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The human genome encodes instructions for which genes are expressed in what cell type, along with other molecules that control how much and when these genes are expressed. Variation in the regulation of gene expression gives rise to the diverse tissue types, with diverse functions, in the human body. Finding new clues about the molecular origins of disease is the goal for a comprehensive atlas of variation in gene expression published this week in Nature and Nature Genetics.

“Finding associations between genetic variation and gene expression in healthy tissue could help us to identify the genes and mechanisms that underlie human-disease-associated variation,” said Christopher Brown, PhD, an assistant professor of Genetics, in the Perelman School of Medicine at the University of Pennsylvania. Penn is one of four core collaborating institutions — along with Princeton, Johns Hopkins University, and Stanford — on the Nature paper. Brown, a co-lead author, has been involved with this project for the past four years.

The Nature paper describes data generated by the Genotype Tissue Expression (GTEx) consortium, which collected and studied more than 7,000 post-mortem samples representing 42 distinct tissue types from over 400 healthy donors. The samples comprise 31 solid-organ tissues, ten brain regions, whole blood, and two cell lines from donor blood and skin.

The Broad Institute of MIT and Harvard University sequenced all of the tissue samples, while the analysis of the data has been spread out among many organizations. Brown’s group developed methods to identify genetic factors that cause changes in gene expression and to eventually relate that to human disease.

Penn labs have already used the freely available GTEx data to explore how genetic variants found in genome-wide association studies relate to disease risk. The findings of the Nature paper allow researchers to see how a particular gene variant might generate risk for conditions such as cardiovascular disease or diabetes. They can ask, for instance, if a disease-associated variant causes too much or too little of a certain protein to be made. So far Penn researchers have been mining GTEx to find genes important in driving chronic kidney disease and metabolic diseases, among other disorders.

This work was funded in part by the National Institutes of Health (R01MH101822).

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Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

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