusl
131616701A1008838ff ESTs, Highly similar
to RIKEN cDNA
1300002A08 [Mus musculus]
[M.musculus]
13269150 A1009198h ESTs, Highly similar
to UNRI_MOUSE UNR-
interacting protein
(Serine-threonine kinase
receptor-associated
protein) [M.musculus]
133819092A1009501h, ESTs, Highly similar
w to SU11 MOUSE
Protein translation
factor SU11 homolog
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
112
TABLE
1
Attorney:Docket
No:
44921-5113W0
Document
No.
t192627~~.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
' Title
ID D Acc~ Code
- IVO.or
I
N0 RefSeq
ID '
No.
13413926A1009592e, ESTs, Highly similar
o to molybdenum
cofactor synthesis 2
[Mus musculus]
[ M.musculus]
13528431A1009761y Rattus norvegicus Non01p54nrb
homolog
mRNA, partial cds
136815644A1010256a, H3 histone, familyH3 histone, family 3B
d, 3B
n,
kk
137515624A1010449qq follistatin-relatedfollistatin-related
protein protein precursor
precursor
13874203A1011082j ESTs, Highly similar
to IMA3_MOUSE
Importin alpha-3 subunit
(Karyopherin alpha-
3 subunit) (Importin
alpha Q2) [M.musculus]
138822030A1011177n ESTs, Moderately similar
to 0806162L
protein URF5 [Mus musculus]
[M.musculus]
139316702A1011436ss ESTs, Highly similar
to RIKEN cDNA
1300002A08 [Mus musculus
[M.musculus]
13983941A1011598xx ESTs, Moderately similar
to LMA5 MOUSE
_
Laminin alpha-5 chain
precursor
f M.musculus]
14003995A1011678I,'j RyudocanlsyndecanRyudocan/syndecan 2
2
140414267A1011738d, ESTs, Highly similar
o to P044_RAT 0-44
protein [R.norvegicus]
14137104A10121030o ESTs, Moderately similar
to low density
lipoprotein B [Mus musculus]
[M.musculus]
142612766A1012505ee ESTs, Highly similar
to diacylglycerol 0-
acyltransferase 2; diacylglycerol
acyltransferase 2 [Mus
musculus]
iM.musculusl
14644251A1013494a ATP-binding cassette,ATP-binding cassette,
sub- sub-family F
family F (GCN20),(GCN20), member 1
member 1
14747310A1013816ff ESTs, Moderately similar
to RIKEN cDNA
0610006108 [Mus musculus]
[M.musculus]
147621950A1013861h 3-hydroxyisobutyrate3-hydroxyisobutyrate
dehydrogenase
dehydrogenase
14807316A1013883s ESTs, Highly similar
to MKR1 MOUSE
Makorin 1 [M.musculus]
149323530A1014148t, ESTs, Highly similar
w to A4B1 MOUSE
Adapter-related protein
complex 4 beta 1
subunit (Beta subunit
of AP-4) (AP-4 adapter
complex beta subunit)
[M.musculus]
15052699A1029306ii ESTs, Highly similar
to 158376 hypothetical
protein unp - mouse
[M.musculus]
15154679A1029847General ESTs, Moderately similar
to IRF3_MOUSE
Interferon regulatory
factor 3 (IRF-3)
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
113
TABLE
1
:
Attorney
Docket
No..44921=5113W0
Document
No:1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene.Sequence-.Cluster
Title
ID D-N0.Accor Code
.
I
NO.. RefSeq
ID
-
No.
154616169A1030932nn, ESTs, Moderately similar
rr to ADFP_MOUSE
ADIPOPHILIN (ADIPOSE
DIFFERENTIATION-RELATED
PROTEIN)
( ADRP) fM.musculusl
155318002A1043655g, spp-24 precursor spp-24 precursor
x,
dd
15607913 A1043849ff ESTs, Weakly similar
to ELL MOUSE RNA
_
POLYMERASE II ELONGATION
FACTOR
ELL (ELEVEN-NINETEEN
LYSINE-RICH
LEUKEMIA PROTEIN) iM.musculusl
157115240A1044241General ESTs, Highly similar
to CIDB_MOUSE Cell
death activator CIDE-B
(Cell death-inducing
DFFA-like effector B)
[M.musculus]
159018422A1044827a ESTs, Highly similar
to nitrilase 1 [Mus
musculus] [M.musculus]
16025712 A1045154n ESTs, Moderately similar
to ORCS_MOUSE
Origin recognition complex
subunit 5
[M.musculusl
16086241 A1045321bb ESTs, Weakly similar
to IGEB MOUSE IGE-
_
BINDING PROTEIN [M.musculus]
163321490A1045764jj ESTs, Weakly similar
to 149523 tumor
necrosis factor alpha-induced
protein 2 -
mouse fM.musculus]
164415241A1058382General ESTs, Highly similar
to CIDB_MOUSE Cell
death activator CIDE-B
(Cell death-inducing
DFFA-like effector B)
[M.musculus]
1677965 A1059340I huntingtin-associatedhuntingtin-associated
protein protein interacting
interacting proteinprotein (duo)
(duo)
16848347 A1059519dd ESTs, Weakly similar
to EGRT epidermal
growth factor precursor
- rat [R.norve icus]
1698900 A1059963ii, vacuolar protein vacuolar protein sorting
jj sorting homolog r-vps33b
homolog r-vps33b
17098590 A1060207nn ESTs, Highly similar
to splicing factor
3b,
subunit 1,155 kDa [Mus
musculus]
[M.musculus]
17189054 A1070138dd ESTs, Moderately similar
to RIKEN cDNA
1110028N05 [Mus musculus]
[M.musculus]
172917871A1070601ii ESTs, Weakly similar
to NOE1 RAT Noelin
precursor (Neuronal
olfactomedin-related
ER
localized protein) (Olfactomedin
1)
(Pancortin) (1B426B)
fR.norveQicusl
17898856 A1072402b, ESTs, Weakly similar
h, to S42077 finger
a
protein 30 - mouse [M.musculus]
179512863A1072467nn ESTs, Highly similar
to 2207230A
transcription factor
ATBF1 [Mus musculus]
[M.musculusl
18069399 A1072812a ESTs, Highly similar
to glioma-amplified
se uence-41 Mus musculus
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
114
TABLE
1
~
Attorney
Docket
No.:44929~5113W0
Document
No.19262T1.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Cluster
Title
ID ID Acc. Code
' NO. or
=
N0: RefSeq
ID
No
181115308A1072896nn ESTs, Weakly similar
to catenin delta 2;
neural plakophilin-related
arm-repeat
protein; catenin (cadherin-associated
protein), delta 2 (neural
plakophilin-related
arm-repeat protein);
neurojungin [Mus
musculusl iM.musculusl
181720834A1073056cc kinesin li ht kinesin light chain
chain 1 1
185415080AI102045I ESTs, Moderately similar
to NIF1 MOUSE
_
Nuclear LIM interactor-interacting
factor 1
(NLI-interacting factor
1) (NIF-like protein)
[M.musculusl
186413892AI102438gg, ESTs, Highly similar
hh to CNIH_MOUSE
CORNICHON HOMOLOG (M.musculus]
186615218AI102495cc ESTs, Moderately similar
to PNPH_MOUSE
Purine nucleoside phosphorylase
(Inosine
phosphorylase) (PNP)
[M.musculus]
18735910 AI102689k ESTs, Highly similar
to RPP20 protein [Mus
musculus] [M.musculus]
188618607AI103105z ESTs, Highly similar
to RL12_RAT 60S
RIBOSOMAL PROTEIN L12
[R.norvegicus]
19072297 AI103602General ESTs, Highly similar
to SAP3_MOUSE
Ganglioside GM2 activator
precursor (GM2-
AP) (Cerebroside sulfate
activator protein)
(Shingolipid activator
protein 3) (SAP-3)
fM.musculusl
190913317AI103637ee ESTs, Moderately similar
to RIKEN cDNA
2810411623 [Mus musculus]
[M.musculus]
19184402 AI103874kk ESTs, Weakly similar
to FKB1 RAT FK506-
BINDING PROTEIN (FKBP-12)
(PEPTIDYL-
PROLYL CIS-TRANS ISOMERASE)
(PPIASE) (ROTAMASE)
(IMMUNOPHILIN
FKBP121 fR.norveaicusl
192220833AI104035mm ESTs, Highly similar
to COXG_MOUSE
Cytochrome c oxidase
polypeptide Vlb
(AED) (M.musculusl
19288372 AI104256pp ESTs, Highly similar
to MUS81
endonuclease [Mus musculus]
[M.musculus]
193122211AI104279tt ESTs, Highly similar
to IF6_MOUSE
Eukaryotic translation
initiation factor 6
(eIF-
6) (B4 integrin interactor)
(CAB) (p27(BBP))
fM.musculusl
194622822AI104679p, ESTs, Moderately similar
z to RIKEN cDNA
2310016K22; RIKEN cDNA
2310016K22
gene [Mus musculusl
(M.musculusl
19586225 AI105105ss ESTs, Highly similar
to tangerin [Mus
musculus M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
11.5
TABLE
1
:
Attorney
Docket
No:
44921-5113W0
Document
No.19262712
SEQ GLGCGenBank.Model Known Gene Name Unigene Sequence;Cluster
Title
ID D Acc: Code
I N0. or
NO:: RefSeq
ID
No.
195921253AI105110i, ESTs, Highly similar
i ww to S58180 suit protein
-
mouse (fra ment) [M.musculus]
196018742AI105131bb, ESTs, Highly similar
qq to lung alphalbeta
hydrolase 1; alphalbeta
hydrolase-1 [Mus
musculus] [M.musculus]
19867266AI112237d, ESTs, Moderately similar
kk, to RIKEN cDNA
nn
1810011001 [Mus musculus]
[M.musculus]
19879575AI112250General,protein tyrosine protein tyrosine phosphatase
phosphatase type IVA,
kk, type IVA, member member 2
nn 2
19892501AI112343f, ubiquitin fusion ubiquitin fusion degradation
nn, degradation 1- 1-like
ww
like
199023099AI112365y, ESTs, Highly similar
nn, to MGN HUMAN Mago
ww
nashi protein homolo
[M.musculus]
19952296AI112979q, ESTs, Highly similar
x, to SAP3_MOUSE
General Ganglioside GM2 activator
precursor (GM2-
AP) (Cerebroside sulfate
activator protein)
(Shingolipid activator
protein 3) (SAP-3)
fM.musculusl
200423653AI136396bb farnesyltransferasefarnesyltransferase
beta subunit beta subunit
201324212AI136747c ESTs, Highly similar
to H33_HUMAN
Histone H3.3 (H3.A)
(H3.B) (H3,3Q)
[M.musculus]
201613090AI136977m, ESTs, Highly similar
II to S14538 transition
protein - mouse [M.musculus]
201613091AI136977v ESTs, Highly similar
to S14538 transition
protein - mouse [M.musculus]
202811270AI137480nn ESTs, Weakly similar
to A39066 proline-rich
protein 4 - rat [R.norve
icus]
203018943AI137495d, ESTs, Highly similar
II to H2A1 RAT Histone
H2A.1 [R.norvegicus]
206519034AI145768a ESTs, Weakly similar
to A55817 cyclin-
dependent kinase p130-PITSLRE
- mouse
[M.musculusl
207123224AI146033h, translocase of translocase of inner
z, inner mitochondria)
II
mitochondria) membrane 9 homolog (yeast)
membrane 9
homolog (yeast)
207711693AI168953mm sulfotransferase sulfotransferase family,
family, cytosolic, 1 C,
cytosolic,1 C, member 2
member 2
208016580AI1689890o ESTs, Highly similar
to DP30_MOUSE Dpy-
30-like protein [M.musculus]
20976732AI169269kk ESTs, Highly similar
to dim1 (S. pombe)
[Mus musculus] [M.musculus]
209916879AI169284ww ESTs, Highly similar
to AR61 MOUSE ARL-
6 interacting protein-1
(Aip-1) (TBX2 protein)
[M.musculusl
210124213AI169289c ESTs, Highly similar
to H33_HUMAN
Histone H3.3 (H3.A)
(H3.B) (H3.3Q)
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
a~~
TABLE
~
~.
Attorney
Docket
No:
44921:5113W0
Document
No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence-Cluster
. Title
ID= ID Acc. Code
N0. or
N0. RefSeq
ID ' .
T:F
No ~ ,
211421660AI169751b, Rattus norvegicus interferon-inducible
dd
protein variant 10 mRNA,
complete cds
21163909AI169903I ESTs, Moderately similar
to lymphocyte
antigen 96 [Mus musculus]
[M.musculus]
212218367AI170064j ESTs, Moderately similar
to JC7279 Down
syndrome critical region
gene-2 (DSCR2)
protein - mouse [M.musculus]
213423966AI170442t, ESTs, Highly similar
mm to JE0223 destrin -
rat
R.norvegicus]
215416170AI170894ii ESTs, Moderately similar
to ADFP_MOUSE
ADIPOPHILIN (ADIPOSE
DIFFERENTIATION-RELATED
PROTEIN)
(ADRP) fM.musculusl
216720905AI171273t, ESTs, Moderately similar
mm to C54819 actin-
capping protein beta
chain, splice form
2 -
mouse M.musculus
217117529AI171460a ESTs, Weakly similar
to HCD2_RAT 3-
hydroxyacyl-CoA dehydrogenase
type II
(Type II HADH) (Endoplasmic
reticulum-
associated amyloid beta-peptide
binding
protein) IR.norveqicusl
217515684AI171535n, ESTs, Weakly similar
General to PAB1 MOUSE
Polyadenylate-binding
protein 1 (Poly(A)-
binding protein 1) (PABP
1) (PABP1)
fM.musculusl
21836582AI171726bb ESTs, Weakly similar
to 167424 hERR-2
homolog - rat (fragment)
[R.norvegicus]
21967733AI172086z ESTs, Highly similar
to SH3 domain binding
glutamic acid-rich protein-like
3 [Mus
musculus] [M.musculus]
2197537 AI172097y heat shock transcriptionheat shock transcription
9 factor 1 factor 1
2200398 AI172105kk ESTs, Highly similar
1 to potassium channel
modulatory factor DEBT-91;
clone DEBT-91
[Mus musculus] [M.musculusl
2207147 AI172236a ESTs, Highly similar
6 to RIKEN cDNA
1110063805 [Mus musculus]
[M.musculus]
2210140 AI172272g, ESTs, Weakly similar
2 g hh to A53004
transcription elongation
factor S-II - rat
[R.norvegicus]
2211193 AI172274d ESTs, Weakly similar
4 d to A Chain A, 2-Enoyl-
Coa Hydratase, Data
Collected At 100 K,
Ph
6.5 [R.norvegicus]
22253098AI172610, ii ESTs, Moderately similar
1 c to STT3_MOUSE
OLIGOSACCHARYL TRANSFERASE
STT3
SUBUNIT HOMOLOG (B5)
(INTEGRAL
MEMBRANE PROTEIN 1)
[M.musculusj
2231926 AI175034 ESTs, Highly similar
4 II to RIKEN cDNA
2410002022 Mus musculus
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
117
TABLE:1
Attorney
Docket
No.
44921=5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene SequenceCluster-Title
ID D Acc. Code
I NO. or
NOs RefSeq
ID
No.T-
224318507AI175551z ESTs, Highly similar
to EF1 B_MOUSE
Elongation factor 1-beta
(EF-1-beta)
[M.musculusl
225124214AI175794s ESTs, Highly similar
to H33_HUMAN
Histone H3.3 (H3.A)
(H3.B) (H3.3Q)
[M.musculusl
225219004AI175875i Rattus norvegicus Sprague-Dawley
i lipid-
binding protein mRNA,
complete cds
22537647 AI175991d ESTs, Moderately similar
to
minichromosome maintenance
deficient (S.
cerevisiae) 3-associate;
nuclear protein
GANP [Mus musculusl
iM.musculusl
225824745AI176101d, ESTs, Highly similar
j to MTRP_MOUSE
Lysosomal-associated
transmembrane
protein 4A (Golgi 4-transmembrane
spanning transporter)
(Mouse transporter
protein) (MTP) fM.musculusl
227619006AI176393f Rattus norvegicus Sprague-Dawley
lipid-
bindin protein mRNA,
complete cds
227815191AI176456t, ESTs, Highly similar
w to SMRT2
metallothionein II -
rat [R.norvegicus]
228121661AI176479y, Rattus norvegicus interferon-inducible
nn
protein variant 10 mRNA,
complete cds
22832993 AI176492j, ESTs, Highly similar
II to eukaryotic
translation initiation
factor 3, subunit 2
(beta,
36kD); TGF-beta receptor
binding protein;
DNA segment, Chr 4,
ERATO Doi 632,
expressed fMus musculusl
fM.musculusl
22943034 AI176613b ESTs, Moderately similar
to PEX7 MOUSE
PEROXISOMAL TARGETING
SIGNAL 2
RECEPTOR (PTS2 RECEPTOR)
(PEROXIN
7)iM.musculusl
230023403A1176714bb ESTs, Highly similar
to CHD1 MOUSE
CHROMODOMAIN-HELICASE-DNA-
BINDING PROTEIN 1 (CHD-1)
[M.musculus]
23173862 AI177052nn, Nuclear pore complexNuclear pore complex
tt protein protein
232514083AI177181n ESTs, Weakly similar
to FYV1 MOUSE
FYVE finger-containing
phosphoinositide
kinase (1-phosphatidylinositol-4-phosphate
kinase) (PIPSK) (Ptdlns(4)P-5-kinase)
(0235) fM.musculusl
233714910AI177631z ESTs, Moderately similar
to MYPS_RAT
MYOSIN-BINDING PROTEIN
C, SLOW-
TYPE (SLOW MYBP-C) (C-PROTEIN,
SKELETAL MUSCLE SLOW-ISOFORM)
fR.norveaicusl
23491131 AI177919nn, Rat cytochrome P450CMF1
pp, b mRNA,
ww
corn lete cds
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
118
TABLE
1
_
~
Attorney
Docket
No:
44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc: Code
~ NQ. or
N0: RefSeq
ID
No.:
235119184AI178025d ESTs, Highly similar
to TGIF_MOUSE 5'-TG-
3' INTERACTING FACTOR
(HOMEOBOX
PROTEIN TGIF) [M.musculus]
235413389AI178104d ESTs, Highly similar
to RIKEN cDNA
2400009811 [Mus musculus]
[M.musculus]
238115091AI178740 ESTs, Highly similar
f to A56418 transcription
f actor delta - mouse
[M.musculus]
23832825 AI178752, nn ESTs, Highly similar
I to CLN3_MOUSE CLN3
PROTEIN (BATTENIN) [M.musculus]
239719041AI1790490o ESTs, Weakly similar
to RN12_MOUSE
RING finger protein
12 (LIM domain
i nteracting RING finger
protein) (RING finger
LIM domain-binding protein)
(R-LIM)
[M.musculusl
24015887 AI179099, o ESTs, Moderately similar
j to VNN1 MOUSE
Pantetheinase precursor
(Pantetheine
hydrolase) (Vascular
non-inflammatory
molecule 1) (Vanin 1)
[M.musculus]
241116703AI179300ff ESTs, Highly similar
to RIKEN cDNA
1300002A08 [Mus musculus]
[M.musculus]
243614803AI179906r ESTs, Highly similar
to transformed mouse
3T3 cell double minute
4 [Mus musculus]
[M.musculusl
24412099 AI180015w, ribosomal proteinribosomal protein L14
tt L14
24439821 AI180114ss ESTs, Highly similar
to NIP2_MOUSE
BCL21ADENOVIRUS E1 B
19-KDA
PROTEIN-INTERACTING
PROTEIN 2
fM.musculusl
246222366AI227743tt ESTs, Highly similar
to Fas-activated
serine/threonine kinase
[Mus musculus]
[M.musculusl
247014230AI228064y ESTs, Weakly similar
to A47179 homeotic
protein LH-2 - rat [R.norvegicus]
247216970AI228112tt protein phosphataseprotein phosphatase
2 (formerly 2 (formerly 2A),
2A), regulatory regulatory subunit B
subunit B (PR (PR 52), alpha isoform
52), alpha isoform
247922915AI228299m, ESTs, Highly similar
II to craniofacial
development protein
1 [Mus musculus]
[M.musculusl
248322455AI228524s ESTs, Moderately similar
to RIKEN cDNA
1700021 F05 [Mus musculus]
[M.musculus]
249515078AI228830s stearoyl-CoenzymeRat DNA polymerase alpha
A mRNA, 3' end,
desaturase 2 stearo I-Coenz me A
desaturase 2
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
119
TABLE
1
-
Attorney
Docket
No.
4492-5113W0
Document
No.1926271;2
SEQ GLGC GenBankModel Known Gene Name Jnigene Sequence Cluster
t Title :.
ID D Acc. Code
' NO. or
I .
N0. _
RefSeq
ID
No.'
252113977AI229707, bb, Rattus norvegicus mRNA
j nn for class I beta-
t ubulin, complete cds
254513555AI230547d ESTs, Moderately similar
to 1920362A tumor
suppressor gene mgl1
[Mus musculus]
[M.musculus]
255422387AI230753a, ESTs, Highly similar
tt to BI3_MOUSE Brain
protein 13 [M.musculus]
256014224AI230956rr ESTs, Highly similar
to Trk-fused gene;
TFG
[Mus musculus] [M.musculus]
25632299 AI231094w ~ ESTs, Highly similar
to SAP3_MOUSE
Ganglioside GM2 activator
precursor (GM2-
AP) (Cerebroside sulfate
activator protein)
(Shingolipid activator
protein 3) (SAP-3)
fM.musculusl
257513092AI2315470o ESTs, Highly similar
to S14538 transition
protein - mouse [M.musculus]
25784703 AI231606k, ESTs, Moderately similar
r to RIKEN cDNA
6330579817 [Mus musculus]
[M.musculus]
258317297AI231785ii, ESTs, Moderately similar
rr to Niemann Pick
type C2 [Mus musculus]
[M.musculus]
259514102AI232131rr ESTs, Highly similar
to 148253 beta-N-
acetylhexosaminidase
(EC 3.2.1.52) alpha
chain precursor- mouse
[M.musculus]
259619274AI232135ii ESTs, Highly similar
to COG2_MOUSE
Coatomer gamma-2 subunit
(Gamma-2 coat
protein) (Gamma-2 COP)
[M.musculus]
2602409 AI232268p, low density lipoproteinlow density lipoprotein
r receptor- receptor-related
related protein protein associated protein
associated 1
protein 1
260815582AI232320k, Rat mitochondrial 3-hydroxy-3-
methylglutaryl
o,
oo
CoA synthase mRNA, complete
cds
261814547AI232431z, ESTs, Highly similar
ww to TLP1 MOUSE TATA
BOX BINDING PROTEIN-LIKE
PROTEIN 1
(TBP-LIKE PROTEIN 1)
(21-KDATBP-LIKE
PROTEIN) iM.musculusl
26228709 AI232534ii ESTs, Weakly similar
to DnaJ (Hsp40)
homolog, subfamily B,
member 3; heat
shock protein, DNAJ-like
3 [Mus musculus]
iM.musculusl
264014098AI233114j ESTs, Moderately similar
to S29510
ubiquinol--cytochrome-c
reductase (EC
1.10.2.2) core protein
II precursor- rat
iR.norveqicusl
265210378AI233300I ESTs, Moderately similar
to C05 MOUSE
_
Complement C5 precursor
(Hemolytic
complement) [Contains:
C5A anaphylatoxin]
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
120
TABLE
1
Attorney
Docket
No44921-5113W0
Document
No:19262T1:2
SEQ GLGC GenBankModel Known Gene Name Uniger~e Sequence Cluster
Title ,-
ID ID Acc. Code
N 0. or
N0. RefSeq
ID
No:
267615685AI233870m ESTs, Weakly similar
to PAB1 MOUSE
Polyadenylate-binding
protein 1 (Poly(A)-
binding protein 1) (PABP
1) (PABP1)
fM.musculusl
270015034AI235054s ESTs, Weakly similar
to RIKEN cDNA
0610008N23 [Mus musculus]
[M.musculus]
270315004AI235224k tissue inhibitor tissue inhibitor of
of metalloproteinase 1
metalloproteinase
1
271115858AI235455rr ESTs, Moderately similar
to 854745 beta-N-
acetylhexosaminidase
(EC 3.2.1.52) beta
chain - mouse [M.musculusl
27283617 AI236021d ESTs, Highly similar
to JC4857
hepatocarcinogenesis-related
transcription
factor- rat fR.norveqicusl
273120788AI236053qq acyl-coenzyme acyl-coenzyme A:cholesterol
A:cholesterol acyltransferase
acyltransferase
273311465AI236084q ESTs, Moderately similar
to TNR9_MOUSE
Tumor necrosis factor
receptor superfamily
member 9 precursor (4-1
BB ligand receptor)
(T-cell antigen 4-1
BB) (CD137 antigen)
iM.musculusl
27369543 AI236164k ESTs, Moderately similar
to A41641
mannosyl-oligosaccharide
1,3-1,6-alpha-
mannosidase (EC 3.2.1.114)
- mouse
fM.musculusl
274719035AI236576pp, ESTs, Highly similar
rr to S06147 GTP-binding
protein rab1 B - rat
[R.norvegicus]
27527691 AI236611v, isopentenyl-diphosphateisopentenyl-diphosphate
x, delta delta isomerase
bb
isomerase
276415850AI236795b, ESTs, ESTs, Highly similar
tt to HS9B_RAT
Heat shock protein HSP
90-beta (HSP 84)
[R.norveqicusl
276911404AI237002v, spermidine synthasespermidine synthase
w,
bb
277714841AI237372v ESTs, Highly similar
to RTC1 MOUSE RNA
3'-terminal phosphate
cyclase (RNA-3'-
phosphate cyclase) (RNA
cyclase)
iM.musculusl
27853489 AI237620n ESTs, Highly similar
to IF36_HUMAN
Eukaryotic translation
initiation factor 3
subunit 6 (eIF-3 p48)
(Mammary tumor-
associated protein INT-6)
(Viral integration
site protein INT-6 fM.musculusl
278618854AI237636I ESTs, Weakly similar
to CNE6_MOUSE
Copine VI (Neuronal-copine)
(N-copine)
[M.musculusl
278714837AI237638k, EST, Highly similar
mm to VAT1 MOUSE
Synaptic vesicle membrane
protein VAT-1
homolo M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
121
TABLE
1
Attor=ney
Docket
No44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
NO. or
N0. RefSeq
ID
No:_
280717108AI639017bb ESTs, Weakly similar
to T17453 ERG-
associated protein ESET
- mouse
[ M.musculus~
281318504AI639044cc ESTs, Moderately similar
to T4S9_MOUSE
TRANSMEMBRANE 4 SUPERFAMILY,
MEMBER 8 (TETRASPANIN
5) (TSPAN-5)
[M.musculusl
284819152AI639387c ESTs, Highly similar
to RT06_MOUSE
Mitochondria) 28S ribosomal
protein S6
(MRP-S6) [M.musculus)
286823220AJ000347pp 3'(2'),5'-bisphosphate3'(2'),5'-bisphosphate
nucleotidase
nucleotidase
287014332AJ001044q, tumor-associated tumor-associated calcium
ff calcium signal signal transducer
transducer 1 1
28739866 AJ005424ss mitogen-activatedmitogen-activated protein
protein kinase kinase 7
7
28739867 AJ005424tt mitogen-activatedmitogen-activated protein
protein kinase kinase 7
7
288319053D12770 j, solute carrier solute carrier family
o family 25 25 (mitochondria)
(mitochondria) adenine nucleotide translocator)
adenine member 4
nucleotide transl0cator)
member
4
293016986H33020 bb ESTs, Highly similar
to EF1 G MOUSE
Elongation factor 1-gamma
(EF-1-gamma)
(eEF-1B gamma) [M.musculus~
295323485K02816 ww pR-ET2 encoded pR-ET2 encoded oncodevelopmental
protein
oncodevelopmental
protein
295323486K02816 kk, pR-ET2 encoded pR-ET2 encoded oncodevelopmental
ww protein
oncodevelopmental
protein
297613499L26267 s nuclear factor nuclear factor kappa
kappa B p105 B p105 subunit
subunit
299419256M15562 xx Rat (diabetic BB) MHC
class II alpha chain
RT1.D alpha (u)
300811956M28255 ff cytochrome c oxidase,cytochrome c oxidase,
subunit subunit Vllla
Vllla
300917123M29295 nn, small nuclear small nuclear ribonucleoprotein
tt ribonucleoprotein,polypeptides
polypeptides B B and B1
and B1
301315579M33648 d, Rat mitochondria) 3-hydroxy-3-
methylglutaryl
k,
I,
o,
ff,
oo, CoA synthase mRNA, complete
ss cds
301315580M33648 k, Rat mitochondria) 3-hydroxy-3-
methylglutaryl
I,
o,
ff
CoA synthase mRNA, complete
cds
301416807M33936 k, Rat Cyp4a locus, encoding
o, cytochrome
v,
ss,
uu, P450 (IVA3) mRNA, complete
xx cds
301817145M38566 b, Serine protease Serine protease inhibitor
qq inhibitor
302920836M75148 I, kinesin light kinesin light chain
General,chain 1 1
qq
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
177
TABLE
1
'
Attorney
Docket
No.:44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence.Cluster
- Title
I17 ID Acc, Code
N0. or
NO.. RefSeq
ID
No.
30301138 M76740 cc Mucin3 Mucin3
303524651M83678 u, RAB13 RAB13
y,
nn
304125467M93297 t ornithine aminotransferaseornithine aminotransferase
30423424 M94557 o Single-stranded ESTs, Highly similar
DNA-binding to SSB RAT SINGLE-
protein STRANDED DNA-BINDING
PROTEIN,
MITOCHONDRIAL PRECURSOR
(MT-SSB)
(MTSSB) (P16) fR.norveaicusl
308017292NM 012584General,Hydroxy-delta-5-steroidHydroxy-delta-5-steroid
dehydrogenase, 3
cc dehydrogenase, beta- and steroid delta-isomerase
3 beta- and
steroid delta-isomerase
3086382 NM 012599a, Mannose binding Mannose binding protein
d, protein A, A, serum
gg,
hh serum
310117147NM 012657e, Serine protease Serine protease inhibitor
n, inhibitor
r,
ii
310117148NM 012657r, Serine protease Serine protease inhibitor
ii inhibitor
31081514 NM 012678b, Tropomyosin 4 Tropomyosin 4
t
31171602 NM 012697dd, Or anic ration Organic ration transporter
mm transporter
312418730NM_012730a, Cytochrome P450, Cytochrome P450, subfamily
j subfamily IID2
I ID2
313413731NM 012755bb Fyn proto-oncogeneFyn proto-oncogene
313617257NM 012766x, Cyclin D3 Cyclin D3
II,
rr,
ww
313617258NM 012766I, Cyclin D3 Cyclin
Ic, D 3
nn,
ww
321517174NM_013030gg, R.norvegicus ASl mRNA
hh for mammalian
equivalent of bacterial
large ribosomal
subunit protein L22
32271859 NM 013063p, ADP-ribosyltransferaseADP-
_ y, (NAD+; ribosyltransferase (NAD+;
nn poly (ADP-
poly (ADP-ribose)ibose) polymerase)
polymerase) r
3228675 NM 013066g Microtubule-associatedMicrotubule-associated
protein protein 2
2
32299335 NM 013067x, Ribophorin I Ribophorin I
1 dd
3234529 NM 013082b, Ryudocan/syndecanyudocan/syndecan 2
1 e, 2 R
h,
I,
General
3241793 NM 013105j Cytochrome P450, Cytochrome
1 j subfamily 450, subfamily IIIA,
P
I IIA, pol peptide olypeptide 3
3 p
3241794 NM 013105j Cytochrome P450, Cytochrome
1 j subfamily 450, subfamily IIIA,
P
I IIA, polypeptide ol peptide 3
3 p
3241795 NM 013105j Cytochrome P450, Cytochrome
1 j subfamily 450, subfamily IIIA,
P
I IIA, polypeptide olypeptide 3
3 p
3241796 M 013105C ytochrome P450, Cytochrome P450, subfamily
1 N v subfamily IIIA,
I IIA, polypeptide olypeptide 3
3 p
3241797 M 013105, r, ytochrome P450, ytochrome
1 N j jj subfamily C 450, subfamily IIIA,
C P
I IIA, polypeptide olypeptide 3, Rattus
3 p norvegicus Sprague
D awley testosterone 6-beta-hydroxylase,
c ytochrome P450/6-beta-A,
(CYP3A2)
mRNA. complete cds
324328 M 013112A oli o rotein A-IIoli o rotein A-II
4 N x A
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1~R
TABLE
1
Attorney
Docket
No.
44921-51131N0
Document
No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
ID D Accor Code Title
I N0. RefSeq ~ Y ,
N0. ID - - ~:_
No.
~
324423709NM_013113, w, ATPase Na+IK+ ATPase Na+IK+ transporting
I z transporting beta 1
beta 1 polypeptidepolypeptide
324423710NM 013113ww ATPase Na+IK+ ATPase Na+IK+ transporting
transporting beta 1
beta 1 polypeptidepolypeptide
324522582NM 013120b, Glucokinase re Glucokinase re ulatory
kk ulatory protein protein
324716650NM 013132a Annexin V Annexin V
324920150NM 0131350o RAS p21 protein RAS p21 protein activator
activator
325216982NM 013144f, Insulin-like growthInsulin-like growth
r, factor binding factor binding protein
z, protein 1 1
ee,
ff,
rr
325346 NM 013151I, Plasminogen activator,Plasminogen activator,
vv tissue tissue
32571309NM 013159e, Insulin degradingInsulin degrading enzyme
bb, enzyme
oo
32621451NM 013168tt HydroxymethylbilaneHydroxymethylbilane
synthase synthase
32621452NM 013168ii Hydroxymeth IbilaneHydroxymethylbilane
synthase synthase
326424774NM 013176uu Transcription Transcription factor
factor 12 12
32671258NM_013185o Hemopoietic cell Hemopoietic cell tyrosine
tyrosine kinase kinase
32681255NM 013189ff, Guanine nucleotideGuanine nucleotide binding
xx binding protein, alpha
protein, alpha
32691300NM_013190t Phosphofructokinase,Phosphofructokinase,
liver, B- liver, B-type
type
327121396NM 013198k, Monoamine oxidaseMonoamine oxidase B
jj B
327620826NM 013218gg, adenylate kinase adenylate kinase 3
hh 3
327718313NM 013220x cardiac ankyrin cardiac ankyrin repeat
repeat protein protein
32791567NM 013223p, hemin-sensitive hemin-sensitive initiation
s initiation factorfactor 2a kinase
2a kinase
3280815 NM 013224h, ribosomal proteinribosomal protein S26
I, S26
II,
oo
329780 NM 017021cc Interleukin 9 Interleukin 9 receptor
receptor
33151523NM 017079GeneralCD1D anti en CD1D antigen
33191968NM 017091g Proprotein convertaseProprotein convertase
subtilisinlkexin subtilisinlkexin type
type 2 2
332220653NM_017104s Colony stimulatingColony stimulating factor
factor 3 3 (granulocyte)
(granulocyte)
33432968NM 017158n cytochrome P450, cytochrome P450, 2c39
2c39
33432970NM 017158f, cytochrome P450, cytochrome P450, 2c39
rr, 2c39
ss
334820702NM_017166General,Leukemia-associatedLeukemia-associated
dd, cytosolic cytosolic
oo, phosphoprotein phosphoprotein stathmin
pp stathmin
336618445NM 017220y growth and transformation-growth and transformation-
dependent
dependent proteinprotein
340718142NM 017314r ubiquitin C ubiquitin C
34091894NM 017320ii, cathepsin S cathepsin S
nn,
pp
341017516NM 0173210, iron-responsive iron-responsive element-binding
ii, element-binding protein
jj, protein
tt
341124766NM 017322k stress activated stress activated protein
protein kinase kinase alpha II
alpha II
341124767NM 017322a stress activated stress activated protein
protein kinase kinase alpha II
alpha II
341324247NM 017332n, fatty acid synthasefatty acid synthase
rr
34142000NM 017333g endothelin receptorendothelin receptor
341525515NM 017339 isl-1=homeobox isl-1=homeobox
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
124
TABLE
1
Attorney
Dockef
No:'44921-5113W0
Document
No.1926271':2
SEQ GLGC GenBankModef Known Gene Name Unigene Sequence.ClusterTitle
ID D Acc: Code
- N0. or
I
NO.'_ RefSeq
ID
No.
341716381NM_017343, y, myosin regulatorymyosin regulatory light
I z, light chain chain
General,
ee
341716382NM 017343z myosin regulatorymyosin regulatory light
light chain chain
3418520 NM 017345n neural cell adhesionneural cell adhesion
molecule molecule L1
L1
342420778NM 019124a, rabaptin 5 rabaptin 5
ww
343417304NM 019144d, Acid phosphatase Acid phosphatase 5,
p, 5, tartrate tartrate resistant
gg,
hh resistant
34551386 NM 019226d dynein, cytoplasmic,dynein, cytoplasmic,
heavy heavy chain 1
chain 1
347810016NM 019289v, Actin-related Actin-related protein
x protein complex complex 1b
1b
347923678NM 019290I, B-cell translocationB-cell translocation
u, gene 3 gene 3
General
347923679NM_019290General,B-cell translocationB-cell translocation
gene 3 gene 3
ss
348117507NM_019299w clathrin, heavy clathrin, heavy polypeptide
polypeptide (Nc) (Hc)
348451 NM 019335a Protein kinase, Protein kinase, interferon-inducible
interferon- double
inducible double stranded RNA dependent
stranded RNA
dependent
348452 NM_019335a Protein kinase, Protein kinase, interferon-inducible
interferon- double
inducible double stranded RNA dependent
stranded RNA
dependent
34884592 NM 019356h eukaryotic translationeukaryotic translation
initiation initiation factor 2,
factor 2, subunitsubunit 1 (alpha )
1 (alpha )
349420057NM 019370General,alkaline phosphodiesterasealkaline phosphodiesterase
nn
349615066NM 019373cc, apolipoprotein apolipoprotein M
rr M
350224066NM 019384d, CTD-binding SR-likeCTD-binding SR-like
kk rA1 rA1
350316 NM 019386b, tissue-type transglutaminasetissue-type
transglutaminase
I,
q,
General,
dd,
kk
350520716NM 019623b, cytochrome P450 cytochrome P450 4F1
I, 4F1
General,
gg,
hh,
II,
uu
351118702NM 0200800o nuclear protein nuclear protein E3-3
E3-3 orf1 orf1
351413485NM_020306d, a disintegrin a disintegrin and metalloproteinase
bb and domain
metalloproteinase17
domain 17
351413486NM 020306s a disintegrin a disintegrin and metalloproteinase
and domain
metalloproteinase17
domain 17
351718727NM 021577g, ar ininosuccinateargininosuccinate lyase
m lyase
352018544NM 021592a eHand protein eNand protein
352519696NM 021699I, serinelthreonine serinelthreonine kinase
nn kinase
352819710NM 021744bb CD14 anti en CD14 anti en
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
125
TABLE
1
'
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Urrigene SequenceiGluter
ID' D Arc. Code: Title
I N0: or.
N0. RefSeq
ID
=.
No:'
353019824NM 021750c, cysteine-sulfinatecysteine-sulfinate decarboxylase
General,decarboxylase
kk
353019825NM 021750, General,cysteine-sulfinatecysteine-sulfinate decarboxylase
I dd, decarboxylase
ii,
qq,
vv
353120035NM 021754qq Nopp140 associatedNopp140 associated protein
protein
353120036NM 021754r Nopp140 associatedNopp140 associated protein
protein
353317884NM 021765q beta prime COP beta prime COP
353317885NM 021765q beta prime COP beta prime COP
353620161NM 0218360o jun B proto-oncogenejun B proto-oncogene
353718839NM 021840g histone 2a histone 2a
353820129NM 021850gg, Bcl-w protein Bcl-w protein
hh
354217100NM 022179d, Hexokinase 3 Hexokinase 3
h,
I,
ee
354217101NM 022179b, Hexokinase 3 Hexokinase 3
General,
ii,
kk,
ss
354520194NM_022192v putative protein putative protein kinase
kinase C C inhibitor
inhibitor
354620204NM 022196f leukemia inhibitoryleukemia inhibitory
factor factor
354820269NM 022214bb CXC chemokine CXC chemokine LIX
LIX
354920299NM 022220j L-gulono-gamma-lactoneL-gulono-gamma-lactone
oxidase oxidase
3551762 NM 022245t, cytochrome b5 cytochrome b5
mm
35526585 NM 022266y connective tissueconnective tissue rowth
rowth factor factor
355717158NM 022298c, alpha-tubulin alpha-tubulin
f,
vv,
xx
355717160NM 022298nn alpha-tubulin alpha-tubulin
355717161NM 022298y, alpha-tubulin alpha-tubulin
nn,
tt
356023980NM 022383w cyclase-associatedcyclase-associated protein
protein homologue
homologue
356312082NM 022389jj 7-dehydrocholesterol7-dehydrocholesterol
reductase reductase
356312083NM 022389jj 7-dehydrocholesterol7-dehydrocholesterol
reductase reductase
356413479NM 022390e, quinoid dihydropteridinequinoid dihydropteridine
y, reductase reductase
xx
356413480NM 022390r, quinoid dihydropteridinequinoid dihydropteridine
ss reductase reductase
356623060NM 022394a scaffold attachmentscaffold attachment
factor B factor B
35781610 NM 022509ee, survival motor survival motor neuron
gg, neuron
hh
35781611 NM 022509h, survival motor survival motor neuron
I neuron
35802384 NM 022513b, dopaltyrosine dopaltyrosine sulfotransferase
k, sulfotransferase
I,
qq,
uu,
vv
35844145 NM 022518j, ADP-ribosylation ADP-ribosylation factor
ii factor 1 1
35844153 NM 022518bb ADP-ribosylation ADP-ribosylation factor
factor 1 1
35864242 NM 022521xx ornithine aminotransferaseornithine aminotransferase
35874256 NM 02252200, cas ase 2 cas ase 2
uu
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1~~,
TABLE
1
Aftorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Cluster
ID D Acc: Code Title
I NO. or
NO. '
RefSeq
ID
No.
35874257 NM 022522k, caspase 2 caspase 2
mm
35884412 NM 022523, x CD151 antigen CD151 anti en
j
359720803NM 022592d, transketolase transketolase
q
360020944NM 022597m, cathepsin B cathepsin B
ff,
ii
360120960NM_022598a cellular nucleic cellular nucleic acid
acid binding binding protein
protein
360421115NM 022602r, serine threonine serine threonine kinase
z, kinase pima pima
ss
360621211NM 022607t, MIPP65 protein MIPP65 protein
nn
361420506NM 022686ii germinal histone erminal histone H4 ene
H4 gene
361520509NM 022689f, synaptosomal-associatedsynaptosomal-associated
cc, protein, 23 kD protein, 23 kD
dd,
ff
361617586NM 022694u, p105 coactivator p105 coactivator
ff
361617587NM 022694u, p105 coactivator p105 coactivator
w
361817757NM 022698y bcl-2 associated bcl-2 associated death
death agonist a onist
361917808NM 022699h, ribosomal proteinribosomal protein L30
II L30 ,
362424540NM 022707a phospholamban phospholamban
362553 NM_022714v, corticotropin-releasingcorticotropin-releasing
jj factor factor receptor
receptor subtype subtype 2
2
3628194 NM 022861s Munc13-1 Munc13-1
36322006 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase
xx hydrolase
36322007 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase
s hydrolase
36322008 NM 0229360, cytosolic epoxidecytosolic epoxide hydrolase
s, hydrolase
xx
36322009 NM 022936n, cytosolic epoxidecytosolic epoxide hydrolase
o hydrolase
363415696NM 022939a syntaxin 12 syntaxin 12
363718100NM 022948y tricarboxylate tricarboxylate carrier-like
carrier-like protein
protein
363818107NM 022949b, ribosomal proteinribosomal protein L14
I, L14
General,
ee
363921491NM 022951tt putative protein putative protein phosphatase
phosphatase 1 1 nuclear
nuclear targetin targeting subunit
subunit
36431053 NM 022962pp CL1BA protein CL1BA protein
36458266 NM 023103a, alpha(1)-inhibitoralpha(1)-inhibitor 3,
j, 3, variant I variant I
r,
cc
36458267 NM 023103r alpha(1)-inhibitoralpha(1)-inhibitor 3,
3, variant I variant I
36458268 NM 023103r, alpha(1)-inhibitoralpha(1)-inhibitor 3,
mm, 3, variant I variant I
xx
36458269 NM 023103r, alpha(1)-inhibitoralpha(1)-inhibitor 3,
jj, 3, variant I variant I
xx
364623976NM 023104jj acetoacetyl-CoA acetoacetyl-CoA synthetase
synthetase
365917517NM 024151q, ADP-ribosylation ADP-ribosylation factor
u, factor 4 4
dd
3663220 NM 024161c, cysteine string cysteine strin protein
m protein
3671771 NM 024368a, src related tyrosinesrc related t rosine
qq kinase kinase
367223489NM 024375xx prepro bone inducinprepro bone inducin
protein protein
3674768 NM 024382u, leuserpin-2 leuserpin-2
rr
36762733 NM 024385bb, hematopoieticallyhematopoietically expressed
jj expressed homeobox
homeobox
3678713 NM 024391pp 17-beta hydroxysteroid17-beta hydroxysteroid
dehydro enase dehydrogenase type
type 2 2
367925070NM 0243920, peroxisomal multifunctionalperoxisomal multifunctional
Generalenz me t a II enzyme type II
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1?7
TABLE
1
Attorney
Docket
No.~:44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModeh Known Gene Name Unigene:Sequence Cluster
Title
ID D Acc: Code
I N0. or
N0: RefSeq
ID
No.
s
36799929 NM 024392p, peroxisomal multifunctionalperoxisomal multifunctional
w, enzyme type II
ss
enzyme type II
36799931 NM 0243920, peroxisomal multifunctionalperoxisomal multifunctional
xx enzyme type II
enzyme type II
368213633NM 024403w activating transcriptionactivating transcription
factor factor ATF-4
ATF-4
368213634NM 024403r, activating transcriptionactivating transcription
w, factor factor ATF-4
z,
General,ATF-4
ee,
rr
368817916NM 024488g, CDK5 activator-bindingCDK5 activator-binding
q protein protein C53
C53
369010305NM_030835ee, ribosome associatedribosome associated
ff membrane membrane protein 4
protein 4
369010306NM 030835b, ribosome associatedribosome associated
q, membrane membrane protein 4
x,
General,protein 4
dd
369010308NM_030835I, ribosome associatedribosome associated
q membrane membrane protein 4
protein 4
369218728NM 030846b, growth factor growth factor receptor
ww receptor bound bound protein 2
protein 2
369218023NM 030846k growth factor growth factor receptor
receptor bound bound protein 2
protein 2
369321509NM 030847f epithelial membraneepithelial membrane
protein 3 protein 3
36951035 NM 030851y Bradykinin receptorBrad kinin receptor
B1 B1
37018815 NM 030991ff ESTs, Highly similar
to LAS1 MOUSE LIM
AND SH3 DOMAIN PROTEIN
1 CLASP-1)
(MLN 50) (M.musculusl
370125130NM 030991k Synaptosomal-associatedSynaptosomal-associated
protein, 25 kDa
protein, 25 kDa
37021991 NM 030995xx Microtubule-associatedMicrotubule-associated
protein protein 1a
1a
3704135 NM 031003I, 4-aminobutyrate 4-aminobutyrate aminotransferase
General
aminotransferase
371524658NM 031018ff RATF2 RATF2
37171480 NM 031021 casein kinase casein kinase II beta
II beta subunit subunit
37181624 NM 031023q, di-N-acetylchitobiasedi-N-acetylchitobiase
z,
General
372315886NM 031035k, GTP-binding proteinGTP-binding protein
nn (G-alpha- (G-alpha-i2)
i2)
372421095NM 031039a glutamic-pyruvateglutamic-pyruvate transaminase
transaminase (alanine
(alanine aminotransferase)aminotransferase)
372617726NM 031043jj lycogenin lyco enin
372617727NM 031043pp, glycogenin lycogenin
uu
372625328NM 031043e, glycogenin glycogenin
bb
37271731 NM 031047tt unction plako unction plakoglobin
lobin
37319516 NM 031053g mismatch repair mismatch repair protein
protein
373724508NM 031073nn neurotrophin-3 neurotrophin-3 (HDNFINT-3)
(HDNF/NT-3)
37404683 NM 031083d, hos hatid linositolhos hatid linositol
f 4-kinase 4-kinase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
128
TABLE
1
~
Attorney
Docket
No.
44921=5113W0
Document
No.1926271:2
~
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
. Title
ID ID Acc. Code
N0. or
N0. Ref$eq
ID
No:
37404684 NM 031083k phosphatidylinositol4-kinasephosphatidylinositol4-
kinase
374315201NM 031093gg, #NAME? #NAME?
hh
374315203NM 031093I, #NAME? #NAME?
m,
s,
w,
General,
tt
37451515 NM 031095uu renin-binding renin-binding protein
protein
37451516 NM 031095x renin-binding renin-binding protein
protein
37451517 NM 031095ss renin-binding renin-binding protein
protein
374612639NM_031099I, ribosomal proteinribosomal protein L5
General,L5
ee,
II
375316929NM 031108h, mRNA for ribosomalmRNA for ribosomal protein
I, protein S9 S9
w,
z,
General,
ee,
ii,
II
375416847NM 031109h, ribosomal proteinribosomal protein S10
xx S10
37591580 NM 03111700, small nuclear small nuclear ribonucleoparticle-
associated
ww ribonucleoparticle-
associated proteinprotein (snRNP) mRNA,
(snRNP) clone Sm51
mRNA, clone Sm51
376114970NM 031127I, sulfite oxidase sulfite oxidase
p,
x,
z,
General,
kk,
nn
376313358NM_031135xx TGFB inducible TGFB inducible early
early growth growth response
response
376415052NM 031136s thymosin beta-4 thymosin beta-4
376715185NM 031140s, vimentin vimentin
ii
37701291 NM 031149w for proteasomal for proteasomal ATPase
ATPase (SUG1)
(SUG1 )
37711201 NM 031150v zona pellucida zona pellucida 2 glycoprotein
2 glycoprotein
37761963 NM 031236xx Alpha1,2-fucosyltransferaseAlpha1,2-fucosyltransferase
a a
37811422 NM 031324ss prolyl endopeptidaseprolyl endopeptidase
378218597NM 031325y, UDP- lucose dehydrogeanseUDP-glucose dehydrogeanse
uu
378418373NM 031331ii, proteasome (prosome,proteasome (prosome,
ww macropain) 26S
macropain) 26S subunit, non-ATPase,4
subunit, non-
ATPase,4
378418375NM 031331h proteasome (prosome,proteasome (prosome,
macropain) 26S
macropain) 26S subunit, non-ATPase,4
subunit, non-
ATPase,4
37856671 NM 031333t, cadherin 2, type cadherin 2, type 1,
General,1, N-cadherin N-cadherin (neuronal)
mm (neuronal)
37856672 NM 031333g cadherin 2, type cadherin 2, type 1,
1, N-cadherin N-cadherin (neuronal)
(neuronal)
37856673 NM_031333j cadherin 2, type cadherin 2, type 1,
1, N-cadherin N-cadherin (neuronal)
(neuronal)
378811962NM 031337rr sialyltransferasesialyltransferase 9
9 (CMP- (CMP-
NeuAc:lactosylceramideNeuAc:lactosylceramide
alpha- alpha-2,3-
2,3-sialyltransferase;sialyltransferase; GM3
GM3 synthase)
s nthase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
129
TABLE
1
Attorney
Docket
Nor
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigerte Sequence Cluster
Title
ID D-.NO.Acc.. Code-
- or
I
N0. Ref$eq
ID .
No. s _ ,
' . s
378811963NM 031337xx sialyltransferasesialyltransferase 9 (CMP-
9 (CMP-
NeuAc:lactosylceramideeuAc:lactosylceramide
alpha- N alpha-2,3-
2,3-sialyltransferase;sialyltransferase; GM3
GM3 synthase)
svnthase)
37904346 NM 031343k solute carrier solute carrier family
family 6 6 (neurotransmitter
(neurotransmittertransporter,noradrenalin),
member 2
transporter,noradrenalin),
member 2
37915821 NM 031351I attractin attractin
I
379218538NM 031353t, voltage-dependentvoltage-dependent anion
y, anion channel 1
mm
channel 1
379218539NM 031353t, voltage-dependentvoltage-dependent anion
mm anion channel 1
channel 1
38033292 NM 031531dd Serine protease Serine protease inhibitor
inhibitor
380414633NM 031533b, Androsterone UDP-Androsterone UDP-
glucuronosyltransferase
I,
s,
General,glucuronosyltransferase
vv
3805444 NM 031535t, B cell lymphoma B cell lymphoma 2 like
mm 2 like
3805445 NM 031535t, B cell lymphoma B cell lymphoma 2 like,
mm 2 like ESTs, Moderately
similar to ilvB (bacterial
acetolactate
synthase)-like; acetolactate
synthase
homoloq fHomo sapiensl
fH.sapiensl
3805446 NM 031535t, B cell lymphoma B cell lymphoma 2 like,
w, 2 like ESTs, Moderately
ii,
II,
mm similar to ilvB (bacterial
acetolactate
synthase)-like; acetolactate
synthase
homoloa fHomo sapiensl
fH.sapiensl
381715024NM 031572General,Cytochrom P45015-betaCytochrom P45015-beta
II, gene gene
qq
381715025NM 031572bb, Cytochrom P45015-betaCytochrom P45015-beta
qq ene gene
382318005NM 031588j neuregulin 1 neuregulin 1
382318011NM 031588dd neuregulin 1 neuregulin 1
384620766NM 031643nn mitogen-activatedmitogen-activated protein
protein kinase kinase kinase 1
kinase 1
384620767NM 031643s mitogen-activatedmitogen-activated protein
protein kinase kinase kinase 1
kinase 1
387713543NM 031749q, glucosidase 1 glucosidase 1
oo
387713544NM 031749c lucosidase 1 glucosidase 1
387713545NM 031749a glucosidase 1 glucosidase 1
387725209NM 031749v, glucosidase 1 glucosidase 1
w,
bb,
rr
387816624NM 031751k Shank1 Shank1
387920724NM 031753w activated leukocyteactivated leukocyte cell
cell adhesion molecule
adhesion molecule
388216003NM 031757j matrix metalloproteinasematrix metalloproteinase
24 24 (membrane-
(membrane-inserted)inserted)
38844314 NM_031760b, ATP-binding cassette,ATP-binding cassette,
m, sub- sub-family B
dd,
uu, family B (MDRITAP),(MDRITAP), member 11
vv member
11
388814184NM 031776' uanine deaminase uanine deaminase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
130
TABLE
1
'
Attorney
packet
No:
44921=5113W0
Document
No:.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
' . Title
ID= ID Acc. Code'
N0. or
N0. l2efSeq
1D
Ho:
388814185NM 031776j, guanine deaminaseguanine deaminase
r,
y
38891184 NM 031778cc Shab-related delayed-rectifierShab-related delayed-
rectifier
K+ channel
K+ channel (Kv9.3)(Kv9.3)
38914325 NM 031784u, potassium channelpotassium channel regulatory
v, regulatory protein
tt
protein KChAP KChAP
38971000 NM 031809j cyclic nucleotide-gatedcyclic nucleotide-gated
channel channel beta subunit
beta subunit 1 1
389816155NM 031810bb, defensin beta defensin beta 1
ff 1
389916039NM 031811b, transaldolase transaldolase 1
c, 1
ee,
xx
390710176NM 031837w E-septin E-septin
39111302 NM 031841pp stearoyl-Coenzymestearoyl-Coenzyme A
A desaturase 1
desaturase 1,
stearoyl-
Coenzyme A desaturase
2
39161475 NM 031971ee Heat shock proteinESTs, Highly similar
70-1 to S10A_RAT S-100
protein, alpha chain
[R.norvegicus], Heat
shock protein 70-1
391916257NM 031975I, parathymosin parathymosin
s,
General,
II,
rr
392217805NM 031980b, UDP-glucuronosyltransferaseUDP-glucuronosyltransferase
General,
gg,
hh,
vv
392217806NM_031980General,UDP-glucuronosyltransferaseUDP-
glucuronosyltransferase
ii,
II
392315265NM 031981p, p47 protein 47 protein
w,
ff
392518898NM 031985pp S6 kinase S6 kinase
3929964 NM 032062v huntingtin-associatedhuntingtin-associated
protein protein interacting
interactin proteinprotein (duo)
(duo)
393919148NM 0330960o Protein phosphataseProtein phosphatase
type 1 B type 1 B (formely 2C),
(formely 2C), Mg-dependent, beta isoform
Mg-dependent,
beta isoform
39414723 NM 033235j, Malate dehydrogenase-likeMalate dehydrogenase-like
II, enzyme
qq
enzyme
39414724 NM 033235j Malate dehydrogenase-likeMalate dehydrogenase-like
enzyme
enzyme
39422577 NM 033236u, Proteasome (prosome,Proteasome (prosome,
bb macropain) 26S
macropain) 26S subunit, ATPase
subunit,
ATPase
394924484NM 052806k Acetylcholine Acetylcholine receptor
receptor beta beta 4
4
396123211NM 053334f, calcium modulatingcalcium modulating ligand
nn li and
396315790NM 053341a regulator of G-proteinregulator of G-protein
signaling signaling 19
19
39662548 NM 053359rr ATX1 (antioxidantATX1 (antioxidant protein
protein 1) 1) homolog 1
homolog 1 (yeast)(yeast)
396719512NM 053365xx adipocyte lipid-bindingadipocyte lipid-binding
protein protein
396912223NM 053370nn, translocase of translocase of inner
qq inner mitochondria)
mitochondria) membrane 8 (yeast) homolog
membrane 8 A
east homolo A
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
131
TABLE
1
'
Aftorney
Docket
No:
44921-5113W0
Document
No.1926271:2
SEQ.GLGC GengankModel:Known Gene Name Jpigene Sequence-ClusterTitle
t
lD D Accor Code
I N0.
N0 RefSeq
ID
No.
397113492NM 053400ss ransducin-like ransducin-like enhancer
t enhancer of splitof split 3, homolog
t
3, homolog of of Drosophila
Drosophila
397216017NM 053401a brain expressed brain expressed X-linked
X-linked 3 3
397216018NM 053401a, brain expressed brain expressed X-linked
j X-linked 3 3
39736773 NM 053410rr acyl- acyl-CoA:dihydroxyacetonephosphate
CoA:dihydroxyacetonephosphatacyltransferase
a acyltransferase
397413903NM 053412Generalnterleukin enhancernterleukin enhancer
i binding i binding factor 3
factor 3
39766186 NM 053430i Flap structure-specificFlap structure-specific
i endonuclease 1
endonuclease 1
39772242 NM_053433 flavin-containingflavin-containing monooxygenase
I 3
monooxygenase
3
398123274NM_053467b, integral membraneintegral membrane protein
j, protein Tmp21-I (p23)
q,
ee
Tmp21-I (p23)
398123276NM 053467n integral membraneintegral membrane protein
protein Tmp21-I (p23)
Tmp21-I (p23
39843860 NM 053477, o, malonyl-CoA decarboxylasemalonyl-CoA decarboxylase
ff,
ii
39854290 NM 0534870, peroxisomal membraneperoxisomal membrane
y, protein protein Pmp26p
xx
Pmp26p (Peroxin-11)(Peroxin-11)
398623558NM 053507Generalexpressed in non-metastaticexpressed in non-
metastatic
cells 3, protein
cells 3, protein (nucleoside diphosphate
(nucleoside kinase)
diphosphate kinase)
398716133NM 053516dd, unknown Glu-Pro unknown Glu-Pro dipeptide
jj dipeptide repeat protein
repeat protein
398819199NM 053522a ras-like protein ras-like protein
398819200NM 053522k, ras-like protein ras-like protein
I,
s,
cc
398819205NM 053522cc, ras-like protein ras-like protein
pp
398819206NM 053522a, ras-like protein ras-like protein
cc
398918826NM 053523x, homocysteine-inducible,homocysteine-inducible,
ff, endoplasmic
nn,
ss
endoplasmic reticulumreticulum stress-inducible,
stress- ubiquitin-like
inducible, ubiquitin-likedomain member 1
domain
member 1
399231 NM 053537j solute carrier solute carrier family
family 22 (organic22 (organic anion
anion transporter),transporter), member
member 7 7
399232 NM 053537h, solute carrier solute carrier family
k, family 22 (organic22 (organic anion
I,
uu
anion transporter),transporter), member
member 7 7
39931058 NM 053539d, isopentenyl-diphosphateisopentenyl-diphosphate
o, delta delta isomerase
q,
v,
jj, isomerase
pp
399412496NM 053541kk low density lipoproteinlow density lipoprotein
receptor- receptor-related
related protein protein 3
3
399515829NM 053551y, pyruvate dehydrogenasepyruvate dehydrogenase
nn, kinase, isoenzyme
xx
kinase, isoenzyme4
4
39961198 NM 053554t, phosphatidylinositolphosphatidylinositol
mm binding binding clathrin
clathrin assemblyassembly protein
protein
399711843NM_053555Generalvesicle-associatedvesicle-associated membrane
membrane protein 5
rotein 5
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
132
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.-1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
fD ID Acc. Codev
' NO. or
,
N0. RefSeq
ID
__
No:
399711844NM 053555v vesicle-associatedvesicle-associated membrane
membrane protein 5
protein 5
39994327 NM 053563w, nuclear RNA helicase,nuclear RNA helicase,
tt DECD DECD variant of
variant of DEAD DEAD box family
box famil
400021940NM 053568Generalphosphate cytidylyltransferasephosphate
cytidylyltransferase
2,
2, ethanolamine ethanolamine
400021941NM_053568f phosphate cytidylyltransferasephosphate
cytidylyltransferase
f 2,
2, ethanolamine ethanolamine
400322617NM 053578d vacuolar proton-ATPasevacuolar proton-ATPase
subunit subunit M9.2
M9.2
400521423NM_053586r cytochrome c oxidasecytochrome c oxidase
subunit subunit Vb
Vb
400521424NM 053586e, cytochrome c oxidasecytochrome c oxidase
Generalsubunit subunit Vb
Vb
400820842NM 053590mm proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type 1
beta type 1
400920896NM 053592w, DeoxyuridinetriphosphataseDeoxyuridinetriphosphatase
x, (dUTPase)
bb
(dUTPase)
401121709NM 053596kk, Endothelin-convertingEndothelin-converting
ss enzyme 1 enzyme 1
401211830NM_053598Generaldiphosphoinositoldiphosphoinositol polyphosphate
polyphosphate phosphohydolase type
II
phosphohydolase
type II
401218795NM 053598bb diphosphoinositoldiphosphoinositol polyphosphate
polyphosphate phosphohydolase type
II
phosphohydolase
type II
401223192NM 053598a, diphosphoinositoldiphosphoinositol polyphosphate
pp
polyphosphate phosphohydolase type
II
phosphohydolase
type II
40131390 NM 053599c, ephrin A1 ephrin A1
p,
v
4024857 NM 053633tt early growth responseearly growth response
2 2
402721637NM 053653kk vascular endothelialvascular endothelial
growth growth factor C
factor C
40287228 NM 053654jj platelet-activatingplatelet-activating
factor factor acetylhydrolase,
acetylhydrolase, isoform 1b, alpha1 subunit
isoform 1b,
alpha1 subunit
40301318 NM_053656g purinergic receptorpurinergic receptor
P2X, ligand- P2X, ligand-gated ion
gated ion channel,channel, 2
2
40313454 NM 053662ii, cyclin L c clin L
tt
40313455 NM 053662w, cyclin L cyclin L
tt
403324204NM_053670b, calcitonin gene-relatedcalcitonin gene-related
General,peptide- peptide-receptor
uu receptor componentcomponent protein
protein
40346784 NM 053671v TATA element modulatoryTATA element modulatory
factor factor 1
1
40351957 NM 053674ii phytanoyl-CoA phytanoyl-CoA hydroxylase
hydroxylase (Refsum
Refsum disease disease
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
133
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Tifle
ID> ID Acc. Code
NO. or
N0. RefSeq
ID
No:
403616122NM_053698mm CbpIp300-interactingCbp/p300-interacting
transactivator, with
transactivator, GIulAsp-rich carboxy-terminal
with GIu/Asp-richdomain, 2
carboxy-terminal
domain, 2
403616123NM 053698ee CbpIp300-interactingCbpIp300-interacting
transactivator, with
transactivator, GIulAsp-rich carboxy-terminal
with GIu/Asp-richdomain, 2
carboxy-terminal
domain, 2
403713622NM 053713I Kruppel-like factorKru pel-like factor
4 (gut) 4 (gut)
403722411NM 053713f, Kruppel-like factorKruppel-like factor
qq 4 (gut) 4 (gut)
403725379NM 053713qq Kruppel-like factorKruppel-like factor
4 ( ut) 4 (gut)
40404324 NM 053744cc delta-like homologdelta-like homolo (Drosophila)
(Drosophila)
40483828 NM 053785b, transmembrane transmembrane 4 superfamily
ss 4 superfamily member 4
member 4
40516004 NM 053796rr functional adhesionfunctional adhesion
molecule 1 molecule 1
40516005 NM 053796a, functional adhesionfunctional adhesion
q, molecule 1 molecule 1
s
405325594NM 053799m aspartyl-tRNA aspartyl-tRNA synthetase
synthetase
405415615NM 053800a thioredoxin thioredoxin
405615800NM 053810w, synaptosomal-associatedsynaptosomal-associated
cc protein, 29kD
protein, 29kD
406220270NM 053827bb, procollagen-lysine,procollagen-lysine,
mm 2- 2-oxoglutarate 5-
oxoglutarate 5-dioxygenasedioxygenase (lysine
hydroxylase, Ehlers-
(lysine hydroxylase,Danlos syndrome type
Ehlers- VI)
Danlos syndrome
type VI)
406317154NM 053835d clathrin, light clathrin, light polypeptide
polypeptide (Lcb)(Lcb)
406416590NM 053838v natriuretic peptidenatriuretic peptide
receptor 2 receptor 2
406517299NM 053842ww mitogen activatedmitogen activated protein
protein kinase kinase 1
1
40671508 NM 053845e, ureidopropionase,ureidopropionase, beta
uu, beta
vv
406819018NM_053849y, protein disulfideprotein disulfide isomerase
xx isomerase related protein
related protein (calcium-binding protein,
(calcium-binding intestinal-related)
protein, intestinal-related)
406924705NM 053850ww biliverdin reductasebiliverdin reductase
A A
40791337 NM 053895p, FGF receptor activatingFGF receptor activating
tt protein protein 1
1
408315706NM 053921a peroxisomal biogenesisperoxisomal biogenesis
factor factor 12
12
40861288 NM 053949I, potassium voltage-gatedpotassium voltage-gated
s channel, subfamily
channel, subfamilyH (eag-related), member
H (eag- 2
related), member
2
40871029 NM 053953mm interleukin 1 interleukin 1 receptor,
receptor, type type II
II
408815822NM 053957Generalamyloid beta (A4)amyloid beta (A4) precursor
precursor protein-binding,
protein-binding, family B, member 3
family B,
member 3
40896538 NM 053959I myc box dependentmyc box dependent interacting
interacting protein 1
protein 1
40896539 NM 053959ss, myc box dependentmyc box dependent interacting
uu interacting protein 1
rotein 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
134
TABLE
1
Attorney
Docket
No:
44921=5113W0
Document
No.1926271.2
SE4 GI:GCGenBankModel Known Gene Name Unigene Sequence Cluster
Title .'
ID ID Acc. Code
N0. or
N0. RefSeq
ID
-.
No ' -
409016552NM 053961Generalendoplasmic retuclumendoplasmic retuclum
protein protein 29
29
409016554NM 053961 endoplasmic retuclumendoplasmic retuclum
f protein protein 29
29
409215135NM 053971w r ibosomal protein ribosomal protein L6
L6
409215136NM 053971h r ibosomal protein ribosomal protein L6
L6
40931764 NM 053974ff, eukaryotic translationeukaryotic translation
pp initiation initiation factor 4E
f actor 4E
40961292 NM_053980m ADP-ribosylation ADP-ribosylation factor
factor related related protein 1
protein 1
409815642NM 053985d, H3 histone, familyH3 histone, family 3B
r, 3B
kk,
rr
409815645NM 053985n, H3 histone, familyH3 histone, family 3B
rr 3B
409918025NM 053989vv pro estin inducedprogestin induced protein
protein
410016809NM 053990I, protein tyrosine protein tyrosine phosphatase,
oo phosphatase, non-receptor
non-receptor typetype 2
2
410224430NM 053996w proline transporterproline transporter
410316965NM 053999v protein phosphataseprotein phosphatase
2 (formerly 2 (formerly 2A),
2A), regulatory regulatory subunit B
subunit B (PR (PR 52), alpha isoform
52), alpha isoform
410421066NM 054001c, CD36 antigen (collagenCD36 antigen (collagen
v, type I type I receptor,
ii,
rr
receptor, thrombospondinthrombospondin receptor)-like
2
receptor)-like
2
410516566NM 054004a TBP-interactin TBP-interacting protein
protein 120A 120A
410617431NM 054006rr unr protein unr protein
411415391NM 057114I peroxiredoxin peroxiredoxin 1
1
411520254NM 057116ii protein phosphataseprotein phosphatase
2 (formerly 2 (formerly 2A),
2A), regulatory regulatory subunit B
subunit B (PR (PR 52), gamma
52), gamma isoformisoform
411815151NM_057131ss phosphoribosyl phosphoribosyl pyrophosphate
pyrophosphate synthetase-
synthetase-associatedassociated protein 2
protein 2
41208592 NM 057137q, phenylalkylamine phenylalkylamine Ca2+
xx Ca2+ antagonist
antagonist (emopamil)(emopamil) binding protein
binding
protein
4124358 NM 057146u, complement componentcomplement component
vv 9 9
4125706 NM 057147II sec22 homolog sec22 homolog
413123129NM 078622t, phosphate cytidylyltransferasephosphate
cytidylyltransferase
ff 1, choline,
1, choline, alphaalpha isoform
isoform
413523550NM 080698f fibromodulin fibromodulin
414023033NM 080888tt BCL2ladenovirus BCL2ladenovirus E1 B
E1 B 19 kDa- 19 kDa-interacting
interacting proteinprotein 3-like
3-like
414123477NM 080891w Fas death domain-associatedFas death domain-associated
protein
protein
41426143 NM 080892a selenium binding selenium binding protein
protein 2 2
41464739 NM_130400ff Dihydrofolate Dihydrofolate reductase
reductase 1 1 (active)
active
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
135
TABLE
1
'
Attorney
t)ocket
No44921-5113W0
Document
No.926271:2
SEQ GLGG GenBankModel ~(nown Gene Name Unigene Sequence Clusfer
' Title
ID ID Acc. Code
N0. or
NO. RefSeq
ID
No:'
414711421NM_130405w, src associated src associated in mitosis,
tt in mitosis, 68 68 kDa
kDa
41503579 NM 130409uu complement componentcomplement component
factor h factor h
41513458 NM 130412ii stromal cell derivedstromal cell derived
factor 4 factor 4
41526909 NM_130413qq src family associatedsrc family associated
phosphoprotein 2
phosphoprotein
2
415518293NM_1304330, acetyl-Coenzyme acetyl-Coenzyme A acyltransferase
ii, A 2
ss,
xx
acyltransferase (mitochondria) 3-oxoacyl-Coenzyme
2 (mitochondria) A
3-oxoacyl-Coenzymehiolase)
A thiolase) t
41573880 NM 130749bb MAP/microtubule MAPlmicrotubule affinity-regulating
affinity- kinase 3
regulating kinase
3
415818846NM 130755b, citrate synthase citrate synthase
dd
416116767NM_130826o hydroxyacyl-Coenzymehydroxyacyl-Coenzyme
A A dehydrogenasel3-
dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
hiolase/enoyl-
Coenzyme A hiolaselenoyl-Coenzyme A hydratase
(trifunctional
Coenzyme A hydrataseprotein), alpha subunit
(trifunctional
protein), alpha
subunit
416116768NM_1308260, hydroxyacyl-Coenzymehydroxyacyl-Coenzyme
ss A A dehydrogenasel3-
dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
hiolaselenoyl-
Coenzyme A hiolase/enoyl-Coenzyme A hydratase
(trifunctional
Coenzyme A hydrataseprotein), alpha subunit
(trifunctional
protein), alpha
subunit
416925405NM 133307s, protein kinase protein kinase C, delta
t, C, delta
mm
417817634NM_133418q, solute carrier solute carrier family
z, family 25 25 (mitochondria)
General,(mitochondria) carrier; dicarboxylate
carrier; transporter), member
uu dicarboxylate 10
transporter),
member 10
417817635NM_133418I, solute carrier solute carrier family
x family 25 25 (mitochondria)
(mitochondria) carrier; dicarboxylate
carrier; transporter), member
dicarboxylate 10
transporter),
member 10
417817636NM_133418pp solute carrier solute carrier family
family 25 25 (mitochondria)
(mitochondria) carrier; dicarboxylate
carrier; transporter), member
dicarboxylate 10
transporter),
member 10
417919326NM_133419q, dyskeratosis congenitadyskeratosis congenita
ss 1, 1, dyskerin
dyskerin
419225821NM 133570cc astrin-releasing astrin-releasin peptide
peptide
41981271 NM_133593a adaptor-related adaptor-related protein
protein complex complex AP-3, mu 1
AP-3, mu 1 subunitsubunit
41991546 NM_133595a, GTP cyclohydrolaseGTP cyclohydrolase I
s, I feedback feedback regulatory
uu,
vv
re ulatory proteinprotein
420017758NM_133606k, enoyl-Coenzyme enoyl-Coenzyme A, hydratasel3-
hydroxyacyl
o, A, hydratase/3-
v,
xx
hydroxyacyl CoenzymeCoenzyme A dehydrogenase
A
deh dro enase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
136
TABLE
1
'
Attorney
Docket
No:
44921-5113W0
Document
No.1926271.2
SEQGLGC GenBank Model Known Gene Name Unigene Sequence Cluster
Title
ID'ID Acc. Code.
N0. or .
N0. RefSeq
ID '
No:
4203699 NM 133617b, serine (or cysteine)serine (or cysteine)
q, proteinase proteinase inhibitor,
Generalnhibitor, Glade Glade A (alpha-1 antiproteinase,
i A (alpha-1 antitrypsin),
antiproteinase, member 10
antitrypsin),
member 10
42041728 NM_133618b, hydroxyacyl-Coenzymehydroxyacyl-Coenzyme
m, A A dehydrogenase/3-
o,
cc
dehydrogenasel3-ketoacyl-ketoacyl-Coenzyme A
thiolase/enoyl-
Coenzyme A thiolase/enoyl-Coenzyme A hydratase
(trifunctional
Coenzyme A hydrataseprotein), beta subunit
(trifunctional
protein), beta
subunit
42071463 NM 134334e, cathepsin D cathepsin D
'j
420816456NM_134346w RAP1 B, member RAP1 B, member of RAS
of RAS oncogene family
oncogene family
420816457NM 134346a RAP1 B, member RAP1 B, member of RAS
of RAS oncogene family
oncogene family
4209517 NM_134350ee Myxovirus (influenza)myxovirus (influenza
virus) resistance 3
resistance, homolog
of murine
Mx (also interferon-inducible
protein IFI78),
myxovirus
(influenza virusl
resistance 3
4210606 NM_134352f, Plasminogen activator,Plasminogen activator,
kk, urokinase receptor
tt
urokinase receptor
421114876NM 134361h small inducible small inducible cytokine
cytokine subfamily C,
subfamily C, member 1 (lymphotactin)
member 1
(I m hotactiN
42141530 NM 134397h, LL5 protein LL5 protein
vv
42161557 NM 134403qq, Cca3 protein Cca3 protein
ss,
vv
42182641 NM_134408w, calcium-independentcalcium-independent
Generalalpha- alpha-latrotoxin
latrotoxin receptorreceptor homolo 2
homolo 2
42232801 NM 134449j, PKC-delta bindingPKC-delta binding protein
j oo protein
42232802 NM 134449c PKC-delta bindingPKC-delta binding protein
protein
42275208 NM_138504w, pregnancy-inducedpregnancy-induced growth
rr growth inhibitor
inhibitor
4230534 NM 138512b, cytochrome P450 cytochrome P450 2c22
a 2c22
423115054NM 138515p cytochrome P450 cytochrome P450 2D18
2D18
423224672NM_138517j Rat natural killer (NK)
j cell protease 1 (RNKP
1) mRNA, complete Gds
424323166NM 138839m, Vacuole MembraneVacuole Membrane Protein
rr Protein 1 1
42441896 NM 138840 traps- of i networktraps- of i network
protein 1 protein 1
42441899 NM 138840w traps-gol i networktraps- olgi network
protein 1 protein 1
424917530NM_138877s Diaphorase (NADH)Diaphorase (NADH) (cytochrome
b-5
(cytochrome b-5 reductase)
reductase)
424917532NM 138877I, Diaphorase (NADH)Diaphorase (NADH) (cytochrome
z, b-5
General,(cytochrome b-5 reductase)
reductase)
nn
424917533NM_138877General,Diaphorase (NADH)Diaphorase (NADH) (cytochrome
b-5
g, (cytochrome b-5 reductase)
hh, reductase)
II
424925039NM 138877General,Diaphorase (NADH)Diaphorase (NADH) (cytochrome
b-5
ss c tochrome b-5 reductase
reductase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
137
TABLE
1
Attorney
Docket
No.
44921-5113WQ
Documenf
No.1926271.2
SEQ GLGCGenBank Model Known Gene Name Unigene SeguenceCluster
Title
ID D Acc: Code
I N0. or
N0: RefSeq
1D
No.
42514593NM 138881a Best5 protein Best5 protein
42514594NM 138881a, BestS protein Best5 protein
qq
42514595NM 138881k Best5 protein Best5 protein
42527395NM_138883p, ATP synthase, ATP synthase, H+ transporting,
ff H+ transporting,
mitochondria) mitochondria) F1 complex,
F1 complex, 0 0 subunit
subunit (oligomycin(oligomycin sensitivity
sensitivity conferring protein)
conferring protein)
425314964NM 138884s, aldo-keto reductasealdo-keto reductase
uu family 1, family 1, member D1
member D1 (delta (delta 4-3-ketosteroid-5-beta-reductase)
4-3-
ketosteroid-5-beta-reductase)
425314965NM_138884m aldo-keto reductasealdo-keto reductase
family 1, family 1, member D1
member D1 (delta (delta 4-3-ketosteroid-5-beta-reductase)
4-3-
ketosteroid-5-beta-reductase)
425718867NM 138900b, complement componentcomplement component
h, 1, s 1, s subcomponent
General,subcomponent
dd,
rr
426217185NM 138919dd unc-50 related unc-50 related protein
protein (UNCL) (UNCL)
4263287 NM_139042xx guanylyl cyclase guanylyl cyclase with
with kinase-like kinase-like domain,
domain, soluble soluble
42651674NM 139086a syncollin syncollin
4267809 NM_139089ee small inducible small inducible cytokine
cytokine B B subfamily (Cys-X-
subfamily (Cys-X-Cys),Cys), member 10
member
10
4268737 NM_139093e, CTD-binding SR-likeCTD-binding SR-like
tt protein rA9 protein rA9
427417684NM 139102d, dimethylglycine dimethylglycine dehydrogenase
h, dehydrogenase precursor
uu
precursor
427518108NM_139105I, ribonuclease/angiogeninribonuclease/angiogenin
w, inhibitor
General,inhibitor
uu,
vv
427618450NM_139106r, ATP synthase, ATP synthase, H+ transporting,
ss H+ transporting,
mitochondria) mitochondria) F1 complex,
F1 complex, deltadelta subunit
subunit
42791301NM_139192n stearoyl-Coenzymestearoyl-Coenzyme A
A desaturase 1
desaturase 1
42868717NM_139333gg, neuronal differentiation-relatedneuronal
differentiation-related
hh gene
ene
428923681NM_144746General, Rattus norvegicus protein
rr phosphatase 2A B
regulatory subunit delta
isoform mRNA,
complete cds
43041798NM_145779a, R.norvegicus alpha-1-macroglobulin
d, mRNA,
m,
uu, complete cds
vv
430820740NM_145878bb, Rattus norvegicus Sprague-Dawley
pp lipid-
bindin protein mRNA,
complete cds
431316963NM_147214r, Caldesmon 1, proteinCaldesmon 1, protein
ee phosphatase 2
phosphatase 2 (formerly 2A), regulatory
(formerly 2A), subunit B (PR 52),
regulatory subunitalpha isoform
B (PR 52),
al ha isoform
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
138
TABLE
1
Attorney
Docket
No44921-5113W0
Document
No.19262712
SEQ GLGCGenBank Model Known Gene Name Unigepe.Sequence Cluster
- Title
ID D Accor Code
_ NO.
I .
N0 RefSeq
ID
No.
431510544NM_152935m Rattus norvegicus outer
mitochondrial
membrane receptor rTOM20
mRNA,
complete cds
431510545NM 152935cc Rattus norvegicus outer
mitochondrial
membrane receptor rTOM20
mRNA,
complete cds
431612700NM 152936w Rat pancreatic secretory
trypsin inhibitor
( PSTI-II) mRNA, complete
cds
type II
43201130NM 153313a, Rat cytochrome P450CMF1
cc b mRNA,
complete cds
432114632NM_153314f, Androsterone UDP-Androsterone UDP-
glucuronosyltransferase
uu
lucuronosyltransferase
432114346NM_153314b, Rat UDP-glucuronosyltransferase
I, mRNA,
j,
General, complete cds
qq,
vv,
ww
432114347NM 153314b, Rat UDP-glucuronosyltransferase
General, mRNA,
vv complete cds
43227789NM_153630d Rattus norvegicus putative
four repeat ion
channel mRNA, complete
cds
434321981S75019 ss, ESTs, Highly similar
vv to 854676 antiquitin
-
rat (fragment) [R.norve
icus]
434724469S77858 m, ESTs, Highly similar
rr to MLES_RAT Myosin
light chain alkali,
smooth-muscle isoform
(MLC3SM) [R.norvegicus]
436517999019485 a, spp-24 precursor spp-24 precursor
g,
x,
bb,
rr
436518000019485 g, spp-24 precursor spp-24 precursor
x,
cc,
dd
4366228 020194 uu Rattus norvegicus complement
C8 beta
(C8b) mRNA, partial
cds
4366229 020194 General Rattus norvegicus complement
C8 beta
(C8b) mRNA, partial
cds
43681537027518 ss Rattus norvegicus UDP-
glucuronosyltransferase
mRNA, complete
cds
437121488032575 e, ~ ESTs, Weakly similar
xx to 149523 tumor
necrosis factor alpha-induced
protein 2 -
mouse [M.musculusl
43913387075411 cc Rat Ig active lambda2-like
chain mRNA, 3'
end
4413672 X13722 ff, Rat mRNA for LDL-receptor
jj
441615653X14210 ee, NADH ubiquinone NADH ubiquinone oxidoreductase
II subunit
oxidoreductase 813
subunit 813
441718541X14671 h, ESTs, Highly similar
gg, to RL26_RAT 60S
hh
RIBOSOMAL PROTEIN L26
[R.norvegicus]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
139
TABLE
1
Atkorney
Docket
No.
44921-51
~
3WQ
Document
No.1926271.2
SEQ GLGC GenBankModet Known Gene Name Unigene Sequence Cluster
Title -
(Ds.D Acc. Code
I CVO. or .
N0: RefSeq
ID
No.
441919244X15013 h, ESTs, Highly similar
gg, to RL7A_HUMAN 60S
hh
r ibosomal protein L7a
(Surfeit locus protein
3) (PLA-X polypeptide)
f R.norveqicusl
443018606X53504 h, ESTs, Highly similar
j, to RL12_RAT 60S
General, RIBOSOMAL PROTEIN L12
[R.norvegicus]
gg,
hh,
II
443324577X55153 h, ESTs, Highly similar
v, to R6RTP2 acidic
General ribosomal protein P2,
cytosolic [validated]
-
ratfR.norvegicusl
443817175X58389 rr R.norvegicus ASI mRNA
for mammalian
equivalent of bacterial
large ribosomal
subunit protein L22
444421657X61381 b, Rattus norvegicus interferon-inducible
x,
General, protein variant 10 mRNA,
complete cds
bb,
dd,
II,
nn,
as
445622424X67788 z, villin 2 villin 2
,
hh
4458602 X68101 bb R.norve icus trg mRNA
4459588 X69834 a, R,norvegicus mRNA for
ii, serine protease
rr
inhibitor 2.4
446016300X70706 j plastin 3 (T-isoform)plastin 3 (T-isoform)
4468463 X83579 f, cyclin-dependent cyclin-dependent kinase
q, kinase 7 7 (M015 homolog,
u,
ww
(M015 homolog, Xenopus laevis, cdk-activating
Xenopus kinase)
laevis, cdk-activating
kinase)
447817146Y07534 b, Serine protease Serine protease inhibitor
qq inhibitor
448020695Y09000 gg, Dendrin Dendrin
hh
4481407 211995 gg, low density lipoproteinlow density lipoprotein
hh receptor- receptor-related
related protein protein associated protein
associated 1
protein 1
872 16499AA925300d HHs:mitogen-activatedESTs, Weakly similar
protein to mitogen activated
kinase kinase protein kinase kinase
kinase 3 kinase 1 [Rattus
norveAicuslfR.norvegicusl
19082069 A1103616bb HHs:ras-related ESTs, Weakly similar
C3 botulinum to ras-like protein
toxin substrate [Rattus norvegicus]
1 (rho family, [R.norvegicus]
small GTP binding
protein
Rac1)
26505778 A1233246ii HHs:polymerase ESTs, Weakly similar
(RNA) II (DNA to RNA polymerase I
directed) polypeptide(127 kDa subunit) [Rattus
B (140kD) norvegicus]
fR.norveaicusl
26545779 AI233350I HHs:polymerase ESTs, Weakly similar
(RNA) II (DNA to RNA polymerase I
directed) polypeptide(127 kDa subunit) (Rattus
B (140kD) norvegicus]
fR.norvegicusl
438711 U70210 g amyloid beta (A4)amyloid beta (A4) precursor
precursor protein-binding,
protein-binding, family B, member 2
family B,
member 2
123 18115AA800339d, Transferrin Transferrin
General,
ee,
kk
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
140
TABLE
1
.Attorney
Docket
Nor
44921-5113W0
Document
No.1926271.2
SEQ GLGC GeriBankModel Known Gene Name Jnigene Sequence Cluster
l Title -
ID ID Aca. Code
N0. or
'
NO: RefSeq
ID
No.
184 2143 AA817892e, guanine nucleotideguanine nucleotide binding
gg, binding protein beta 2
hh,
jj
protein beta 2 subunit
subunit
420 2263 AA859757a collagen, type collagen, type V, alpha
V, alpha 1 1
435 23324AA859980a, T-complex 1 T-complex 1
c,
d,
jj
435 18578AA859980a, T-complex 1 T-complex 1
c,
q,
jj,
ss
445 17111AA860062ee Albumin Albumin
497 15342AA875172k SH3-domain kinaseSH3-domain kinase binding
binding protein 1
protein 1
499 18897AA875207g Hemoglobin, beta Hemoglobin, beta
592 17345AA892014c HLA-B associated HLA-B associated transcript
transcript 1A 1A
592 17346AA892014k HLA-B associated HLA-B associated transcript
transcript 1A 1A
656 23180AA892649j, gamma-aminobutyricgamma-aminobutyric acid
I, acid receptor
General,receptor associatedassociated protein
protein
cc
663 12118AA892775I, Lysozyme Lysozyme
General,
gg,
hh,
kk
704 20986AA893242o fatty acid Coenzymefatty acid Coenzyme
A ligase, A ligase, long chain
2
l ong chain 2
756 6377 AA894273t, dimethylarginine dimethylarginine
dimethylaminohydrolase
qq 1
dimethylaminohydrolase
1
989 19421AA945152n, dimethylarginine dimethylarginine
dimethylaminohydrolase
ee 1
dimethylaminohydrolase
1
109424230AA957218ii Cyclin D1 C clip D1
124614583AB008807dd, glutathione S-transferaseESTs, Highly similar
uu to GT01 RAT
omega 1 Glutathione transferase
omega 1 (GSTO 1-
1) (Glutathione-dependent
dehydroascorbate reductase)[R.norvegicus]
124917963AB012231h nuclear factor nuclear factor IIB
IIB
125024414AB012234ii Nuclear factor Nuclear factor IIX (CCAAT-binding
I/X (CCAAT- '
binding transcriptiontranscription factor)
factor)
12514307 AB012600s aryl hydrocarbon aryl hydrocarbon receptor
receptor nuclear
nuclear translocator-liketranslocator-like
125720438AF009656e, hypoxanthine guaninehypoxanthine guanine
a phosphoribosyl
phosphoribosyl transferase
transferase
12594308 AF015953ww aryl hydrocarbon aryl hydrocarbon receptor
receptor nuclear
nuclear translocator-liketranslocator-like
127816006AF062594m, nucleosome assemblynucleosome assembly
ii protein 1- protein 1-like 1
like 1 '
13147785 A1008758vv Dipeptidyl peptidaseDipeptidyl peptidase
4 4
141016010A1011922a nucleosome assemblynucleosome assembly
protein 1- protein 1-like 1
like 1
146517065A1013531qq carbonyl reductasecarbonyl reductase 1
1
159620983A10449000, fatty acid Coenzymefatty acid Coenzyme
v A ligase, A ligase, long chain
2
long chain 2
193818277AI104399t Triose hos hate Triose hos hate isomerase
isomerase 1 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
141
TABLE
1
Aftorney
Docket
No44921=5113WD
Document
No.1926271.2
SEQ GLGC GenBankModel Kriown Gene Name Uraigene Sequence Cluster
Title
ID ID Acc. Code
N(?: or
N0. RefSeq
ID
No
196117171AI10513700, Somatostatin ESTs, Highly similar
rr to GTK1 RAT
Glutathione S-transferase,
mitochondria)
(GST 13-13) (Glutathione
S-transferase
subunit 13) (GST class-kappa)
I R.norveaicusl. Somatostatin
203116510AI137583b, Inhibitor of DNA nhibitor of DNA binding
w, binding 2, I 2, dominant
ii,
rr,
tt dominant negativenegative helix-loop-helix
helix-loop- protein
helix protein
223512614AI175294Generalribosomal proteinribosomal protein L21
L21
242419427AI179510pp dimethylarginine dimethylarginine
dimethylaminohydrolase
1
dimethylaminohydrolase
1
246522845A1227887t cell division cell division cycle
cycle 42 42
248718612AI228624a, ribosomal proteinribosomal protein L29
c, L29
e,
kk
253223041AI230130a ectonucleoside ectonucleoside triphosphate
triphosphate
diphosphohydrolasediphosphohydrolase 2
2
276714666AI236912z Ngfi-A binding Ngfi-A binding protein
protein 1 1
282319112AI639157w ribosomal proteinribosomal protein L13
L13
28969135 D45247 b, proteasome beta ESTs, Highly similar
mm type subunit to PSBS_RAT
5
Proteasome subunit beta
type 5 precursor
(Proteasome epsilon
chain) (Macropain
epsilon chain) (Multicatalytic
endopeptidase
complex epsilon chain)
(Proteasome subunit
X) (Proteasome chain
6) [R.norvegicus]
290120984D90109 0, fatty acid Coenzymefatty acid Coenzyme
gg, A ligase, A ligase, long chain
hh, 2
oo, Ion chain 2
uu
293926368H34047 jj T-complex 1 T-complex 1
296017508L08814 e, Structure specificStructure specific recognition
gg, recognition protein 1
hh,
0o protein 1
297821146L35558 gg, Solute carrier Solute carrier family
hh family 1 A1 (brain1 A1 (brain glutamate
glutamate transporter)transporter)
29891466 M14050 p, Heat shock 70kD ESTs, Heat shock 70kD
q, protein 5 protein 5
General,
dd,
ff
301721399M36410 Generalsepiapterin reductasesepiapterin reductase
301721400M36410 n, sepiapterin reductasesepiapterin reductase
x,
General,
dd,
ee
302713547M63983 a hypoxanthine guanineESTs, Moderately similar
to ICA2_MOUSE
_
phosphoribosyl Intercellular adhesion
transferase molecule-2 precursor
(ICAM-2) (CD102) (Lymphocyte
function-
associated AG-1 counter-receptor)
[M.musculus], hypoxanthine
guanine
ohosohoribosvl transferase
302810743M64780 I, Agrin Agrin
p,
z,
General
302810744M64780 I, Agrin Agrin
p,
z,
General,
ii,
nn
rr
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
142
TABLE
1
Attorney
Docket'No.
44921-5113W0
Document
No.1926271
~2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
_ N0. or .
~
NO. RefSeq
ID
Nor'
303121670M80601 f, programmed cell programmed cell death
I, death 2 2
z,
General
304522513NM 012488nn Alpha-2-macro Alpha-2-macro lobulin
lobulin
305220153NM_012503b, AsialoglycoproteinAsialoglycoprotein receptor
g, receptor 1 1 (hepatic lectin)
v
(hepatic lectin)
3057563 NM 012516I, Complement componentComplement component
vv 4 4 binding protein,
bindin protein, al ha
alpha
306216520NM 012532b, Ceruloplasmin Ceruloplasmin (ferroxidase)
a (ferroxidase)
306821834NM 012555x Ets avian erythroblastosisEts avian erythroblastosis
virus virus E2
E2 oncogene homologoncogene homolog 1 (tumor
1 (tumor progression
progression locuslocus 1)
1)
306821835NM 012555y Ets avian erythroblastosisEts avian erythroblastosis
virus virus E2
E2 oncogene homologoncogene homolog 1 (tumor
1 (tumor progression
progression locuslocus 1)
1)
308220126NM 012591u, Interferon regulatoryInterferon regulatory
nn factor 1, factor 1, sirtuin 2
(silent
sirtuin 2 (silentmating type information
mating type regulation 2,
information regulationhomology 2 (S. cerevisiae)
2,
homoloa) 2 (S.
cerevisiae)
30971840 NM 012637g protein tyrosine protein tyrosine phosphatase,
phosphatase, non-receptor
non-receptor typetype 1
1
30971841 NM 012637ww protein tyrosine protein tyrosine phosphatase,
phosphatase, non-receptor
non-receptor typetype 1
1
30971844 NM 012637ww protein tyrosine ESTs, protein tyrosine
phosphatase, phosphatase, non-
non-receptor typereceptor type 1
1
310521794NM 012670, m, T-complex 1 T-complex 1
s
312516613NM 012732c Cholesterol esteraseCholesterol esterase
(pancreatic)
(pancreatic)
312510260NM 012732y Cholesterol esteraseCholesterol esterase
(pancreatic)
(pancreatic)
312623806NM 012733b, Retinol-binding Retinol-binding protein
qq protein 1 1
3130426 NM 012738I, Apolipoprotein Apolipoprotein A'-I
General,A-I
cc,
nn,
vv
3130427 NM 012738f, Apolipoprotein Apolipoprotein A-I
I, A-I
x,
General,
nn,
vv
31407783 NM 012789qq Dipeptidyl peptidaseDipeptidyl peptidase
4 4
31407784 NM 012789General,Dipeptidyl peptidaseDipeptidyl peptidase
4 4
kk
314124113NM 012791r dual-specificity dual-specificity tyrosine-(Y)-
phosphorylation
tyrosine-(Y)-
phosphorylation regulated kinase 1 a
regulated
kinase 1a
3145556 NM 012803b, Protein C Protein C
u,
x,
dd
314621729NM 0128040, ATP-binding cassette,ATP-binding cassette,
ff sub- sub-family D (ALD),
family D (ALD), member 3
member 3
314621730NM 0128040, ATP-binding cassette,ATP-binding cassette,
v sub- sub-family D (ALD),
family D (ALD), member 3
member 3
316118767NM 012857qq Lysosomal associatedLysosomal associated
membrane protein 1
membrane rotein 120 kDa
1 120 kDa
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
143
TABLE
1
Attorney
Docket
No:
449215113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
. Title
ID ID Ace. Code
N0. or
N0: RefSeq
ID
No.
316118770NM 012857m, Lysosomal associatedLysosomal associated
ff, membrane protein 1
ii,
rr
membrane protein 120 kDa)
1 (120 kDa) (
316816721NM 0128910, Acyl-Coa dehydrogenase,Acyl-Coa dehydrogenase,
General,Very Very long chain
cc, ong chain
kk,
uu
l
317423 NM 012907ii Apolipoprotein Apolipoprotein B editing
B editing proteinprotein
317524431NM 012912c, Activating transcriptionActivating transcription
n, factor 3 factor 3
General,
kk,
tt
318020755NM 012923m, Cyclin G1 Cyclin G1
a
318413723NM 012935a Crystallin, alphaCrystallin, alpha polypeptide
polypeptide 2 2, ESTs, ESTs,
Weakly similar to T46637
transcription factor
1, neural - rat [R.norvegicus]
31859109 NM 012939I, Cathepsin H Cathepsin H
General
31981525 NM_012980v Matrix metalloproteinaseMatrix metalloproteinase
11 11 (stromelysin 3)
(stromelysin 3)
321518078NM 013030r Solute carrier Rattus norvegicus mRNA
family 17 for NaPi-2 alpha,
(sodiumlhydrogen complete cds, Solute
exchanger), carrier family 17
member 2 (sodiumlhydroqen exchanger),
member 2
3219730 NM 013040cc ATP-binding cassette,ATP-binding cassette,
sub- sub-family C
family C (CFTRIMRP),(CFTRIMRP), member 9
member
9
322616511NM 013060rr Inhibitor of DNA Inhibitor of DNA binding
binding 2, 2, dominant
dominant negativenegative helix-loop-helix
helix-loop- protein
helix protein
326524490NM 013178s, Sodium channel, Sodium channel, voltage-gated,
cc voltage-gated, type IV,
type IV, alpha alpha polypeptide
polypeptide
326610499NM 013184r, Neurotrophin 5 ribosomal protein S23
ii (neurotrophin
4I5), ribosomal
protein S23
32721693 NM 013199a Dynamin 2 Dynamin 2
328424649NM 016988b, Acid phosphatase Acid phosphatase 2,
e, 2, lysozymal lysozymal
I,
w,
General
32871958 NM 016994b, Complement componentComplement component
General,3 3
uu,
vv
32871959 NM 016994f, Complement componentComplement component
u, 3 3
uu
32891698 NM 017000a Diaphorase (NADH/NADPH)Diaphorase (NADH/NADPH)
329218989NM 017013qq, Glutathione-S-transferase,Glutathione-S-transferase,
vv alpha type (Yc?)
alpha t pe (Yc?)
330024861NM 017033p, PhosphoglucomutasePhosphoglucomutase 1
General1
330024862NM 017033x, PhosphoglucomutasePhosphoglucomutase 1
General1
33081942 NM 017061a Lysyl oxidase Lysyl oxidase
33081946 NM 017061ss Lysyl oxidase Lysyl oxidase
33141262 NM 017077c, Hepatocyte nuclearHepatocyte nuclear factor
v, factor 3 3 gamma
rr,
xx
amma
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
144
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Kr~own Gene Name tJnigene Sequence-ClusterTitle
ID D Acc. Code
I N0. or
NO. RefSeq
ID
No:'
331623660NM 017080a, Hydroxysteroid Hydroxysteroid dehydrogenase,11
I, dehydrogenase, beta type
vv 11 beta type 1 1
33214392 NM 017101mm Peptidylprolyl Peptidylprolyl isomerase
( isomerase A A (cyclophilin A)
cyclophilin A)
33214393 NM 017101bb, Peptidylprolyl Peptidylprolyl isomerase
mm isomerase A A (cyclophilin A)
( cyclophilin A)
33231548 NM_017112b, hepsin hepsin
General
33261435 NM 017125I, Cd63 anti en Cd63 antigen
cc,
rr
3329169 NM 017131f calsequestrin calsequestrin 2
2
333510503NM 017143a, coa ulation factorcoagulation factor X
x, X
dd
333510504NM 017143d, coagulation factorcoagulation factor X
dd X
33385351 NM 017150j ribosomal proteinribosomal protein L29
L29
334717686NM 017165o glutathione peroxidaseglutathione peroxidase
4 4
33498182 NM 017170a, serum amyloid serum amyloid P-component
bb P-component
335020919NM 017172v, zinc finger proteinzinc finger protein
nn 36, C3H type- 36, C3H type-like 1
l ike 1
3351114 NM 0171750o protein kinase protein kinase C-like
C-like 1 1
33523512 NM_017177d, choline kinase-likecholine kinase-like
o,
q,
v,
dd
33523513 NM 017177d, choline kinase-likecholine kinase-like
n,
dd
33533174 NM 017178qq bone morphogeneticbone morphogenetic protein
protein 2 2
335423961NM 017181b, fumarylacetoacetatefumarylacetoacetate
uu, hydrolase hydrolase
vv
335515434NM 017187y hi h mobility high mobility group
group box 2 box 2
335515437NM 017187r, high mobility high mobilit roup box
y, roup box 2 2
ww
33589124 NM 017199j, si nal sequence si nal sequence receptor,
ii receptor, delta delta
33589125 NM 017199u, signal sequence signal sequence receptor,
dd, receptor, delta delta
ii,
II
33589126 NM 017199g si nal sequence signal sequence receptor,
receptor, delta delta
33625005 NM_017209n nuclear receptor nuclear receptor binding
binding factor factor 1
1
337221743NM 017235jj hydroxysteroid hydroxysteroid 17-beta
17-beta dehydrogenase 7
dehydro enase
7
337221744NM 017235bb, hydroxysteroid ESTs, Highly similar
ii, 17-beta to DHB7_RAT
jj dehydrogenase ESTRADIOL 17 BETA-DEHYDROGENASE
7 7 (17-BETA-HSD 7) (17-BETA-
HYDROXYSTEROID DEHYDROGENASE
7)
(PRL RECEPTOR ASSOCIATED
PROTEIN)
(PRAP) [R.norvegicusj
337410427NM 017237bb ubiquitin carboxy-terminalubiquitin carboxy-terminal
hydrolase L1 hydrolase L1
337410429NM_017237cc ubiquitin carboxy-terminalubiquitin carboxy-terminal
hydrolase L1 hydrolase L1
33751498 NM 017239v myosin heavy chain,myosin heavy chain,
polypeptide 6, polypeptide 6, cardiac
cardiac muscle, muscle, alpha
alpha
337717561NM_017245mm eukaryotic translationeukaryotic translation
elongation elongation factor 2
factor 2
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
145
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Kraown Gene Name Unigene Sequence ClustetTitle
,
ID ID Acc: Code
N0. or
N0 RefSeq
ID
No.:,
337717562NM 017245h, eukaryotic translationeukaryotic translation
t, elongation elongation factor 2,
mt
factor 2, mitogenmitogen activated protein
activated kinase kinase 2
protein kinase
kinase 2
337717563NM 017245gg, eukaryotic translationeukaryotic translation
hh elongation elongation factor 2
factor 2
337917502NM_017248rr heterogeneous heterogeneous nuclear
nuclear ribonucleoprotein A1
ribonucleoprotein
A1
337915012NM 017248kk heterogeneous ESTs, Highly similar
nuclear to DDRT helix-
ribonucleoproteindestabilizing protein
A1 - rat [R.norvegicus],
heterogeneous nuclear
ribonucleoprotein A1
338319 NM 017258s, B-cell translocationB-cell translocation
ss, gene 1, anti- gene 1, anti-proliferative
tt
proliferative
339515535NM 017283I proteasome (prosome,proteasome (prosome,
I macropain) subunit,
macropain) subunit,alpha type 6
alpha type
6
339612523NM_017285tt proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type, 3
beta type, 3
339612524NM_017285kk proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,beta type, 3
beta type, 3
339720579NM 017288a sodium channel, sodium channel, voltage-gated,
voltage-gated, type I, beta
type I, beta polypeptidepolypeptide
340423130NM_017307j, solute carrier solute carrier family
z, family 25 25 (mitochondrial
General(mitochondrial carrier; citrate transporter)
carrier; citrate member 1
transporter) member
1
34121630 NM_017325qq, runt related transcriptionrunt related transcription
vv factor 1 factor 1
342824785NM 019133n Synapsin I Synapsin I
34391608 NM 019166a synaptogyrin 1 ESTs, Moderately similar
to SNG1 RAT
SYNAPTOGYRIN 1 (P29)
[R.norvegicus],
synaptogyrin 1
344117064NM 019170uu carbonyl reductasecarbonyl reductase 1
1
3442269 NM 019180d mast cell proteasemast cell protease 6
6
34512632 NM_019213s jumping translocationjumping translocation
breakpoint breakpoint
345315348NM 019222k, coronin, actin coronin, actin binding
m binding protein protein 1 B
1 B
345620433NM 019232tt, serumlglucocorticoidserumlglucocorticoid
xx regulated regulated kinase
kinase
345715504NM 019237d procollagen C-proteinaseprocollagen C-proteinase
enhancer protein
enhancer protein
346017908NM 019242f, interferon-relatedinterferon-related developmental
General,developmental regulator 1
ee, regulator 1
pp
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
146
TABLE
1
Attorney
Docket
No.
44921-_5113W0
-Document
No.19262712
SEQ GLGC GenBankModel Known.Gene Name Jnigene Sequence Cluster
l Title
ID ID Acc: Code'
. N0. or
N0. _
RefSeq
ID
No:
34641973 NM 019249h, protein tyrosine protein tyrosine phosphatase,
q, phosphatase, receptor-type,
r,
w,
z, eceptor-type, F
General,F
r
ee,
nn
346713450NM 019255k calcium channel, calcium channel, voltage-dependent,
voltage- gamma
dependent, gamma subunit 1
subunit 1
34931818 NM 019369a, nter-alpha-inhibitornter-alpha-inhibitor
uu H4 heavy i H4 heavy chain
i
chain
34951323 NM_019371t, EGL nine homolog EGL nine homolog 3 (C.
mm 3 (C. elegans)
elegans)
34951324 NM 019371t, EGL nine homolog EGL nine homolog 3 (C.
mm 3 (C. elegans)
ele ans)
3507574 NM_019905m calpactin I heavycalpactin I heavy chain,
chain, hydroxyacid oxidase
hydroxyacid oxidase3 (medium-chain), unknown
3 (medium- Glu-Pro
chain), unknown dipeptide repeat protein
Glu-Pro
dipeptide repeat
protein
351212087NM 020082d ribonuclease 4 ribonuclease 4
351919059NM 021587a transforming growthtransforming growth
factor-beta factor-beta (TGF-beta)
(TGF-beta) maskingmasking protein large
protein subunit
large subunit
352219679NM 021653a, Thyroxine deiodinase,Thyroxine deiodinase,
d, type I ' type I
ii
354423782NM 022183xx topoisomerase topoisomerase (DNA)
(DNA) II alpha II alpha
355619422NM 022297j, dimethylarginine dimethylarginine
dimethylaminohydrolase
z 1
dimethylaminohydrolase
1
355619423NM_022297I dimethylarginine dimethylarginine
dimethylaminohydrolase
1
dimethylaminohydrolase
1
35738214 NM 022500f, ferritin light ferritin light chain
n chain 1 1
35755319 NM 022502r, palmitoyl-proteinpalmitoyl-protein thioesterase
u, thioesterase
z
35771468 NM 022507dd protein kinase protein kinase C, zeta
C, zeta
35894601 NM 022524g sushi-repeat-containingsushi-repeat-containing
protein, protein, X
X chromosome chromosome
359920925NM_022594o Peroxisomal enoylPeroxisomal enoyl hydratase-like
hydratase- protein
like protein
361217661NM 022674c, H2A histone family,H2A histone family,
d, member Z member Z
oo,
xx
36511785 NM 024130x, dynactin 1 dynactin 1
oo
36891853 NM 030826g Glutathione peroxidaseESTs, Glutathione peroxidase
1 1
370020410NM 030990g, Proteolipid proteinProteolipid protein
bb, (Pelizaeus- (Pelizaeus-Merzbacher
cc
Merzbacher disease,disease, spastic paraplegia
spastic 2,
paraplegia 2, uncomplicated)
uncomplicated)
370521165NM 031005mm actinin, alpha actinin, alpha 1
1
370521166NM 031005t, actinin, alpha actinin, alpha 1
mm 1
3707997 NM 031007a adenylyl cyclase adenylyl cyclase 2
2
3722690 NM_031034t, guanine nucleotideguanine nucleotide binding
v, binding protein (G
General,protein (G protein)protein) alpha 12
alpha 12
mm
3722691 NM 031034t, guanine nucleotideguanine nucleotide binding
mm binding protein (G
protein (G protein)protein) alpha 12
alpha 12
37381855 NM 031074d nucleoporin 98 nucleoporin 98
~
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
147
TABLE
1
Attorney
Docket
No:
4492~5113W0
Document
No.1926279.2
SEQ GLGC GenBankModel Known Gene Name' Unigene Sequence Cluster
Title
ID ID Acc. Code
j N0. or
N0. RefSeq
ID
No..
374823854NM 031101Generalibosomal protein ibosomal protein L13
r L13 r
375016938NM 031103ee ibosomal protein ibosomal protein L19
r L19 r
375819040NM 031114qq, S-100 related S-100 related protein,
vv protein, clone clone 42C
42C
376215539NM 031132v proteasome (prosome,proteasome (prosome,
macropain) subunit,
macropain) subunit,alpha type 6, transforming
alpha type growth factor-b
6, transforming ype II receptor
growth factor-b
t
t ype II receptor
37863519 NM 031334h, Cadherin 1 Cadherin 1
o,
dd
379618990NM_031509a Glutathione-S-transferase,Glutathione-S-transferase,
alpha type (Yc?)
alpha type (Yc?)
379717427NM 031510p Isocitrate dehydrogenasesocitrate dehydrogenase
1, I 1, soluble
soluble
380012580NM_031514m, Janus kinase 2 Janus kinase 2 (a protein
v (a protein tyrosine kinase)
tyrosine kinase)
380220448NM 031530vv Small inducible Small inducible gene
gene JE JE
380220449NM 031530vv Small inducible Small inducible ene
gene JE JE
3812692 NM_031557g Prostaglandin Prostaglandin 12 (prostacyclin)
12 (prostacyclin)synthase
synthase
38169620 NM 031570h, ribosomal proteinribosomal protein S7
General,S7
II
38169621 NM_031570General,ribosomal proteinribosomal protein S7
rr S7
382814295NM 031599f, eukaryotic translationeukaryotic translation
I, initiation initiation factor 2
pp alpha
factor 2 alpha kinase 3
kinase 3
383721585NM_031620j 3-phosphoglycerate3-phosphoglycerate dehydrogenase
dehydrogenase
383721586NM 031620j, 3-phosphoglycerate3-phosphoglycerate dehydrogenase
u,
dd,
00
dehydrogenase
383721587NM_031620k 3-phosphoglycerate3-phosphoglycerate dehydrogenase
dehydrogenase
38381683 NM 031621e, linker of T-cell linker of T-cell receptor
ww receptor pathways
pathways
383914956NM_031622I mitogen-activatedmitogen-activated protein
protein kinase kinase 6
6
38411639 NM 031627c, nuclear receptor nuclear receptor subfamily
x, subfamily 1, 1, group H,
General,group H, member member 3
3
ss
38451727 NM 031642r, core promoter core promoter element
tt element binding binding protein
protein
385418403NM 031677r four and a half four and a half LIM
LIM domains 2 domains 2
38562327 NM 031683II SMC (segregation SMC (segregation of
of mitotic mitotic chromosomes
chromosomes 1)-like1)-like 1 (yeast)
1 (yeast)
385720743NM 031684dd solute carrier solute carrier family
family 29 29 (nucleoside
(nucleoside transporters),transporters), member
1
member 1
385919727NM_031687h, ubiquitin A-52 ubiquitin A-52 residue
ff residue ribosomalribosomal protein
protein fusion fusion product 1
product 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1dR
TABLE
1
Attorney
Docket
No.
44921-51.13W0
Document
No.19262712
SEQ GLGGGenBank Model Known Gene Name nigene Sequence Cluster
. U Title
lD D-N0.cc. or ode
I A = C .
N0. RefSeq
- ID .
No. -
3862 3706NM 031699s c laudin 1 c laudin 1
1 s
3864 25652NM 031704q s yntaxin 5a s yntaxin 5a
3864 20718NM 031704n s yntaxin 5a s yntaxin 5a
3864 20719NM 031704b, syntaxin 5a syntaxin 5a
q,
y,
dd
3874 17554NM 0317360, solute carrier solute carrier family
vv family 27 (fatty27 (fatty acid
acid transporter),ransporter), member 2
member 2 t
3886 15647NM 031773, y RNA polymerase RNA polymerase I (127
I I (127 kDa kDa subunit)
subunit)
3896 2114NM 031798u, solute carrier solute carrier family
kk family 12, member12, member 2
2
3901 10676NM 031818t intracellular intracellular chloride
chloride ion ion channel protein
channel
protein p64H1 p64H1
3902 2655NM 031821I, serum-inducible serum-inducible kinase
kk, kinase
nn,
tt
3904 4748NM 031834k, sulfotransferasesulfotransferase family
cc, family 1A, 1A, phenol-
vv
phenol-preferring,preferring, member 1
member 1
3904 4749NM 031834b, Aryl sulfotransferaseAryl sulfotransferase
k, cytosolic, cytosolic,1A, phenol-
I,
ii
1A, phenol-preferring,preferring, member 3,
member sulfotransferase
3, sulfotransferasefamily 1A, phenol-preferring,
family 1A, member 1
phenol-preferring,
member 1
3910 15069NM 031840k, Farnesyl diphosphateFarnesyl diphosphate
s, synthase synthase
jj
3910 15070NM 031840ii, Farnesyl diphosphateFarnesyl diphosphate
jj, synthase synthase
rr
3910 25460NM 031840k, Farnesyl diphosphateFarnesyl diphosphate
jj synthase synthase
3930 860 NM 032063mm delta (Drosophila)-likedelta (Drosophila)-like
1 1
3931 18494NM 032079n, DnaJ (Hsp40) DnaJ (Hsp40) homolog,
ff, homolog, subfamily A,
pp
subfamily A, member 2
member 2
3934 12299NM 032416a, aldehyde dehydrogenasealdehyde dehydrogenase
General2, 2, mitochondria)
mitochondria)
3940 17829NM 033234v Hemo lobin, betaHemoglobin, beta
3952 1311NM 053291j, phospho lyceratephosphoglycerate kinase
s, kinase 1 1
t
3958 1063NM 053328p, basic helix-loop-helixbasic helix-loop-helix
t, domain domain containing,
ff
containing, classclass B2
B2
3960 14928NM 053330ff, ribosomal proteinribosomal protein L21
gg, L21
hh
3965 14042NM 053348cc fetuin beta fetuin beta
4007 20831NM 053589g GTPase Rab14 GTPase Rab14
4020 1178NM 053620II Cdc42-binding Cdc42-binding protein
protein kinase kinase beta
b eta
4072 17728NM 053867n, tumor protein, tumor protein, translationally-
controlled
ee translationally-1
controlled 1
4073 19781NM 053883, tt dual specificitydual specificity phosphatase
phosphatase 6
6
4075 14992NM 053886dd lectin, mannose-bindinlectin, mannose-binding,1
,1
4107 23250NM 057097m vesicle-associatedvesicle-associated membrane
membrane protein 3
protein 3
4122 2413NM 057141I, heterogeneous heterogeneous nuclear
n nuclear ribonucleoprotein K
ribonucleoprotein
K
4122 2416NM 057141w heterogeneous heterogeneous nuclear
nuclear ribonucleoprotein K
ribonucleo rotein
K
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1~1~
TABLE
1
:
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ
GLGC
GenBank:
Model
Known
Gene
Name
Unigene
Sequence
Cluster
Title
Y
lD
IDN0.
Acc.
or
Code
N0.
l2efSeq
ID
.
No:
,
41288641 NM 057211f Kruppel-like factorKruppel-like factor
9 9
413010498'NM 078617w, ribosomal proteinribosomal protein S23
y S23
41688436 NM 133299b, erosisomal 2-enoyl-CoAperosisomal 2-enoyl-CoA
General, reductase
p
vv reductase
4175656 NM 133380x Interleukin 4 Interleukin 4 receptor
receptor
420617112NM_134326ee Albumin, GlutathioneAlbumin, Glutathione
peroxidase 1
peroxidase 1
423915189NM 138826q, Metallothionein Metallothionein
w 1 A
423915190NM 138826n, Metallothionein Metallothionein
w, 1 A
ii
424516354NM 138843v, ercaptopyruvate mercaptopyruvate sulfurtransferase
xx
m
sulfurtransferase
42509896 NM_138878p Neural precursor Neural precursor cell
cell expressed, expressed,
developmentally developmentally down-regulated
down-regulated gene 8
gene 8
_
42601858 NM_1389070, acyl-CoA thioesteraseacyl-CoA thioesterase
q, 1, 1, cytosolic,
jj,
xx
cytosolic, mitochondria)mitochondria) acyl-CoA
acyl- thioesterase 1
CoA thioesterase
1
432519429847028 n dimethylarginine dimethylarginine dimethylaminohydrolase
1
dimethylaminohydrolase
1
43338210 S61960 a ferritin light ferritin light chain
chain 1 1
43611392 010188 j Polo-like kinase Polo-like kinase homolog
homolog
438317078053859 k, calpain, small calpain, small subunit
jj subunit 1 1
438317079053859 jj calpain, small calpain, small subunit
subunit 1 1
438525608053927 t, cationic amino cationic amino acid
ff acid transporter-transporter-2A
2A
442210819X51536 h, ibosomal protein ESTs, Highly similar
k S3 to RS3_MOUSE 40S
r
r ibosomal protein S3
[R.norvegicus]
44341037 X57523 a, Transporter 1, Transporter 1, ABC (ATP
qq ABC (ATP binding cassette)
b inding cassette)
443718611X58200 h, ibosomal protein ibosomal protein L29
I, L29 r
r
General,
ee
44451587562145 ee, ibosomal protein STs, Highly similar
X gg, L8 E to RL8 HUMAN 60S
hh
r
r ibosomal protein L8
[R.norvegicus]
44502082162671 II inkel-Biskis-ReillySTs, Highly similar
X F murine E to UBIM_RAT
s arcoma virus (FBR-MuSV)BIQUITIN-LIKE PROTEIN
U FUBI
u biquitously expressedR.norvegicus]
(fox [
d erived)
44526376 62951 xx imethylarginine imethylarginine dimethylaminohydrolase
X d d 1
d imethylaminoh
drolase 1
44541641365036 0o lpha 7A inte rin lpha 7A integrin
X a a
44541641465036 a a lpha 7A inte rin lpha 7A integrin
X a
44631260 77934 , mm myloid protein myloid protein precursor-like
1 X t A precursor-like protein 2
A
p rotein 2
80 21042A799814p H Mm:MAP kinase-activatedSTs, Weakly similar
A E to A34366
p rotein kinase a2+/calmodulin-dependent
2 C protein kinase
( EC 2.7.1.123) II delta
chain - rat
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
150
TABLE
1
:
Attorney
Docket
No:
44921-5113W0
Document
No.19262712
SE GLGC GenBankModef Known Gene Name Unigene Sequence Cluster
: 4 Title
ID ID-N0.Acc. Code
or
NO RefSeq
ID
No.;
119 19020AA800291e, HMm:guanylate ESTs, Weakly similar
h, kinase 1 to discs, large
n
homolog 3 (Drosophila)
[Rattus norvegicus]
[ R.norvegicusl
665 22537AA892799kk HMm:glyoxylate ESTs, Weakly similar
to 3-phosphoglycerate
reductase/hydroxypyruvatedehydrogenase [Rattus
norvegicus]
reductase [ R.norvegicusl
665 22538AA892799z HMm:glyoxylate ESTs, Weakly similar
to 3-phosphoglycerate
reductaselhydroxypyruvatedehydrogenase [Rattus
norvegicus]
reductase [R.norvegicusl
850 22540AA924630ff HMm:glyoxylate ESTs, Weakly similar
to 3-phosphoglycerate
reductaselhydroxypyruvatedehydrogenase [Rattus
norvegicus]
reductase [R.norvegicusl
873 21010AA925306o HMm:carnitine ESTs, Weakly similar
acetyltransferaseto 1701410A choline
acetyltransferase [Rattus
norvegicus]
[R.norvegicusl
11652915 AA996782ww HMm:lamin B2 ESTs, Moderately similar
to lamin B1
[Rattus norve icus]
[R.norve icus]
129521563A1007750gg, HMm:ubiquitin-conjugatingESTs, Weakly similar
hh to ubiquitin-
enzyme E2L 3 conjugating enzyme E2D
2 [Rattus
norvegicusl R.norvegicusl
137312310A1010362gg, HMm:cullin 1 ESTs, Weakly similar
hh to vasopressin-
activated calcium-mobilizing
receptor protein
fRattus norvegicusl
[R.norvegicusl
142920817A1012589c lutathione S-transferase,glutathione S-transferase,
pi 2 pi 2
18942364 AI103379GeneralHMm:ubiquitin-activatingESTs, Highly similar
to 163168 gene Ube1x
enzyme E1, Chr protein - rat (fra ment)
X [R.norvegicus]
208417812AI169075uu HMm:glutathione ESTs, Weakly similar
transferase to GT01 RAT
zeta 1 (maleylacetoacetateGlutathione transferase
omega 1 (GSTO 1-
isomerase) 1) (Glutathione-dependent
dehydroascorbate reductase)[R.norvegicus]
232014384A1177096a HMm:adenine phosphoribosylESTs, Highly similar
to APT_RAT ADENINE
transferase PHOSPHORIBOSYLTRANSFERASE
(APRT) [R.norvegicus]
23368949 AI177593I, HMm:ATPase, H+ ESTs, Weakly similar
Generaltransporting, to VATL_MOUSE
lysosomal 21 kDa,Vacuolar ATP synthase
VO subunit B 16 kDa proteolipid
subunit [R.norvegicusl
246921505AI228005bb HMm:deoxyguanosineESTs, Weakly similar
kinase to deoxycytidine
kinase [Rattus norvegicus]
[R.norvegicus]
259122542AI232066ff HMm:glyoxylate ESTs, Weakly similar
to 3-phosphoglycerate
reductaselhydroxypyruvatedehydrogenase [Rattus
norvegicus]
reductase [R.norvegicusl
279321043A1237813mm HMm:MAP kinase-activatedESTs, Weakly similar
to A34366
protein kinase Ca2+Icalmodulin-dependent
2 protein kinase
(EC 2.7.1.123) II delta
chain - rat
iR.norveaicusl
338917715NM 017274ss, glycerol-3-phosphateglycerol-3-phosphate
xx acyltransferase,
ac Itransferase mitochondria)
mitochondria)
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
151
TABLE
1
Attorney
Docket
No.'44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known-Gene Name Unigene Sequence Cluster
Title
fD fD Aca. Code
N0: or
N0. RefSeq
ID
No.
338920282NM 017274y glycerol-3-phosphateglycerol-3-phosphate
acyltransferase,
acyltransferase, mitochondria)
mitochondria)
342514979NM 019126u, Carcinoembryonic Carcinoembryonic antigen
bb, antigen gene gene family
jj
f amily (CGM3) ( CGM3)
3504904 NM 019620d, Kruppel associatedKruppel associated box
n, box (KRAB) (KRAB) zinc finger
gg, 1
hh, zinc finger 1
kk,
tt
360221023NM 022599h, synaptojanin 2 synaptojanin 2 binding
I, binding protein protein
General
376821624NM 031144mm actin, beta actin, beta
376821625NM 031144z actin, beta actin, beta
42422100 NM 138829I golgi reassembly golgi reassembly stacking
I stacking protein 2
protein 2
426018082NM_138907nn mitochondria) mitochondria) acyl-CoA
acyl-CoA thioesterase 1
t hioesterase 1
426018083NM_138907m, mitochondria) mitochondria) acyl-CoA
o, acyl-CoA thioesterase 1
jj,
nn,
xx thioesterase 1
439723926086635 d, glutathione S-transferase,lutathione S-transferase,
oo mu 5 mu 5
33 17613AA799511ww ESTs, Weakly similar
to DDRT helix-
destabilizing protein
- rat [R.norvegicus]
38 17599AA799539o ESTs, Weakly similar
to KEAP_RAT Kelch-
l ike ECH-associated protein
1 (Cytosolic
i nhibitor of Nrf2) (INrf2)
[R.norveqicusl
45 18361AA799591, tt ESTs, Highly similar
j to TBB1 RAT TUBULIN
BETA CHAIN (T BETA-15)
[R.norvegicus]
56 20982AA799657x, ESTs, Weakly similar
qq to 568418 protein
phosphatase 1 M chain
M110 isoform - rat
(fragment) [R.norvegicusl
77 20998AA799803b, ESTs, Weakly similar
General to JC6554
complement subcomponent
C1s (EC
3.4.21.42) precursor
[similarity] - rat
IR.norveqicusl
97 16712AA800015v integrin-linked integrin-linked kinase
kinase
117 21665AA800272e, ESTs, Highly similar
s to RM03_RAT
Mitochondria) 60S ribosomal
protein L3
[R.norvegicusl
124 9089 AA800389d ESTs, Weakly similar
to A48157 renal
transcription factor
Kid-1- rat [R.norvegicus]
126 6892 AA800551p DnaJ-like proteinDnaJ-like protein
140 12072AA800680g ESTs, Weakly similar
to S68418 protein
phosphatase 1 M chain
M110 isoform - rat
(fragment) [R.norvegicusl
165 21415AA800948I, ESTs, Highly similar
mm to 0812252A tubulin
alpha [Rattus norvegicus]
[R.norvegicus]
189 9840 AA817964g paraoxonase 1 paraoxonase 1
199 6526 AA818118gg, ESTs, Weakly similar
hh to cold inducible RNA-
binding protein [Rattus
norvegicus]
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
152
TABLE
1
Attorney:Docket
No"
44921-5113W0
Document
No.1926271-:2
SEQ GLGG GenBank'Model Known Gene Name Jnigene Sequence GlusterTitle
l
lD ID Acc. Code
NO. or a
NO'., Ref~eq
)D
No.
201 6016 AA818163x ESTs, Weakly similar
to PON1 RAT Serum
paraoxonase/arylesterase
1 (PON 1) (Serum
aryldiakylphosphatase
1) (A-esterase 1)
( Aromatic esterase 1)
[R.norvegicus]
202 17771AA818224I Rat mRNA for beta-tubulin
T beta15
269 17614AA848306t, ESTs, Weakly similar
II, to DDRT helix-
tt
destabilizin protein
- rat [R.norve icus]
277 23355AA848530I, ESTs, Weakly similar
bb to retinoblastoma
binding protein 7 [Rattus
norvegicus]
f R.norvegicusl
297 6635 AA849786bb, ESTs, Weakly similar
II to CLK3_RAT Protein
kinase CLK3 (CDC-like
kinase 3)
[R.norvegicusl
316 14324AA850402n ESTs, Moderately similar
to S21348
probable pol polyprotein-related
protein 4 -
ratfR.norvegicus
372 14987AA858640o heat shock proteinRattus norvegicus CDK110
60 (liver) mRNA, heat
shock protein 60 (liver)
390 19105AA859230v, ESTs, Weakly similar
x to HG17_RAT
NONHISTONE CHROMOSOMAL
PROTEIN
HMG-17 [R.norvegicusl
410 11317AA8596310o ESTs, Weakly similar
to ZF37_RAT Zinc
finger protein 37 (Zfp-37)
[R.norve icus]
411 16318AA859648c ESTs, Weakly similar
to DJA1 MOUSE
DnaJ homolog subfamily
A member 1 (Heat
shock 40 kDa protein
4) (DnaJ protein
homoloa 2) (HSJ-2) fR.norveaicusl
433 23301AA859975w 2-oxoglutarate 2-oxo lutarate carrier
carrier
439 19332AA860014a EST, Moderately similar
to 2206405A
hemoglobin:SUBUNIT=zeta
[Rattus
norvegicuslfR.norvegicusl
465 16082AA874887ww ESTs, Weakly similar
to segregation of
mitotic chromosomes
b; SMC (segregation
of mitotic chromosomes
1 )-like 1 (yeast)
fRattus norveaicusl
fR.norveaicusl
478 14951AA875037y ESTs, Weakly similar
to plasminogen
activator inhibitor
2 type A [Rattus
norvegicusl [R.norvegicusl
482 16327AA875050c, ESTs, Weakly similar
oo to KICE_RAT
Cholinelethanolamine
kinase [Includes:
Choline kinase (CK);
Ethanolamine kinase
(EK)1 fR.norveqicusl
486 20701AA875097b, EST, Highly similar
m, to FIBA_RAT Fibrinogen
General alphalalpha-E chain
precursor
[R.norvegicusl
501 15933AA875253 ADP-ribos lation ADP-ribos lation factor-like
factor-like 1 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
153
TABLE
1
Attorney
Docket
No44921=5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
-= Title
ID ID Aca. Code
N0. or'
NO RefSeq
ID
No:v
516 16516AA875563x ESTs, Weakly similar
to 156519 taipoxin-
associated calcium binding
protein-49
precursor - rat [R.norveqicusl
533 9136 AA891226rr, ESTs, Highly similar
tt to PSBS_RAT
Proteasome subunit beta
type 5 precursor
(Proteasome epsilon
chain) (Macropain
epsilon chain) (Multicatalytic
endopeptidase
complex epsilon chain)
(Proteasome subunit
X) (Proteasome chain
6) [R.norvegicus]
547 2753 AA891589a sarcosine dehydroESTs, sarcosine dehydrogenase
enase
562 18269AA891769z ESTs, Weakly similar
to SC65
synaptonemal complex
protein [Rattus
norvegicusl [R.norvegicusl
606 17350AA892240k ESTs, Weakly similar
to 2008109A set gene
[Rattus norvegicus]
[R.norvegicus]
613 4486 AA892298w ESTs, Weakly similar
to matrin cyclophilin
(matrin-cyp) [Rattus
norvegicus]
[R.norvegicusl
621 13647AA892367z, ESTs, Highly similar
General, to RL3_RAT 60S
ii, RIBOSOMAL PROTEIN L3
rr (L4)
[R.norveaicusl
623 19226AA892394a ESTs, Weakly similar
to ELV4_RAT ELAV-
like protein 4 (Paraneoplastic
encephalomyelitis antigen
HuD) (Hu-antigen
D) fR.norveaicusl
623 19227AA892394a, ESTs, Weakly similar
w to ELV4 RAT ELAV-
_
like protein 4 (Paraneoplastic
encephalomyelitis antigen
HuD) (Hu-antigen
D)fR.norveqicust
631 9254 AA892470j, ESTs, Highly similar
q, to S03644 histone
nn,
oo
H2A.Z - rat [R.norve
icus]
632 11992AA892485kk dihydrolipoamide dihydrolipoamide acetyltransferase
acetyltransferase
649 15876AA892582I, ESTs, Highly similar
General to RL8_HUMAN 60S
ribosomal protein L8
[R.norvegicus]
658 4487 AA892680e, ESTs, Weakly similar
p to matrin cyclophilin
(matrin-cyp) [Rattus
norvegicus]
[R.norvegicusl
667 6951 AA892820bb ESTs, Weakly similar
to S70642 ubiquitin
ligase Nedd4 - rat (fragment)
[R.norvegicus]
671 7148 AA892842gg, ESTs, Weakly similar
hh to CAZ3_RAT F-actin
capping protein alpha-3
subunit (CAPZ
alpha-3) [R.norvegicusl
679 3438 AA892921r ESTs, Weakly similar
to A55143 calpain (EC
3.4.22.17) light chain
- rat (fragment)
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
154
TABLE
1
Attorney
Docket
No.
X4921-5113VIIQ
Document
No.1-926271.2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster
- ' Tifle
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No
68016482AA892940x ESTs, Weakly similar
to EF2_RAT
Elon ation factor 2
(EF-2) [R.norve icus]
69124179AA893091nn, ESTs, Weakly similar
tt to TC17_RAT Zinc
finger protein 354A
(Transcription factor
17)
(Renal transcription
factor Kid-1) (Kidney,
ischemia, and developmentally
regulated
protein-11 IR.norveaicusl
72517836AA893626uu ESTs, Weakly similar
to guanine nucleotide-
binding protein, beta-1#
subunit [Rattus
norvegicusl[R.norvegicusl
7437637 AA894089k, rotein carrying rotein carrying the
x the RING-H2 RING-H2 sequence motif
sequence motif
74618419AA894130n, ESTs, Weakly similar
General, to 2019243A amyloid
ww precursor-like protein
2 [Rattus norvegicus]
[R.norvegicusl
75415274'AA894258General,ubiquitin-conjugatingubiquitin-conjugating
enzyme enzyme E2D 3
kk E2D 3 (homologous(homologous to yeast
to yeast UBC4/5)
UBC4/5)
7553908 AA894259j ESTs, Weakly similar
to hypoxia induced
gene 1 [Rattus norvegicus]
[R.norvegicus]
7956483 AA900461v ESTs, Weakly similar
to OBRG_RAT Leptin
receptor gene-related
protein (OB-R gene
related protein) (OB-RGRP)
[R.norvegicus]
80418547AA900722ii solute carrier solute carrier family
family 9 9 (sodium/hydrogen
(sodiumlhydrogen exchanger), isoform
exchanger), 3 regulator 2
isoform 3 regulator
2
82422980AA923973y seven in absentiaseven in absentia 1A
1A
8555019 AA924768b ESTs, Weakly similar
to DnaJ (Hsp40)
homolog, subfamily A,
member 2 [Rattus
norvegicusl[R.norvegicusl
86723261AA925145b, ESTs, Weakly similar
uu, to betaine-
vv
homocysteine methyltransferase
[Rattus
norveqicusl R.norvegicusl
86810666AA925212kk siah binding proteinsiah binding protein
1; FBP 1; FBP interacting
interacting repressor;repressor; pyrimidine
pyrimidine tract binding splicing
tract binding factor; Ro ribonucleoprotein-binding
splicing factor; protein
Ro
ribonucleoprotein-binding1
protein 1
96414763AA944481s, ESTs, Weakly similar
ff, to FCN2_RAT Ficolin
nn
2 precursor (Collagenlfibrinogen
domain-
containing protein 2)
(Ficolin-B) (Ficolin
B)
(Serum lectin P35) (EBP-37)
(Hucolin)
fR.norve4icusl
9772893 AA944833kk ESTs, Weakly similar
to ROD RAT
Heterogeneous nuclear
ribonucleoprotein DO
(hnRNP DO) (AU-rich
element RNA-binding
rotein 1 R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
155
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271.2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster
- Title
lD ID Acc. Code
' NO. or
N0. RefSeq
ID
No.
99922607AA945580b ESTs, Weakly similar
to ARG2_RAT
Arginase II, mitochondria)
precursor (Non-
hepatic arginase) (Kidney-type
arginase)
i R.norveaicusl
101217721AA945762General ESTs, Weakly similar
to 2102279A protein
Tyr phosphatase [Rattus
norvegicus]
[ R.norvegicus]
101722680AA945883j ESTs, Weakly similar
to JC5598 mucin - rat
[ R.norvegicus]
103022753AA946300I, Rattus norvegicus cytochrome
General P450-like
protein mRNA, partial
cds
1041643 AA946439c, ESTs, Highly similar
ii, to HSRT4 histone H4
tt -
rat [R.norvegicus]
104823584AA955071ff retinoid X receptorretinoid X receptor
gamma ( gamma
105222596AA955298c ESTs, Weakly similar
to T46637
transcription factor
1, neural - rat
fR.norvegicusl
105523542AA955389pp ESTs, Weakly similar
to GRB2_HUMAN
Growth factor receptor-bound
protein 2
(GRB2 adapter protein)
(SH2/SH3 adapter
GRB2) (ASH protein)
fR.norveqicusl
107911050AA956164ii ESTs, Weakly similar
to JQ0866 T-complex
protein 1 - rat [R.norvegicus]
108223747AA956329gg, ESTs, Moderately similar
hh to delta-6 fatty
acid desaturase [Rattus
norvegicus]
fR.norvegicus]
108425112AA956437d ESTs, Weakly similar
to TERA_RAT
TRANSITIONAL ENDOPLASMIC
RETICULUM ATPASE (TER
ATPASE) (15S
MG(2+)-ATPASE P97 SUBUNIT)
(VALOSIN
CONTAINING PROTEIN)
(VCP)
[CONTAINS: VALOSIN]
[R.norvegicus]
10916174 AA957063tt ESTs, Weakly similar
~ to E2BE_RAT
_
TRANSLATION INITIATION
FACTOR EIF-
2B EPSILON SUBUNIT (EIF-2B
GDP-GTP
EXCHANGE FACTOR) [R.norvegicus]
109924050AA957449v ESTs, Weakly similar
to SNK_RAT
Serine/threonine-protein
kinase SNK (Serum
inducible kinase) [R.norvegicus]
110112479AA957557a, ESTs, Weakly similar
vv to ITH3_RAT Inter-
alpha-trypsin inhibitor
heavy chain H3
precursor (ITI heavy
chain H3)
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1.5R
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQ GLGC Genl3ankModet Known Gene Name Unigene Sequence Clusfer
Title
ID ID Acc. Code
NO. or
N0. RefSeq
ID_
No.
111023541AA957999f, I, ESTs, Weakly similar
nn to TXTP_RAT
Tricarboxylate transport
protein,
mitochondria) precursor
(Citrate transport
protein) (CTP) (Tricarboxylate
carrier
protein) IR.norveaicusl
119013330AA997716II Kelch-like ECH-associatedKelch-like ECH-associated
protein 1
protein 1
12133746 AA998268b, bb ESTs, Weakly similar
to SYPH_RAT
SYNAPTOPHYSIN (MAJOR
SYNAPTIC
VESICLE PROTEIN P38)
[R.norveqicus]
121614379AA998415rr ESTs, Weakly similar
to A40016 matrin 3 -
rat [R.norve icus]
124411745AB006450gg, translocator translocator of inner
hh of inner mitochondria)
mitochondria) membrane 17 kDa, a
membrane 17
kDa, a
125518192AF000899s, tt nucleoporin p58 Rattus norvegicus p58/p45
mRNA,
alternatively spliced
form, clone H6, 3' end,
nucleoporin p58
126019649AF016387pp retinoid X receptorretinoid X receptor ammo
gamma (
126019650AF016387s retinoid X receptorretinoid X receptor gamma
gamma (
12708008 AF039584xx decay-accelaratingdecay-accelaratin factor
factor
127415715AF053092ii Rattus norvegicus polo-like
kinase isoform
mRNA, partial cds
12813896 AF077000m protein tyrosineprotein tyrosine phosphatase
phosphatase TD14
TD14
128320741AF084186nn alpha-fodrin alpha-fodrin
12882947 AF099093f, kk ubiquitin-conjugatingubiquitin-conjugating
enzyme enzyme UBC7
UBC7
128912932AF102552x ankyrin 3 (G) ankyrin 3 (G)
129211251A1007666i ESTs, Weakly similar
i to JC4647 KW8
protein - rat [R.norve
icus]
129422332A1007748f ESTs, Weakly similar
f to OZF_RAT Zinc
f inger protein OZF (POZF-1)
[R.norvegicus]
132221838A1009131ee, aminin, gamma aminin, ammo 1
kk 1 l
l
133310820A1009411ee ESTs, Highly similar
to RS3_MOUSE 40S
r ibosomal protein S3 [R.norve
icus]
13399746 A1009555d, g Rattus norvegicus dynein
light intermediate
c hain 1 mRNA, complete
cds
135022545A1009747z t ransducer of ransducer of ERBB2, 1
ERBB2, 1 t
136523540A1010110x S H3-domain GRB2-likeH3-domain GRB2-like 1
x 1 S
140116112A1011706t E STs, Weakly similar to
t SFRS_RAT Splicing
f actor, arginine/serine-rich
5 (Pre-mRNA
s plicing factor SRP40)
(Insulin-induced
g rowth response protein
CL-4) (Delayed-
e arly protein HRS) [R.norvegicus]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1 ~7
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271:2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
Title
ID D Acc. Code
- N0. or ~
~~
I
N0. RefS
eq ID
_
No.
141521796A1012221v ESTs, Weakly similar
v to intracellular
chloride ion channel
protein p64H1 [Rattus
norvegicusl[R.norvegicusl
14223417A1012337h, ESTs, Highly similar
w to NHPX_RAT NHP2-
l ike protein 1 (High
mobility group-like
nuclear protein 2 homolog
1) ([U41U6.U5] tri-
snRNP 15.5 kDa protein)
(OTK27)
IR.norveaicusl
14271263A1012567bb ESTs, Weakly similar
to ZF94_RAT Zinc
-
finger protein 94 (Zfp-94)
(Zinc finger protein
Y1) (RLZF-Y) [R.norvegicusl
14346489A1012636d ESTs, Weakly similar
to RBMA_RAT RNA-
binding protein 10 (RNA
binding motif
protein 10) (S1-1 protein)
[R.norvegicus]
14627258A1013475h ESTs, Moderately similar
to SORT_RAT
Sortilin (Glycoprotein
110) (Gp110)
[R.norvegicus]
147224239A1013781d ESTs, Weakly similar
to S19586 N-methyl-D-
aspartate receptor glutamate-binding
chain -
rat [R.norvegicusl
154823949A1031019q translation initiationtranslation initiation
factor eIF- factor eIF-2B alpha-
2B alpha-subunit subunit
154823950A1031019n, translation initiationtranslation initiation
q, factor eIF- factor eIF-2B alpha-
x,
II
2B alpha-subunit subunit
15725431A1044257I ESTs, Weakly similar
to syntenin [Rattus
norvegicus] [R.norve
icus]
159118205A1044836h ESTs, Weakly similar
to NUCL_RAT
-
Nucleolin (Protein C23)
[R.norvegicus]
164710533A1058430qq ESTs, Highly similar
to HG17_RAT
NONHISTONE CHROMOSOMAL
PROTEIN
HMG-17 [R.norvegicusl
16628584A1058911cc, ESTs, Weakly similar
ii, to FIBA_RAT
rr
Fibrinogen alphalalpha-E
chain precursor
[R.norvegicusl
167014984A1059174h Rattus norvegicus CDK110
mRNA
16866370A1059568g ESTs, Highly similar
to B48213 syntaxin
1 B -
rat [R.norvegicus]
173326184A1070784m ESTs, Weakly similar
to OZF_RAT Zinc
finger protein OZF (POZF-1)
[R.norvegicus]
174110999A1071110t ESTs, Weakly similar
to A44437
regenerating liver inhibitory
factor RLIIF-1 -
rat[R.norvegicusl
176221839A1071644f laminin, amma laminin, gamma 1
1
17647092A1071668c ' ESTs, Weakly similar
to E2BE_RAT
TRANSLATION INITIATION
FACTOR EIF-
2B EPSILON SUBUNIT (EIF-2B
GDP-GTP
EXCHANGE FACTOR) [R.norvegicus]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
15~
TABLE
1
Attorney
Docket
No.
44921=5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID D Acc. Code
I N0. or
N0. RefSeq
ID _
No. ,
177116376A1071866a, Rattus norvegicus Nclone10
a mRNA
179421797A1072439qq ESTs, Weakly similar
to intracellular
chloride ion channel
protein p64H1 [Rattus
norveqicus][R.norveqicus]
18021501 A1072634e, Rattus norvegicus cytokeratin-18
I, mRNA,
t,
bb,
dd, partial cds
ww
182511183AI100768b ESTs, Weakly similar
to CAH2_RAT
_
Carbonic anhydrase II
(Carbonate
dehydratase II) (CA-II)
[R.norveqicusl
18326321 AI101256i, ESTs, Weakly similar
i II to S09017
heterogeneous ribonuclear
particle protein
type C - rat (fragment)
[R.norveqicusl
185118649AI101926q ESTs, Weakly similar
to HS9B_RAT Heat
_
shock protein HSP 90-beta
(HSP 84)
[R.norveqicus]
187523538A1102727I, solute carrier solute carrier family
n, family 20 20 (phosphate
p
(phosphate transporter),transporter), member
1
member 1
188515026AI103094Generalras-related proteinras-related protein
_ 15981AI103150nn ESTs, Weakly similar
1889 to ubiquitin
conjugating enzyme [Rattus
norvegicus]
[R.norveaicusl
18958919 A1103388dd, ESTs, Weakly similar
kk to ARF6_HUMAN ADP
ribosylation factor
6 [R.norvegicus]
189614981AI103396ee Rattus norvegicus CDK110
mRNA
1935_ AI104357a ESTs, Highly similar
18831 to ACTB_HUMAN
Actin, cytoplasmic 1
(Beta-actin)
[R.norveqicusl
194412342AI1046580o ESTs, Weakly similar
to A48152 zinc finger
protein Gfi-1 - rat
[R.norve icus]
195615065AI105050p, ATP synthase, ATP synthase, H+ transporting,
ii, H+ transporting,
II
mitochondrial mitochondrial F1 complex,
F1 complex, beta beta polypeptide
poIVPeptide
197911192AI11198(ig ESTs, Weakly similar
to S41067 collagen
alpha 1 (III) chain
- rat [R.norvegicus]
200611735AI136540j ESTs, Highly similar
to TRT3_RAT Troponin
T, fast skeletal muscle
isoforms betalalpha
(Betalalpha TnTF) [R.nonregicus]
200710780AI136555j Rattus norvegicus mRNA
for Castration
Induced Prostatic Apoptosis
Related protein-
1 (CIPAR-1)
20238924 AI137283z ESTs, Weakly similar
to TC17_RAT Zinc
finger protein 354A
(Transcription factor
17)
(Renal transcription
factor Kid-1) (Kidney,
ischemia, and developmentally
regulated
protein-1) [R.norveQicusl
20721358 AI146154mm hos hatid linositol4-kinasehos hatid linositol4-kinase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
159
TABLE
1
.
Attorney
Docket
No.
44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
- Title
ID D Accor Code
I NO.
NO RefSeq
ID
No..
20851335 AI169105ss ESTs, Weakly similar
to PON1 RAT Serum
paraoxonase/arylesterase
1 (PON 1) (Serum
aryldiakylphosphatase
1) (A-esterase 1)
(Aromatic esterase 1)
[R.norvegicus]
209418641AI169225ee Rattus norvegicus mRNA
for ribosomal
protein L35
209622661AI169265t, ATPase, H+ transporting,ATPase, H+ transporting,
mm lysosomal
lysosomal (vacuolar(vacuolar proton pump),
proton subunit 1
pump), subunit
1
213114938AI170362qq ESTs, Weakly similar
to 167414 nuclear
factor kappa B - rat
(fragment)
[R.norvegicus]
214515403AI170714m, ESTs, Weakly similar
dd to A40389 translation
elongation factor eEF-1
alpha chain (clone
pS1) - rat [R.norvegicus
215518535AI170979dd, ESTs, Weakly similar
oo to REQN_RAT Zinc-
finger protein neuro-d4
[R.norve icus]
216017783AI171206vv ESTs, Weakly similar
to 2118320A
neurodegeneration-associated
protein 1
[Rattus norvegicus]
[R.norvegicus]
217011419A1171365k ESTs, Weakly similar
to A57514 RNA
helicase HEL117 - rat
[R.norve icus]
21816879 AI171674t Very low density Very low density lipoprotein
lipoprotein receptor
receptor
22046630 AI172184b ESTs, Weakly similar
to SYPH_RAT
SYNAPTOPHYSIN (MAJOR
SYNAPTIC
VESICLE PROTEIN P38)
f R.norvegicus]
221623325AI172405bb ESTs, Highly similar
to 2008109A set gene
[Rattus norvegicus]
[R.norvegicus]
224715404AI175760dd ESTs, Weakly similar
to A40389 translation
elongation factor eEF-1
alpha chain (clone
pS1) - rat [R.norvegicusl
227113339AI176308r ESTs, Weakly similar
to C01 B RAT Coronin
_
1 B (Coronin 2) [R.norvegicus]
233517773AI177513y ESTs, Weakly similar
to CLK3_RAT Protein
_
kinase CLK3 (CDC-like
kinase 3)
[R.norvegicus]
23554979 AI178133ss ESTs, Weakly similar
to LIS1 MOUSE
Platelet-activating
factor acetylhydrolase
IB
alpha subunit (PAF acetylhydrolase
45 kDa
subunit) (PAF-AH 45
kDa subunit) (PAF-AH
alpha) (PAFAH alpha)
(Lissencephaly-1
protein) (LIS-1) [R.norvegicus]
238412408AI178762qq ESTs, Moderately similar
to delta-6 fatty
acid desaturase [Rattus
norvegicus]
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
160
TABLE
1
v
Aftorneypocket
No.
44921'~5113W0
Document
No:1926271:2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID ID Acc, Code=
NO. or
N0. Ref$eq
ID
No
239523043AI178968nn ESTs, Weakly similar
to S70642 ubiquitin
ligase Nedd4 - rat (fragment)
[R.norvegicus]
240317890AI179123j, ESTs, Weakly similar
mm to NF-E2-related
factor 2 Rattus norve
icus] [R.norvegicus]
242916656AI179634h ESTs, Weakly similar
to Gasz [Rattus
norve icus] [R.norve
icus]
24406455 AI179984vv ESTs, Weakly similar
to CPI3_RAT
CONTRAPSIN-LIKE PROTEASE
INHIBITOR 3 PRECURSOR
(CPI-23)
(SERINE PROTEASE INHIBITOR
1) (SPI-1)
fR.norveaicusl
246812413AI227953t, ESTs, Weakly similar
mm to K6A1 RAT
Ribosomal protein S6
kinase alpha 1 (S6K-
alpha 1) (90 kDa ribosomal
protein S6
kinase 1) (p90-RSK 1)
(Ribosomal S6 kinase
1) (RSK-1) (pp90RSK1)
[R.norvegicus]
25056604 AI229192xx ESTs, Weakly similar
to 2209311A
coagulation factor X
[Rattus norvegicus]
[R.norveqicusl
251523858AI229450r ESTs, Weakly similar
to A57514 RNA
helicase HEL117 - rat
[R.norvegicus]
253018650AI230121q, ESTs, Weakly similar
ii, to HS9B_RAT Heat
II
shock protein HSP 90-beta
(HSP 84)
[R.norvegicus]
256621816A1231217ee ESTs, Highly similar
to S611 HUMAN
Protein transport protein
Sec61 alpha
subunit isoform 1 (Sec61
alpha-1)
fR.norveaicusl
26058390 AI232288ww ESTs, Weakly similar
to retinoblastoma
binding protein 7 [Rattus
norvegicus]
[R.norvegicusl
26245602 AI2326110, ESTs, Weakly similar
ff, to MTE1 RAT Acyl
xx
coenzyme A thioester
hydrolase,
mitochondrial precursor
(Very-long-chain
acyl-CoA thioesterase)
(MTE-I)
iR.norveaicusl
263612873AI232984tt ESTs, Weakly similar
to OZF_RAT Zinc
finger protein OZF (POZF-1)
[R.norvegicus]
26414442 AI233163gg, ESTs, Highly similar
hh to RL11 HUMAN 60S
ribosomal protein L11
[R.norvegicus]
271322070AI235528jj ESTs, Weakly similar
to synuclein, gamma
Rattus norve icus R.norve
icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
161
TABLE
1
Attorney
Docket
No44921-5113WQ
Document
No.1926271~2
SEQGLGC GenBankModel Kriawn Gene Name Unigene Sequence Cluster
Title
ID ID Acc. Code
NO. or
N0. RefSeq
ID
'
No
27267307 AI235935g, ESTs, Weakly similar
oo to C1TC_RAT C-1-
tetrahydrofolate synthase,
cytoplasmic (C1-
THF synthase) [Includes:
Methylenetetrahydrofolate
dehydrogenase ;
Methenyltetrahydrofolate
cyclohydrolase ;
Formyltetrahydrofolate
synthetase ]
IR.norveaicusl
27307604 AI236039II reticulocalbin reticulocalbin
274013911AI236262ww Rattus norvegicus epidermal
Langerhans
cell rotein LCP1 mRNA,
complete cds
274210667AI236366dd siah binding proteinsiah binding protein
1; FBP 1; FBP interacting
interacting repressor;repressor; pyrimidine
pyrimidine tract binding splicing
tract binding factor; Ro ribonucleoprotein-binding
splicing factor; protein
Ro
ribonucleoprotein-binding1
protein 1
27556207 AI236681gg, ESTs, Weakly similar
hh to SUIS RAT Sucrase-
isomaltase, intestinal
[Contains: Sucrase
;
Isomaltase 1 fR.norveAicusl
276217618AI236786p, ESTs, Weakly similar
rr to FK506 binding
protein 2 (13 kDa) [Rattus
norvegicus]
fR.norveaicus~
277823076A1237388q, ESTs, Weakly similar
dd to IFR1 RAT
INTERFERON-RELATED
DEVELOPMENTAL REGULATOR
1
(NERVE GROWTH FACTOR-INDUCIBLE
PROTEIN PC4) (IRPRI
IR.norveaicusl
285118338AI639422g ESTs, Moderately similar
to CAQC_RAT
CALSEQUESTRIN, CARDIAC
MUSCLE
ISOFORM PRECURSOR ~R.norvegicusl
285826012AI639478pp ESTs, Weakly similar
to PDI RAT Protein
disulfide isomerase
precursor (PDI) (Prolyl
4-
hydroxylase beta subunit)
(Cellular thyroid
hormone binding protein)
(Thyroxine
deiodinase) (lodothyronine
5'-
monodeiodinasel (5'-MDl
fR.norveaicusl
28678107 AI639534pp ESTs, Weakly similar
to ATS4_RAT
ADAMTS-4 precursor (A
disintegrin and
metalloproteinase with
thrombospondin
motifs 4) (ADAM-TS 4)
(ADAM-TS4)
(Aaarecanase 11 fR.norveaicusl
28727602 AJ001929b, reticulocalbin reticulocalbin
q,
v,
ii,
II,
xx
287620519C06598 v, ESTs, Weakly similar
w to FK506 binding
protein 2 (13 kDa) [Rattus
norvegicus]
[R.norveqicusl
28775048 D00092 0o dihydrolipoamide dihydrolipoamide acetyltransferase
acetyltransferase
28815049 D10655 m dihydrolipoamide dihydrolipoamide acetyltransferase
acet Itransferase
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
162
Ti4BLE
~(
Attorney
Docket.No.
44921-5113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence GlusterTitle
IDw ID Acc. Code
N0. or
NO. RefSeq
ID
No:.
28865082 D14015 ii, Cyclin E1 ESTs, Highly similar
ww to CGE1 RAT G1lS-
specific cyclin E1 [R.norve
icus]
28981041 D78610 x Protein tyrosine Protein tyrosine phosphatase,
phosphatase, receptor type,
receptor type, epsilon polypeptide
epsilon
polypeptide
28991356 D83538 y phosphatidylinositol4-kinasephosphatidylinositol4-kinase
29002744 D87991 b, ESTs, Highly similar
e, to JC5026 UDP-
q,
dd
galactose transporter
related protein 1-
rat
[ R.norvegicus]
29154352 H31692 x GERp95 GERp95
29199745 H31847 c, Rattus norvegicus dynein
h light intermediate
chain 1 mRNA, complete
cds
29213815 H31907 a G protein pathwayG protein pathway suppressor
suppressor 1 1
295214968K02815 f butyrophilin-likebutyrophilin-like 2
2 (MHC class (MHC class II associated)
II
associated)
2964107 L14001 General, Rattus norvegicus clone
15 polymeric
mm i mmunoglobulin receptor
mRNA, 3'UTR
microsatellite repeats
2965108 L14002 I, Rattus norvegicus clone
m, 15 polymeric
u,
General,i mmunoglobulin receptor
~ mRNA, 3'UTR
cc, microsatellite repeats
kk,
vv
2967109 L14004 b, Rattus norvegicus clone
General, 15 polymeric
vv immunoglobulin receptor
mRNA, 3'UTR
microsatellite repeats
297224518L19927 t, ATP synthase, ATP synthase, H+ transporting,
y, H+ transporting,
mm
mitochondria) mitochondria) F1 complex,
F1 complex, gamma
gamma polypeptidepolypeptide 1
1
298118620L40364 gg, Rattus norvegicus MHC
hh class I RT1.0 type
-
149 processed pseudogene
mRNA
298225389L41684 II FAT tumor suppressorFAT tumor suppressor
(Drosophila) homolog
(Drosophila) homolog
298417883M11851 ss Rat heart myosin light
chain 2 (MLC2)
mRNA, 3' end
298824554M13749 m Chorionic somatomammotropinChorionic somatomammotropin
hormone 2;
hormone 2; PlacentalPlacental lactogen-2
lactogen-2
301517211M34331 ee, Rattus norvegicus mRNA
II for ribosomal
protein L35
301526030M34331 bb, Rattus norvegicus mRNA
II for ribosomal
protein L35
30402694 M92340 rr Interleukin 6 Interleukin 6 signal
si nal transducertransducer
309918726NM 012645b, Rattus norvegicus MHC
q, class Ib RT1.S3
v,
General, (RT1.S3) mRNA, partial
cds
dd,
oo,
rr
31097101 NM 012679nn Clusterin Clusterin
31321478 NM 012744kk Pyruvate carboxylasePyruvate carboxylase
31338829 NM 012749q, Nucleolin Nucleolin
xx
31338831 NM 012749 Nucleolin Nucleolin
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
163
T=ABLE
1
Attorney.D~cket
No.
44921=5113W0
Document
No:1926271.2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence ClusterTitle
- '
ID ID Acc. Code=
CVa. or ,
N0: RefSeq
ID
No:
3138721 NM 012780tt Aryl hydrocarbon Aryl hydrocarbon receptor
receptor nuclear
nuclear translocatortranslocator 1
1
316420945NM 012875gg, Ribosomal proteinRibosomal protein L39
hh L39
319119106NM 012963ss Hi h mobility Hi h mobility roup 1
roup 1
319119107NM 012963cc High mobility High mobility group
group 1 1
319119108NM 012963ii Hi h mobility High mobility group
grow 1 1
319119109NM 012963ee Hi h mobility Hi h mobility roup 1
roup 1
319119110NM 012963jj High mobility Hi h mobility group
roup 1 1
323124607NM 013075n Homeo box A1 Homeo box A1
32368898 NM 013087q, CD81 antigen (targetCD81 antigen (target
tt of of antiproliferative
antiproliferativeantibody 1)
antibody 1)
325524867NM_013155t, Very low density Very low density lipoprotein
mm lipoprotein receptor
receptor
32583465 NM 013160ww ESTs, Moderately similar
to MXI1 RAT MAX
interacting protein
1 (MXI1 protein)
[R.norvegicusl
32701969 NM 013194k, Myosin, heavy Myosin, heavy polypeptide
t, polypeptide 9, 9, non-muscle
mm
non-muscle
32701970 NM 013194t, Myosin, heavy Myosin, heavy polypeptide
mm polypeptide 9, 9, non-muscle
non-muscle
327818230NM 013221r ESTs, Moderately similar
to 158311 HMG-
box containing protein
1- rat [R.norvegicus]
32781495 NM_013221f, HMG-box containingHMG-box containing protein
General,protein 1 1
qq,
vv
330018139NM 017033General ESTs, Highly similar
to PMRT
phosphoglucomutase (EC
5.4.2.2) 1- rat
[R.norveqicus)
341720848NM 017343x Rat mRNA for myosin
regulatory light chain
(RLC)
341720849NM 017343r, ' Rat mRNA for myosin
ff regulatory light chain
(RLC)
3419537 NM 017351h, pre-alpha-inhibitor,pre-alpha-inhibitor,
ss, heavy chain heavy chain 3
uu
3
342124428NM 017356nn neural visinin-likeneural visinin-like
Ca2+-binding Ca2+-binding protein
type
protein type 3 3
342624732NM 019130 Insulin 2 Insulin 2
343220351NM 019142kk 5'-AMP-activated 5'-AMP-activated protein
protein kinase kinase alpha-1
alpha-1 catalyticcatalytic subunit
subunit
34492933 NM_019204e, ESTs, Highly similar
m to BACE_RAT Beta-
secretase precursor
(Beta-site APP cleaving
enzyme) (Beta-site amyloid
precursor
protein cleaving enzyme)
(Aspartyl protease
2) (Asp 2) (ASP2) (Membrane-associated
aspartic protease 2)
(Memapsin-2)
IR. orveai 1
348024883NM 019293e, carbonic anhydrasecarbonic anhydrase 5
k, 5
a
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
164
TABLE
1
~
Attorney
Docket
No.
44931-5113W0
.
bocument
No.1926271.2
SEQGLGC GenBankModel Known Gene.Name Unigene Sequence Cluster
' Title
ID ID Acc. Code=
NO. or .
N0. RefSeq
ID
No:
34821099 NM 019303y Cytochrome P450,Cytochrome P450, subfamily
subfamily IIF, polypeptide
IIF, polypeptide1
1
348316330NM 019331General,Paired basic Paired basic amino acid
amino acid cleaving enzyme
kk cleaving enzyme furin)
(furin) (
348316331NM 019331h, m, Paired basic Paired basic amino acid
amino acid cleaving enzyme
General,cleaving enzyme furin)
(furin) (
mm
348616697NM 019349s SerinelthreonineSerine/threonine kinase
kinase 2 2
348616698NM 019349a SerinelthreonineSerine/threonine kinase
kinase 2 2
349023226NM 019360v, y, cytochrome oxidasecytochrome oxidase subunit
gg, subunit Vlc Vlc
hh
351320635NM 020099ee OB-receptor geneOB-receptor gene related
related protein (OB-
protein (OB-RGRP)RGRP)
351818724NM 021585b, ss Rattus norvegicus MHC
class Ib RT1.S3
(RT1.S3) mRNA, partial
cds
352117340NM_021594General,ERM-binding phosphoproteinERM-binding phosphoprotein
dd
352319173NM_021661n regulator of regulator of G-protein
G-protein signallingsignalling 19
19
354720248NM 022205y Chemokine receptorChemokine receptor (LCR1)
(LCR1)
354720249NM 022205tt Chemokine receptorChemokine receptor (LCR1)
(LCR1)
356115932NM 022385q, x, ADP-ribosylationADP-ribosylation factor-like
dd factor-like 1
1
356522412NM 022392f, p, growth response growth response protein
s, protein (CL-6) (CL-6)
General,
ee,
ft
356522413NM 022392a, f, growth response growth response protein
p, protein (CL-6) (CL-6)
General,
ee,
ff,
qq
356522414NM_022392ff growth response growth response protein
protein (CL-6) (CL-6)
356522415NM 022392p, General,growth response growth response protein
protein (CL-6) (CL-6)
ff
35681141 NM 022401f, n, plectin plectin
r,
z
35833902 NM 022516ss polypyrimidine polypyrimidine tract
tract binding binding protein
protein
35918097 NM 022536j, q, cyclophilin B cyclophilin B
w,
x
35928597 NM 022538h, I phosphatidate phosphatidate phosphohydrolase
type 2a
phosphohydrolase
type 2a
35928598 NM 022538d phosphatidate phosphatidate phosphohydrolase
type 2a
phosphohydrolase
type 2a
359412422NM 022546bb Death-associatedDeath-associated like
like kinase kinase
359512606NM 022547General,10-formyltetrahydrofolate10-formyltetrahydrofolate
dehydrogenase
vv dehydrogenase
359820820NM 022593a elongation factorelongation factor SIII
SIII p15 p15 subunit
subunit
360912542NM_022647c, d, ESTs, Highly similar
qq to 0506206A histone
H2B Rattus norve icus
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
165
TABLE
1-
Attorney
Docket
No.
44921-5113W0
Document
No:1926271~2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title.
ID 1D Acc. Code
N0. or
N0. RefSeq
ID
No;
361024442NM 022667u, Matrin FlG Matrin F/G
General,
rr
362224423NM 022703m, small glutamine-richsmall glutamine-rich
r, tetratricopeptide repeat
gg,
hh, tetratricopeptide(TPR) containing protein
pp repeat (TPR) (SGT)
containing protein
(SGT)
362324458NM 022706b GABA(A) receptor-associatedGABA(A) receptor-associated
protein like 2
protein like 2
36316891 NM 022934t, DnaJ-like proteinDnaJ-like protein
,
hh
364020681NM 022952a clathrin-associatedclathrin-associated
protein 17 protein 17
365815367NM 024149r ADP-ribosylation ADP-ribosylation factor
factor 5 5
366021696NM 024152f, ADP-ribosylation ADP-ribosylation factor
oo factor 6 6
368323386NM 024404gg, RNA binding proteinRNA binding protein
hh p45AUF1 p45AUF1
368325682NM 024404c, RNA bindin proteinRNA binding protein
w p45AUF1 p45AUF1
36941995 NM 030850d, betaine-homocysteinebetaine-homocysteine
h, methyltransferase
uu
methyltransferase
369615186NM 030861g, N- N-acetylglucosaminyltransferase
p, I
General,acetylglucosaminyltransferase
rr I
369615187NM 030861n, N- N-acetylglucosaminyltransferase
z, I
General,acetylglucosaminyltransferase
rr I
369615188NM 030861d, N- N-acetylglucosaminyltransferase
s, I
Generalacetylglucosaminyltransferase
I
369821800NM_030987r, Guanine nucleotide-bindingGuanine nucleotide-binding
w, protein beta 1
z
protein beta 1
369821801NM 030987gg, Guanine nucleotide-bindingGuanine nucleotide-binding
hh protein beta 1
protein beta 1
369821806NM 030987s, Guanine nucleotide-bindingGuanine nucleotide-binding
a protein beta 1
protein beta 1
370817302NM 031008tt alpha-c large alpha-c large chain
chain of the of the protein complex
protein complex AP-2 associated with
AP-2 clathrin
associated with
clathrin
37111538 NM 031012k, alanyl (membrane)alanyl (membrane) aminopeptidase
mm
aminopeptidase
37111540 NM_031012n, alanyl (membrane)alanyl (membrane) aminopeptidase
dd,
ee
aminopeptidase
371616560NM 031020t p38 mitogen activatedp38 mitogen activated
protein protein kinase
kinase
371616562NM_031020I, p38 mitogen activatedp38 mitogen activated
p, protein protein kinase
ss,
uu
kinase
371616564NM_031020k, p38 mitogen activatedp38 mitogen activated
I protein protein kinase
kinase
371616565NM 031020t p38 mitogen activatedp38 mitogen activated
protein protein kinase
kinase
371916210NM 031026r, LIC-2 dynein lightLIC-2 dynein light intermediate
w intermediate chain 53/55
chain 53155
372915137NM 031051w, macrophage migrationmacrophage migration
y, inhibitory inhibitory factor
ee,
tt
factor
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1FR
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No:1926271.2
SEQ GLGC GenBank Model Knowri Gene NameUnigene=Sequence Cluster
Title
ID ID:NO.Acc. Code
or
N0. RefSeq
ID
No:
373011899NM 031052rr mitochondria) mitochondria) intermediate
intermediate peptidase
peptidase
37396348 NM 031077mm PCTAIRE-1 proteinCTAIRE-1 protein kinase,
kinase, P alternatively
alternatively spliced
spliced
374217173NM 031090u, ras-related proteinras-related protein
cc
374720812NM 031100y, ribosomal proteinribosomal protein L10
ee L10
375220807NM 031106h ribosomal proteinribosomal protein L37
L37
375510878NM 031110, Generalribosomal proteinribosomal protein S11
j S11
376016671NM 031125tt syntaxin 4 syntaxin 4
376515487NM 031137q, tripeptidylpeptidasetripeptidylpeptidase
ww II II
376515489NM 031137bb, ripeptidylpeptidasetripeptidylpeptidase
II, II II
ww
t
376617378NM 031138q ubiquitin conjugatingubiquitin conjugating
enzyme enzyme
376617379NM 031138Generalubiquitin conjugatinubiquitin conju ating
enzyme enzyme
376923097NM 031145h, calcium- and calcium- and integrin-binding
bb integrin-bindingprotein
protein
3772164 NM 031151v malate dehydrogenasemalate dehydrogenase
mitochondria)
mitochondria)
3773238 NM 031152ee RAB11a, member RAB11a, member RAS oncogene
RAS family
oncogene family
3773240 NM 031152x RAB11a, member RAB11a, member RAS oncogene
RAS family
oncogene family
377715277NM 031237n ubiquitin-conjugatingubiquitin-conjugating
enzyme enzyme
E 2D 3
E2D 3 (homologous(homologous to yeast
to yeast UBC4/5)
UBC415)
378715360NM 031335p, polymerase II EST, Moderately similar
v D to RPB6_RAT
NA-
directed RNA polymerase
ll 14.4 kDa
polypeptide (RPB6) (RPB14.4)
f R.norveaicush polvmerase
II
38111822 NM 031553c, CCAAT binding CCAAT binding transcription
ww transcription factor of CBF-
f actor of CBF-B/NFY-BBINFY-B
383020840NM 031604d ATPase, H+ transporting,ATPase, H+ transporting,
lysosomal
l ysosomal (vacuolarvacuolar proton pump)
proton ( noncatalytic
pump) noncatalyticaccessory protein 1
accessory (1101160 kDa)
protein 1 (1101160
kDa)
383020841NM 031604bb ATPase, H+ transporting,ATPase, H+ transporting,
lysosomal
l ysosomal (vacuolarvacuolar proton pump)
proton ( noncatalytic
p ump) noncatalyticaccessory protein 1
accessory (1101160 kDa)
p rotein 1 (1101160
kDa)
388520752NM 031763i p latelet-activatingplatelet-activating
i factor factor acetylhydrolase
a cetylhydrolase eta subunit (PAF-AH
beta subunit beta)
b
( PAF-AH beta)
388520753NM 031763, General,latelet-activatinglatelet-activating factor
I p factor p acetylhydrolase
d d, cetylhydrolase eta subunit (PAF-AH
pp beta subunit beta)
a b
( PAF-AH beta)
389216178NM_031785i ATPase, H+ transporting,ATPase, H+ transporting,
i lysosomal
l ysosomal (vacuolarvacuolar proton pump),
proton ( subunit 1
p ump), subunit
1
38931169 NM 031789, w, NF-E2-related NF-E2-related factor
d bb, factor 2 2
II
38931170 NM 031789, II NF-E2-related NF-E2-related factor
. d factor 2 2
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
167
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID' ID Acc. Code
N0. or
N0. RefSeq
ID
No.
390810267NM 031838h ribosomal proteinribosomal protein S2
S2
390810269NM 031838w ribosomal proteinribosomal protein S2
S2
390910949NM 031839rr arachidonic acid arachidonic acid epoxy
epoxy enase enase
391422301NM 031967d development-relateddevelopment-related
protein protein
392619768NM 031986pp syntenin syntenin
39331573 NM 032083bb, chimerin (chimaerin)chimerin (chimaerin)
ss 1 1
39471410 NM 052798o zinc finger proteinzinc finger protein
354A 354A
397823811NM 053436ww staufen (Drosophila,staufen (Drosophila,
RNA- RNA-binding protein)
binding protein)
398014670NM 053439ee RAN, member RAS RAN, member RAS oncogene
oncogene family
family
401020902NM 053593cc cyclin-dependent cyclin-dependent kinase
kinase 4 4
402620951NM 053651nn NK2 transcriptionNK2 transcription factor
factor related, related, locus 5
locus 5 (Drosophila)(Drosophila)
403215735NM 053665n, A kinase (PRKA) A kinase (PRKA) anchor
ee anchor protein protein 1
1
403215738NM_053665cc A kinase (PRKA) A kinase (PRKA) anchor
anchor protein protein 1
1
404310909NM 053756o ATP synthase, ATP synthase, H+ transporting,
H+ transporting,
mitochondria) mitochondria) FO complex,
FO complex, subunit c (subunit
subunit c (subunit9) isoform 3
9) isoform 3
404714015NM_053770n, Arg/Abl-interactingArglAbl-interacting
w protein protein ArgBP2
ArgBP2
404714016NM_053770xx Arg/Abl-interactingArg/Abl-interacting
protein protein ArgBP2
ArgBP2
40506290 NM 053795tt kinase D-interactingkinase D-interacting
substance substance of 220 kDa
of 220 kDa
405516921NM 053806gg, ESTs, Weakly similar
hh, to S18140
jj
hypoxanthine phosphoribosyltransferase
EC 2.4.2.8) - rat fR.norvegicusl
405519827NM 0538060o ESTs, Weakly similar
to OZF_RAT Zinc
finger protein OZF (POZF-1)
[R.norvegicus]
405920421NM 053821a, v-ral simian leukemiav-ral simian leukemia
vv viral viral oncogene
oncogene homolog homolog B (ras related)
B (ras
related)
40606110 NM 053824x casein kinase casein kinase II, alpha
II, alpha 1 1 polypeptide
polypeptide
40611601 NM 053826t pyruvate dehydrogenasepyruvate dehydrogenase
kinase, isoenzyme
kinase, isoenzyme1
1
40701570 NM 053857k, eukaryotic translationeukaryotic translation
I, initiation initiation factor 4E
m,
Generalfactor 4E bindingbinding protein 1
protein 1
40701571 NM 053857I, eukaryotic translationeukaryotic translation
m, initiation initiation factor 4E
q,
General,factor 4E bindingbinding protein 1
protein 1
dd
407118358NM 053864x valosin-containingvalosin-containing protein
protein
40761453 NM 053887ff mitogen activatedmitogen activated protein
protein kinase kinase kinase
kinase kinase kinase 1
1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
168
TABLE
1
Attorney
Docket
No.
44921=5113W0
Document
No19262712
SEQGLGC GenBankModel Known Gene Name lJnigene Sequence Cluster
Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No,
40761454 NM 053887gg, mitogen activatedmitogen activated protein
hh protein kinase kinase kinase
kinase kinase kinase 1
1
40771660 NM_053891bb, cyclin-dependent cyclin-dependent kinase
II, kinase 5, 5, regulatory
ww
regulatory subunitsubunit 1 (p35)
1 (p35)
407816147NM 053892y phospholipase phospholipase A2, group
A2, group VI VI
409016190NM_053961o ESTs, Weakly similar
to F Chain F, 2-Enoyl-
Coa Hydratase, Data
Collected At 100 K,
Ph
6.5 fR.norveqicusl
409116546NM 0539650, solute carrier solute carrier family
ii family 25 25
(carnitinelacylcarnitine(carnitine/acylcarnitine
translocase), member
translocase), 20
member 20
409116547NM 053965o solute carrier solute carrier family
family 25 25
(carnitine/acylcarn'itine(carnitine/acylcarnitine
translocase), member
translocase), 20
member 20
409417279NM 053977t, cadherin 17 cadherin 17
mm
409417280NM 053977mm cadherin 17 cadherin 17
409515325NM 053979j ADP-ribosylation ADP-ribosylation factor-like
factor-like 5 5
410117739NM_053995h, 3-hydroxybutyrate3-hydroxybutyrate dehydrogenase
General, (heart,
qq dehydrogenase mitochondrial)
(heart,
mitochondrial)
410916043NM 057100jj ESTs, Highly similar
to growth arrest
specific 6 [Rattus norvegicusj
[R.norvegicusj
411017709NM 057101y Tenascin X Tenascin X
411623310NM 057119w splicing factor, splicing factor, argininelserine-rich
argininelserine-
rich (transformer(transformer 2 Drosophila
2 Drosophila homology 10
homology 10
412315839NM 057143bb, fertility proteinfertility protein SP22
kk SP22
412718122NM 057208ee tropomyosin 3, tropomyosin 3, gamma
gamma
41293831 NM 057213e, ATPase, H+ transporting,ATPase, H+ transporting,
General, lysosomal
cc, lysosomal (vacuolar(vacuolar proton pump),
qq proton beta 56/58 kDa,
pump), beta 56/58isoform 2
kDa, isoform
2
41449952 NM 080902xx hypoxia induced hypoxia induced ene
gene 1 1
415418810NM 130430w, mitochondrial mitochondrial H+-ATP
ss H+-ATP synthase synthase alpha
alpha subunit subunit
41607864 NM_130823c, ATPase, H+ transporting,ATPase, H+ transporting,
gg, lysosomal
hh,
oo, lysosomal (vacuolar(vacuolar proton pump)
qq proton 16 kDa
pump) 16 kDa
4170505 NM 133309ss calpain 8 calpain 8
4173252 NM 133323d zinc fin er proteinzinc finger protein
111 111
418010660NM 133423r, splicing factor splicing factor YT521-B
w YT521-B
418116736NM 133427j flavohemoprotein flavohemoprotein b5+b5R
b5+b5R
41825686 NM 133428dd histidine-rich histidine-rich glycoprotein
lycoprotein
41861791 NM_133541ww general transcriptiongeneral transcription
factor III C factor III C 1
1
41891558 NM 133554e, solute carrier solute carrier family
pp family 17 vesicular17 vesicular glutamate
glutamate transporter),transporter), member
member 1
1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
169
TABLE
1
Attot'ney
Docket
No.
44921-5113W0
Document
No.1926271.2
SEQGLGC GenBankModel Known Gene Name Unigene Sequence Cluster
- Title
lD-ID Acc. Code
N0. or
N0. RefSeq
ID
'-
No.
41891559 NM_133554a solute carrier solute carrier family
family 17 vesicular17 vesicular glutamate
glutamate transporter),transporter), member
member 1
1
4191745 NM 133567cc centaurin, alpha centaurin, alpha 1
1
419316993NM_133583a, N-myc downstream-regulatedN-myc downstream-regulated
d, gene 2
m
gene 2
419315029NM 1335830o N-myc downstream-regulatedN-myc downstream-regulated
gene 2
gene 2
41941164 NM 133584g phosphodiesterasephosphodiesterase 5A,
5A, cGMP- cGMP-specific
specific
41954312 NM_133586y, carboxylesterase carboxylesterase 2 (intestine,
rr, 2 (intestine, liver)
ww
liver)
419619822NM_133590x Ras-related GTP-bindingRas-related GTP-binding
protein protein Rab29
Rab29
41971308 NM_133591a rabphilin 3A-likerabphilin 3A-like (without
(without C2 C2 domains)
domains)
420225200NM 133610cc potassium voltage-gatedpotassium voltage-gated
channel, subfamily
channel, subfamilyH (eag-related), member
H (eag- 5
related), member
5
42138692 NM 134387a diacetyI/L-xylulosediacetyI/L-xylulose
reductase reductase
42153074 NM 134399kk Mk1 protein Mk1 protein
421723321NM_134407ss aldo-keto reductasealdo-keto reductase
family 7, family 7, member A2
member A2 (aflatoxin(aflatoxin aldehyde
aldehyde reductase)
reductase)
42241440 NM 134456a SH2-B PH domain SH2-B PH domain containing
containing signaling
signalin mediatormediator 1
1
42251373 NM_134468n calcium/calmodulin-dependentcalcium/calmodulin-
dependent
protein
protein kinase kinase I
I
422961 NM_138510a 20 alpha-hydroxysteroid20 alpha-hydroxysteroid
dehydrogenase
dehydrogenase
42355283 NM 138535xx glutamate receptorglutamate receptor interacting
interacting protein 2
protein 2
423716922NM 138549x synaptic glycoproteinsynaptic lycoprotein
SC2 SC2
423725479NM 138549e, synaptic glycoproteinsynaptic glycoprotein
x SC2 SC2
4247891 NM 138863x, dithiolethione-inducibledithiolethione-inducible
bb gene-1 gene-1
42545655 NM 138885f, golgi-associated golgi-associated protein
q, protein GCP360
ff
GCP360
42545656 NM 138885d, golgi-associated golgi-associated protein
q protein GCP360
GCP360
42553015 NM 138895h, polyubiquitin polyubiquitin
w
42567636 NM_138896s rotein carrying rotein carrying the
the RING-H2 RING-H2 sequence motif
sequence motif
425917115NM_138905I, ER transmembrane ER transmembrane protein
m, protein Dri Dri 42
General,42
kk
426121915NM 138910dd defender against defender against cell
cell death 1 death 1
426121916NM 138910II defender a ainst defender a ainst cell
cell death 1 death 1
4269734 NM_139094d CTD-binding SR-likeCTD-binding SR-like
protein rA8 protein rA8
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~~n
TABLE
1
Attorney
Docket
No:
44921-5113W0
Document
No.1926271:2
SEQ GLGGGenBank Model-Known Gene Name Unigene Sequence Cluster
Title
ID D Acc. Coded
- N0. or F -
I
N0. Ref$eq
ID ' . -
No. ~ . .
~ .
4270 7119NM 139098p RNA helicase RNA helicase
1
4277 5023NM 139113n, nuclear receptornuclear receptor subfamily
1 z, subfamily 2, 2, group F,
General,group F, member member 6
6
kk,
pp
4278 15239NM_139114h, ibosomal proteinribosomal protein L15
I, L15
v,
r
General
4281 22970NM 139254c, ubulin, beta tubulin, beta 3
d, 3
a
t
4285 1962NM 139329i CCA2 protein CCA2 protein
i
4287 4949NM_139338s Na+IPi-cotransporterRattus norvegicus mRNA
type Ilc for Na+IPi-
cotransporter type I
Ic, complete cds
4290 15703NM_144750f, LysophospholipaseRattus norvegicus mRNA
n, for
gg,
hh, Lysophospholipase, complete
pp cds
4291 11493NM_144755f, ESTs, Weakly similar
q, to A53621 AMP-
z,
dd,
oo, activated protein kinase
qq - rat [R.norve icus]
4291 11494NM_144755f, ESTs, Weakly similar
I, to A53621 AMP-
q;
v,
z,
General, activated protein kinase
- rat [R.norvegicus]
dd,
00
4292 1623NM_144757s Cys21His2 zinc Rattus norvegicus Cys21His2
finger protein zinc finger
(rKr1) protein (rKr1) mRNA,
complete cds
4296 1949NM_145092f, Rattus norvegicus lamina
I, associated
ii,
nn
polypeptide 1C (LAP1C)
mRNA, complete
cds, Rattus norvegicus
lamina-associated
polypeptide 1 C (LAP1
C) mRNA, complete
cds
4298 1562NM_145097j, Rattus norvegicus kallistatin
o, mRNA,
x,
uu
complete cds
4302 16343NM_145724uu Rattus norvegicus zinc
finger protein Y1
(RLZF-Y) mRNA, complete
cds
4302 16345NM_145724j, Rattus norvegicus zinc
uu finger protein Y1
(RLZF-Y) mRNA, complete
cds
4303 22975NM 145778jj Rattus norvegicus mRNA
for tubulin,
complete cds
4338 18647S69316 q, ESTs, Weakly similar
dd to HS9B_RAT Heat
shock protein HSP 90-beta
(HSP 84)
(R.norvegicusl
4345 1460S76054 t, ESTs, Highly similar
General, to K2C8_RAT Keratin,
ll, type II cytoskeletal
ww 8 (Cytokeratin 8)
(Cytokeratin endo A)
(R.norveqicusl
4348 17626S78556 qq ESTs, Highly similar
to 156581 dnaK-type
molecular chaperone grp75
precursor - rat
[R.norveqicusl
4354 110 001145 I, Rattus norvegicus clone
General, 15 polymeric
kk immunoglobulin receptor
mRNA, 3'UTR
microsatellite repeats
4356 347 001914 s, A kinase anchor A kinase anchor protein
tt protein 8 8
4357 111 002506 b, , Rattus norvegicus clone
General 15 polymeric
kk, immunoglobulin receptor
vv mRNA, 3'UTR
microsatellite re eats
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
171
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.192627~1~3
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
Title
ID D Acc.'or Code
I N0.
NO. RefSeq
ID
No:
43582010005675 y, Rattus norvegicus Sprague-Dawley
vv
fibrinogen B beta chain
mRNA, complete cds
4370399 031668 ww, E2F transcriptionE2F transcription factor
xx factor 5 5
43751357039572 mm phosphatidylinositol4-kinasephosphatidylinositol4-kinase
437618038039943 x Rattus norvegicus cytochrome
P450
pseudogene (CYP2J3P1)
mRNA
438615516068544 b Rattus norvegicus cyclophilin
D mRNA,
nuclear gene encoding
mitochondria)
protein, complete cds
43981153089280 h, Rattus norvegicus oxidative
n 17 beta
hydroxysteroid dehydrogenase
type 6
mRNA, complete cds
44009841094856 w paraoxonase 1 paraoxonase 1
44009842094856 pp paraoxonase 1 paraoxonase 1
441419584X13905 General,, ESTs, Moderately similar
to TVRTYP GTP-
mm binding protein Rab1
- rat [R.norve icus]
444018924X58830 g ~ Bone morphogeneticBone morphogenetic protein
protein 6 6
44464441X62146 ee ESTs, Highly similar
to RL11 HUMAN 60S
ribosomal protein L11
[R.norve icus]
444713646X62166 I, ESTs, Highly similar
m, to RL3_RAT 60S
s,
z,
General, RIBOSOMAL PROTEIN L3
(L4)
bb, [R.norvegicus]
cc,
ii,
4q,
rr
444815387X62482 h, ESTs, Highly similar
gg, to R3RT25 ribosomal
hh
protein S25, cytosolic
[validated] - rat
[R.norvegicus]
445520844X65228 y, ESTs, Highly similar
II to R3RT3A ribosomal
protein L23a, cytosolic
[validated] - rat
[R.norvegicusl
446423302X78949 ff, prolyl 4-hydroxylaseprolyl 4-hydroxylase
xx alpha alpha subunit
subunit
447318031X94551 y laminin, gamma laminin, amma 1
1
250 10157AA819527rr HHs:amyloid beta ESTs, Highly similar
(A4) to S23094 beta-amyloid
precursor proteinprotein precursor -
(protease rat [R.norvegicus]
nexin-II, Alzheimer
disease)
235210156AI178039bb HHs:amyloid beta ESTs, Highly similar
(A4) to S23094 beta-amyloid
precursor proteinprotein precursor -
(protease rat [R.norvegicus]
nexin-II, Alzheimer
disease)
441010154X07648 m HHs:amyloid beta ESTs, Highly similar
(A4) to S23094 beta-amyloid
precursor proteinprotein precursor -
(protease rat [R.norvegicus]
nexin-II, Alzheimer
disease)
442420872X51707 h ribosomal proteinESTs, Highly similar
S19 to R3RT19 ribosomal
protein S19, cytosolic
[validated] - rat
R.norve icus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
17~
TABLE
1
Attorney
Docket
No:'44921-5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID D Aocor Code
I NO..
NO: RefSeq
ID
;
No.
221818498AI172452m, ESTs, Weakly similar
ii, to COXJ RAT
II,
uu
Cytochrome c oxidase
polypeptide Vlla-
l iverlheart, mitochondria)
precursor
(Cytochrome c oxidase
subunit Vlla-L)
IR.norveaicusl
232416175A1177145w ESTs, Weakly similar
to CAG7_RAT ALPHA-
N-ACETYLGALACTOSAMINIDE
ALPHA-2,6
SIALYLTRANSFERASE (ST6GALNACI11)
(STY) fR.norveaicusl
239812033AI179066ee ESTs, Highly similar
to SL52_RAT
-
SODIUMIGLUCOSE COTRANSPORTER
2
(NA(+)/GLUCOSE COTRANSPORTER
2)
(LOW AFFINITY SODIUM-GLUCOSE
COTRANSPORTER) (R.norveaicusl
255620055AI230762rr ESTs, Weakly similar
to A53742 calponin,
acidic - rat [R.norve
icusl
260718497AI232307c ESTs, Weakly similar
to COXJ_RAT
Cytochrome c oxidase
polypeptide Vlla-
liverlheart, mitochondria)
precursor
(Cytochrome c oxidase
subunit Vlla-L)
(R,norveaicusl
350122726NM 019383r ATP synthase subunitATP synthase subunit
d d
36082250 NM_022643c, ESTs, Highly similar
d, to 0506206A histone
m,
cc,
kk, H2B [Rattus norvegicus]
qq, [R.norvegicus]
vv
375619161NM 031111j, ribosomal proteinribosomal protein S21
ee S21
409715468NM 053982h, ribosomal proteinribosomal protein S15a
g, S15a
hh
409719544NM_053982h, EST, Moderately similar
I, to JC2234
qq
ribosomal protein S15a,
cytosolic [validated]
rat [R.norveaicusl
42999845 NM_145672m ESTs, Weakly similar
to JN0572 neutrophil
chemo-attractant Gro
protein precursor -
rat
[R.norvegicusl
442816716X53054 c Rat mRNA for RT1.D beta
chain
488 4339 AA875121d CCAAT binding CCAAT binding factor
factor of CBF- of CBF-CINFY-C
C/NFY-C
130417353A1008020o Malic enzyme 1, Malic enzyme 1, soluble
soluble
16818330 A1059434g peroxisome proliferativeperoxisome proliferative
activated receptor,
activated receptor,gamma, coactivator 1
gamma,
coactivator 1
182918838AI101102ee Prosaposin (sulfatedProsaposin (sulfated
glycoprotein,
glycoprotein, sphingolipid hydrolase
sphingolipid activator)
hydrolase activator)
189011486AI103162j Glycoprotein-4-beta-Glycoprotein-4-beta-
galactosyltransferase
2
galactosyltransferase
2
21126479 AI169690h, Fibrinogen, gammaFibrinogen, gamma polypeptide
I, polypeptide
q
245521296AI227641j Myosin, light Myosin, light polypeptide
polypeptide 2, 2, alkali;
alkali ventricularventricular skeletal
skeletal slow slow
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
173
TABLE
1
Afforney
Dockef
No44921=5118W0
t)ocument
No.
X926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence-Clustex
Title
ID l) Acc. Code
_- N0. or
I
N0. RefSe_q
iD
'
No.
255213618AI230724kk, SAC1 (supressor SAC1 (supressor of actin
tt of actin mutations 1,
mutations 1, homology-likehomology-like (S. cerevisiae)
(S.
cerevisiae)
272421414AI235842x Superoxide dismutaseSuperoxide dismutase
2, 2, mitochondria)
mitochondria)
2961790 L10073 g 5-hydroxytryptamine5-hydroxytryptamine
(serotonin) (serotonin) receptor
5B
receptor 5B, ER01-like
(S.
cerevisiae), Lysosomal
associated membrane
protein 1
(120 kDa), apoptotic
protease
activating factor
1, ceroid-
lipofuscinosis,
neuronal 2,
cysteine-sulfinate
rianarhnxvlasP
296916119L16532 q 2',3'- Cyclic 2',3'- Cyclic nucleotide
nucleotide 3'- 3'-phosphodiesterase
phosphodiesterase
299221053M15481 qq Insulin-like growthInsulin-like rowth factor
factor I I
_ 6477 NM_012559dd Fibrinogen, gammaFibrinogen, gamma polypeptide
3071 polypeptide
3073619 NM 012565h, Glucokinase Glucokinase
r,
kk
307620744NM 012571e, Glutamic-oxaloaceticGlutamic-oxaloacetic
II, transaminase 1,
oo
transaminase 1, soluble (aspartate aminotransferase,
soluble
(aspartate aminotransferase,cytosolic) see also
D1Mgh12
cvtosolic) see
also D1Mah12
308718746NM 012600gg, Malic enzyme 1, Malic enzyme 1, soluble
hh soluble
30909174 NM 012612g Natriuretic peptideNatriuretic peptide
precursor A, precursor A,
(pronatriodilatin,(pronatriodilatin, also
also Anf, Pnd) Anf, Pnd)
310216198NM 012663kk, Vesicle-associatedVesicle-associated membrane
tt membrane protein
protein (synaptobrevin(synaptobrevin 2)
2)
310216199NM 012663bb, Vesicle-associatedVesicle-associated membrane
kk membrane protein
protein (synaptobrevin(synaptobrevin 2)
2)
310216200NM_012663ii Vesicle-associatedVesicle-associated membrane
membrane protein
protein (synaptobrevin(synaptobrevin 2)
2)
3119503 NM_012704k Rat kidney prostaglandinRat kidney prostaglandin
EP3 EP3 receptor
receptor
312124545NM 012713s Protein kinase Protein kinase C beta
C beta
31311260 NM_012743d Hepatocyte nuclearHepatocyte nuclear factor
factor 3 3 beta
beta
315411138NM_012839jj Cytochrome C, Cytochrome C, expressed
expressed in in somatic tissues
somatic tissues
3162395 NM_012864v Matrix metalloproteinaseMatrix metalloproteinase
7 7 (matrilysin)
(matrilysin)
31634338 NM 012866II CCAAT binding CCAAT binding factor
factor of CBF- of CBF-CINFY-C
CINFY-C
31881720 NM 012943cc Distal-less homeoboxDistal-less homeobox
320519391NM 012998t, Protein disulfideProtein disulfide isomerase
y, isomerase (Prolyl 4-
mm
(Prolyl 4-hydroxylase,hydroxylase, beta polypeptide)
beta
of a tide
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
174
TABLE
1
Attorney
Docket
Nor
44921=5113W0
Document
No.19262713
SEQ GLGC GenBankModel Known Gene Name Unigene-Sequence ClusferTitle
ID ID.NO.Ace. Code
or
N0. RefSeq
ID
No.
320519392NM 012998j, Protein disulfideProtein disulfide isomerase
gg, isomerase (Prolyl 4-
hh
(Prolyl 4-hydroxylase,hydroxylase, beta polypeptide)
beta
polypeptide)
320519393NM 012998gg, Protein disulfideProtein disulfide
hh, isomerase somerase (Prolyl 4-
II i
(Prolyl 4-hydroxylase,hydroxylase, beta polypeptide)
beta
polypeptide)
320923543NM 013013w, Prosaposin (sulfatedProsaposin (sulfated
y glycoprotein,
glycoprotein, sphingolipid hydrolase
sphingolipid activator)
hydrolase activator)
320923544NM 013013c Prosaposin (sulfatedProsaposin (sulfated
glycoprotein,
glycoprotein, sphingolipid hydrolase
sphingolipid activator)
hydrolase activator)
3211208 NM 013025vv Macrophage inflammatoryMacrophage inflammatory
protein 1 alpha
protein 1 alpha (Small inducible cytokine
(Small inducible A3)
cytokine A3)
32331583 NM 013079a, Asparagine synthetaseAsparagine synthetase
m,
s,
General,
dd
3306910 NM 017059bb, Bcl2-associated Bcl2-associated X protein
ss X protein
3306911 NM 017059ss Bcl2-associated Bcl2-associated X protein
X protein
3306912 NM 017059qq Bcl2-associated Bcl2-associated X protein
X protein
333620859NM 017144cc Troponin I Troponin I
33571541 NM 017193ee kynurenine aminotransferasekynurenine aminotransferase
II II
336413938NM 017212g microtubule-associatedmicrotubule-associated
protein protein tau
tau
339812347NM 017290j ATPase, Ca++ transporting,ATPase, Ca++ transporting,
j cardiac muscle,
cardiac muscle, slow twitch 2
slow twitch 2
339812348NM 017290f, ATPase, Ca++ transporting,ATPase, Ca++ transporting,
f pp cardiac muscle,
cardiac muscle, slow twitch 2
slow twitch 2
339812349NM 017290 ATPase, Ca++ transporting,ATPase, Ca++ transporting,
I cardiac muscle,
cardiac muscle, slow twitch 2
slow twitch 2
34595661 NM 019241a gap junction membranegap junction membrane
channel channel protein beta
protein beta 5 5
34921070 NM 019368, q, blocked early blocked early in transport
f z in transport 1
1 omolog
h
homolo (S.cerevisiaeS.cerevisiae) - like
- like (
349715680NM 019376i, 14-3-3 protein 4-3-3 protein gamma-subtype
i II gamma-subtype
1
350815911NM 019907ww postsynaptic proteinpostsynaptic protein
Cript Cript
351615335NM_021264General,ribosomal proteinibosomal protein L35a
L35a r
kk
354023151NM_022005a FXYD domain-containingFXYD domain-containing
ion ion transport
transport regulatoregulator 6
6 r
358525681NM_022519 serine (or cysteine)erine (or cysteine)
r proteinase s proteinase inhibitor,
i nhibitor, Glade lade A (alpha-1 antiproteinase,
A (alpha-1 G antitrypsin),
antiproteinase, member 1
antitrypsin),
member 1
35854212 NM 022519a serine (or cysteine)erine (or
proteinase s ysteine) proteinase
c inhibitor,
i nhibitor, Glade lade A (alpha-1 antiproteinase,
A (alpha-1 G antitrypsin),
antiproteinase, member 1
antitrypsin),
member 1
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
175
TABLE
1
Aftorney
Docket
Nor
44921-5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
' Title
ID D Accor Code
I N0.
NO RefSeq=ID
No.'
35854213 NM 022519ee serine (or cysteine)serine (or cysteine)
proteinase proteinase inhibitor,
i nhibitor, Glade Glade A (alpha-1 antiproteinase,
A (alpha-1 antitrypsin),
antiproteinase, member 1
antitrypsin),
member 1
35905666 NM 022529r mitochondrial mitochondrial ribosomal
ribosomal proteinprotein L23
L23
362658 NM 022715nn major vault proteinmajor vault protein
363618098NM 0229470o suppressor of suppressor of K+ transport
K+ transport defect 3
defect 3
364215755NM_022960k neutral solute neutral solute channel
channel aquaporin 9
aquaporin 9
3703248 NM_030998gg, anti-Mullerian anti-Mullerian hormone
hh hormone type type 2 receptor
2
receptor
372015805NM 031028g gamma-aminobutyricgamma-aminobutyric acid
acid (GABA) B
(GAGA) B receptor,receptor, 1
1
372015807NM 031028s gamma-aminobutyricgamma-aminobutyric acid
acid (GABA) B
(GABA) B receptor,receptor,1
1
379924710NM 031512vv Interleukin 1 Interleukin 1 beta
beta
38074010 NM 031543e, Cytochrome P450, Cytochrome P450, subfamily
r subfamily 2e1 (ethanol-
2e1 (ethanol-inducible)inducible)
38074011 NM 031543j, Cytochrome P450, Cytochrome P450, subfamily
w subfamily 2e1 (ethanol-
2e1 (ethanol-inducible)inducible)
38074012 NM 031543e, Cytochrome P450, Cytochrome P450, subfamily
rr subfamily 2e1 (ethanol-
2e1 (ethanol-inducible)inducible
38181920 NM 031576c, P450 (cytochrome)P450 (cytochrome) oxidoreductase
cc
oxidoreductase
3819939 NM 031577z growth hormone growth hormone releasing
releasing hormone
hormone
382714542NM_031596a squamous cell squamous cell carcinoma
carcinoma antigen
antigen recognizedrecognized by T-cells
by T-cells
382714543NM 031596jj squamous cell squamous cell carcinoma
carcinoma antigen
anti en reco nizedrecognized by T-cells
by T-cells
3843906 NM 031633ss forkhead box M1 forkhead box M1
38489427 NM 031656c, syntaxin-like syntaxin-like protein
kk protein 3135 3135
38489428 NM 031656p syntaxin-like syntaxin-like protein
protein 3135 3135
385020467NM 031662r, calcium/calmodulin-dependentcalcium/calmodulin-
dependent
ee protein
protein kinase kinase kinase 1, alpha
kinase 1, alpha
385223656NM 031673bb calpain 10 calpain 10
393617933NM_032615m, membrane interactingmembrane interacting
o, protein of protein of RGS16
z,
General,RGS16
dd,
rr
393617934NM 0326150, membrane interactingmembrane interacting
z, protein of protein of RGS16
General,RGS16
nn
393617935NM 0326150, membrane interactingmembrane interacting
s protein of protein of RGS16
RGS16
399114380NM 053536tt Kruppel-like factorKruppel-like factor
15 (kidney) 15 (kidney)
402213005NM 053623a fatty acid-Coenzymefatty acid-Coenzyme
A ligase, A ligase, long chain
4
Ion chain 4
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
178
TABLE
1
Attorney
Docket
No:
44921-5~131N0
Document
No.19262712
SEO.GLGC GenBankModel fnown Gene Name Unigene Sequence Cluster
I Title
ID D Accor Code
- N0.
I
N0~ RefSeq
ID
No. _
_
40523677 NM 053798x SAC1 (supressor SAC1 (supressor of actin
of actin mutations 1,
mutations 1, homology-likehomology-like (S. cerevisiae)
(S.
cerevisiae)
405816311NM 053818 glycine transporterlycine transporter 1
j 1
406620868NM 053843y, Fc receptor, I Fc receptor, IgG, low
xx G, low affinity affinity III
III
4137132 NM 080782I, cyclin-dependent cyclin-dependent kinase
I tt kinase inhibitor 1A (P21)
i nhibitor 1A (P21)
4137133 NM 080782p, cyclin-dependent cyclin-dependent kinase
II, kinase inhibitor 1A (P21)
ss
i nhibitor 1A (P21)
416417560NM_133283e, eukaryotic translationmitogen activated protein
t, elongation kinase kinase 2
mm
factor 2, mitogen
activated
protein kinase
kinase 2
416417564NM_133283ff mitogen activatedmitogen activated protein
protein kinase kinase kinase 2
kinase 2
416421848NM_133283v, mitogen activatedmitogen activated protein
y protein kinase kinase kinase 2
kinase 2
416421849NM_133283ff mitogen activatedmitogen activated protein
protein kinase kinase kinase 2
kinase 2
417610195NM_133383w retinoid-inducibleretinoid-inducible serine
serine caroboxypetidase
caroboxypetidase
43241937 846934 k amelogenin amelogenin
440621054X06107 g, Insulin-like rowthInsulin-like growth
v factor I factor I
60 2040 AA799700w HMmaelenophosphateESTs, Highly similar
to SPS2_MOUSE
synthetase 2 Selenide,water dikinase
2 (Selenophosphate
synthetase 2) (Selenium
donor protein 2)
fM.musculusl
209 12160AA8184120, cytochrome P450, cytochrome P450, 2b19
qq 2b19
495 10936AA875146f HMm:ubiquitin ESTs, Highly similar
conjugating to ubiquitin conjugating
enzyme 6 enzyme 6; Ubc6p homolog
[Mus musculus]
~M.musculusl
590 2107 AA892006a HMm:ATPase, H+ ESTs, Highly similar
transporting, to VAA1 MOUSE
lysosomal 70kD, Vacuolar ATP synthase
V1 subunit A, catalytic subunit A,
isoform 1 ubiquitous isoform (V-ATPase
A subunit 1)
(Vacuolar proton pump
alpha subunit 1) (V-
ATPase 69 kDa subunit
1) fM.musculusl
815 3959 AA901338z HMm:eukaryotic ESTs, Highly similar
translation to eukaryotic
initiation factortranslation initiation
2, subunit 2 factor 2, subunit 2
(beta,
(beta, 38kDa) 38kDa) fMus musculus)
[M.musculusl
10962702 AA957307I, HMmaeryl-aminoacyl-tRNAESTs, Highly similar
I, to A41019 serine--tRNA
p,
z,
General,synthetase 1 ligase (EC 6.1.1.11)
- mouse (fragment)
dd, [M.musculus]
ii,
pp,
aa,
rr
15172108 A1029960ee HMm:ATPase, H+ ESTs, Highly similar
transporting, to VAA1 MOUSE
lysosomal 70kD, Vacuolar ATP synthase
V1 subunit A, catalytic subunit A,
isoform 1 ubiquitous isoform (V-ATPase
A subunit 1)
(Vacuolar proton pump
alpha subunit 1) (V-
ATPase 9 kD subuni 1
M.musculu
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
177
TABLE
1
:
Attorney
Docket
No~
44927-5113W0
Document
No.19262712
$EC GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
fD ID Acc. Code
N0. or
:
N0. RefSeq
ID
NQ.:
208917914AI169159I HMm:ATPase, H+ ESTs, Moderately similar
I transporting, to VATE_MOUSE
' lysosomal 31 kDa,Vacuolar ATP synthase
V1 subunit E subunit E (V-
ATPase E subunit) (Vacuolar
proton pump E
subunit) (V-ATPase 31
kDa subunit) (P31)
[ M.musculusl
231215588AI176916dd HMm:phosphomannomutaseESTs, Highly similar
1 to PMM1 MOUSE
Phosphomannomutase 1
(PMM 1)
[ M.musculusl
294812156K00996 o cytochrome P450, cytochrome P450, 2b19
2b19
295012157K01721 o cytochrome P450, cytochrome P450, 2b19
2b19
296823897L15011 g cortexin cortexin
31786107 NM 012915b, ATPase inhibitor ATPase inhibitor (rat
General,(rat mitochondria) IF1
gg, mitochondria) protein)
hh, IF1 protein)
uu
31786108 NM 012915b, ATPase inhibitor ATPase inhibitor (rat
General,(rat mitochondria) IF1
uu mitochondria) protein)
IF1 protein)
31786109 NM 012915n ATPase inhibitor ATPase inhibitor (rat
(rat mitochondria) IF1
mitochondria) protein)
IF1 protein)
3196956 NM 012976GeneralLectin, galactoseLectin, galactose binding,
binding, soluble 9 (Galectin
' soluble 5 (Galectin-5),9)
Lectin,
galactose binding,
soluble 9
(Galectin-9)
3197958 NM 012977b, Lectin, galactoseLectin, galactose binding,
tt binding, soluble 9 (Galectin
soluble 9 (Galectin-9)9)
354120309NM 022175gg, Homeobox gene Homeobox gene Pem
hh Pem
3655504 NM 024136x epididymal retinoicepididymal retinoic
acid-binding acid-binding protein
protein
3796635 NM 031509vv Glutathione-S-transferase,Glutathione-S-transferase,
alpha type (Ya)
alpha type (Ya)
4312683 NM_147206ii HMm:cytochrome Rattus norvegicus cytochrome
P450, steroid P450 3A9
inducible 3a13 mRNA, complete cds
4439 AA685175h, ESTs, Moderately similar
m, to ribosome
s,
General binding protein 1 isoform
mRRp61 [Mus
musculusl [M.musculusl
14 19222AA799279d, ESTs, Highly similar
f, to mitochondria) carrier
I,
General, homolog 2 [Mus musculus]
[M.musculus]
pp
37 15560AA799538z ESTs, Highly similar
to SFR2_MOUSE
Splicing factor, argininelserine-rich
2
(Splicing factor SC35)
(SC-35) (Splicing
component, 35 kDa) (PR264
protein)
[M.musculusl
85 21006AA799861rr ESTs, Highly similar
to IRF7_MOUSE
Interferon regulatory
factor 7 (IRF-7)
[M.musculusl
85 21007AA799861g ESTs, Highly similar
to IRF7_MOUSE
Interferon regulatory
factor 7 (IRF-7)
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
~ ~n
TABLE
1
Attorney=Docket
No.
44921=5113WQ
Document
No.1926271:2
SEQ GLGCGenBank Model Known Gene Name Unigene Sequence Cluster
ID ID Acc. . Title
N0. or Code
N0. RefSeq
ID :
No
101 15394AA800039z, ESTs, Weakly similar
II to FAF1 MOUSE FAS
associated factor 1
(FAF1 protein)
fM.musculus]
121 24228AA8003180o ESTs, Moderately similar
to IC1 MOUSE
Plasma protease C1 inhibitor
precursor (C1
Inh) (C1lnh) [M.musculus]
147 17648AA800735I ESTs, Weakly similar
to VIL1 MOUSE Villin
1 [M.musculus]
147 17649AA800735w, ESTs, Weakly similar
gg, to VIL1 MOUSE Villin
hh
1 [M.musculus]
174 2425AA817722mm ESTs, Highly similar
to CTN1 MOUSE
Alpha-1 catenin (102
kDa cadherin-
associated protein)
(CAP102) (Alpha E-
catenin) fM.musculusl
186 11215AA817921xx ESTs, Highly similar
' to ubiquitin-like 5
[Mus
musculus] [M.musculus]
191 10623AA817987c, Sulfotransferase Sulfotransferase hydroxysteroid
- f, hydroxysteroid gene 2
n,
v
ene 2
204 6522AA818261c ' ESTs, Moderately similar
to A47318 RNA-
bindin protein Raly
- mouse [M.musculus]
222 18868AA818759dd ESTs, Moderately similar
to S12207
hypothetical protein
(B2 element) - mouse
f M.musculusl
233 6132AA819055v, ESTs, Weakly similar
uu to 635070
apolipoprotein H-related
protein 1361 -
mouse [M.musculusl
249 9987AA819502c ESTs, Weakly similar
to ELL MOUSE RNA
POLYMERASE II ELONGATION
FACTOR
ELL (ELEVEN-NINETEEN
LYSINE-RICH
LEUKEMIA PROTEIN) fM.musculusl
258 6297AA819681General, ESTs, Highly similar
to RIKEN cDNA
uu 1 200014P03 [Mus musculus]
[M
musculus]
.
283 16128AA848807I, ESTs, Highly similar
r, to RIKEN cDNA
nn
2 410017118 [Mus musculus]
[M.musculus]
307 12129AA849966n ESTs, Moderately similar
to Mpv17
t ransgene, kidney disease
mutant-like [Mus
musculusl fM.musculus]
319 19621AA850634v E STs, Moderately similar
to S12207
h ypothetical protein
(B2 element) - mouse
f M.musculusl
330 8872AA851050v, lutathione reductaselutathione reductase
qq g
334 15561AA851202II E STs, Highly similar
to SFR2_MOUSE
S plicing factor, arginine/serine-rich
2
( Splicing factor SC35)
(SC-35) (Splicing
c omponent, 35 kDa) (PR264
protein)
f M.musculusl
337 17699AA851233gg, E STs, Highly similar
hh to RIKEN cDNA
4 930548607 Mus musculus
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
179
TABLE
1
~'
Attorney
Docket
No.
44921-51131Na
Document
No.1926271:2
SEQ GLGC GeriBankModel Kr~own Gene Name Jnigene Sequence ClusterTitle
_ t
ID D Acc: Code'
: NO. or
I
N0. RefSeq
ID
No.
371 1801 AA858636r, ESTs, Highly similar
rr to mini chromosome
maintenance deficient
7 (S. cerevisiae) [Mus
musculus] [M.musculusl
386 18765AA859019a ESTs, Weakly similar
to 635070
apolipoprotein H-related
protein 1361 -
mouse [M.musculusl
398 6464 AA859401II ESTs, Highly similar
to JC7321 N-
acetylneuraminic acid
9-phosphate synthase
(EC 4.1.3.-) - mouse
[M.musculus]
419 22670AA859750y ESTs, Weakly similar
to ERF_MOUSE ETS-
domain transcription
factor ERF
[M.musculusl
421 14213AA859827bb, ESTs, Moderately similar
dd, to URK1 MOUSE
jj,
oo, URIDINE KINASE (URIDINE
pp
MONOPHOSPHOKINASE) [M.musculus]
432 19377AA859971I ESTs, Highly similar
to RIKEN cDNA
0610010112 [Mus musculus]
[M.musculus]
459 9391 AA866477d ESTs, Moderately similar
to COXM_MOUSE
Cytochrome c oxidase
polypeptide Vllb,
mitochondria) precursor
[M.musculus]
476 16241AA875019pp ESTs, Highly similar
to ZAP3_MOUSE
Nuclear protein ZAP3
[M.musculus]
487 16416AA875098j, ESTs, Highly similar
q, to RIKEN cDNA
dd
1110002023 [Mus musculus]
[M.musculus]
509 18864AA875470a ESTs, Highly similar
to COP9 (constitutive
photomorphogenic) homolog,
subunit 7a
(Arabidopsis thaliana);
DNA segment, Chr 6,
ERATO Doi 35, expressed;
COP9 complex
S7a; COP9 (constitutive
photomorphogenic),
subunit 7a (Arabidopsis)
[Mus musculus]
fM.m ulusl
515 15558AA875537tt ESTs, Highly similar
to SFR2_MOUSE
-
Splicing factor, argininelserine-rich
2
(Splicing factor SC35)
(SC-35) (Splicing
component, 35 kDa) (PR264
protein)
IM.musculusl
524 15688AA875664x ESTs, Highly similar
to mitochondria
associated granulocyte
macrophage CSF
signaling molecule [Mus
musculus]
fM.musculusl
526 17057AA891049General ESTs, Highly similar
to PFD2_MOUSE
-
Prefoldin subunit 2
[M.musculus]
531 24814AA891209m ESTs, Highly similar
to interleukin 25;
lymphocyte antigen 6
complex, locus E
li and Mus musculus
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
180
TABLE
1
~
Attorney
Docket
No44921=5113W0
Document
No.1926271:2
SEQ GLGC Genl3ankModel Known Gene Name Unigene Sequence Cluster
: Title
117yID Acc. Code'
X10..or-
N0. RefSeq G
ID= v~
No:
,. _
574 16602AA891864t, ESTs, Highly similar
mm to RIKEN cDNA
2900054013 gene; nuclear
ATP/GTP-
binding protein; Purkinje
cell degeneration
[Mus musculusl [M.musculusl
594 6362 AA892053q ESTs, Highly similar
to T42204 chromatin
structural protein homolog
SuptShp - mouse
[M.musculus]
628 18150AA892422a ESTs, Moderately similar
to RIKEN cDNA
2410001 P07; RIKEN cDNA
2410001 P07
gene [Mus musculus]
(M.musculus]
633 1522 AA892486e, ESTs, Weakly similar
ii, to A36690 sucrose
rr,
uu
alpha-glucosidase (EC
3.2.1.48) - rat
(fragment) R.norveqicusl
648 18274AA892572bb ESTs, Highly similar
to RIKEN cDNA
1110001J03 [Mus musculus]
[M.musculus]
666 20359AA892817f, EST, Weakly similar
s to S12207 hypothetical
protein (B2 element)
- mouse [M.musculus]
684 11189AA892960ee ESTs, Highly similar
to RIKEN cDNA
1200011118 Mus musculus]
[M.musculus]
696 19745AA893199t ESTs, Highly similar
to RIKEN cDNA
1500004D14 [Mus musculus]
[M.musculus]
701 548 AA893235c, ESTs, Highly similar
ww, to GOS2_MOUSE
xx
Putative lymphocyte
GO/G1 switch protein
2
(GOS2-like protein)
[M.musculusl
720 17698AA893596ww ESTs, Highly similar
to RIKEN cDNA
4930548607 [Mus musculus]
[M.musculus]
745 3217 AA894101jj ESTs, Moderately similar
to PNAD_MOUSE
PROTEIN N-TERMINAL ASPARAGINE
AMIDOHYDROLASE (PROTEIN
NH2-
TERMINAL ASPARAGINE
DEAMIDASE)
(NTN-AMIDASE) (PNAD)
(PROTEIN NH2-
TERMINAL ASPARAGINE
AMIDOHYDROLASE) (PNAA)
[M.musculus]
764 3910 AA894345b, ESTs, Weakly similar
k, to 2021425A MAT1
I,
cc
ene [Mus musculus] [M.musculus]
765 18094AA899051rr SH-PTP2 protein SH-PTP2 protein tyrosine
tyrosine phosphatase, non-
phosphatase, non-receptorreceptor type 11
type
11
807 22666AA900974r, ESTs, Highly similar
y, to p34SEl-1; PHD zinc
kk
finger- and bromodomain-interacting
protein
1 [Mus musculus] [M.musculusl
840 18434AA924413kk, ESTs, Moderately similar
tt to hypothetical
protein MNCb-0169 [Mus
musculus]
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1S1
TABLE
1
Attorney
Docket
No~
44921=5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Knowrt Gene Name Unigene Sequence Cluster
Title
ID. 1D Acc. Code
NO.~ or
~
N0, RefSeq
ID
No:
843 3631 AA924460m ESTs, Weakly similar
to PMC1 MOUSE
Polymyositislscleroderma
autoantigen 1
( Autoantigen PM/Scl 1
)
( Polymyositislscleroderma
autoantigen 75
kDa) (PM/Scl-75) (P75
polymyositis-
scleroderma overlap
syndrome associated
aut nti nl fM.musculusl
864 5073 AA925061d ESTs, Moderately similar
to S20710
hypothetical protein,
16K - mouse
[ M.musculus
916 16909AA942704bb ESTs, Moderately similar
to SUR2_MOUSE
Surfeit locus protein
2 (Surf 2) [M.musculusj
918 6039 AA942716nn ESTs, Highly similar
to hematological and
neurological expressed
sequence 1 [Mus
musculus] [M.musculusl
976 21581AA944828ff ESTs, Highly similar
to RIKEN cDNA
2610524607 [Mus musculus]
[M.musculus]
984 22667AA945069r ESTs, Highly similar
to p34SEl-1; PHD zinc
finger- and bromodomain-interacting
protein
1 [Mus musculus] [M.musculus]
102612321AA946166d ESTs, Highly similar
to RIKEN cDNA
2410003020 [Mus musculus]
[M.musculus]
105715329AA955427k ESTs, Highly similar
to LMA1 MOUSE
Laminin alpha-1 chain
precursor (Laminin
A
chain) [M.musculusl
10609984 AA955536c ESTs, Weakly similar
to ELL_MOUSE RNA
POLYMERASE II ELONGATION
FACTOR
ELL (ELEVEN-NINETEEN
LYSINE-RICH
LEUKEMIA PROTEIN) fM.musculusl
10609985 AA955536c ESTs, Weakly similar
to ELL_MOUSE RNA
POLYMERASE II ELONGATION
FACTOR
ELL (ELEVEN-NINETEEN
LYSINE-RICH
LEUKEMIA PROTEIN) fM.musculusl
106623662AA955640jj ESTs, Highly similar
to RIKEN cDNA
2610002M06 [Mus musculus]
[M.musculus]
108823805AA956558jj ESTs, Moderately similar
to MTG8_MOUSE
MTG8 protein [M.musculus]
112316603AA964059mm ESTs, Highly similar
to RIKEN cDNA
2900054013 gene; nuclear
ATPIGTP-
binding protein; Purkinje
cell degeneration
fMus musculusl IM.musculusl
112912166AA964426a ESTs, Moderately similar
to RIKEN cDNA
2810433K01 [Mus musculus]
[M.musculus]
115521008AA965186II ESTs, Highly similar
to IRF7_MOUSE
Interferon regulatory
factor 7 (IRF-7)
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1R~
TABLE
1
Attorney
Docket
No.
44921-5113WQ
Document
No:19262712
SEGtGLGC GenBankModel:Known Gene Name Unigene-SequenceClusterTitle
ID' DNO. Acc: Code
I of
N0 RefSeq
ID
No,
11772988 AA997030rr ESTs, Moderately similar
to guanine
nucleotide exchange
factor (RCC1 related)
[ Mus musculusl [M.musculusl
11933269 AA997800k ESTs, Moderately similar
to T30249 cell
proliferation antigen
Ki-67 - mouse
[M.musculus]
12033357 AA998078v ESTs, Moderately similar
to RaIBP1
associated Eps domain
containing protein
[Mus musculusl [M.musculus]
12333069 AA998910ss ESTs, Highly similar
to endoplasmic
reticulum chaperone
SIL1 homolog (S.
cerevisiae) [Mus musculus]
fM.musculusl
126523044AF034218s, hyaluronidase hyaluronidase 2
kk, 2
pp
12984740 A1007847k ESTs, Weakly similar
to S26689 hypothetical
protein hc1 - mouse
(fragment)
f M.musculusl
13403464 A1009589ww ESTs, Highly similar
to RIKEN cDNA
4921524J17 [Mus musculus]
[M.musculus]
1345994 A1009693bb ESTs, Highly similar
to RIKEN cDNA
2310050K10 [Mus musculus]
[M.musculus]
13626874 A1010057g EST, Weakly similar
to A26621 retrovirus-
related endonuclease
(EC 3.1.-.-) - mouse
(fragment) [M.musculusl
13786943 A1010637ss ESTs, Moderately similar
to peptide N-
glycanase; peptide:N-glycanase
[Mus
musculus] fM.musculusl
15102340 A1029499s, ESTs, Weakly similar
oo to JC4524 aldehyde
dehydrogenase (NAD(P)+)
(EC 1.2.1.5) - rat
[R.norve icusl
151122469A1029506dd ESTs, Moderately similar
to COG2_MOUSE
Coatomer gamma-2 subunit
(Gamma-2 coat
protein) (Gamma-2 COP)
[M.musculus]
15617916 A1043855s, sterol-C5-desaturasesterol-C5-desaturase
t (fungal (fungal ERG3, delta-5-
ERG3, delta-5-desaturase)-likedesaturase)-like
15699829 A1044063x ESTs, Weakly similar
to carcinoma related
gene [Mus musculus]
[M.musculus]
158924174A1044826gg, ESTs, Highly similar
hh to CC45_MOUSE
CDC45-related protein
(PORC-PI-1)
[M.musculusl
161019782A1045333r ESTs, Moderately similar
to tumor necrosis
factor induced protein
1 [Mus musculus]
[M.musculusl
163523712A1045827h ESTs, Weakly similar
to T00043 BH-
protocadherin-a - mouse
[M.musculus]
165210084A1058674s ESTs, Highly similar
to MTR3_MOUSE
Myotubularin-related
protein 3 [M.musculus]
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
ERR
T;~BLE
1
AttoKney
Dobket
No.
'44921=5113W0
Document
No.19262712
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence_ClusterTitle
ID D Acc. Code
' N0. or
I .
N0. RefSeq
ID
No.
168214518A1059477gg, ESTs, Moderately similar
hh to POL3_MOUSE
Retrovirus-related POL
polyprotein
(Endonuclease) [M.musculus]
172611821A1070350mm ESTs, Weakly similar
to JC4667 TB21DP1
protein homolo - mouse
[M.musculus]
17479079 A1071251b, ESTs, Moderately similar
x to A57050 K-
~
lypican recursor- mouse
[M.musculus]
175716788A1071557ii Orthodenticle Orthodenticle (Drosophila)
(Drosophila) homolog 1
homolo 1
17656521 A1071688c, ESTs, Moderately similar
w to A47318 RNA-
bindin protein Raly
- mouse [M.musculus]
17889162 A1072392jj ESTs, Highly similar
to C2MS classical-
complement-pathway C3/C5
convertase (EC
3 .4.21.43) C2 component
precursor - mouse
[M.musculusl
182623124AI100785y, ESTs, Highly similar
nn to germ cell-less
homolog (Drosophila)
[Mus musculus]
[M.musculusl
187419379AI102711d, ESTs, Highly similar
j to RIKEN cDNA
0610010112 [Mus musculus]
[M.musculus]
19367223 AI104373x ESTs, Highly similar
to RIKEN cDNA
2810428115 [Mus musculus]
M.musculus]
19425084 AI104587z ESTs, Moderately similar
to RIKEN cDNA
1810008A14 [Mus musculus]
M.musculus]
19772539 AI111960y ESTs, Weakly similar
to FKBS_MOUSE 51
kDa FK506-binding protein
(FKBP51)
(Peptidyl-prolyl cis-trans
isomerase)
- (PPiase) (Rotamase)
[M.musculusl
199711180AI11300300, ESTs, Highly similar
vv to gene rich cluster,
C9
ene [Mus musculus] [M.musculus]
201416187AI136838gg, ESTs, Highly similar
hh to A55053 endothelial
monocyte-activating
protein I I precursor
-
mouse [M.musculus]
201523851AI136862v ESTs, Highly similar
to carcinoma related
gene [Mus musculus]
[M.musculus]
202713129AI137413p ESTs, Weakly similar
to T14318 ubiquitin-
protein ligase E3-alpha
- mouse
[M.musculus]
20341556 AI137790xx R.norvegicus mRNA from
Leydig cell
hypercalcemic tumour
H-500
204122987AI138061s ESTs, Moderately similar
to JC4761
recombination activating
gene 1 inducing
protein - mouse [M.musculusl
205213190AI144981c ESTs, Weakly similar
to Fas-activated
serinelthreonine kinase
[Mus musculus]
[M.musculus]
205323106AI145081ww ESTs, Highly similar
to S56766 replication
licensing factor MCM4
- mouse
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1R4
TABLE
1
Attorriey_Docket
No:
44921-5113W0
_
Document
No.1926271.2
SEQ GLGC GenBankModel Known Geae Name Unigene Sequence'ClusterTitle
.
ID D Acc: Code
' NO. or
I
N0: RefSeq
ID
No:
206818522AI145870, ff ESTs, Moderately similar
t to RIKEN cDNA
1110025H10 [Mus musculus]
M.musculus]
207013401AI146008pp ESTs, Moderately similar
to S12207
hypothetical protein
(B2 element) - mouse
[M.musculusl
207514519AI168947tt ESTs, Moderately similar
to POL3_MOUSE
_
Retrovirus-related POL
polyprotein
(Endonuclease) M.musculusl
20835683 AI169034p DEADIH (Asp-Glu-Ala-Asp/His)DEADIH (Asp-Glu-Ala-
AspIHis)
box
box polypeptide polypeptide 20,103kD
20,103kD
20876392 AI169154q ESTs, Weakly similar
to SSXT_MOUSE
SSXT protein (SYT protein)
(Synovial
sarcoma associated Ss18-alpha)
f M.musculusl
20932607 AI169211c ESTs, Highly similar
to A47318 RNA-binding
protein Ral - mouse
[M.musculus]
2095806 AI169231r ESTs, Highly similar
to G33_RAT GENE 33
POLYPEPTIDE [R.norvegicus]
211015665AI169611I ESTs, Moderately similar
to steroid receptor
RNA activator 1 [Mus
musculus]
[M.musculus]
211320466AI169735h Rat cytochrome P45011B3
(P45011B
subfamily) mRNA, complete
cds
2115804 AI169756n, ESTs, Highly similar
r, to G33_RAT GENE 33
ee
POLYPEPTIDE [R.norve
icus]
21254368 AI170265xx ESTs, Highly similar
to RIKEN cDNA
1700006006 [Mus musculus]
[M.musculus]
217621698A1171574tt ESTs, Highly similar
to RNA and export
factor binding protein
1; Tcra enhancer-
binding factor interacting
protein 1 [Mus
musculusl iM.musculusl
218710087AI171803w, methylmalonate methylmalonate semialdehyde
semialdehyde
General,dehydrogenase dehydrogenase gene
gene
uu
219122239A1171982qq ESTs, Moderately similar
to 148672 p8
MTCP-1 - mouse [M.musculus]
22015080 AI172106qq ESTs, Highly similar
to cDNA sequence
AB028863; Mmrp19 [Mus
musculus]
[M.musculusl
221415382AI172302rr ESTs, Weakly similar
to S43056 hypothetical
protein - mouse [M.musculus]
22235044 AI172572m ESTs, Moderately similar
to expressed
sequence tag mouse EST
12 [Mus
musculusl [M.musculus]
225422451AI175992d, ESTs, Highly similar
t to beta-catenin-
interacting protein
ICAT [Mus musculus]
- M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
185
TABLE
1
-
Attorney
Docket
No:
44921-5113W0
Document
No.1926271.2
S~QGLGC GenBankModel Knov~n Gene Name tJnigene Sequence Cluster
Title -
ID ID Acc. Code'
N0. or
N0. RefSeq
ID
Nor
232921279AI177356bb ESTs, Highly similar
to mitochondria)
ribosomal protein 64
[Mus musculus]
fM.musculus]
233218095AI177482rr SH-PTP2 protein SH-PTP2 protein tyrosine
tyrosine phosphatase, non-
phosphatase,non-receptortypereceptortype 11
11
234422249A1177809I zyxin zyxin
241212011AI1793800o ESTs, Highly similar
to open reading frame
12 [Mus musculus] [M.musculus]
241319783AI179388y ESTs, Highly similar
to RIKEN cDNA
0610040D20 [Mus musculus]
[M.musculus]
242223515AI179498I ESTs, Highly similar
to SEC23B (S.
cerevisiae) [Mus musculus]
[M.musculus]
243017865AI179636ss ESTs, Highly similar
to RIKEN cDNA
0610009822 [Mus musculus]
[M.musculus]
244817089AI180281h ESTs, Moderately similar
to JC4978
oxidative stress protein
A170 - mouse
[M.musculus]
248521898AI228595ss ESTs, Moderately similar
to CN07_MOUSE
CCR4-NOT transcription
complex, subunit 7
(CCR4-associated factor
1) (CAF1)
IM.musculusl
249415873AI228798pp ESTs, Weakly similar
to 152657 seizure-
related protein SEZ-6
precursor - mouse
[M.musculus]
249723824AI229059h, ESTs, Moderately similar
q, to retinoic acid
x,
dd
induced 12; Clone 13u
[Mus musculus]
[M.musculus]
24995143 AI229087s ESTs, Highly similar
to TPS1 MOUSE
Protein-tyrosine sulfotransferase
1
(Tyrosylprotein sulfotransferase-1)
(TPST-1)
fM.musculusl
250119063AI229166nn ESTs, Highly similar
to mitochondria)
ribosomal protein S14;
1810032L21 Rik [Mus
musculus][M.musculusl
251421237A1229430cc Rattus norvegicus Tclone4
mRNA
253418088AI230199xx ESTs, Weakly similar
to POL3_MOUSE
Retrovirus-related POL
polyprotein
(Endonuclease) [M.musculusl
255014388AI230702q, ESTs, Highly similar
bb to hematological and
neurological expressed
sequence 1 [Mus
musculusl [M.musculusl
255919765AI230945j, ESTs, Highly similar
bb to synbindin; syndecan
binding protein 2 [Mus
musculus]
[M.musculusl
25852339 A1231798x ESTs, Highly similar
to T-complex
expressed gene 2 [Mus
musculus]
M.musculus
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
186
TABLE1
Attorney
Docket
No:
44921-5113W0
'
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Jnigene Sequence Cluster
t Title
ID ID Acc. Code
N0. or
N0: RefSeq
ID
No."
261414521AI232350m ESTs, Moderately similar
to POL3_MOUSE
Retrovirus-related POL
polyprotein
( Endonuclease) [M.musculus]
262921664AI232734kk ESTs, Highly similar
to DD15 MOUSE
Putative pre-mRNA splicing
factor RNA
helicase (DEAN box protein
15)
f M.musculusl
267515085AI233829x, P11 protein P11 protein
ff,
ii
271022805AI235403v ESTs, Highly similar
to adaptor-related
protein complex AP-3,
delta subunit [Mus
musculus] [M.musculusl
272115200AI235736a ESTs, Moderately similar
to CD34_MOUSE
Hematopoietic progenitor
cell antigen CD34
precursor [M.musculus]
273415467AI236106jj ESTs, Moderately similar
to S15785 heat-
stable antigen-related
hypothetical protein
HSA-C - mouse fM.musculusl
275620992AI236719k ESTs, Highly similar
to N-acetylglucosamine
kinase; GIcNAc kinase
[Mus musculus]
[M.musculusl
275816609AI23674pp 8 ESTs, Moderately similar
to CENB_MOUSE
MAJOR CENTROMERE AUTOANTIGEN
B
(CENTROMERE PROTEIN
B) (CENP-B)
[M.musculusl
277616063AI237314q ESTs, Highly similar
to zinc finger like
protein 1 [Mus musculus]
[M.musculus]
280220000AI638989j ESTs, Moderately similar
to T14273 zinc
fin er protein 106 -
mouse [M.musculus]
281510071AI639058y, ESTs, Highly similar
xx to Nedd4 WW binding#
protein 4; Nedd4 WW-binding
protein 4 [Mus
musculus] [M.musculusl
28195545 AI639117h, ESTs, Highly similar
cc, to CFAB_MOUSE
ii,
vv
Complement factor B
precursor (C3/C5
convertase) [M.musculusl
291211358H31610 00, ESTs, Highly similar
pp to JW0059 mtprd
protein - mouse [M.musculus]
293618281H33459 ss ESTs, Highly similar
to SWI/SNF related,
matrix associated, actin
dependent regulator
of chromatin, subfamily
b, member 1;
integrase interactor
1 [Mus musculus]
fM.musculusl
294416256J02861 dd, cytochrome P450 cytochrome P450 2c13,
rr 2c13, cytochrome P450,
cytochrome P450, 2c38
2c38
295117270K02111 jj Rat embryonic myosin
heavy chain gene,
partial 5' region, mRNA
299620464M20406 I, Rat cytochrome P45011B3
v, (P45011B
vv
subfamil mRNA com lete
cds
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1R7
TABLE
1
Aftorney
Docket
No.
449215113W0
Document
No.1926271.2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequertca Cluster
. Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No:
301216305M33312 0, Cytochrome P450 Cytochrome P450 IIA1
GeneralIIA1 (hepatic (hepatic steroid
steroid hydroxylasehydroxylase IIA1) gene
IIA1) gene
303316255M82855 g, cytochrome P450 cytochrome P450 2c13,
dd 2c13, cytochrome P450,
cytochrome P450, 2c38
2c38
307016895NM 012558a, Fructose-1,6- Fructose-1,6- biphosphatase
cc, biphosphatase
gg,
hh,
ss,
uu
310724589NM 012674d, Serine protease Serine protease inhibitor,
kk inhibitor, kanzalkanzal type 1/
type 1/ Trypsin Trypsin inhibitor-like
inhibitor-like protein, pancreatic
protein, pancreatic
311316306NM 012692uu Cytochrome P450 Cytochrome P450 IIA1
IIA1 (hepatic (hepatic steroid
steroid hydroxylasehydroxylase IIA1) gene,
IIA1) gene, Cytochrome P450
Cytochrome P450 IIA2
IIA2
311424707NM 012693c, Cytochrome P450 Cytochrome P450 IIA2
r, IIA2
s
311510622NM_012695f, Sulfotransferase Sulfotransferase hydroxysteroid
n hydroxysteroid gene 2
ene 2
311510624NM 012695n, Sulfotransferase Sulfotransferase hydroxysteroid
xx hydroxysteroid gene 2
gene 2
311510625NM 012695k, Sulfotransferase Sulfotransferase hydroxysteroid
n, hydroxysteroid gene 2
ii
gene 2
311510626NM 012695f Sulfotransferase Sulfotransferase hydroxysteroid
hydroxysteroid gene 2
gene 2
315021350NM 012823a Annexin A3 Annexin A3
3235357 NM 013086w CAMP responsive CAMP responsive element
element modulator
modulator
323718096NM 013088ff SH-PTP2 protein SH-PTP2 protein tyrosine
tyrosine phosphatase, non-
phosphatase, non-receptorreceptor type 11
type
11
3259200 NM 013161k, Pancreatic lipasePancreatic lipase
v
32632012 NM 013173r Solute carrier Solute carrier family
family 11 member 11 member 2 (natural
2 (natural resistance-associatedesistance-associated
r macrophage protein
macrophage protein2)
2)
32632013 NM_013173r Solute carrier Solute carrier family
family 11 member 11 member 2 (natural
2 (natural resistance-associatedesistance-associated
r macrophage protein
macrophage protein2)
2)
330718973NM 017060kk E STs, Moderately similar
to S14234
h ypothetical protein
- mouse [M.musculus]
336621903M 017220ss cytochrome P450, ytochrome P450, 2c37
N 2c37 c
338820914M 017272, o, aldehyde dehydrogenaseldehyde dehydrogenase
N j v, family a family 1, subfamily
vv
1, subfamily A4 A4
341616148M_0173400, acyl-coA oxidase cyl-coA oxidase
N y, a
jj,
ss,
x x
341616150M 017340, jj acyl-coA oxidase cyl-coA oxidase
N 0 a
34431173 M 019184, rr Cytochrome ytochrome P450, subfamily
N j P 450, subfamily IIC
IIC C
( mephenytoin 4-hydroxylase)mephenytoin 4-hydroxylase)
(
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1 StR
TABLE
1
Attorney
Docket
No.
44921-5113WQ
'
Document
No.19262712
SEQ GLGC G-enBankModel Known Gene Name nigene Sequence Cluster
' U Title
ID. ID Acc. Code
N0. or
N0. RefSeq
1D
. ' No
34431174 NM 019184rr Cytochrome P450, Cytochrome P450, subfamily
subfamily IIC IIC
(mephenytoin 4-hydroxylase)(mephenytoin 4-hydroxylase)
348020553NM 019293I, ESTs, Moderately similar
p to S12207
hypothetical protein
(B2 element) - mouse
[M.musculus]
349918032NM 019380w stromal cell derivedtromal cell derived
factor s factor receptor 1
receptor 1
355443 NM 022287General,sulfate anion sulfate anion transporter
transporter
dd,
ff,
rr
360321072NM_022601k pyridoxine 5'-phosphatepyridoxine 5'-phosphate
oxidase oxidase
360521203NM 022606a protein phosphataseprotein phosphatase
2C 2C
360521204NM 022606a protein phosphataseprotein phosphatase
2C 2C
36075336 NM 022631v ESTs, Highly similar
to synembryn [Mus
musculus] [M.musculus]
362923606NM 022867ii microtubule-associatedicrotubule-associated
proteins m proteins 1A/1B light
1AI1 B light chainchain 3
3
362923608NM 022867II microtubule-associatedmicrotubule-associated
proteins proteins 1A/1B light
1A/1 B li ht chainchain 3
3
364417486NM 023092g, unconventional unconventional myosin
cc myosin Myr2 I Myr2 I heavy chain
heavy chain
364417487NM_023092mm unconventional unconventional myosin
myosin Myr2 I Myr2 I heavy chain
heavy chain
36772811 NM 024386j 3-hydroxy-3-methylglutaryl3-hydroxy-3-methylglutaryl
j C0A CoA lyase
lyase
36772812 NM 024386rr 3-hydroxy-3-methylglutaryl-hydroxy-3-methylglutaryl
CoA 3 CoA lyase
lyase
36772813 NM 0243860, 3-hydroxy-3-methylglutaryl-hydroxy-3-methylglutaryl
ii C0A 3 CoA lyase
lyase
368416141NM 024405nn GSK-3beta interactingGSK-3beta interacting
protein protein rAxin
rAxin
36914057 NM 030844a islet cell autoantigenislet cell autoanti
1, 69 kDa en 1, 69 kDa
3714485 NM 031017c cAMP response cAMP response element
element binding binding protein 1 ,
protein 1
373217269NM 031057General,methylmalonate methylmalonate semialdehyde
semialdehyde
kk dehydro enase dehydrogenase gene
gene
37411403 NM 031087j presenilin-2
j presenilin-2
37431175 NM 031093x, Cytochrome P450, Cytochrome
xx subfamily IIC 450, subfamily IIC
P
(mephenytoin 4-hydroxylase)(mephenytoin 4-hydroxylase)
377415238NM 031153 shank-interactingshank-interactin protein
I protein
37788149 NM 031242i CDP-diacylglycerolCDP-diacylglycerol synthase
i s ynthase (phosphatidate
(phosphatidate cytidylyltransferase)
1
cytidylyltransferase)
1
378923358NM 031342r lysophospholipaselysophospholipase II
r II
382515803NM 031593bb s na tic vesicle s na tic vesicle rotein
rotein 2C 2C
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
189
TABLE
1
Attoiney
Docket
No:
4.4921~5113W0
Document
No.1926271:2
SEQ GLGC GenBankModel Known Gene Name Unigene Sequence Cluster
Title
ID D Acc: Code
' NO_ or
I
N0. RefSeq
ID
No.
389021646NM 031781General,amyloid beta (A4)amyloid beta (A4) precursor
II precursor protein-binding,
protein-binding, amily A, member 3 (X11-like
family A, f 2)
member 3 (X11-like
2)
389415794NM 031796qq UDP-GaINAc:polypeptideUDP-GaINAc:polypeptide
N- N-
acetylgalactosaminyltransferaseacetylgalactosaminyltransferase
T5
T5
390015759NM 031815kk activin beta E activin beta E
39057914 NM 031835b, beta-alanine-pyruvatebeta-alanine-pyruvate
h, aminotransferase
I,
General,aminotransferase
nn
393821102NM 033021q vesicle associatedvesicle associated protein
protein
393821103NM 033021q, vesicle associatedvesicle associated protein
x protein
397523338NM 053416n, double-stranded double-stranded RNA-binding
rr RNA-binding protein p74
protein p74
397914621NM 0534370, diacylglycerol diacyl lycerol acyltransferase
ss acyltransferase
400621534NM 053588f Trif ene Trif gene
40151126 NM 053605v, sphingomyelin sphingomyelin phosphodiesterase
y, 3, neutral
oo
phosphodiesterase
3, neutral
402315777NM 053630v potassium voltage-gatedpotassium voltage-gated
channel, subfamily
channel, subfamilyH (eag-related), member
H (eag- 4
related), member
4
405715103NM 053814I, Rho interacting Rho interacting protein
bb protein 3 3
408117090NM 053906t, glutathione reductaseglutathione reductase
mm
408117091NM 053906qq glutathione reductaseglutathione reductase
4119968 NM 057133I, nuclear receptor nuclear receptor subfamily
v, subfamily 0, 0, group B,
bb
group B, member member 2
2
41714956 NM_133315n solute carrier solute carrier family
family 39 (iron- 39 (iron-regulated
regulated transporter),transporter), member
member 1
1
41714957 NM_133315f, solute carrier solute carrier family
n, family 39 (iron- 39 (iron-regulated
y,
ll
regulated transporter),transporter), member
member 1
1
417721576NM 1333980o LYRIC LYRIC
418711483NM_133546f, myeloid differentiationmyeloid differentiation
n, primary primary response
General,response gene gene 116
116
kk
418718043NM_133546w, myeloid differentiationmyeloid differentiation
z, primary primary response
General,response gene gene 116
116
kk,
tt
418813968NM_133553kk UDP-Gal:betaGIcNAcUDP-Gal:betaGIcNAc beta
beta 1,3- 1,3-
galactosyltransferase,galactosyltransferase,
polypeptide 4
polypeptide 4
418813969NM_133553a UDP-Gal:betaGIcNAcUDP-Gal:betaGIcNAc beta
beta 1,3- 1,3-
galactosyltransferase,galactosyltransferase,
polypeptide 4
polypeptide 4
419017886NM 133561t, brain protein brain protein 44-like
g, 44-like
hh
419017887NM 133561q brain protein brain protein 44-like
44-like
42204849 NM 134415h, CDK105 rotein CDK105 rotein
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
190
TABLE
1;
Attorney
Docket
No,
44921=5113W0
Document
No.1926271.2
SEQGLGC GerlBankModel Known Gene Name Unigene Sequence Cluster
' Title
ID ID Acc. Code
N0. or
N0. RefSeq
ID
No.
423648 NM 138547b 3-alpha-hydroxysteroid3-alpha-hydroxysteroid
dehydrogenase
dehydro enase
423625475NM_138547b 3-alpha-hydroxysteroid3-alpha-hydroxysteroid
dehydrogenase
dehydrogenase
42469796 NM_138847f, Saccharomyces Saccharomyces cerevisiae
q cerevisiae Nip7p homolog
Nip7p homolog
424811435NM 138865tt testis specific testis specific protein
protein
428211502NM_139255I, RDCR-0918-3 proteinRDCR-0918-3 protein
p,
q,
y,
ww
431423070NM_148891m, ESTs, Highly similar
to NMT1 MOUSE
General, Glycylpeptide N-tetradecanoyltransferase
1
ee, (Peptide N-myristoyltransferase
oo 1 ) (Myristoyl
CoA:protein N-myristoyltransferase
1) (NMT
1) (Type I N-myristoyltransferase)
IM.musculusl
431917995NM_153312e, Rattus norvegicus Sprague
j Dawley
testosterone 6-beta-hydroxylase,
cytochrome P450I6-beta-A,
(CYP3A2)
mRNA, complete cds
435915462U06230 ii protein S protein S
436217281U10697 j, carboxylesterase carboxylesterase 1
x, 1
dd,
rr
437218302U33500 n, Rattus norvegicus retinol
tt dehydrogenase
type II mRNA, complete
cds
4374212 U36895 cc Rattus norvegicus putative
pheromone
receptor VN3 mRNA, complete
cds
443515106X57529 v ESTs, Highly similar
to RS18 HUMAN 40S
ribosomal protein S18
(KE-3) (KE3)
f R.norvegicus)
4457436 X67877 pp R.norvegicus mRNA for
cytosolic
resiniferatoxin-binding
protein
447925777Y08355 h, oxidative stress oxidative stress induced
I, induced
General,
uu,
xx
194023574AI104520II Cytochrome c oxidaseCytochrome c oxidase
subunit subunit Vla (liver)
Vla (liver)
2592573 AI232087h, hydroxyacid oxidasehydroxyacid oxidase
I, 3 (medium- 3 (medium-chain)
m,
qq
chain)
292621011H32189 nn Glutathione-S-transferase,Glutathione-S-transferase,
mu mu type 2 (Yb2)
type 2 (Yb2)
294221012J02592 b, Glutathione-S-transferase,Glutathione-S-transferase,
I, mu mu type 2 (Yb2)
General,type 2 (Yb2)
gg,
hh,
kk,
II
294521014J03914 b, Glutathione-S-transferase,Glutathione-S-transferase,
I, mu mu type 2 (Yb2)
o,
x,
General,type 2 (Yb2)
II,
rr
_302519823M61725 0o Transcription Transcription factor
factor UBF UBF
31812830 NM 012925I, CD59 anti en CD59 anti en
,
nn
CA 02471631 2004-07-13
WO 03/065993 PCT/US03/03482
1q1
TABLE
1
Attorney
Docket
No.
44921-5113W0
Document
No.1926271:2
SEQ GL.GCGenBank Model Known Gene Name Unigene Sequence:Cluster
Title
ID D Acc. Code
I N0. or
NO. RefSeq
. ID
No.
329321013NM 017014cc Glutathione-S-transferase,Glutathione-S-transferase,
mu mu type 2 (Yb2)
type 2 (Yb2)
329321015NM 017014s, Glutathione-S-transferase,Glutathione-S-transferase,
cc mu mu type 2 (Yb2)
type 2 (Yb2)
334221975NM 017154 xanthine dehydrogenasexanthine dehydrogenase
I
343624362NM 019156a vitronectin vitronectin
347021443NM 019262nn complement componentcomplement component
1, q 1, q subcomponent,
subcomponent, beta polypeptide
beta
polypeptide
351520816NM 021261e, thymosin, beta thymosin, beta 10
ii, 10
II
3627180 NM_022853s solute carrier solute carrier family
family 30 (zinc 30 (zinc transporter),
transporter), member 1
member 1
3666844 NM 024352h, Macrophage stimulatingMacrophage stimulating
I, 1 1 (hepatocyte
n,
uu
(hepatocyte growthgrowth factor-like)
factor-like)
3687862 NM 024487w GrpE-like 1, mitochondria)GrpE-like 1, mitochondria)
38723548NM 031723u, signal peptidase signal peptidase complex
ww complex (18kD)
(18kD)
38723549NM 031723r, signal peptidase signal peptidase complex
tt complex (18kD)
(18kD)
391216535NM 031853bb Diazepam binding Diazepam binding inhibitor
inhibitor (GABA receptor
(GABA receptor modulator, acyl-Coenxyme
modulator, acyl- A binding
Coenxyme A bindingprotein)
protein)
404218174NM 053752o succinate-CoA succinate-CoA ligase,
ligase, GDP- GDP-forming, alpha
forming, alpha subunit
subunit
426415134NM_139081c Ornithine decarboxylaseESTs, Highly similar
to OAZ_RAT Ornithine
antizyme 1 decarboxylase antizyme
(ODC-Az)
[R.norveqicus]
226 4877AA818887nn Rattus norvegicus MHC
class I mRNA,
complete cds
545 13307AA891576d ESTs, Weakly similar
to S49158
complement protein C1q
beta chain
precursor - rat [R.norveqicusl
844 15577AA924557p ESTs, Highly similar
to vesicle-associated
calmodulin-binding protein
[Rattus
norvegicusl fR.norveqicusl
871 5110AA925274ii ESTs, Highly similar
to OIfRT2R protein
kinase (EC 2.7.1.37),
cAMP-dependent, type
II-alpha regulatory
chain - rat (fragment)
[R.norveaicusl
15597912A104383600 ESTs, Weakly similar
to S53340 CD59
protein - rat [R.norve
icus]
185211636AI101967r amyotrophic lateralamyotrophic lateral
sclerosis 2 sclerosis 2 (juvenile)
Quvenile) chromosomechromosome region, candidate
region, 3
candidate 3
DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 5
CONTENANT LES PAGES 1 A 191
NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME
THIS IS VOLUME 1 OF 5
CONTAINING PAGES 1 TO 191
NOTE: For additional volumes, please contact the Canadian Patent Office
NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:
