Genome-wide profiling of gene expression in 29 normal human tissues with a cDNA microarray.

We have performed a comprehensive analysis of the expression profiles in 25 adult and 4 fetal human tissues by means of a cDNA microarray consisting of 23,040 human genes. This study revealed a number of genes that were expressed specifically in each of those tissues. Among the 29 tissues examined, 4,080 genes were highly expressed (at least a five-fold expression ratio) in one or only a few tissues and 1,163 of those were expressed exclusively (more than a ten-fold higher expression ratio) in a particular tissue. Expression of some of the genes in the latter category was confirmed by northern analysis. A hierarchical clustering analysis of gene-expression profiles in nerve tissues (adult brain, fetal brain, and spinal cord), lymphoid tissues (bone marrow, thymus, spleen, and lymph node), muscle tissues (heart and skeletal muscle), or adipose tissues (mesenteric adipose and mammary gland) identified a set of genes that were commonly expressed among related tissues. These data should provide useful information for medical research, especially for efforts to identify tissue-specific molecules as potential targets of novel drugs to treat human diseases.

[1]  J. Boulter,et al.  α-Fetoprotein and Albumin gene expression in brain and other tissues of fetal and adult rats , 1985 .

[2]  A. Kahn,et al.  Molecular mechanisms of McArdle's disease (muscle glycogen phosphorylase deficiency). RNA and DNA analysis. , 1987, The Journal of clinical investigation.

[3]  A. Kerlavage,et al.  Complementary DNA sequencing: expressed sequence tags and human genome project , 1991, Science.

[4]  T. Morisaki,et al.  Molecular basis of AMP deaminase deficiency in skeletal muscle. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Colten,et al.  Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. , 1993, The New England journal of medicine.

[6]  M. Dalakas,et al.  Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  X. Estivill,et al.  Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine , 1994, Nature Genetics.

[8]  J. Weissenbach,et al.  Localization of a gene causing cystinuria to chromosome 2p , 1994, Nature Genetics.

[9]  Christine E. Seidman,et al.  α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: A disease of the sarcomere , 1994, Cell.

[10]  F. Baas,et al.  Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis , 1995, Human mutation.

[11]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[12]  M. Matsuzaki,et al.  Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy , 1997, Nature Genetics.

[13]  Y. Nakamura,et al.  Isolation and characterization of a novel human lung-specific gene homologous to lysosomal membrane glycoproteins 1 and 2: significantly increased expression in cancers of various tissues. , 1998, Cancer research.

[14]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[16]  A. Børglum,et al.  α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy , 1999 .

[17]  L. Larsson,et al.  The basic region/helix – loop – helix/leucine zipper domain of Myc proto-oncoproteins: Function and regulation , 1999, Oncogene.

[18]  J. Cha,et al.  Identification of Transacting Factors Responsible for the Tissue-specific Expression of Human Glucose Transporter Type 2 Isoform Gene , 2000, The Journal of Biological Chemistry.

[19]  K Shimizu,et al.  BodyMap: a collection of 3' ESTs for analysis of human gene expression information. , 2000, Genome research.

[20]  M. Yacoub,et al.  Identification of cis-acting DNA elements required for expression of the human cardiac troponin I gene promoter. , 2000, Journal of molecular and cellular cardiology.

[21]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[22]  T Tanaka,et al.  Identification by cDNA microarray of genes involved in ovarian carcinogenesis. , 2000, Cancer research.

[23]  D. Nettelbeck,et al.  Gene therapy: designer promoters for tumour targeting. , 2000, Trends in genetics : TIG.

[24]  D. Botstein,et al.  A gene expression database for the molecular pharmacology of cancer , 2000, Nature Genetics.

[25]  A. V. van Kampen,et al.  Cloning of tissue-specific genes using serial analysis of gene expression and a novel computational substraction approach. , 2001, Genomics.

[26]  P. Wade.  Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. , 2001, Human molecular genetics.

[27]  T. Takagi,et al.  Alterations of gene expression during colorectal carcinogenesis revealed by cDNA microarrays after laser-capture microdissection of tumor tissues and normal epithelia. , 2001, Cancer research.

[28]  T Tanaka,et al.  Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles. , 2001, Cancer research.

[29]  Seth Blackshaw,et al.  Comprehensive Analysis of Photoreceptor Gene Expression and the Identification of Candidate Retinal Disease Genes , 2001, Cell.

[30]  T. Tsunoda,et al.  Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. , 2001, Cancer research.