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.

Description: METHODS FOR IDENTIFYING AND USING MAINTENANCE GENES RELATED APPLICATIONS This application claims the priority of U.S. Provisional Application Number 60/161,000, filed on October 21, 1999. The 60/161,000 application is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION 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. 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,\o\.\, 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, CM., R.D. Campbell. Genes, Genes and More Genes in the Human Major Histocompatibility Complex. Bioessays , 14(8):565-571, 1992; Rifl ind, 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. Ill :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. Meek 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.Gerce 80 2:337-343, 1989). 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. Patent Numbers 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 Saccharomvces 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. This application is related to U.S. Patent No. 6,033,860 which is incoφorated herein by reference in its entirety. SUMMARY OF THE INVENTION 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.). 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. 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 1 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 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. Methods for Gene Expression Monitoring: Various techniques for large scale polymer synthesis and probe array manufacturing are known. Some examples include the U.S. Patents 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. 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 incoφorated 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, US Patent No. 5,871,928 which is hereby incoφorated in its entirety for all puφoses. 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 No. 08/630,427 which is hereby incoφorated by reference in its entirety for all puφoses. Samples are then washed and stained using a robotic liquid handling machine such as the GeneChip® Fluidic Station 400 (Affymetrix, Inc., Santa Clara, CA). Fluidics stations have been described in, for example, US Patent Application 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™ scanner (Agilent Technologies). Scanners have been described in, for example, US Patent Nos. 5,578,832, 5,834,748,and 5,837,832, US Patent Application Nos. 08/456,598, 09/238,131, 08/856,642 (now allowed), 09/295,214, 08/456,782, 08/999,188, US Provisional Patent Application No. 60/106,397 and European Patent No. 97925605 each of which is hereby incoφorated by reference in its entirety for all puφoses. 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. Patent Nos. 5,733,729, and 5,795,716, U.S. Patent Application 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 incoφorated by reference in its entirety for all puφoses. Methods for Detecting Maintenance Genes: 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. 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. ll(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). Maintenance Genes: 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. Example Identification of Maintenance Genes METHODS Sample preparation All samples were prepared from pools of human adult poly(A) RNA purchased from Clontech (Palo Alto, CA). 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 <32) . First strand cDNA synthesis was carried out at 37°C for 60 minutes. The amplified cRNA (target) was purified on an affinity resin (RNeasy, Qiagen) and quantitated. Fragmentation, array hybridization and scanning Labeled target was fragmented by incubation at 94°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 lOOmM MES, lm[Na " ], 20mMEDTA, 0.01%Tween 20 (MES). The hybridization mixture was heated to 99°C for 5 min. followed by incubation at 45°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 °C for 16 - 17 hr with mixing on a rotisserie at 60 φm. Following hybridization, the solutions were removed, arrays were rinsed with IX MES (lOOmM MES, lm[Na + ], 20mMEDTA, 0.01%Tween 20). Subsequent washing and staining of the arrays was carried out using the GeneChip® 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 (6X SSPE, 0.01% Tween20, 0.005% Antifoam) at 25°C. The second wash consisted of 4 cycles of 15 mixes per cycle with Stringent Wash Buffer (100mm MES, 0.1 M [Na + ], 0.01 % Tween 20) at 50°C. The probe arrays were stained for 10 minutes in streptavidin-phycoerythrin solution (SAPE) (IX MES solution, 0.005% antifoam, lOμg/ml SAPE (Molecular Probes, Eugene, OR) 2μg/μl acetylated BSA (Sigma, St. Louis, MO) at 25°C. The post stain wash consisted of 10 cycles of 4 mixes per cycle at 25°C. The probe arrays were treated for 10 minutes in antibody solution (IX MES solution, 0.005% antifoam, 2μg/μl acetylated BSA, O.lμg/μl normal goat IgG (Sigma Chemical, St. Louis MO), 3μg/μl antibody (goat), antistreptavidin, biotinylated (Vector Laboratories, Burlingame, CA) at 25°C. The final wash consisted of 15 cycles of 4 mixes per cycle at 30 °C . Following washing and staining, probe arrays were scanned 2 times (multiple image scan) at 3 μm resolution using the GeneChip ® System confocal scanner made for Affymetrix Inc. by Hewlett Packard. Probe arrays The arrays were synthesized using light-directed combinatorial chemistry as described previously. The Hu6.8K_all GeneChip ® 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. Analysis 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 ® 3.0 software was used to scan and analyze the data. Microsoft Excel and Microsoft Access were also used for data analysis. RESULT Using GeneChip® probe arrays (Affymetrix, Santa Clara, CA), 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 ). Table 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 Number Description ATPase M37104 mitochondrial ATPase coupling factor 6 subunit (ATP5A) M U51478 sodium/potassium-transporting ATPase beta-3 subunit M Z71460 vacuolar-type H(+)- ATPase 115 kDa subunit LM Channels, pores D31846 aquaporin-2 water channel M L08666 porin (por) M Cytochrome AC002115 COX6B (COXG) on chromosome 19 cosmids M M22760 nuclear-encoded mitochondrial cytochrome c oxidase Va M subunit L32977 ubiquinol cytochrome c reductase Rieske iron-sulphur M protein X13238 cytochrome c oxidase subunit Vic M X16560 COX VIIc subunit Vile of cytochrome c oxidase M M28713 NADH-cytochrome b5 reductase (b5R) LM Dehydrogenase D90086 pyruvate dehydrogenase (EC 1.2.4.1 ) beta subunit M D43682 very-long-chain acyl-CoA dehydrogenase (VLCAD) M U17886 succinate dehydrogenase iron-protein subunit (sdhB) LM U05861 hepatic dihydrodiol dehydrogenase L L13761 dihydrolipoamide dehydrogenase L DNA binding J03827 Y box binding protein- 1 ( YB- 1 ) MH M26730 mitochondrial ubiquinone-binding protein with an LTR-like M sequence X75593 rab l3 M U79528 SR31747 binding protein 1 M L37368 RNA-binding protein M U33821 taxi -binding protein TXBP 151 M Z29505 nucleic acid binding protein sub2.3 M U07857 18 kDa Alu RNA binding protein M M94556 mitochondrial specific single stranded DNA binding protein LM N31 M28209 GTP-binding protein (RAB1) LM D13988 rab GDI LM U51334 putative RNA binding protein (RBP56) , LM D43951 KIAA0099, (pumilio-like, putative DNA binding) LM U65928 Jun activation domain binding protein L Electron transfer X71129 electron transfer flavoprotein beta subunit LM J04058 electron transfer flavoprotein alpha-subunit G protein relate U20285 Gpsl (GPS1) M U45982 G protein-coupled receptor GPR-9-6 LM U31384 ~ G protein gamma- 11 subunit LM X81625 Cll 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 (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 family H X59892 IFN-inducible gamma-2 protein M J00212 leukocyte interferon (ifn-alpha) alpha-f L Kinase M14676 src-like kinase (slk) M L08835 DM kinase (myotonic dystrophy kinase) M M30448 casein kinase II beta subunit LM Lysosome associated AJ000099 lysosomal hyaluronidase M U91932 AP-3 complex sigma3A subunit M M15182 beta-glucuronidase (lysosomal enzyme) LM M29877 alpha-L-fucosidase, (lysosomal enzyme) LM Membrane D29963 SFA-1, a member of transmembrane 4 superfamily M LI 0284 IP90, integral membrane protein, calnexin M U57877 nuclear-encoded mitochondrial integral membrane protein LM CII-3 Metabolism D78361 ornithine decarboxylase antizyme H M33764 ornithine decarboxylase amino acid metabolism M HG2279-HT2375 Triosephosphate Isomerase M U86070 phosphomannomutase (carbohydrate metabolism) LM U32114 caveolin-2 (lipid metabolism) L Mitochondrial associated Z70759 mitochondrial 16S rRNA H M22538 nuclear-encoded mitochondrial NADH-ubiquinone M reductase 24kD subunit M22760 nuclear-encoded mitochondrial cytochrome c oxidase Va M subunit X60036 mitochondrial phosphate carrier protein M M37104 mitochondrial ATPase coupling factor 6 subunit (ATP5A) M M26730 mitochondrial ubiquinone-binding protein with an LTR-like M sequence X99728 NDUFV3, mitochondrial NADH ubiquinone M oxidoreductase U59309 nuclear-encoded mitochondrial fumarase precursor (FH) LM L15189 mitochondrial HSP75 LM M94556 mitochondrial specific single stranded DNA binding protein LM U57877 nuclear-encoded mitochondrial integral membrane protein LM CII-3 L07033 hydroxymethylglutaryl-CoA lyase LM U15174 Nip3 (NIP3) (mitochondrial, pro-apoptotic protein family) L Phosphatase U45975 phosphatidylinositol (4,5) bisphosphate 5-phosphatase M homolog X74008 phosphatase 1 gamma LM X81003 HCG V (phosphatase inhibitor) LM M65254 phosphatase 2A 65 kDa regulatory subunit-beta L Polymerase Z27113 RNA polymerase II subunit 14.4 kD M U37690 RNA polymerase II subunit (hsRPB 10) M Z47727 RNA polymerase II subunit LM Protease, proteinase related L02426 26S protease (S4) regulatory subunit M M23254 Ca2-activated neutral protease large subunit (CANP) M X12451 pro-cathepsin L (major excreted protein MEP) M S69272 cytoplasmic antiproteinase, 38kD intracellular serine M proteinase inhibitor Proteasome D29012 proteasome subunit Y M D26598 proteasome subunit HsC 10-11 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 protein, LM 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-associated protein M D23673 insulin receptor substrate- 1 -like (IRS-1) M X07979 fibronectin receptor beta subunit M U83239 CC chemokine STCP-1 (immune function, T-receptor M assoc) M88279 immunophilin (FKBP52) M U45982 G protein-coupled receptor GPR-9-6 LM X56253 MPR46 46kd mannose 6-phosphate receptor LM X80763 5-HT2c receptor LM L40357 thyroid receptor interactor (TRIP7) L Reductase M22538 nuclear-encoded mitochondrial NADH-ubiquinone M reductase 24kD 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 (hmlhl) U49785 D-dopachrome tautomerase LM Replication J05249 replication protein A 32-kD subunit LM Ribonucleoprotein HG3076-HT3238 heterogeneous nuclear ribonucleoprotein K, alt. splice 1 M X16135 novel heterogeneous nuclear RNP protein, L protein M X78136 hnRNP-E2 M M94630 hnRNP-C like protein M Ml 6342 nuclear ribonucleoprotein particle (hnRNP) C protein LM Z23064 hnRNP G protein L Ribosomal X81625 ribosomal protein L37a (RPL37A) H Z 12962 homologue to yeast ribosomal protein L41 H HG3214-HT3391 Metallopanstimulin , MPS-1 (S27, Zinc finger) H HGl 800-HT1823 ribosomal protein S20 H U 14973 ribosomal protein S29 H Z26876 ribosomal protein L38 MH M77232 ribosomal protein S6 MH HG821-HT821 ribosomal protein S 13 MH 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 vimentm MH X51521 ezrin M HG2238-HT2321 nuclear mitotic apparatus protein 1 , alt.splice form 2 M M64571 microtubule-associated protein 4 M M31013 nonmuscle myosin heavy chain (NMHC) M V00599 fragment encoding beta-tubulin (D-beta-1) M U24105 coatomer protein (HEPCOP) , M M95627 angio-associated migratory cell protein (AAMP) LM D38549 KIAA0068 LM U56637 capping protein alpha subunit isoform 1 LM X72964 caltractin LM X70476 subunit of coatomer complex LM D28915 hepatitis C-associated microtubular aggregate protein p44 L 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 homologue LM Transcription L49380 transcription factor ZFM1 M U95040 transcriptional corepressor hKAPl/TIFIB M U10323 nuclear factor NF45 M L12168 adenylyl cyclase-associated protein (CAP) , M M97935 transcription factor ISGF-3 sequence LM X52882 t-complex polypeptide 1 LM LI 9067 NF-kappa-B transcription factor p65 subunit L D63478 KIAA0144 L U15782 cleavage stimulation factor 77kDa subunit L (polyadenylation) L20298 transcription factor (CBFB) Transferase U56417 lysophosphatidic acid acyltransferase-alpha M U62739 branched-chain amino acid aminotransferase (ECA40) M Y08200 rab geranylgeranyl transferase, alpha-subunit M U82010 heme A: farnesyltransferase (COX 10) LM U86529 glutathione transferase Zeta 1 (GSTZ1) LM D26535 dihydrolipoamide succinyltransferase L Transformation related U50523 BRCA2 region M U57342 myelodysplasia/myeloid leukemia factor 2 (MLF2) , M HG4541 -HT4946 transformation-related protein M Ml 5990 c-yes-1 L L12535 RSU-l/RSP-1 (Ras suppressor) L Translation, inititiation and elongation J04617 elongation factor EF-1 -alpha H X51466 elongation factor 2 MH L26247 suil,N278 isol MH U46025 translation initiation factor eIF-3 pi 10 subunit M X55733 initiation factor 4B LM X98743 RNA helicase (Myc-regulated dead box protein) L U36341 SLC6A8 (creatine transporter) M U51478 sodium/potassium-transporting . M 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,SRP 19kD protein (ER) Ubiquitin related X56997 UbA52 coding for ubiquitin-52 amino acid fusion protein MH M26880 ubiquitin M U46751 phosphotyrosine independent ligand p62 for the Lck SH2 M domain U39317 E2 ubiquitin conjugating enzyme UbcH5B (UBCH5B) , Zinc finger HG3214-HT3391 Metallopanstimulin , MPS-1 (S27, Zinc finger) H X70394 OZF L U09412 zinc finger protein ZNF134 L HG3454-HT3647 zinc finger protein 20 L Undefined X67698 unknown product M LI 1066 unknown product M U79294 unknown product M D28124 unknown product M " D21261 KIAA0120 M D87451 KIAA0262 M - D 14694 KIAA0024 M ISGF3A/M97935 unknown product LM L20773 unknown product LM D42043 KIAA0084 LM D50911 KIAA0121 LM D79994 KIAA0172 LM D29643 KIAA0115 LM D 14662 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 X98482 TNNT2, (troponin) H U06155 chromosome 1 q subtelomeric sequence H M33680 26-kDa cell surface protein TAPA-1 H M13450 esterase D M U11861 G10 homolog, edg-2 M U62317 hypothetical protein 384D8 2 on chromosome 22ql3 M (other) HG3991 -HT4261 Cpg-enriched DNA (other) M X80199 MLN51 M X80200 MLN62 M U46570 tetratricopeptide repeat protein (tprl) N297 (other) M HG3597-HT3800 major histocompatibility complex, class I M X71428 fus (nuclear RNA binding protein) M U73824 p97 M Y00433 glutathione peroxidase (peroxide clearance) M U02493 54 kDa protein M U88964 HEM45 LM D78129 squalene epoxidase (sterol biosynthesis) LM D43951 KIAA0099, (pumilio-like, putative DNA binding) LM X96484 DGCR6 protein (organization, migration during LM development) HGl 155-HT4822 colony-stimulating factor 1, macrophage, alt. splice 3 LM L38932 GT197 N305 LM X66397 tpr LM L42572 p87/89 (ER transmembrane protein) LM X80695 OXAlHs (cytochrome oxidase assembly) LM Y00097 p68 (membrane associated, calcium binding protein) LM Z48042 GPI-anchored protein p 137 LM Z35093 SURF-1 (Surfeit gene family, biogenesis of cytochrome C LM oxidase) U54644 tub homolog LM Z93784 mouse brain protein E46-like sequence L L38616 brain and reproductive organ-expressed protein (BRE) L D63506 unc- 18 homologue L U18009 human gene on chromosome 17q21 L L27476 XI 04 (membrane associated, kinase containing protein L family) M73720 mast cell carboxypeptidase A (MC-CPA) L 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 (Ml 0277) 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. 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-lV/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 (LI 3258) 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 suφrisingly, the greatest number of uniquely expressed genes, 91 and 94 respectively, were found in brain and testis. Table II. Genes Uniquely Expressed in a Comparison of Eleven Human Tissues Accession No. Description Uniquely Expressed in Adult Heart J04501 Muscle glycogen synthase M M24248 MLC- 1 V/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 U 19906 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 D 16611 Copropoφhyrinogen oxidase M D 16626 Histidase M D21063 KIAA0030 M D26361 KIAA0042 L D38535 PK-120 H D38537 Protopoφhyrinogen 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 (EC 6.3.4.16) MH HGl 148-HT1148 Lipopolysaccharide-Binding Protein H HG1227-HT1227 Collagen, Type II, Alpha 1 M HG1649-HT1652 Elastase 1 M HG2730-HT2827 Fibrinogen, A Alpha Polypeptide, Alt. Splice 2, E H HG3105-HT3281 Atpase, Cu2+ Transporting L HG3565-HT3768 Zinc Finger Protein M HG627-HT5097 Rhesus (Rh) Blood Group System Ce-Antigen, Alt. Splice 2, MH 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 LOO 190 Antithrombin III (ATAIII) H L01664 Eosinophil Charcot-Leyden crystal (CLC) protein L (lysophospholipase) L06133 Putative Cu++-transporting P-type ATPase L L09708 Complement component 2 (C2), allele b MH LI 1244 C4b-binding protein beta-chain M L31860 Glycophorin A, MN-types (GYP A) M L32140 Afamin M L34081 Bile acid CoA: Amino acid N-acyltransferase LM L48516 Paraoxonase 3 (PON3) M L76571 Nuclear hormone receptor (shp) M L77567 Mitochondrial citrate transport protein (CTP) M M10014 Fibrinogen gamma chain and gamma-prime chain H M10058 Asialoglycoprotein receptor HI M M10950 Alpha-fetoprotein (AFP) M Ml 1025 Asialoglycoprotein receptor H2 M M11567 Angiogenin and three Alu repetitive sequences M M13699 Ceruloplasmin (ferroxidase) MH M14091 Thyroxine-binding globulin M Ml 5205 Thymidine kinase with clustered Alu repeats in the introns M M16961 Alpha-2-HS-glycoprotein alpha and beta chain H M16967 Coagulation factor V M Ml 6973 Complement protein C8 beta subunit M Ml 7262 Prothrombin (F2) gene, and Alu and Kpnl repeats H 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 transcript of extended H (alpha-E) variant M58600 Heparin cofactor II (HCF2), exons 1 through 5 H M59820 Granulocyte colony-stimulating factor receptor (CSF3R) LM M60298 Erythrocyte membrane protein band 4.2 (EPB42) MH M61827 Leukosialin (CD43) LM M61855 Cytochrome P4502C9 (CYP2C9), clone 25 L M64554 F13A1 gene (coagulation factor XHIb) 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 chl 38 LM S77763 Nuclear factor erythroid 2 M S77893 Glycophorin SAT MH S78234 Nuc2 homolog LM U00001 Homologue of S. pombe nuc2+ and A. nidulans bimA L U01317 Epsilon-globin LM U05255 Glycophorin HeP2 H U08006 Complement 8 alpha subunit (C8A) M U 12778 Acyl-CoA dehydrogenase LM U 13061 Dehydroepiandrosterone sulfotransferase (STD) L U 14518 Centromere protein- A (CENP- A) L U 18919 Clone pOV-2 L U20530 Bone phosphoprotein spp-24 precursor M U20979 Chromatin assembly factor-I pi 50 subunit L U32989 Tryptophan oxygenase (TDO) M U61836 Putative cyclin Gl interacting protein M U65404 Erythroid-specific transcription factor EKLF M 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 Alphal-acid glycoprotein (orosomucoid) H X03473 Histone HI (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 (EC 3.4.17.3) LM XI 4690 Plasma inter-alpha-trypsin inhibitor heavy chain H(3) H XI 5422 Mannose-binding protein C M XI 6260 Inter-alpha-trypsin inhibitor subunit 3 H X16983 Integrin alpha-4 subunit L XI 7059 NAT1 gene for arylamine N-acetyltransferase L XI 7254 Transcription factor Eryfl M X51688 Cyclin A LM X53414 Peroxisomal L-alanine:glyoxylate aminotransferase MH X55668 Proteinase 3 M X56692 C-reactive protein M X56741 Rab8 L X58199 Beta adducin M X59618 RR2 small subunit ribonucleotide reductase LM X5971 1 CAAT-box DNA binding protein subunit A L X59812 CYP 27 vitamin D3 25-hydroxylase M X62822 Beta-galactoside alpha-2,6-sialyltransferase LM X63097 Rhesus polypeptide (RhXIII) L X64594 Erythrocyte plasma membrane glycoprotein MH 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, Band 3) H X80907 P85 beta subunit of phosphatidyl-inositol-3 -kinase M X91148 Microsomal triglyceride transfer protein LM X98337 Complement factor H-related protein 4 M Y00317 Liver microsomal UDP-glucuronosyltransferase (UDPGT) LM Z15005 CENP-E LM Z26248 Eosinophil granule major basic protein LM Z28339 Delta 4-3-oxosteroid 5 beta-reductase LM Z32684 XK membrane transport protein M Z83821 DNA sequence from PAC 296K21 on chromosome X H contains cytokeratin exon, delta-aminolevulinate synthase (erythroid); 5-aminolevulinic acid synthase Z84721 DNA sequence from cosmid GGl from a contig from the tip H of the short arm of chromosome 16, spanning 2Mb of 16pl3.3 Uniquely Expressed in Fetal Lung D87071 KIAA0233 LM HG4638-HT5050 Spliceosomal Protein Sap 49 L U 18671 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-HT2348 Tubulin, Alpha 1 , Isoform 44 M HG3437-HT3628 Myelin Proteolipid Protein, Alt. Splice 2 H L00354 Cholecystokinin (CCK) M L76224 NMDA receptor M L76627 Metabotropic glutamate receptor 1 alpha (mGluRl alpha) L M55267 EV 12 protein LM M59488 S 100 protein beta-subunit M S50017 2' ,3' -cyclic nucleotide 3' -phosphodiesterase M 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-1 15 LM X99076 NRGN, exons 2, 3 & 4 Coined CDS) H Z48051 Myelin oligodendrocyte glycoprotein (MOG) M Uniquely Expressed in Adult Kidney J04093 Phenol UDP-glucuronosyltransferase (UDPGT) LM LI 3258 Renal Na/Pi-cotransporter M Ml 9878 Calbindin 27, exons 1 and 2, and Alu repeat M S77576 ERV9 reverse transcriptase homolog (clone RT 18) L U 17418 Hormone/parathyroid hormone-related peptide receptor M XI 3227 D-amino acid oxidase M X60708 PcHDP7, liver dipeptidyl peptidase IV L Uniquely Expressed in Adult Uterus D21337 Collagen L D86961 KIAA0206 L 721-HT4828 Placental Protein 14, Endometrial Alpha 2 Globulin, Alt. M 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 LI 0343 Elafin M L14848 MHC class I-related protein L M19888 Small proline rich protein (sprl) M M21 121 T cell-specific protein (RANTES) L M21389 Keratin type II (58 kD) M M55543 Guanylate binding protein isoform II (GBP-2) L 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, serine protease inhibitor L S72493 Keratin 16 homolog M S81661 Keratinocyte growth factor L U07969 Intestinal peptide-associated transporter HPT-1 L U09278 Fibroblast activation protein L U09584 PL6 protein (PL6) L U11717 Calcium activated potassium channel (hslo) L U24488 Tenascin-X (XA) M U25138 MaxiK potassium channel beta subunit M U37283 Microfibril-associated glycoprotein-2 MAGP-2 M U43185 Signal transducer and activator of transcription Stat5A L U60325 DNA polymerase gamma, nuclear gene encoding L mitochondrial protein U76764 CD97 LM U81523 Endometrial bleeding associated factor M X03635 Oestrogen receptor M X06256 Fibronectin receptor alpha subunit LM X07695 Cytokeratin 4 C-terminal region M X07696 Cytokeratin 15 L XI 6662 Vascular anticoagulant-beta (VAC-beta) L X54162 64 Kd autoantigen expressed in thyroid and extra-ocular M JD muscle X63629 P cadherin L X75535 PxF protein L X83857 Prostaglandin E receptor (EP3al) L X92521 MMP- 19 protein L X93510 37 kDa LIM domain protein LM X96719 AICL (activation-induced C-type lectin) LM X9831 1 Carcinoembryonic antigen. CGM2 L Y07755 S 100A2, exon 1 , 2 and 3 M Uniquely Expressed in Adult Testis Dl 7570 Zona-pellucida-binding protein (sp38). M D50925 KIAA0135 L D64109 Tob family L D78333 Testis-specific TCP20 M D78334 Ankyrin motif MH HG2075-HT2137 Camp-Responsive Element Modulator, Alt. Splice 1 M HG36-HT4101 Polymyositis/Scleroderma (Pm-Scl) Autoantigen, Alt. Splice L 2 HG3725-HT3981 Insulin-Like Leydig Hormone M HG4316-HT4586 Transketolase-Like Protein L L01042 HIV 1 tata element modulatory factor L L07515 Heterochromatin protein homologue (HP 1 ) LM L 14754 DN A-binding protein (SMBP2) LM L22214 Denosine A 1 receptor (ADORA 1 ), exons 1 -6 L L36861 Guanylate cyclase activating protein (GCAP), exons 1-4 L L42324 G protein-linked receptor (GPCR) L L76687 Grbl4 L M13981 Inhibin A-subunit M Ml 4565 Cholesterol side-chain cleavage enzyme P450scc L M21539 Small proline rich protein (sprll) L M31606 Phosphorylase kinase (PSK-C3) M M63256 Major Yo paraneoplastic antigen (CDR2) L M73077 Glucocorticoid receptor repression factor 1 (GRF-1) LM M86808 Pyruvate dehydrogenase complex (PDHA2) L M91438 Kazal-type serine proteinase (HUSI-II) M S68134 CREM, cyclic AMP-responsive element modulator beta LM isoform S78873 Zn2+ binding protein/guanine nucleotide exchange factor L U03644 Recepin L U 10362 GP36b glycoprotein L U 13680 Lactate dehydrogenase-C (LDH-C) M U 15422 Protamine 1 (PRM1), protamine 2 (PRM2) and transition H protein 2 (TNP2) U17032 P190-B(pl90-B) L U17280 Steroidogenic acute regulatory protein (StAR) LM U19147 GAGE-6 protein LM U20362 Tg737 LM U22815 LAR-interacting protein 1 a L U31929 Oφhan nuclear receptor (DAX1) L U38175 HuR RNA binding protein (HuR) L U41763 Muscle specific clathrin heavy chain (CLTD) L U43944 Breast cancer cytosolic NADP(+)-dependent malic enzyme L U47054 Putative mono-ADP-ribosyltransferase (htMART) LM U58970 Putative outer mitochondrial membrane 34 kDa Translocase M hTOM34 U60665 Testis specific basic protein (TSBP) L U65011 Preferentially expressed antigen of melanoma (PRAME) LM U65092 Melanocyte-specific gene 1 (msgl) M U65533 Regulator of nonsense transcript stability (RENT1) L U65918 Putative RNA binding protein (DAZH) L U66726 Testis specific RNA binding protein (SPGYLA) LM U70981 Interleukin-13 receptor L U78722 Zinc finger protein 165 (Zpfl65) 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 phosphoglycerate kinase M (ATP:3-phospho-D-glycerate 1 -phosphotransferase, EC 2.7.2.3) X07948 Transition protein 1 (TP1) H XI2433 PHSl-2, ORF homologous to membrane Receptor proteins LM XI4968 Rll-alpha subunit of cAMP dependent protein kinase L 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 translocation junction M X89960 Mitochondrial capsule selenoprotein M X95239 Cysteine-rich secretory protein-2/type I M 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 Spl 7 LM Z49105 HD21 M Z50115 Thimet oligopeptidase (metalloproteinase) L Z75190 Apolipoprotein E receptor 2. L Uniquely Expressed in Fetal Brain HG1996-HT2044 Guanine Nucleotide-Binding Protein Rap2, Ras-Oncogene LM Related HG4063-HT4333 Transcription Factor Hbf-2 M L07919 Homeodomain protein DLX-2 M LI 3744 AF-9 LM M64358 Rhom-3 LM M88461 Neuropeptide Y peptide YY receptor M U00802 Drebrin E2 (DBN 1 ) M U04735 Microsomal stress 70 protein ATPase core (stch) L U09413 Zinc finger protein ZNF135 L U 11701 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 (GPR19) L U66198 Fibroblast growth factor homologous factor 2 (FHF-2) M U79247 Clone 23599 LM U81262 Lerk-5 (Lerk-5) LM X95425 EHK-1 receptor tyrosine kinase L Zl 1933 N-Oct 3, N-Oct5a, and N-Oct 5b proteins M Z70220 Unknown protein (clone ICRFp507O0882) M Uniquely Expressed in Adult Pancreas AFO 14958 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 L 14813 Carboxyl ester lipase like protein (CELL) MH M 16652 Pancreatic elastase II A H Ml 6653 Elastase IIB H M21056 Pancreatic phospholipase A-2 (PLA-2) H M22612 Pancreatic trypsin 1 (TRY 1) H M24349 Parathyroid hormone-like protein (PLP) L M24400 Chymotrypsinogen H M55131 Cystic fibrosis transmembrane conductance regulator (CFTR) M M74096 Long chain acyl-CoA dehydrogenase (ACADL) L M81057 Procarboxypeptidase B H M93284 Pancreatic lipase related protein 2 (PLRP2) H S82198 Caldecrin, serum calcium-decreasing factor H X54457 Bile-salt-stimulated lipase (BSSL) H X67318 Procarboxypeptidase A 1 H X71877 Chymotrypsin-like protease CTRL- 1 H Y00705 Pancreatic secretory inhibitor (expressed in neoplastic tissue) H 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 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. All references cited in this application are incoφorated by reference for all puφoses.

Claims: What is claimed is: 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. The method of Claim 1 wherein said at least one hundred genes comprise at least one thousand genes. 3. The method of Claim 1 wherein said at least two types of tissues comprise at least five different types of tissues. 4. The method of Claim 1 wherein said determining uses nucleic acid probe arrays. 5. The method of Claim 1 wherein a gene is considered as expressed at the same level if the variation of its expression is within 10 fold. 6. The method of Claim 5 wherein a gene is considered as expressed at the same level if the variation of its expression is within 5 fold. 7. The method of Claim 6 wherein a gene is considered as expressed at the same level if the variation of its expression is within 2 fold. 8. The method of Claim 1 wherein a gene is considered as expressed at the same level if the variation of its expression is not statistically significant. A method for comparing the expression of a gene in a plurality of biological samples comprising: measuring the expression of at least three maintenance genes selected from the group consisted of: HG2815- Myosin, Light Chain, Alkali,(Gb:U02629), Alt. Splice 2 HT2931 J03191 Profilin M 10277 Cytopl asmi c beta-actin Ml 4483 PTMA gene extracted from prothymosin alpha M 17733 Thymosin beta-4 mR A M 19283 Cyto skel etal gamma-actin M26708 Prothymosin alpha mRNA (ProT-alpha) S65738 Actin depolymerizing factor U37122 Adducin gamma subunit X00351 Beta-actin X54304 Myosin regulatory light chain X95404 Non-muscle type cofilin D 15057 DAD-1 L08246 Myeloid cell differentiation protein (MCL 1 ) M63379 TRPM-2 protein, Clusterin Dl 3118 ATP synthase subunit c encoded by PI D 14710 ATP synthase alpha subunit Dl 6469 Vacuolar ATP synthase subunit AC45 precursor D 16562 ATP synthase gamma-subunit (L-type) D49400 Fetus brain vacuolar ATPase Ml 9483 ATP synthase beta subunit M37104 Mitochondrial ATPase coupling factor 6 subunit (ATP5A) U09813 Mitochondrial ATP synthase subunit 9, P3 gene copy U 16799 NaK- ATPase beta- 1 subunit U51478 Sodium/potassium-transporting ATPase beta-3 subunit X60221 H+- ATP synthase subunit b X64330 ATP-citrate lyase X83218 ATP synthase Z71460 Vacuolar-type H(+)- ATPase 115 kDa subunit AB001325 AQP3 aquaporine 3 (water channel) L06132 Voltage-dependent anion channel isoform 1 (VDAC) L08666 Porin (por) AC002115 COX6B (COXG) J04823 Cytochrome c oxidase subunit VIII (COX8) J04973 Cytochrome bc-1 complex core protein II L32977 Clone fl 7252 ubiquinol cytochrome c reductase Rieske iron- sulphur protein (UQCRFSl) U90915 Clone 23600 cytochrome c oxidase subunit IV X13238 Cytochrome c oxidase subunit Vie X15341 COX Vla-L cytochrome c oxidase liver-specific subunit Via (EC 1.9.3.1) X15822 COX VIIa-L liver-specific cytochrome c oxidase (EC 1.9.3.1.) XI 6560 COX VIIc subunit VIIc of cytochrome c oxidase (EC 1.9.3.1) Z 14244 CoxVIIb cytochrome c oxidase subunit Vllb D50310 Cyclin I D89667 C-myc binding protein M93651 SET (Suvar3-9, Enhancer-of-zeste, Trithorax) X61123 BTG1 mRNA, B-cell translocation gene 1 D43682 Very-long-chain acyl-CoA dehydrogenase (VLCAD) D55654 Cytosolic malate dehydrogenase D90086 Pyruvate dehydrogenase (EC 1.2.4.1) beta subunit M91432 Medium-chain acyl-CoA dehydrogenase (MCAD) X01677 Liver glyceraldehyde-3-phosphate dehydrogenase (G3PD EC 1.2.1.12) X02152 Lactate dehydrogenase-A (LDH-A EC 1.1.1.27) X05409 RNA mitochondrial aldehyde dehydrogenase I ALDH I (EC 1.2.1.3) X13794 Lactate dehydrogenase B exon 1 and 2 (EC 1.1.1.27) D78134 Glycine-rich RNA binding protein CIRP D90209 DNA binding protein TAXREB67 HG4264- Guanine Nucleotide-Binding Protein Rab5c-Like Protein HT4534 HG662-HT662 Epstein-Barr Virus Small Rna-Associated Protein J03827 Y box binding protein- 1 (YB-1) L37368 (Clone E5.1) RNA-binding protein L43631 Scaffold attachment factor (SAF-B) M21142 Guanine nucleotide-binding protein G-s-alpha-3 extracted from guanine nucleotide-binding protein alpha-subunit (G- s-alpha) M23613 Nucleophosmin M34539 FK506-binding protein (FKBP) S78771 NAT=CpG island-associated [ 1741 nt] U02493 54 kDa protein, 54 KD Nuclear RNA binding protein U07857 18 kDa Alu RNA binding protein U 10439 Double-stranded RNA adenosine deaminase U20998 Signal recognition particle subunit 9 (SRP9) U30827 Splicing factor SRp40-3 (SRp40) U33818 Inducible poly(A)-binding protein U33821 Tax 1 -binding protein TXBP 151 U38846 Stimulator of TAR RNA binding (SRB) U51334 Putative RNA binding protein (RBP56) U68105 Poly(A)-binding protein (PABP) U79528 SR31747 binding protein 1 X04347 DNA binding protein UPI homologue (C-terminus) X63753 Son-a X71428 Fus, R A binding protein X75252 Phosphatidylethanolamine binding protein Z48501 Polyadenylate binding protein II Z71460 Vacuolar-type H(+)- ATPase 115 kDa subunit. D78132 Ras homologue enriched in brain (RHEB) Ras-related GTP binding protein HG4264- Guanine Nucleotide-Binding Protein Rab5c-Like Protein HT4534 L25080 GTP-binding protein (rhoA) L33075 Ras GTPase-activating-like protein (IQGAP1 ) M21 142 Guanine nucleotide-binding protein G-s-alpha-3 M24194 MHC protein homologous to chicken B complex protein U20285 Gpsl (GPSl), G PROTEIN PATHWAY SUPPRESSOR 1 U41654 Adenovirus protein E3 - 14.7k interacting protein 1 (FIP- 1 ) D32129 HLA class-I (HLA-A26) heavy chain (clone cMI Y- 1 ) D49824 HLA-B null allele M59830 MHC class III HSP70-2 (HLA) X75091 HLA-DR associated protein II (PHAPII) HG2855- Heat Shock Protein 70 Kda (Gb:Y00371) HT2995 J04988 90 kD heat shock protein M 1 1717 Heat shock protein (hsp 70) XI 5183 90-kDa heat-shock protein Z23090 28 kDa heat shock protein L20941 Ferritin heavy chain, iron storage Ml 1147 Ferritin L chain, iron storage M69023 Globin LI 9779 Histone H2A.2 Ml 1353 Histone class C M37583 Histone (H2A.Z) U50079 Histone deacetylase HD 1 X05855 Histone H3.3 exon 2 X13546 HMG- 17 protein X72841 IEF 7442, Histone acetyl transferase type B subunit 2 Z48950 HH3.3B histone H3.3 X57351 1-8D from interferon-inducible family X59892 IFN-inducible gamma2 protein K03515 Neuroleukin L76191 Interleukin-1 receptor-associated kinase (IRAK) HG1153- Nucleoside Diphosphate Kinase Nm23-H2s HT1 153 L36151 Phosphatidylinositol 4-kinase L40027 Glycogen synthase kinase 3 L76191 Interleukin-1 receptor-associated kinase (IRAK) Ml 4676 Src-like kinase (slk) M30448 Casein kinase II beta subunit M33336 CAMP-dependent protein kinase type I-alpha subunit (PRKAR1A) U40282 Integrin-linked kinase (ILK) U51004 Putative protein kinase C inhibitor (PKCI-1) U77948 Bruton tyrosine kinase-associated protein- 135 V00572 Encoding phosphoglycerate kinase X56468 14.3.3 protein a protein kinase regulator X57152 Casein kinase II subunit beta (EC 2.7.1.37) D10522 80K-L protein HGl 862- Calmodulin Type I HT1897 M1931 1 Calmodulin X57346 HS1 protein AJ000099 Lysosomal hyaluronidase J04182 Lysosomal membrane glycoprotein- 1 (LAMP1) M15182 Beta-glucuronidase M29877 Alpha-L-fucosidase U91932 AP-3 complex sigma3A subunit 658-HT658 Major Histocompatibility Complex Class I C (Gb:X58536) J00105 Beta-2 microglobulin M1 1313 Alpha-2-macroglobulin S82297 Beta 2-microglobulin M84349 Transmembrane protein (CD59) X59405 Membrane cofactor protein D13315 Lactoyl glutathione lyase D49489 Protein disulfide isomerase-related protein P5 D78361 Ornithine decarboxylase antizyme ORF 1 and ORF 2 D85758 Protein homologous to DROER protein, Enhancer of rudimentary homolog HG2279- Triosephosphate Isomerase HT2375 HG4073- Cytosolic Acetoacetyl-Coenzyme A Thiolase HT4343 J03077 Co-beta glucosidase (proactivator) J03459 Leukotriene A-4 hydrolase J04173 Phosphoglycerate mutase (PGAM-B) LI 9437 Transaldolase containing transposable element L48513 Paraoxonase 2 (PON2) Ml 4328 Alpha enolase M32405 Homologue of rat insulinoma gene (rig), exons 4 M33764 Ornithine decarboxylase M37721 Peptidylglycine alpha-ami dating monooxygenase M83088 Phosphoglucomutase 1 (PGM1) M86400 Phospholipase A2 U29607 Methionine aminopeptidase U31930 Deoxyuridine nucleotidohydrolase U44772 Palmitoyl protein thioesterase U67171 Selenoprotein W (sel W) U86070 Phosphomannomutase U94586 NADH:ubiquinone oxidoreductase MLRQ subunit U97105 Dφ2, Dihyrdropyrimidinase related protein X02317 Cu/Zn superoxide dismutase (SOD) X05130 Prolyl 4-hydoxylase beta subunit (EC 1.14.1 1.2) (procollagen-L-proline, 2-oxoglutarate:oxygen oxidoreductase, 4-hydroxylating) X 12447 Aldolase A gene (EC 4.1.2.13) XI 4448 GLA alpha-D-galactosidase A X52851 Peptidylprolyl isomerase gene extracted from cyclophilin gene (EC 5.2.1.8) X71973 GPx-4 phospholipid hydroperoxide glutathione peroxidase Y09616 Putative carboxylesterase Z151 15 TOP2, DNA topoisomerase II Z49835 Protein disulfide isomerase L 11066 Mitochondrial stress-70 protein precursor M22382 Mitochondrial matrix protein PI (nuclear encoded) M22538 Nuclear-encoded mitochondrial NADH-ubiquinone reductase 24Kd subunit M22760 Nuclear-encoded mitochondrial cytochrome c oxidase Va subunit M26730 Mitochondrial ubiquinone-binding protein 5' flank with an LTR-like sequence M37104 Mitochondrial ATPase coupling factor 6 subunit (ATP5A) M94556 Mitochondrial specific single stranded DNA binding protein U54778 14-3-3 epsilon, Mitochondrial import stimulation factor L U62739 Branched-chain amino acid aminotransferase (ECA40), Mitochrondrial precursor X05409 Mitochondrial aldehyde dehydrogenase I ALDH I (EC 1.2.1.3) X60036 Mitochondrial phosphate carrier protein Y00764 Mitochondrial hinge protein Z70759 Mitochondrial 16S rRNA Ml 4200 Diazepam binding inhibitor (DBI) J03805 Phosphatase 2A X68277 CL 100 protein tyrosine phosphatase X74008 Protein phosphatase 1 gamma X81003 HCG V U37690 RNA polymerase II subunit (hsRPBlO) Z27113 RNA polymerase II subunit 14.4 kD Z47727 RNA polymerase II subunit HG417-HT417 Cathepsin B L02426 26S protease (S4) regulatory subunit M23254 Ca2-activated neutral protease large subunit (CANP) M27891 Cystatin C (CST3) U14394 Tissue inhibitor of metalloproteinases-3, TIMP3 U46692 Cystatin B gene X12451 MrRNA pro-cathepsin L (major excreted protein MEP) D00761 Proteasome subunit HC5 D00762 Proteasome subunit HC8 D00763 Proteasome subunit HC9 D26598 Proteasome subunit HsC 10-11 D26599 Proteasome subunit HsC7-I D26600 Proteasome subunit HsN3 D29012 Proteasome subunit Y D38047 26S proteasome subunit p31 D38048 Proteasome subunit z D50063 Proteasome subunit p40_/ Mov34 protein M64992 Prosomal protein P30-33K (pros-30) U70735 34 kDa mov34 isologue X61970 Macropain subunit zeta, Proteasome Zeta chain X95586 MB1 D23673 Clone HH109 (screened by the monoclonal antibody of insulin receptor substrate- 1 (IRS-1)) L40357 Thyroid receptor interactor (TRIP7) M 14199 Laminin receptor (2H5 epitope) M88279 Immunophilin (FKBP52), P59 Protein (HSP binding immunophilin) (HBI) M88458 ELP-1 , Er lumen protein retaining receptor 2 (KDEL receptor 2) U43901 37 kD laminin receptor precursor/p40 ribosome associated protein U7251 1 B-cell receptor associated protein (hBAP) X07979 Fibronectin receptor beta subunit X80763 5-HT2c receptor Z32765 CD36 M 16447 Dihydropteridine reductase (hDHPR) mRNA M28713 NADH-cytochro e b5 reductase (b5R) X 15414 Aldose reductase X91247 Thioredoxin reductase U49785 D-dopachrome tautomerase J05249 Replication protein A 32-kDa subunit XI 5729 Nuclear p68 protein L20688 RHO GDP-dissociation inhibitor protein (Ly-GDI) U02570 CDC42 GTPase-activating protein Z24725 Mitogen inducible mig-2 HGl 322- Small Nuclear Ribonucleoprotein Polypeptide C Alt. Splice 2 HT5143 HG3076- Heterogeneous Nuclear Ribonucleoprotein K Alt. Splice 1 HT3238 J04615 Lupus autoantigen (small nuclear ribonuclepoprotein snRNP SM-D) L03532 M4 protein, Heterogeneous Nuclear Ribonucleoprotein M L22009 HnRNP H mRNA L28010 HnRNP F protein mRNA Ml 6342 Nuclear ribonucleoprotein particle (hnRNP) C protein M21259 Alu repeats in the region 5' to the small nuclear ribonucleoprotein E M29064 HnRNP Bl protein M74002 Arginine-rich nuclear protein M88108 P62 M94630 HnRNP-C like protein U00947 Heterogeneous Nuclear Ribonucleoprotein Al Ul 5008 SnRNP core protein Sm D2 XI 2671 Heterogeneous nuclear ribonucleoprotein (hnRNP) core protein Al X 16135 Novel heterogeneous nuclear RNP protein L protein X78136 HnRNP-E2 D14530 Homolog of yeast ribosomal protein S28 D23660 Ribosomal protein D79205 Ribosomal protein L39 D87735 Ribosomal protein LI 4 HGl 800- Ribosomal Protein S20 HT1823 HG2873- Ribosomal Protein L30 Homolog HT3017 HG31 1-HT31 1 Ribosomal Protein L30 HG3364- Ribosomal Protein L37 HT3541 HG33-HT33 Ribosomal Protein S4, X-Linked HG384-HT384 Ribosomal Protein L26 HG4319- Ribosomal Protein L5 HT4589 HG4542- Ribosomal Protein L 10 HT4947 HG613-HT613 Ribosomal Protein S 12 HG821-HT821 Ribosomal Protein S 13 L04483 Ribosomal protein S21 (RPS21) L06499 Ribosomal protein L37a (RPL37A) L06505 Ribosomal protein L12 L11566 Ribosomal protein LI 8 (RPL18) LI 9527 Ribosomal protein L27 (RPL27) L38941 Ribosomal protein L34 (RPL34) M13934 Ribosomal protein SI 4 M15661 Ribosomal protein M17885 Acidic ribosomal phosphoprotein P0 M17886 Acidic ribosomal phosphoprotein PI Ml 8000 Ribosomal protein S 17 M31520 Ribosomal protein S24 M36072 Ribosomal protein L7a (surf 3) large subunit M60854 Ribosomal protein SI 6 M64716 Ribosomal protein S25 M77232 Ribosomal protein S6 M81757 S 19 ribosomal protein U09953 Ribosomal protein L9 U 12404 Csa-19 U 12465 Ribosomal protein L35 U 14968 Ribosomal protein L27a U14969 Ribosomal protein L28 U14970 Ribosomal protein S5 U14971 Ribosomal protein S9 U14972 Ribosomal protein S 10 U 14973 Ribosomal protein S29 U25789 Ribosomal protein L21 U58682 Ribosomal protein S28 U78027 L44L (L44-like ribosomal protein) X03342 Ribosomal protein L32 X06617 Ribosomal protein S 1 1 XI 5940 Ribosomal protein L31 XI 7206 LLRep3, 40S RIBOSOMAL PROTEIN S2 X52966 Ribosomal protein L35a X53777 L23 putative ribosomal protein X55715 Hums3 40S Ribosomal protein s3 X55954 HL23 ribosomal protein homologue X56932 23 kD highly basic protein X57959 Ribosomal protein L7 X62691 Ribosomal protein (homologuous to yeast S24) X63527 Ribosomal protein LI 9 X64707 BBC1 X67247 RpS8 gene for ribosomal protein S8 X69150 Ribosomal protein SI 8 X69391 Ribosomal protein L6 X69654 Ribosomal protein S26 X73460 Ribosomal protein L3 X79234 Ribosomal protein LI 1 Z 12962 Homologue to yeast Ribosomal protein L41 Z25749 Gene for ribosomal protein S7 Z26876 Ribosomal protein L38 Z28407 Ribosomal protein L8 Z49148 Ribosomal protein L29 M36341 ADP-ribosylation factor 4 (ARF4) M74491 ADP-ribosylation factor 3 M84332 ADP-ribosylation factor 1 U70439 Silver-stainable protein SSP29 X04526 Liver beta-subunit signal transducing proteins Gs/Gi (beta- G) D28915 Hepatitis C-associated microtubular aggregate protein p44 D38549 KIAA0068 HG1980- Tubulin, Beta 2 HT2023 HG2238- Nuclear Mitotic Apparatus Protein 1 Alt. Splice 2 HT2321 HG3514- Tropomyosin Tm30nm, Cytoskeletal HT3708 987-HT987 Mac25 LI 1373 Protocadherin 43, PC43 L14837 Tight junction (zonula occludens) protein ZO-1 M20471 Brain-type clathrin light-chain a mRNA M31013 Nonmuscle myosin heavy chain (NMHC) M33308 Vinculin mRNA M33680 26-kDa cell surface protein TAPA-1, CD81 ANTIGEN M55998 Alpha- 1 collagen type I gene, 3' end M57710 LgE-binding protein (epsilon-BP) M69066 Moesin M69181 Nonmuscle myosin heavy chain-B (MYH10) M96803 Ral beta-spectrin (SPTBN1) S54005 Thymosin beta-10 [, metastatic melanoma cell line, 453 nt] U03100 Alpha2(E)-catenin U24105 Coatomer protein (HEPCOP) U45976 Clathrin assembly protein lymphoid myeloid leukemia (CALM) U56637 Capping protein alpha subunit isoform 1 , F-actin capping protein alpha- 1 subunit (CAPZ) U57341 Neurofilament triplet L protein U60115 Skeletal muscle LIM-protein SLIM1 U83463 Scaffold protein Pbpl V00599 Beta-tubulin (from clone D-beta-1) X51521 Ezrin X53331 Matrix Gla protein X57398 PM5 protein X72964 Caltractin X82103 Beta-COP, coatomer protein X97074 MRNS for clathrin-associated protein Z19554 Vimentin Z24727 Tropomyosin isoform Z47038 Putative microtubule-associated; protein 1A (MAPI A) J03473 Poly(ADP-ribose) synthetase U09510 Glycyl-tRNA synthetase U43286 Selenophosphate synthetase 2 (SPS2) U79262 Deoxyhypusine synthase X76013 QRSHs glutaminyl-tRNA synthetase X91257 Seryl-tRNA synthetase X94754 Yeast methionyl-tRNA synthetase homologue Z47055 CDNA sequence farnesyl pyrophosphate synthetase like-4 HG1515- Transcription Factor Btf3b HT1515 HG4297- Transcriptional Coactivator Pc4 HT4567 L12168 Adenylyl cyclase-associated protein (CAP) L20298 Transcription factor (CBFB) L34587 RNA polymerase II elongation factor SIII, pi 5 subunit L49380 Transcription factor ZFM1 M81601 Transcription elongation factor (SII) M97935 Transcription factor ISGF-3 U 10323 Nuclear factor NF45 U14193 TFIIA gamma subunit mRNA U95040 Transcriptional corepressor hKAPl/TIFlB X52882 T-complex polypeptide 1 X80909 Alpha NAC Z47087 RNA polymerase II elongation factor-like protein D26535 Dihydrolipoamide succinyltransferase (exon 1-15) L10413 Farnesyltransferase alpha-subunit mRNA M24485 Glutathione S-transferase pi (GSTP1) U56417 Lysophosphatidic acid acyltransferase-alpha U90313 Glutathione-S-transferase homolog D13413 Tumor-associated 120 kDa nuclear protein pi 20 (carboxyl terminus) D61380 DJ-1 protein HGl 102- Ras-Related C3 Botulinum Toxin Substrate HT1102 HG3549- Wilm'S Tumor-Related Protein HT3751 HG4541 - Transformation-Related Protein HT4946 M15990 C-yes-1, Proto-oncogene tyrosine protein kinase YES M55409 Pancreatic tumor-related protein M8471 1 V-fos transformation effector protein (Fte-1) S79219 Metastasis-associated U50523 BRCA2 region sequence CG037 U57342 Myelodysplasia myeloid leukemia factor 2 (MLF2) V01512 Cellular onco c-fos ( sequence) XI 6064 Translationally controlled tumor protein X16416 C-abl encoding pi 50 protein, Proto-oncogene tyrosine protein kinase ABL X56681 JunD X67951 Proliferation-associated gene (pag) X72727 Tunp transformation upregulated nuclear protein X81817 BAP31, CDM Protein (6C6-AG Tumor associated antigen) D30655 Eukaryotic initiation factor 4AII J04617 Elongation factor EF- 1 -alpha L26247 Suilisol U46025 Translation initiation factor eIF-3 pi 10 subunit U62962 Int-6, Viral integration site protein INT-6 U94855 Translation initiation factor 3 47 kDa subunit X03689 Fragment elongation factor TU (N-terminus) X51466 Elongation factor 2 X55733 Initiation factor 4B X60489 Elongation factor- 1 -beta Z21507 EF- 1 delta gene encoding elongation factor- 1 -delta Z37166 BAT1 , nuclear RNA helicase (DEAD family) AB002533 Qipl AJ001421 Rerl protein J02683 ADP/ATP carrier protein J03592 ADP/ATP translocase, clone pHAT8 M28209 TGTP-binding protein (RAB 1 ) M34175 Beta adaptin mRNA U32944 Cytoplasmic dynein light chain 1 (hdlcl) U36341 SLC6A8 (creatine transporter) U41740 Trans-Golgi p230 U51478 Sodium potassium-transporting ATPase beta-3 subunit U61734 Protein trafficking protein (S31 Hi 125) U70660 Copper transport protein HAH 1 (HAH 1 ) X74104 TRAP beta subunit, Translocon-associated protein Y00281 Ribophorin I Y00282 Ribophorin II Z69043 Translocon-associated protein delta subunit precursor D23662 Ubiquitin-like protein LI 0284 Integral membrane protein calnexin (IP90) M26880 Ubiquitin M58028 Ubiquitin-activating enzyme El (UBE1) S79522 Ubiquitin carboxyl extension protein [ 540 nt] U39317 E2 ubiquitin conjugating enzyme UbcH5B (UBCH5B) U44839 Putative ubiquitin C-terminal hydrolase (UHX 1 ) U46751 Phosphotyrosine independent ligand p62 the Lck SH2 domain U49869 Ubiquitin X56997 UbA52 coding ubiquitin-52 amino acid fusion protein HG3214- Metallopanstimulin 1 HT3391 L 11672 Kruppel related zinc finger protein (HTF 10) M94046 Zinc finger protein (MAZ) X70394 OZF AC002045 A-589H1.2 from Chromosome 16 BAC clone CIT987-SKA- 589H1 D13641 KIAA0016 D14658 KIAA0102 D14662 KIAA0106 D 14694 KIAA0024 D14695 KIAA0025 D14812 KIAA0026 D21260 KIAA0034 D21261 KIAA0120 D21853 KIAA011 1 D25274 Unknown function D26068 KIAA0038 D29643 KIAA0115 D31767 KIAA0058 D31883 KIAA0059 D31890 KIAA0070 D42043 KIAA0084 D43950 KIAA0098 D63476 KIAA0142 D63477 KIAA0143 D63478 KIAA0144 D63878 KIAA0158 D63878 KIAA0158 D79986 KIAA0164 D79994 KIAA0172 D80005 KIAA0183 D84294 TPRDI, maps to Down's syndrome region D86963 KIAA0208 D86974 KIAA0220 D87451 KIAA0262 D87953 RTP, Tunicamycin responsive protein L20773 In the region near the btk involved in a-gamma-globulinemia L40391 Clone si 53 L40395 Clone S20iii 15 L40397 Clone S311125 S73591 VDUP1, vitamin D(3) up-regulated protein 1 S77356 Transcript ch21=oligomycin sensitivity conferral protein oscp homolog U34343 13kD differentiation-associated protein U72342 Platelet activating factor acetylhydrolase brain isoform 45 kDa subunit (LIS1) U79254 Clone 23693 U79294 Clone 23748 U81556 Hypothetical protein A4 U90909 Clone 23722 sequence X14684 La protein C-terminal region X15187 Tral homologue of murine tumor rejection antigen gp96 X62654 Me491/CD63 antigen gene X75861 TEGT, testis-enhanced gene transcript X80822 ORF X83416 PrP exon 2 Z11793 Selenoprotein P D86479 AEBP1 AB001 106 Glia maturation factor D13370 APX encoding APEX nuclease D 14043 MGC-24, mucin-like glycoprotein D63506 Unc-18homologue, Syntaxin binding protein D63851 Unc-18 homologue D78129 Adult (34 year old) Male liver squalene epoxidase HGl 869- Male Enhanced Antigen HT1904 HG2917- Major Histocompatibility Complex Class I E (Gb:M21533) HT3061 HG3342- Ldl HT3519 HG3597- Major Histocompatibility Complex Class I (Gb:X 12432) HT3800 HG3638- Amyloid Beta (A4) Precursor Protein, Alt. Splice 2, A4(751) HT3849 651-HT4201 Adducin, Alpha Subunit, Alt. Splice 2 J04456 14 kd lectin L09209 Amyloid protein homologue M13450 Esterase D M60858 Nucleolin M63483 Major nuclear matrix protein M86667 NAP (nucleosome assembly protein) U01691 Annexin V (ANX5) gene, 5' -untranslated region U06155 Chromosome lq subtelomeric sequence D1S553 U11861 G10 homolog (edg-2) U35048 TSC-22 protein U41635 OS -9 precursor U46570 Tetratricopeptide repeat protein (tprl) U50733 Dynamitin mRNA U62317 Hypothetical protein 384D8 2 extracted from Chromosome 22ql3 U73824 P97 V00594 Metallothionein from cadmium-treated cells X66397 Tpr X73358 HAES-1, GRG protein (ESP1 protein) -Amino enhancer of split X76534 NMB X77584 ATL(Adult T cell leukemia)-derived factor/thioredoxin X80199 MLN51 X80200 MLN62 X82456 MLN50 X87838 Beta-catenin X96484 DGCR6 protein X98482 TNNT2 (troponin) Y00264 Amyloid A4 precursor of Alzheimer disease Y00433 Glutathione peroxidase Z35093 SURF-1 Z93784 Mouse Brain Protein E46 like sequences ESTs and evaluating said expression of said gene in said plurality of samples using the expression of said at least three maintenance genes. 10. The method of Claim 9 wherein said at least three maintenance genes comprise at least five maintenance genes selected from said group. 11. The method of Claim 10 wherein said at least five maintenance genes comprise at least ten maintenance genes selected from said group. 12. The method of Claim 9 wherein said evaluating comprises calculating expression ratio of said gene over said maintenance genes.

Inventors: MAHADEVAPPA MAMATHA, NAIR ARCHANA, WARRINGTON JANET A, MAHADEVAPPA, MAMATHA, NAIR, ARCHANA, WARRINGTON, JANET, A.
Applicants: AFFYMETRIX INC, MAHADEVAPPA MAMATHA, NAIR ARCHANA, WARRINGTON JANET A, AFFYMETRIX, INC., MAHADEVAPPA, MAMATHA, NAIR, ARCHANA, WARRINGTON, JANET, A.
Application year: 2000
Main classification: C12Q1
IPC codes: C07H21, C07K14, C12Q1