The link between inherited DNA variation and numerous diseases has been well established, but an important question still looms – What are the precise mechanisms linking genetic variation to disease? Despite decades of research and the development of sophisticated tools, important gaps remain in understanding human genetic processes, which vary widely across the organs and tissues of the body.

[Photo: Pictured is a small DNA sequence, on display in the London Museum of Science. One way to think of DNA is as the ‘controller of a giant genetic switchboard,’ said UNC biostatistician Dr. Andrew Nobel. “When DNA switches on a gene, the gene produces proteins with specific functions,” he said. “In the case of many common diseases, even small changes in protein output can have profound effects upon disease risk.” Photo by John Goode (©2005)]

Described in an article published May 8 in the journal Science, the Genotype-Tissue Expression (GTEx) project, funded by the National Institutes of Health, aims to fill these gaps by looking at ways genetic variation affects gene expression.

Dr. Andrew Nobel, professor of biostatistics at The University of North Carolina at Chapel Hill’s Gillings School of Global Public Health and study co-author, said the research is analogous to deciphering genetic “recipes.”

“Our DNA acts like a cookbook, containing recipes for distinct tissues – such as skin, blood, lung, heart and brain – which we all share,” said Dr. Nobel, who is also professor of statistics and operations research in the UNC College of Arts and Sciences. “Unlike an ordinary cookbook, the recipes in DNA have been broken up into microscopic instructions and spread throughout our chromosomes. Some of these instructions are unique to specific tissues or tissue groups, while others are shared by most, or all, tissues. Understanding how different genetic instructions are carried out in different tissues is an important scientific problem, and an important first step in understanding mechanisms that link genetic variation and disease.’’

Dr. Fred Wright, professor of statistics and biological sciences at N.C. State University and study co-author, agreed.

“We have little understanding of how genetic variants actually cause disease because we haven’t been able to look at the gene expression part of the equation,” Dr. Wright said. “GTEx aims to fill the knowledge gap between the DNA you’re born with and actual disease outcomes.”

Read more: https://sph.unc.edu/sph-news/new-gtex-project-tackles-dnas-genetic-switchboard/