A DNA Microarray Survey of Gene Expression in Normal Human Tissues

Radha Shyamsundar1,2, Young H. Kim1, John P. Higgins1, Kelli Montgomery1, Michelle Jorden1, Anand Sethuraman3,
Matt van de Rijn1, David Botstein3,#, Patrick O. Brown2,4,*, and Jonathan R. Pollack1,*
Department of 1Pathology, 2Biochemistry, 3Genetics, and 4Howard Hughes Medical Institute, Stanford University, Stanford, CA.
# Current address: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ.

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ABSTRACT

Numerous studies have used DNA microarrays to survey gene expression in cancer and other disease states. Comparatively little is known about the genes expressed across the gamut of normal human tissues. Systematic studies of global gene expression patterns, by linking variation in the expression of specific genes to phenotypic variation in the cells or tissues in which they are expressed, provide clues to the molecular organization of diverse cells and to the potential roles of the genes. Here, we describe a systematic survey of gene expression in 115 human tissue samples representing 35 different tissue types, using cDNA microarrays representing ~26,000 different human genes. Unsupervised hierarchical cluster analysis of the gene expression patterns in these tissues identified clusters of genes with related biological functions and grouped the tissue specimens in a pattern that reflected their anatomic locations, cellular compositions, or physiologic functions. In unsupervised and supervised analyses, tissue-specific patterns of gene expression were readily discernable. By comparative hybridization to normal genomic DNA, we were also able to estimate transcript abundances for expressed genes. Our dataset provides a baseline for comparison to diseased tissues, and will aid in the identification of tissue-specific functions. In addition, our analysis identifies potential molecular markers for detection of injury to specific organs and tissues, and provides a foundation for selection of potential targets for selective anti-cancer therapy.


Jon Pollack's Lab

Pat Brown's Lab

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*Address correspondence to Patrick O. Brown, M.D., Ph.D., Department of Biochemistry and the Howard Hughes Medical Institute, Stanford University School of Medicine, 279 Campus Drive, Beckman B439, Stanford, CA 94305-5307, pbrown@cmgm.stanford.edu; or to Jonathan R. Pollack,M.D., Ph.D., Department of Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 3245A, Stanford, CA 94305-5176, pollack1@stanford.edu.

This work was supported by a grant from the National Cancer Institute. P.O.B is an investigator of the Howard Hughes Medical Institute.