U.S. patent application number 10/968652 was filed with the patent office on 2005-03-10 for methods for identifying and using maintenance genes.
This patent application is currently assigned to Affymetrix, INC.. Invention is credited to Mahadevappa, Mamatha, Nair, Archana, Warrington, Janet A..
Application Number | 20050053998 10/968652 |
Document ID | / |
Family ID | 33554750 |
Filed Date | 2005-03-10 |
United States Patent
Application |
20050053998 |
Kind Code |
A1 |
Warrington, Janet A. ; et
al. |
March 10, 2005 |
Methods for identifying and using maintenance genes
Abstract
This invention provides methods for discovering maintenance
genes and for using maintenance genes. In one embodiment, the
expression of at least three maintenance genes are measured and
used as reference (or control) for comparing the expression of
target genes in two or more biological samples.
Inventors: |
Warrington, Janet A.; (Los
Altos, CA) ; Mahadevappa, Mamatha; (Fremont, CA)
; Nair, Archana; (Santa Clara, CA) |
Correspondence
Address: |
AFFYMETRIX, INC
ATTN: CHIEF IP COUNSEL, LEGAL DEPT.
3380 CENTRAL EXPRESSWAY
SANTA CLARA
CA
95051
US
|
Assignee: |
Affymetrix, INC.
Santa Clara
CA
|
Family ID: |
33554750 |
Appl. No.: |
10/968652 |
Filed: |
October 18, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10968652 |
Oct 18, 2004 |
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09693204 |
Oct 19, 2000 |
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6841348 |
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60161000 |
Oct 21, 1999 |
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Current U.S.
Class: |
435/6.12 ;
435/6.13; 800/8 |
Current CPC
Class: |
C07K 14/4738 20130101;
C07H 21/04 20130101; C12Q 1/6809 20130101; C12Q 1/6809 20130101;
C12Q 1/6809 20130101; C12Q 2545/101 20130101; C12Q 2565/501
20130101; C12Q 2565/501 20130101; C12Q 2537/157 20130101; C12Q
2545/101 20130101 |
Class at
Publication: |
435/006 ;
800/008 |
International
Class: |
C12Q 001/68; A01K
067/00 |
Claims
1. A method for identifying a maintenance gene comprising:
determining the expression of at least one hundred genes in at
least two different types of tissues in two different developmental
stages; and indicating a gene that is expressed at the same level
in said tissues in said stages as said maintenance gene.
2-12. (Cancelled)
Description
RELATED APPLICATIONS
[0001] This application claims the priority of U.S. Provisional
Application No. 60/161,000, filed on Oct. 21, 1999. The 60/161,000
application is incorporated herein by reference in its
entirety.
[0002] This application is related to U.S. Pat. No. 6,033,860 which
is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
[0003] This application provides methods, compositions for
identifying and using maintenance genes. The methods and
compositions have extensive practical applications in areas such as
drug discovery and diagnostics.
[0004] Housekeeping genes, or maintenance genes, are those genes
constitutively expressed to maintain cellular function (See,
Watson, J. D., N. H. Hopkins, J. W. Roberts, J. A. Steitz, A. M.
Weiner, A. M. Molecular Biology of the Gene, Vol. 1, 1965).
Previously tens of genes have been reported as putative
housekeeping genes. The genes previously reported were identified
by conventional methods and the putative housekeeping role of the
gene product is an incidental observation (Duhig, T., C. Ruhrberg,
O. Mor, M. Fried. The Human Surfeit Locus. Genomics, 52(1) 72-78,
1998; Hampsey, M. Molecular Genetics of the RNA Polymerase II
General Transcriptional Machinery. Microbiol. Mol. Biol. Rev.
62(2):465-503, 1998; May, B. K., C. R. Bhasker, T. C. Cox..
Molecular Regulation of 5-Amniolevulinate Synthase Diseases Related
to Heme Biosynthesis. Mol. Biol. Med., 7(5):405-421, 1990; Milner,
C. M., R. D. Campbell. Genes, Genes and More Genes in the Human
Major Histocompatibility Complex. Bioessays, 14(8):565-571, 1992;
Rifkind, R. A., P. A. Marks, A. Bank, M. Terada, G. M. Maniatis, F.
E. Reuben, E. Fibach. Erythroid Differentiation and the Cell Cycle:
Some Implications from Murine Foetal and Erythroleukemic Cells.
Ann. Immunol. 127:887-893, 1976; Roberston, H. A. Immediate-Early
Genes, Neuronal Plasticity, and Memory. Biochem. Cell Biol., 70(9):
729-737, 1992; Russo-Marie, F. Macrophages and the Glucocorticoids.
J Neuroimmunol, 40(2-3):281-286, 1992; Strehler, B. L., M. R.
Freeman. Randomness, Redundancy and Repair: Roles and Relevance to
Biological Aging. Mech. Aging Dev. 14(1-2) 15-38, 1980; and
Yamamoto, T., Y. Matsui, S. Natori, M. Obinata. Cloning of a
Housekeeping-Type Gene (MER5) Preferentially Expressed in Murine
Erythroleukemia Cells. Gene 80 2:337-343, 1989).
[0005] Recently, massive parallel gene expression monitoring
methods have been developed to monitor the expression of a large
number of genes using nucleic acid array technology which was
described in detail in, for example, U.S. Pat. Nos. 5,871,928,
5,800,992 and 6,040,138; de Saizieu, et al., 1998, Bacteria
Transcript Imaging by Hybridization of total RNA to Oligonucleotide
Arrays, NATURE BIOTECHNOLOGY, 16:45-48; Wodicka et al., 1997,
Genome-wide Expression Monitoring in Saccharomyces cerevisiae,
NATURE BIOTECHNOLOGY 15:1359-1367; Lockhart et al., 1996,
Expression Monitoring by Hybridization to High Density
Oligonucleotide Arrays. NATURE BIOTECHNOLOGY 14:1675-1680; Lander,
1999, Array of Hope, NATURE-GENETICS, 21(suppl.), at 3.
SUMMARY OF THE INVENTION
[0006] In one aspect of the current invention, methods for
identifying a gene are provided. The methods include the steps of
determining the expression of at least one hundred genes in at
least two different types of tissues in two different developmental
stages; and indicating a gene that is expressed at the same level
in the tissues in the stages as the maintenance gene. In some
embodiments, the method involves determining the expression of one
thousand genes. In some preferred embodiments, the expression of
candidate maintenance genes are measured in at least five different
types of tissues. In one preferred embodiment, gene expression is
determined using nucleic acid probe arrays such as high density
oligonucleotide probe arrays, optical fiber arrays, spotted arrays
(oligonucleotide, cDNA clones, cDNA fragments, etc.).
[0007] In preferred embodiments, a gene is considered as expressed
at the same level if the variation of its expression is within 2, 5
or 10 fold. In another preferred embodiment, a gene is considered
as expressed at the same level if the variation of its expression
is not statistically significant.
[0008] In another aspect of the invention, methods are provided for
comparing the expression of a gene in a plurality of biological
samples. The methods include measuring the expression of at least
three, five, seven or ten maintenance genes selected from the group
of genes listed in table I or subset of the genes from table 1. The
methods further include a step of evaluating the expression of the
gene in the plurality of samples using the expression of the at
least three, five or ten, maintenance genes. In some embodiments,
the expression of a gene is adjusted using the expression of
maintenance genes as a control. For example, the expression
measurement of a target gene may be divided by the expression
measurements of maintenance genes.
DESCRIPTION OF THE INVENTION
[0009] Reference will now be made in detail to the preferred
embodiments of the invention. While the invention will be described
in conjunction with the preferred embodiments, it will be
understood that they are not intended to limit the invention to
these embodiments. On the contrary, the invention is intended to
cover alternatives, modifications and equivalents, which may be
included within the spirit and scope of the invention.
[0010] Methods for Gene Expression Monitoring:
[0011] Various techniques for large scale polymer synthesis and
probe array manufacturing are known. Some examples include the U.S.
Pat. Nos.: 5,143,854, 5,242,979, 5,252,743, 5,324,663, 5,384, 261,
5,405,783, 5,412,087, 5,424,186, 5,445,934, 5,451,683, 5,482,867,
5,489,678, 5,491,074, 5,510,270, 5,527,681, 5,550,215, 5,571,639,
5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,677,195, 5,744,101,
5,744,305, 5,753,788, 5,770,456, 5,831,070, and 5,856,011, all of
which are incorporated by reference in their entirety for all
purposes.
[0012] The hybridization conditions between probe and target should
be selected such that the specific recognition interaction, i.e.,
hybridization, of the two molecules, is both sufficiently specific
and sufficiently stable. See, e.g., Hames and Higgins (1985)
Nucleic Acid Hybridisation: A Practical Approach, IRL Press,
Oxford. These conditions will be dependent both on the specific
sequence and often on the guanine and cytosine (GC) content of the
complementary hybrid strands. The conditions may often be selected
to be universally equally stable independent of the specific
sequences involved. This typically will make use of a reagent such
as an alkylammonium buffer. See, Wood et al. (1985) "Base
Composition-independent Hybridization in Tetramethylammonium
Chloride: A Method for Oligonucleotide Screening of Highly Complex
Gene Libraries," Proc. Natl. Acad. Sci. USA, 82:1585-1588; and
Krupov et al. (1989) "An Oligonucleotide Hybridization Approach to
DNA Sequencing," FEBS Letters, 256:118-122; each of which is hereby
incorporated herein by reference. An alkylammonium buffer tends to
minimize differences in hybridization rate and stability due to GC
content. By virtue of the fact that sequences then hybridize with
approximately equal affinity and stability, there is relatively
little bias in strength or kinetics of binding for particular
sequences. Temperature and salt conditions along with other buffer
parameters should be selected such that the kinetics of
renaturation should be essentially independent of the specific
target subsequence or oligonucleotide probe involved. In order to
ensure this, the hybridization reactions will usually be performed
in a single incubation of all the substrate matrices together
exposed to the identical same target probe solution under the same
conditions. The hybridization conditions will usually be selected
to be sufficiently specific such that the fidelity of base matching
will be properly discriminated. Of course, control hybridizations
should be included to determine the stringency and kinetics of
hybridization. See for example, U.S. Pat. No. 5,871,928 which is
hereby incorporated in its entirety for all purposes. Another
factor that can be adjusted to increase the ability of targets to
hybridize to probes, is the use of nucleic acid analogs or PNAs in
the probes. They can be built into the probes to create a more
uniform set of hybridization conditions across the entire array.
See U.S. patent application Ser. No. 08/630,427 which is hereby
incorporated by reference in its entirety for all purposes.
[0013] Samples are then washed and stained using a robotic liquid
handling machine such as the GeneChip.RTM. Fluidic Station 400
(Affymetrix, Inc., Santa Clara, Calif.). Fluidics stations have
been described in, for example, U.S. patent application Ser. Nos.
08/624,133 and 09/070,689. Finally, samples are placed on an
automated loader which interfaces with a scanner such as the
GeneArray.TM. scanner (Agilent Technologies). Scanners have been
described in, for example, U.S. Pat. Nos. 5,578,832, 5,834,748,and
5,837,832, U.S. patent application Ser. Nos. 08/456,598,
09/238,131, 08/856,642 (now allowed), 09/295,214, 08/456,782,
08/999,188, U.S. Provisional Patent Application No. 60/106,397 and
European Patent No. 97925605 each of which is hereby incorporated
by reference in its entirety for all purposes.
[0014] The results are then analyzed using a computer program.
Computer programs for the analysis of hybridization patterns on
arrays have been described in, for example, U.S. Pat. Nos.
5,733,729, and 5,795,716, U.S. patent application Ser. Nos.
09/309,328, 09/020,743, 08/531,137, 09/158,765, 08/584,754,
09/049,805, 08/828,952, 08/948,896 and U.S. Provisional Patent
Application Nos. 60/033,053 and 60/085,118 each of which is
incorporated by reference in its entirety for all purposes.
[0015] Methods for Detecting Maintenance Genes:
[0016] The term housekeeping gene was broadly defined as a gene
that is constitutively expressed. In this application, housekeeping
genes are also referred to as maintenance genes. Generally, the
housekeeping genes are critical to the processes that must be
carried out for successful completion of the cell cycle and
consequently play a key role in the activity and maintenance of
every cell. It is likely that many genes may be constitutively
expressed but in varying amounts in different tissues. These
differences in level of abundance are probably more relevant to the
characteristic function of each tissue than to the
housekeeping/maintenance role.
[0017] Until recently the technical challenge of accurately
measuring small differences in gene expression have been
practically insurmountable, consequently there is little evidence
to support the importance of small differences. One aspect of the
invention provides methods, compositions, devices and algorithms
for detecting Maintenance genes. The method comprises the step of
measuring the expression of at least 50 genes, preferably 100
genes, more preferably more than 1000 genes, in a variety of
tissues. The method further comprises the step of indicating that
the gene is a Maintenance gene if the expression is the same in all
the tissues of interest or in a subset of the tissues of interest.
The term tissue, as used herein, is intended to describe a
biological material from an organism. Therefore, an organ (or a
homogenate of the organ), such the liver or kidney, may be referred
to as a tissue. The methods are most suitable for simultaneously
detecting a large number Maintenance genes. When it is used for
simultaneous determination of a large number of Maintenance genes,
the method includes the step of simultaneous monitoring of the
expression of a large number of genes. Methods for monitoring a
large number of genes are well known in the art and are described,
for example, in the background section, supra. In some embodiments,
the expression of a gene in a number of tissue is measured. The
gene is considered as expressed at the same level if it is
expressed in all the tissues at levels within ten folds, preferably
within fourfold and more preferably within two fold. In some
embodiments, a gene is considered as expressed at the same level if
it is expressed in all tissues with no statistically difference. In
the example that follows, genes were considered as expressed at the
same level if they were expressed in all seven tissues at levels
within fourfold. For most genes differences less than fourfold are
probably not biologically significant but there is not enough data
to conclude that a five or six-fold difference is more biologically
significant than a three or four-fold difference (Cho, R. J., M. J.
Campbell, E. A. Winzeler, L. Steinmetz, A. Conway, L. Wodicka, T.
G. Wolfsberg, A. E. Gabrielian, D. Landsman, D. J. Lockhart, R. W.
Davis. A Genome-Wide Transcriptional Analysis of the Miotic Cell
Cycle. Molecular Cell, 2: 65-73, 1998; Creanor, J., J. M.
Mitchinson. Nucleoside Diphosphokinase, An Enzyme With Step Changes
in Activity During the Cell Cycle of the Fission Yeast
Schizosaccharomyces Pombe. Journal of Cell Science 207-215, 1986;
Klevecz, R. R.. The Scientist 22-24, 1999; Klevecz, R. R., S. A.
Kaufman, R. M. Shymko, Cellular Clocks and Oscillators.
International Review of Cytology, 86:97-128, 1984). For a subset of
genes it is likely that small differences have biological relevance
such as the genes encoding proteins that function differently when
bound to high affinity versus low affinity receptors or gene
products triggering cellular cascades (Merchav, S.. The
Haematopoietic Effects of Growth Hormone and Insulin-Like Growth
Factor-I. J. Pediatr. Endocrin. Metab. 11(6):677-685, 1998; Skerry,
T. M. Identification of Novel Signaling Pathways During Functional
Adaptation of the Skeleton to Mechanical Loading: The Role of
Glutamate as a Paracrine Signaling Agent in the Skeleton. J. Bone
Miner Metab. 17(1): 66-70, 1999).
[0018] Maintenance Genes:
[0019] In another aspect of the invention, a subset of genes
expressed at the same level in each of seven major tissues are
identified as housekeeping genes (See, Table 1). Most of these
genes have never before been specifically identified as belonging
in this category. This information is useful for establishing
average normal expression levels and will be useful as a reference
in studies of normal expression variation (i.e.
www.HuGEindex.org.). In one aspect of the invention, the
maintenance genes described are used to establish average normal
expression levels. In some embodiments, the expression of at least
one of the genes listed in table 1, preferably at least two of the
genes listed in table 1, more preferably at least 10 of the genes
listed in table 1, and even more preferably at least 100 of the
genes listed in table 1 is monitored along with the expression of a
target gene (gene of interest). The change of the level of
expression of the target gene will be evaluated using the
expression of the maintenance gene(s) as a control.
[0020] Example Identification of Maintenance Genes
[0021] Methods
[0022] Sample Preparation
[0023] All samples were prepared from pools of human adult poly(A)
RNA purchased from Clontech (Palo Alto, Calif.). The tissues
screened are listed followed by the number of tissues pooled and
the Clontech catalog number in parenthesis. Heart, 3 (6533-1),
brain, 5 (6516-1), lung, 5 (6524-1), kidney, 8 (6538-1), pancreas,
10 (6539-1), uterus, 10 (6537-1), testis, 19 (6535-1). Poly(A) RNA
was amplified and labeled with biotin following the procedure
described by Wodicka et al., 1997.sup.(32). First strand cDNA
synthesis was carried out at 37.degree. C. for 60 minutes. The
amplified cRNA (target) was purified on an affinity resin (RNeasy,
Qiagen) and quantitated.
[0024] Fragmentation, Array Hybridization and Scanning
[0025] Labeled target was fragmented by incubation at 94.degree. C.
for 35 minutes in the presence of 40 mM Tris-acetate pH 8.1, 100 mM
potassium acetate, and 30 mM magnesium acetate. The hybridization
solution consisted of 20 ug fragmented cRNA, 0.1 mg/ml sonicated
herring sperm DNA in buffer containing 100 mM MES, 1 m[Na.sup.+],
20 mMEDTA, 0.01% Tween 20 (MES). The hybridization mixture was
heated to 99.degree. C. for 5 min. followed by incubation at
45.degree. C. for 5 min. before injection of the sample into the
probe array cartridge. All hybridizations were performed in
duplicate and were carried out at 45.degree. C. for 16-17 hr with
mixing on a rotisserie at 60 rpm. Following hybridization, the
solutions were removed, arrays were rinsed with 1.times.MES (100 mM
MES, 1 m[Na.sup.+], 20 mMEDTA, 0.01% Tween 20). Subsequent washing
and staining of the arrays was carried out using the GeneChip.RTM.
fluidics station protocol EukGE_WS2. The EukGE_WS2 protocol
included two post hybridization washes, staining, and a post stain
wash. The first wash consisted of 10 cycles of 2 mixes per cycle
with Non Stringent Wash Buffer (6.times.SSPE, 0.01% Tween 20,
0.005% Antifoam) at 25.degree. C. The second wash consisted of 4
cycles of 15 mixes per cycle with Stringent Wash Buffer (100 mm
MES, 0.1M [Na.sup.+], 0.01% Tween 20) at 50.degree. C. The probe
arrays were stained for 10 minutes in streptavidin-phycoerythrin
solution (SAPE) (1.times.MES solution, 0.005% antifoam, 10 .mu.g/ml
SAPE (Molecular Probes, Eugene, OR) 2 .mu.g/.mu.l acetylated BSA
(Sigma, St. Louis, Mo.) at 25.degree. C. The post stain wash
consisted of 10 cycles of 4 mixes per cycle at 25.degree. C. The
probe arrays were treated for 10 minutes in antibody solution
(1.times.MES solution, 0.005% antifoam, 2 .mu.g/.mu.l acetylated
BSA, 0.1 .mu.g/.mu.l normal goat IgG (Sigma Chemical, St. Louis
Mo.), 3 .mu.g/.mu.l antibody (goat), antistreptavidin, biotinylated
(Vector Laboratories, Burlingame, Calif.) at 25.degree. C. The
final wash consisted of 15 cycles of 4 mixes per cycle at
30.degree. C. Following washing and staining, probe arrays were
scanned 2 times (multiple image scan) at 3 .mu.m resolution using
the GeneChip.RTM. System confocal scanner made for Affymetrix Inc.
by Hewlett Packard.
[0026] Probe Arrays
[0027] The arrays were synthesized using light-directed
combinatorial chemistry as described previously. The Hu6.8K_all
GeneChip.RTM. probe arrays used for the current study contain probe
sets representing 7129 genes. The oligonucleotides are 25 bases in
length. Probes are complementary and correspond to human genes
registered in Unigene, GenBank and The Institute for Genomic
Research Database (TIGR). Each probe set has oligonucleotides that
are identical to sequence in the gene and oligonucleotides that
contain a homomeric (base transversion) mismatch at the central
base position of the oligomer used for measuring cross
hybridization. Probes are selected with a bias toward the 3' region
of each gene. Probe pairs representing human genes such as GAPDH,
B-actin, transferrin receptor and transcription factor ISGF-3 serve
as internal controls for monitoring RNA integrity. In addition, the
probe arrays contain oligonucleotides representing sequences of
bacterial genes, BioB, BioC, BioD, and one phage gene, Cre, as
quantitative standards. Copy numbers are determined by correlating
the known concentrations of the spiked standards with their
hybridization. Copies per cell are calculated based on the
assumption that the average transcript length is 1 kb and there are
300,000 transcripts per cell.
[0028] Analysis
[0029] All samples were hybridized in duplicate and only those
transcripts detected as present in duplicate hybridizations or
absent in duplicate hybridizations are reported. Of the transcripts
present in duplicate hybridizations the hybridization values were
within two fold. The values from the duplicate hybridizations were
averaged. GeneChip.RTM. 3.0 software was used to scan and analyze
the data. Microsoft Excel and Microsoft Access were also used for
data analysis.
[0030] Result
[0031] Using GeneChip.RTM. probe arrays (Affymetrix, Santa Clara,
Calif.), 695 genes that are expressed in common among heart, brain,
lung, kidney, pancreas, uterus and testis were identified. 241 of
the genes were detected at similar levels in each of the tissues;
44 genes were detected at low abundance, 72 detected at
low-moderate abundance, 100 at moderate abundance, 13 at
moderate-high abundance, and 12 at high abundance (See Table
1).
1TABLE 1 Maintenance genes sorted by function. Abundance levels are
binned by copies per cell where low, L, <5, low-moderate, LM
> 5 < 10, moderate, M, > 10 < 50, moderate-high, MH,
> 50 < 100, high, H, >100. Accession Abun- Number
Description dance ATPase M37104 mitochondrial ATPase coupling M
factor 6 subunit (ATP5A) U51478 sodium/potassium-transporting M
ATPase beta-3 subunit Z71460 vacuolar-type H(+)-ATPase LM 115 kDa
subunit Channels, pores D31846 aquaporin-2 water channel M L08666
porin (por) M Cytochrome AC002115 COX6B (COXG) on chromosome 19 M
cosmids M22760 nuclear-encoded mitochondrial M cytochrome c oxidase
Va subunit L32977 ubiquinol cytochrome c reductase M Rieske
iron-sulphur protein X13238 cytochrome c oxidase subunit VIc M
X16560 COX VIIc subunit VIIc of M cytochrome c oxidase M28713
NADH-cytochrome b5 reductase (b5R) LM Dehydrogenase D90086 pyruvate
dehydrogenase M (EC 1.2.4.1) beta subunit D43682 very-long-chain
acyl-CoA M dehydrogenase (VLCAD) U17886 succinate dehydrogenase LM
iron-protein subunit (sdhB) U05861 hepatic dihydrodiol
dehydrogenase L L13761 dihydrolipoamide dehydrogenase L DNA binding
J03827 Y box binding protein-1 (YB-1) MH M26730 mitochondrial
ubiquinone-binding M protein with an LTR-like sequence X75593 rab
13 M U79528 SR31747 binding protein 1 M L37368 RNA-binding protein
M U33821 tax1-binding protein TXBP151 M Z29505 nucleic acid binding
protein sub2.3 M U07857 18 kDa Alu RNA binding protein, M M94556
mitochondrial specific single LM stranded DNA binding protein N31
M28209 GTP-binding protein (RAB1) LM D13988 rab GDI LM U51334
putative RNA binding protein (RBP56), LM D43951 KIAA0099,
(pumilio-like, putative LM DNA binding) U65928 Jun activation
domain binding L protein Electron transfer X71129 electron transfer
flavoprotein LM beta subunit J04058 electron transfer flavoprotein
L alpha-subunit G protein related U20285 Gps1 (GPS1) M U45982 G
protein-coupled receptor GPR-9-6 LM U31384 G protein gamma-11
subunit LM X81625 Cl1 protein L HLA D32129 HLA class-I (HLA-A26)
heavy chain M X03100 HLA-SB alpha (class II antigen) M X75091
HLA-DR associated protein II L (PHAPII) Heat shock J04988 90 kD
heat shock protein MH L15189 mitochondrial HSP75 LM Histone M11353
H3.3 histone class C MH U50079 histone deacetylase HD1 LM X05855
histone H3.3 L Interferons X57351 1-8D from interferon-inducible H
family X59892 IFN-inducible gamma-2 protein M J00212 leukocyte
interferon (ifn-alpha) L alpha-f Kinase M14676 src-like kinase
(slk) M L08835 DM kinase (myotonic dystrophy M kinase) M30448
casein kinase II beta subunit LM Lysosome associated AJ000099
lysosomal hyaluronidase M U91932 AP-3 complex sigma3A subunit M
M15182 beta-glucuronidase (lysosomal LM enzyme) M29877
alpha-L-fucosidase, (lysosomal LM enzyme) Membrane D29963 SFA-1, a
member of transmembrane 4 M superfamily L10284 IP90, integral
membrane protein, M calnexin U57877 nuclear-encoded mitochondrial
LM integral membrane protein CII-3 Metabolism D78361 ornithine
decarboxylase antizyme H M33764 ornithine decarboxylase amino acid
M metabolism HG2279- Triosephosphate Isomerase M HT2375 U86070
phosphomannomutase (carbohydrate LM metabolism) U32114 caveolin-2
(lipid metabolism) L Mitochondrial associated Z70759 mitochondrial
16S rRNA H M22538 nuclear-encoded mitochondrial M NADH-ubiquinone
reductase 24 kD subunit M22760 nuclear-encoded mitochondrial M
cytochrome c oxidase Va subunit X60036 mitochondrial phosphate
carrier M protein M37104 mitochondrial ATPase coupling M factor 6
subunit (ATP5A) M26730 mitochondrial ubiquinone-binding M protein
with an LTR-like sequence X99728 NDUFV3, mitochondrial NADH M
ubiquinone oxidoreductase U59309 nuclear-encoded mitochondrial LM
fumarase precursor (FH) L15189 mitochondrial HSP75 LM M94556
mitochondrial specific single LM stranded DNA binding protein
U57877 nuclear-encoded mitochondrial LM integral membrane protein
CII-3 L07033 hydroxymethylglutaryl-CoA lyase LM U15174 Nip3 (NIP3)
(mitochondrial, L pro-apoptotic protein family) Phosphatase U45975
phosphatidylinositol (4,5) M bisphosphate 5-phosphatase homolog
X74008 phosphatase 1 gamma LM X81003 HCG V (phosphatase inhibitor)
LM M65254 phosphatase 2A 65 kDa regulatory L subunit-beta
Polymerase Z27113 RNA polymerase II subunit 14.4 kD M U37690 RNA
polymerase II subunit (hsRPB10) M Z47727 RNA polymerase II subunit
LM Protease, proteinase related L02426 26S protease (S4) regulatory
subunit M M23254 Ca2-activated neutral protease M large subunit
(CANP) X12451 pro-cathepsin L (major excreted M protein MEP) S69272
cytoplasmic antiproteinase, 38 kD M intracellular serine proteinase
inhibitor Proteasome D29012 proteasome subunit Y M D26598
proteasome subunit HsC10-II M D26599 proteasome subunit HsC7-I M
D38047 26S proteasome subunit p31 M AB003177 proteasome subunit p27
LM D00763 proteasome subunit HC9 LM D50063 proteasome subunit
p40_/Mov34 LM protein, X61970 macropain subunit zeta (proteasome)
LM X95586 MB1 LM D00760 proteasome subunit HC3 L D00762 proteasome
subunit HC8 L Receptor and receptor associated proteins M63959
alpha-2-macroglobulin receptor- M associated protein D23673 insulin
receptor substrate-1-like M (IRS-1) X07979 fibronectin receptor
beta subunit M U83239 CC chemokine STCP-1 (immune M function,
T-receptor assoc) M88279 immunophilin (FKBP52) M U45982 G
protein-coupled receptor GPR-9-6 LM X56253 MPR46 46 kd mannose
6-phosphate LM receptor X80763 5-HT2c receptor LM L40357 thyroid
receptor interactor (TRIP7) L Reductase M22538 nuclear-encoded
mitochondrial M NADH-ubiquinone reductase 24 kD subunit X91247
thioredoxin reductase LM X15414 aldose reductase (EC 1.1.1.2) LM
M28713 NADH-cytochrome b5 reductase (b5R) LM Repair U07418 DNA
mismatch repair (hmlh1) L U49785 D-dopachrome tautomerase LM
Replication J05249 replication protein A 32-kD subunit LM
Ribonucleoprotein HG3076- heterogeneous nuclear M HT3238
ribonucleoprotein K, alt. splice 1 X16135 novel heterogeneous
nuclear M RNP protein, L protein X78136 hnRNP-E2 M M94630 hnRNP-C
like protein M M16342 nuclear ribonucleoprotein LM particle (hnRNP)
C protein Z23064 hnRNP G protein L Ribosomal X81625 ribosomal
protein L37a (RPL37A) H Z12962 homologue to yeast ribosomal H
protein L41 HG3214- Metallopanstimulin, MPS-1 (S27 H HT3391 Zinc
finger) HG1800- ribosomal protein S20 H HT1823 U14973 ribosomal
protein S29 H Z26876 ribosomal protein L38 MH M77232 ribosomal
protein S6 MH HG821- ribosomal protein S13 MH HT821 M13934 RPS14,
ribosomal protein S14 MH Ribosylation M84332 ADP-ribosylation
factor 1 M M36341 ADP-ribosylation factor 4 (ARF4) LM Signal
transduction D49396 Apol (MER5-like protein) L Structure U57341
neurofilament triplet L protein MH Z19554 vimentin MH X51521 ezrin
M HG2238- nuclear mitotic apparatus protein M HT2321 1, alt. splice
form 2 M64571 microtubule-associated protein 4 M M31013 nonmuscle
myosin heavy chain (NMHC) M V00599 fragment encoding beta-tubulin M
(D-beta-1) U24105 coatomer protein (HEPCOP), M M95627
angio-associated migratory cell LM protein (AAMP) D38549 KIAA0068
LM U56637 capping protein alpha subunit LM isoform 1 X72964
caltractin LM X70476 subunit of coatomer complex LM D28915
hepatitis C-associated microtubular L aggregate protein p44 X82103
beta-COP L Synthases and synthetases D14710 ATP synthase alpha
subunit MH X76013 QRSHs, glutaminyl-tRNA synthetase M X83218 ATP
synthase M X60221 H+-ATP synthase subunit b M D31890 KIAA0070 M
U09510 glycyl-tRNA synthetase LM U79262 deoxyhypusine synthase LM
J03473 poly(ADP-ribose) synthetase LM X94754 yeast methionyl-tRNA
synthetase LM homologue Transcription L49380 transcription factor
ZFM1 M U95040 transcriptional corepressor M hKAP1/TIF1B U10323
nuclear factor NF45 M L12168 adenylyl cyclase-associated M protein
(CAP), M97935 transcription factor ISGF-3 LM sequence X52882
t-complex polypeptide 1 LM L19067 NF-kappa-B transcription factor L
p65 subunit D63478 KIAA0144 L U15782 cleavage stimulation factor 77
kDa L subunit (polyadenylation) L20298 transcription factor (CBFB)
L Transferase U56417 lysophosphatidic acid M acyltransferase-alpha
U62739 branched-chain amino acid M aminotransferase (ECA40) Y08200
rab geranylgeranyl transferase, M alpha-subunit U82010 heme A:
farnesyltransferase (COX10) LM U86529 glutathione transferase Zeta
1 LM (GSTZ1) D26535 dihydrolipoamide L succinyltransferase
Transformation related U50523 BRCA2 region M U57342
myelodysplasia/myeloid leukemia M factor 2 (MLF2), HG4541-
transformation-related protein M HT4946 M15990 c-yes-1 L L12535
RSU-1/RSP-1 (Ras suppressor) L Translation, inititiation and
elongation J04617 elongation factor EF-1-alpha H X51466 elongation
factor 2 MH L26247 sui 1, N278 iso1 MH U46025 translation
initiation factor M eIF-3 p110 subunit X55733 initiation factor 4B
LM X98743 RNA helicase (Myc-regulated L dead box protein) Transport
U36341 SLC6A8 (creatine transporter) M U51478
sodium/potassium-transporti- ng M ATPase beta-3 subunit X81817
BAP31 (ER, protein sorting) M Y00281 ribophorin I (ER) M Y00282
ribophorin II (ER) M U70660 copper transport protein HAH1 LM U41740
trans-Golgi p230 LM X12791 signal recognition particle, L SRP 19 kD
protein (ER) Ubiquitin related X56997 UbA52 coding for ubiquitin-52
MH amino acid fusion protein M26880 ubiquitin M U46751
phosphotyrosine independent M ligand p62 for the Lck SH2 domain
U39317 E2 ubiquitin conjugating enzyme L UbcH5B (UBCH5B), Zinc
finger HG3214- Metallopanstimulin, MPS-1 (S27, H HT3391 Zinc
finger) X70394 OZF L U09412 zinc finger protein ZNF134 L HG3454-
zinc finger protein 20 L HT3647 Undefined X67698 unknown product M
L11066 unknown product M U79294 unknown product M D28124 unknown
product M D21261 KIAA0120 M D87451 KIAA0262 M D14694 KIAA0024 M
ISGF3A/ unknown product LM M97935 L20773 unknown product LM D42043
KIAA0084 LM D50911 KIAA0121 LM D79994 KIAA0172 LM D29643 KIAA0115
LM D14662 KIAA0106 LM D86963 KIAA0208 LM D21853 KIAA0111 LM D63476
KIAA0142 LM D42087 KIAA0118 L D30756 KIAA0049 L D80004 KIAA0182 L
D79993 KIAA0171 L L40395 unknown product L Others X98482 TNNT2,
(troponin) H U06155 chromosome 1 q subtelomeric H sequence M33680
26-kDa cell surface protein TAPA-1 H M13450 esterase D M U11861 G10
homolog, edg-2 M U62317 hypothetical protein 384D8_2 M on
chromosome 22q13 (other) HG3991- Cpg-enriched DNA (other) M HT4261
X80199 MLN51 M X80200 MLN62 M U46570 tetratricopeptide repeat
protein M (tpr1) N297 (other) HG3597- major histocompatibility
complex, M HT3800 class I X71428 fus (nuclear RNA binding protein)
M U73824 p97 M Y00433 glutathione peroxidase (peroxide M clearance)
U02493 54 kDa protein M U88964 HEM45 LM D78129 squalene epoxidase
(sterol LM biosynthesis) D43951 KIAA0099, (pumilio-like, putative
LM DNA binding) X96484 DGCR6 protein (organization, LM migration
during development) HG1155- colony-stimulating factor 1, LM HT4822
macrophage, alt. splice 3 L38932 GT197 N305 LM X66397 tpr LM L42572
p87/89 (ER transmembrane protein) LM X80695 OXA1Hs (cytochrome
oxidase assembly) LM Y00097 p68 (membrane associated, calcium LM
binding protein) Z48042 GPI-anchored protein p137 LM Z35093 SURF-1
(Surfeit gene family, LM biogenesis of cytochrome C oxidase) U54644
tub homolog LM Z93784 mouse brain protein E46-like L sequence
L38616 brain and reproductive organ- L expressed protein (BRE)
D63506 unc-18 homologue L U18009 human gene on chromosome 17q21 L
L27476 X104 (membrane associated, L kinase containing protein
family) M73720 mast cell carboxypeptidase A L (MC-CPA)
[0032] For example, no difference in expression level was detected
for 5 of the genes and a two-fold difference was detected for 46 of
the genes. 454 genes are expressed in all seven tissues but vary in
expression level by more than fourfold. 333 of the genes vary in
expression level by 5-10 fold. Included in this subset are genes
frequently used as controls in standard expression analysis
including beta actin (M10277) varying by 7-fold with highest
expression in brain and uterus and lowest expression in heart, and
GAPDH (M33197) varying by 8-fold with highest expression in brain,
heart and kidney and lowest in pancreas. Another form of beta actin
(X00351) varied by 22-fold with highest expression in uterus and
lowest in pancreas. Alpha actin (X13839) varied by 23-fold and
gamma actin (M19283) by 9-fold. 40 genes expressed in all seven
tissues differ in transcript levels by greater than 19 fold and of
these eight differ by more than 50-fold, including COX7A muscle
isoform (M83186) varying by 52-fold, highest in heart, lowest in
kidney, pancreas and testis, lectin (J04456) varying by 58-fold,
highest in uterus, lowest in kidney and pancreas, myosin heavy
chain (AF001548) varying by 61-fold, highest in uterus, lowest in
brain and pancreas, elongation factor-1 delta (Z21507) varying by
69-fold, highest in pancreas, lowest in lung and kidney, RNA
polymerase II elongation protein (Z47087) varying by 70-fold,
highest in brain, lowest in pancreas, extracellular mRNA for
glutathione peroxidase (D00632) varying by 78-fold, highest in
kidney, lowest in brain, pancreas and testis, 14-9-9 protein eta
chain (D78577) varying by 81-fold, highest in brain, lowest in
testis, and L-arginie:glycine amidinotransferase (S68805) varying
by 133-fold, highest in pancreas and lowest in heart and lung.
[0033] In the same experiments, genes expressed uniquely in each of
the seven tissues were also identified (Table II). For instance, in
heart there were 4 transcripts not detected in the other 6 tissues;
muscle glycogen synthase (J04501), NADH oxidoreductase subunit
(L04490), MLC-1V/Sb isoform (M24248) and cytokine inducible nuclear
protein (X83703). Twenty nine uniquely expressed transcripts were
identified in the kidney including many that are expected such as
potassium channel ROM-K3 (U65406) and renal Na/Pi cotransporter
(L13258) as well as genes of unknown function such as a gene that
maps to chromosome 19 (U95090). 45 uniquely expressed transcripts
were detected in uterus, 28 in pancreas and 19 in lung. Not
surprisingly, the greatest number of uniquely expressed genes, 91
and 94 respectively, were found in brain and testis.
2TABLE II Genes Uniquely Expressed in a Comparison of Eleven Human
Tissues Accession No. Description Bin* Uniquely Expressed in Adult
Heart J04501 Muscle glycogen synthase M M24248 MLC-1V/Sb isoform M
X83703 Cytokine inducible nuclear protein LM Uniquely Expressed in
Fetal Kidney D88532 P55pik L M26901 Renin M M81829 Somatostatin
receptor isoform 1 L U19107 ZNF127 L U19906 Arginine vasopressin
receptor 1 (AVPR1) L U34301 Nonmuscle myosin heavy chain IIB LM
X58431 HOX 2.2 M Z67743 CLC-7 chloride channel protein LM Uniquely
Expressed in Fetal Liver AF000573 Homogentisate 1,2-dioxygenase LM
D00097 Amyloid P component (SAP) M D16611 Coproporphyrinogen
oxidase M D16626 Histidase M D21063 KIAA0030 M D26361 KIAA0042 L
D38535 PK-120 H D38537 Protoporphyrinogen oxidase M D42055 KIAA0093
L D49357 S-adenosylmethionine synthetase LM D49742 HGF activator
like protein M D79988 KIAA0166 L D84454 UDP-galactose translocator
LM D87116 MAP kinase kinase 3b M D90282 Carbamyl phosphate
synthetase I MH (EC 6.3.4.16) HG1148- Lipopolysaccharide-Binding
Protein H HT1148 HG1227- Collagen, Type II, Alpha 1 M HT1227
HG1649- Elastase 1 M HT1652 HG2730- Fibrinogen, A Alpha
Polypeptide, H HT2827 Alt. Splice 2, E HG3105- Atpase, Cu2+
Transporting L HT3281 HG3565- Zinc Finger Protein M HT3768 HG627-
Rhesus (Rh) Blood Group System MH HT5097 Ce-Antigen, Alt. Splice 2,
Rhvi J00116 Collagen COL2A1 M J02982 Glycophorin B MH J03474 Serum
amyloid A H J03626 UMPS L J05070 Type IV collagenase L J05500
Beta-spectrin (SPTB) M K01383 Metallothionein-I-A MH K02402
Coagulation factor IX M L00190 Antithrombin III (ATAIII) H L01664
Eosinophil Charcot-Leyden crystal L (CLC) protein
(lysophospholipase) L06133 Putative Cu++-transporting L P-type
ATPase L09708 Complement component 2 (C2), allele b MH L11244
C4b-binding protein beta-chain M L31860 Glycophorin A, MN-types
(GYPA) M L32140 Afamin M L34081 Bile acid CoA: Amino acid LM
N-acyltransferase L48516 Paraoxonase 3 (PON3) M L76571 Nuclear
hormone receptor (shp) M L77567 Mitochondrial citrate transport M
protein (CTP) M10014 Fibrinogen gamma chain and gamma- H prime
chain M10058 Asialoglycoprotein receptor H1 M M10950
Alpha-fetoprotein (AFP) M M11025 Asialoglycoprotein receptor H2 M
M11567 Angiogenin and three Alu repetitive M sequences M13699
Ceruloplasmin (ferroxidase) MH M14091 Thyroxine-binding globulin M
M15205 Thymidine kinase with clustered M Alu repeats in the introns
M16961 Alpha-2-HS-glycoprotein alpha and H beta chain M16967
Coagulation factor V M M16973 Complement protein C8 beta subunit M
M17262 Prothrombin (F2) gene, and Alu and H KpnI repeats M19481
Follistatin LM M19828 Apolipoprotein B-100 (apoB) H M20786
Alpha-2-plasmin inhibitor MH M22638 LYL-1 protein M M22898
Phosphoprotein p53 L M27819 Anion exchange protein 1 (AE1, band 3)
MH M29194 Triglyceride lipase M M36803 Hemopexin H M58569
Fibrinogen alpha-subunit bipartite H transcript of extended
(alpha-E) variant M58600 Heparin cofactor II (HCF2), exons 1 H
through 5 M59820 Granulocyte colony-stimulating LM factor receptor
(CSF3R) M60298 Erythrocyte membrane protein band 4.2 MH (EPB42)
M61827 Leukosialin (CD43) LM M61855 Cytochrome P4502C9 (CYP2C9),
clone 25 L M64554 F13A1 gene (coagulation factor XIIIb) M M68895
Alcohol dehydrogenase 6 L M71243 Glycophorin Sta (type A) exons 3
and 4 MH M75106 Prepro-plasma carboxypeptidase B MH M86873 Type A
plasminogen related M S42457 Photoreceptor cGMP-gated channel L
S48983 SAA4, serum amyloid A M S70004 Glycogen synthase LM S72370
Pyruvate carboxylase LM S77393 Transcript ch138 LM S77763 Nuclear
factor erythroid 2 M S77893 Glycophorin SAT MH S78234 Nuc2 homolog
LM U00001 Homologue of S. pombe nuc2+ L and A. nidulans bimA U01317
Epsilon-globin LM U05255 Glycophorin HeP2 H U08006 Complement 8
alpha subunit (C8A) M U12778 Acyl-CoA dehydrogenase LM U13061
Dehydroepiandrosterone L sulfotransferase (STD) U14518 Centromere
protein-A (CENP-A) L U18919 Clone pOV-2 L U20530 Bone
phosphoprotein spp-24 precursor M U20979 Chromatin assembly
factor-I L p150 subunit U32989 Tryptophan oxygenase (TDO) M U61836
Putative cyclin G1 interacting protein M U65404 Erythroid-specific
transcription M factor EKLF U72515 C3f M U73167 H_LUCA14.2a M
U73524 Putative ATP/GTP-binding protein (HEAB) L U90544 Sodium
phosphate transporter (NPT3) M V01514 Alpha-fetoprotein (AFP) H
X02176 Complement component C9 M X02544 Alpha1-acid glycoprotein
(orosomucoid) H X03473 Histone H1(0) M X04898 Apolipoprotein H
X05309 C3b/C4b receptor (CR1) F allotype L X06482 Theta 1-globin M
X06562 Growth hormone receptor L X13293 B-myb M X13589 Aromatase
(estrogen synthetase) LM X14329 Carboxypeptidase N small subunit LM
(EC 3.4.17.3) X14690 Plasma inter-alpha-trypsin inhibitor H heavy
chain H(3) X15422 Mannose-binding protein C M X16260
Inter-alpha-trypsin inhibitor H subunit 3 X16983 Integrin alpha-4
subunit L X17059 NAT1 gene for arylamine L N-acetyltransferase
X17254 Transcription factor Eryf1 M X51688 Cyclin A LM X53414
Peroxisomal L-alanine: glyoxylate MH aminotransferase X55668
Proteinase 3 M X56692 C-reactive protein M X56741 Rab8 L X58199
Beta adducin M X59618 RR2 small subunit ribonucleotide LM reductase
X59711 CAAT-box DNA binding protein subunit A L X59812 CYP 27
vitamin D3 25-hydroxylase M X62822 Beta-galactoside alpha-2,6- LM
sialyltransferase X63097 Rhesus polypeptide (RhXIII) L X64594
Erythrocyte plasma membrane MH glycoprotein X64877 Serum protein LM
X65550 Antigen of monoclonal antibody Ki-67 L X74330 DNA primase
(subunit p48) L X75315 Seb4B M X77737 Red cell anion exchanger
(EPB3, AE1, H Band 3) X80907 P85 beta subunit of M
phosphatidyl-inositol-3-kinase X91148 Microsomal triglyceride
transfer LM protein X98337 Complement factor H-related protein 4 M
Y00317 Liver microsomal UDP- LM glucuronosyltransferase (UDPGT)
Z15005 CENP-E LM Z26248 Eosinophil granule major basic LM protein
Z28339 Delta 4-3-oxosteroid 5 beta- LM reductase Z32684 XK membrane
transport protein M Z83821 DNA sequence from PAC 296K21 on H
chromosome X contains cytokeratin exon, delta-aminolevulinate
synthase (erythroid); 5-aminolevulinic acid synthase Z84721 DNA
sequence from cosmid GG1 H from a contig from the tip of the short
arm of chromosome 16, spanning 2Mb of 16p13.3 Uniquely Expressed in
Fetal Lung D87071 KIAA0233 LM HG4638- Spliceosomal Protein Sap 49 L
HT5050 U18671 Stat2 L U40434 Mesothelin or CAK1 antigen precursor
LM X52896 Dermal fibroblast elastin M X97748 PTX3 LM Uniquely
Expressed in Adult Brain D87463 KIAA0273 M HG2259- Tubulin, Alpha
1, Isoform 44 M HT2348 HG3437- Myelin Proteolipid Protein, H HT3628
Alt. Splice 2 L00354 Cholecystokinin (CCK) M L76224 NMDA receptor M
L76627 Metabotropic glutamate receptor 1 L alpha (mGluR1alpha)
M55267 EV12 protein LM M59488 S100 protein beta-subunit M S50017
2',3'-cyclic nucleotide M 3'-phosphodiesterase S69965
Beta-synuclein M U01824 Glutamate/aspartate transporter II M U06698
Neuronal kinesin heavy chain LM U27768 RGP4 M U62801 Protease M M
U82532 GDI-dissociation inhibitor RhoGDIgammma LM X59065 FGF, exon
3 M X64810 PC1/PC3 LM X73882 E-MAP-115 LM X99076 NRGN, exons 2, 3
& 4 (joined CDS) H Z48051 Myelin oligodendrocyte M glycoprotein
(MOG) Uniquely Expressed in Adult Kidney J04093 Phenol
UDP-glucuronosyl-transferase LM (UDPGT) L13258 Renal
Na/Pi-cotransporter M M19878 Calbindin 27, exons 1 and 2, and Alu M
repeat S77576 ERV9 reverse transcriptase homolog L (clone RT18)
U17418 Hormone/parathyroid hormone-related M peptide receptor
X13227 D-amino acid oxidase M X60708 PcHDP7, liver dipeptidyl
peptidase IV L Uniquely Expressed in Adult Uterus D21337 Collagen L
D86961 KIAA0206 L HG721- Placental Protein 14, Endometrial M HT4828
Alpha 2 Globulin, Alt. Splice 3 L00205 K6b (epidermal keratin, type
II) L L02785 Colon mucosa-associated (DRA) L L06419 Lysyl
hydroxylase (PLOD) LM L08044 Intestinal trefoil factor LM L10343
Elafin M L14848 MHC class I-related protein L M19888 Small proline
rich protein (sprI) M M21121 T cell-specific protein (RANTES) L
M21389 Keratin type II (58 kD) M M55543 Guanylate binding protein
isoform II L (GBP-2) M59979 Prostaglandin endoperoxide synthase L
M60284 Neurokinin A receptor (NK-2R) LM M62783
Alpha-N-acetylgalactosaminidase L M85276 NKG5 M M86757 Psoriasin M
M86849 Connexin 26 (GJB2) L M96233 Transferase class mu number 4
(GSTM4) LM S66896 Squamous cell carcinoma antigen, L serine
protease inhibitor S72493 Keratin 16 homolog M S81661 Keratinocyte
growth factor L U07969 Intestinal peptide-associated L transporter
HPT-1 U09278 Fibroblast activation protein L U09584 PL6 protein
(PL6) L U11717 Calcium activated potassium channel L (hslo) U24488
Tenascin-X (XA) M U25138 MaxiK potassium channel beta subunit M
U37283 Microfibril-associated glycoprotein-2 M MAGP-2 U43185 Signal
transducer and activator L of transcription Stat5A U60325 DNA
polymerase gamma, nuclear gene L encoding mitochondrial protein
U76764 CD97 LM U81523 Endometrial bleeding associated M factor
X03635 Oestrogen receptor M X06256 Fibronectin receptor alpha
subunit LM X07695 Cytokeratin 4 C-terminal region M X07696
Cytokeratin 15 L X16662 Vascular anticoagulant-beta (VAC-beta) L
X54162 64 Kd autoantigen expressed in M thyroid and extra-ocular
muscle X63629 P cadherin L X75535 PxF protein L X83857
Prostaglandin E receptor (EP3a1) L X92521 MMP-19 protein L X93510
37 kDa LIM domain protein LM X96719 AICL (activation-induced C-type
lectin) LM X98311 Carcinoembryonic antigen, CGM2 L Y07755 S100A2,
exon 1, 2 and 3 M Uniquely Expressed in Adult Testis D17570
Zona-pellucida-binding protein (sp38). M D50925 KIAA0135 L D64109
Tob family L D78333 Testis-specific TCP20 M D78334 Ankyrin motif MH
HG2075- Camp-Responsive Element Modulator, M HT2137 Alt. Splice 1
HG36- Polymyositis/Scleroderma (Pm-Scl) L HT4101 Autoantigen, Alt.
Splice 2 HG3725- Insulin-Like Leydig Hormone M HT3981 HG4316-
Transketolase-Like Protein L HT4586 L01042 HIV1 tata element
modulatory factor L L07515 Heterochromatin protein homologue (HP1)
LM L14754 DNA-binding protein (SMBP2) LM L22214 Denosine A1
receptor (ADORA1), L exons 1-6 L36861 Guanylate cyclase activating
protein L (GCAP), exons 1-4 L42324 G protein-linked receptor (GPCR)
L L76687 Grb14 L M13981 Inhibin A-subunit M M14565 Cholesterol
side-chain cleavage enzyme L P450scc M21539 Small proline rich
protein (sprII) L M31606 Phosphorylase kinase (PSK-C3) M M63256
Major Yo paraneoplastic antigen (CDR2) L M73077 Glucocorticoid
receptor repression LM factor 1 (GRF-1) M86808 Pyruvate
dehydrogenase complex (PDHA2) L M91438 Kazal-type serine proteinase
(HUSI-II) M S68134 CREM, cyclic AMP-responsive element LM modulator
beta isoform S78873 Zn2+ binding protein/guanine L nucleotide
exchange factor U03644 Recepin L U10362 GP36b glycoprotein L U13680
Lactate dehydrogenase-C (LDH-C) M U15422 Protamine 1 (PRM1),
protamine 2 (PRM2) H and transition protein 2 (TNP2) U17032 P190-B
(p190-B) L U17280 Steroidogenic acute regulatory protein LM (StAR)
U19147 GAGE-6 protein LM U20362 Tg737 LM U22815 LAR-interacting
protein 1a L U31929 Orphan nuclear receptor (DAX1) L U38175 HuR RNA
binding protein (HuR) L U41763 Muscle specific clathrin heavy chain
L (CLTD) U43944 Breast cancer cytosolic NADP(+)- L dependent malic
enzyme U47054 Putative mono-ADP-ribosyltransferase LM (htMART)
U58970 Putative outer mitochondrial membrane M 34 kDa Translocase
hTOM34 U60665 Testis specific basic protein (TSBP) L U65011
Preferentially expressed antigen of LM melanoma (PRAME) U65092
Melanocyte-specific gene 1 (msg1) M U65533 Regulator of nonsense
transcript L stability (RENT1) U65918 Putative RNA binding protein
(DAZH) L U66726 Testis specific RNA binding protein LM (SPGYLA)
U70981 Interleukin-13 receptor L U78722 Zinc finger protein 165
(Zpf165) L U79266 Clone 23627 L U84720 Export protein Rael (RAE1)
LM U89606 Pyridoxal kinase M X04445 InhA gene exon 1 (and joined
CDS) LM X05246 Testis-specific PGK-2 gene for M phosphoglycerate
kinase (ATP: 3-phospho-D-glycerate 1-phosphotransferase, EC
2.7.2.3) X07948 Transition protein 1 (TP1) H X12433 PHS1-2, ORF
homologous to membrane LM Receptor proteins X14968 RII-alpha
subunit of cAMP dependent L protein kinase X68285 Glycerol kinase L
X69398 OA3 antigenic surface determinant L X70218 Protein
phosphatase X LM X78706 Carnitine acetyltransferase M X78711
Glycerol kinase testis specific 1 L X78712 Glycerol kinase testis
specific 2 M X79200 SYT-SSX, synovial sarcoma M translocation
junction X89960 Mitochondrial capsule selenoprotein M X95239
Cysteine-rich secretory protein-2/ M type I X99374 Fertilin beta L
Y00970 Acrosin (EC 3.4.21.10) M Y12856 AMP-activated protein kinase
alpha-1 L Z22780 Cylicin L Z46788 Cylicin II L Z46967 Calicin M
Z48570 Sp17 LM Z49105 HD21 M Z50115 Thimet oligopeptidase L
(metalloproteinase) Z75190 Apolipoprotein E receptor 2. L Uniquely
Expressed in Fetal Brain HG1996- Guanine Nucleotide-Binding Protein
LM HT2044 Rap2, Ras-Oncogene Related HG4063- Transcription Factor
Hbf-2 M HT4333 L07919 Homeodomain protein DLX-2 M L13744 AF-9 LM
M64358 Rhom-3 LM M88461 Neuropeptide Y peptide YY receptor M U00802
Drebrin E2 (DBN1) M U04735 Microsomal stress 70 protein ATPase L
core (stch) U09413 Zinc finger protein ZNF135 L U11701 LIM-homeobox
domain protein (hLH-2) M U35234 Protein tyrosine phosphatase sigma
M U43843 H-neuro-d4 protein M U64871 Putative G protein-coupled
receptor L (GPR19) U66198 Fibroblast growth factor homologous M
factor 2 (FHF-2) U79247 Clone 23599 LM U81262 Lerk-5 (Lerk-5) LM
X95425 EHK-1 receptor tyrosine kinase L Z11933 N-Oct 3, N-Oct5a,
and N-Oct 5b proteins M Z70220 Unknown protein (clone
ICRFp507O0882) M Uniquely Expressed in Adult Pancreas AF014958
Chemokine receptor X (CKRX) LM D31797 CD40 ligand (CD40L) LM J00268
Insulin H J02883 Colipase H J05125 Triglyceride lipase H L08010 Reg
gene homologue H L14813 Carboxyl ester lipase like protein MH
(CELL) M16652 Pancreatic elastase IIA H M16653 Elastase IIB H
M21056 Pancreatic phospholipase A-2 (PLA-2) H M22612 Pancreatic
trypsin 1 (TRY1) H M24349 Parathyroid hormone-like protein (PLP) L
M24400 Chymotrypsinogen H M55131 Cystic fibrosis transmembrane M
conductance regulator (CFTR) M74096 Long chain acyl-CoA
dehydrogenase L (ACADL) M81057 Procarboxypeptidase B H M93284
Pancreatic lipase related protein 2 H (PLRP2) S82198 Caldecrin,
serum calcium-decreasing H factor X54457 Bile-salt-stimulated
lipase (BSSL) H X67318 Procarboxypeptidase A1
H X71877 Chymotrypsin-like protease CTRL-1 H Y00705 Pancreatic
secretory inhibitor H (expressed in neoplastic tissue) Y08134
ASM-like phosphodiesterase 3b LM *The abundance levels in copies
per cell: L < 5, LM > 5 < 10, M > 10 < 50, MH >
50 < 100, H > 100.
Conclusion
[0034] The present invention provides methods and compositions for
identifying and using maintenance genes. It is to be understood
that the above description is intended to be illustrative and not
restrictive. Many variations of the invention will be apparent to
those of skill in the art upon reviewing the above description. By
way of example, the invention has been described primarily with
reference to the use of a high density oligonucleotide array, but
it will be readily recognized by those of skill in the art that
other nucleic acid arrays, other methods of measuring transcript
levels and gene expression monitoring at the protein level could be
used. The scope of the invention should, therefore, be determined
not with reference to the above description, but should instead be
determined with reference to the appended claims, along with the
full scope of equivalents to which such claims are entitled.
[0035] All references cited in this application are incorporated by
reference for all purposes.
* * * * *
References