Findings reveal new insights into how DNA differences influence gene activity

Researchers funded by the National Institutes of Health Genotype-Tissue Expression (GTEx) project, including scientists from the Broad Institute of MIT and Harvard, have created a new and much-anticipated data resource to help establish how differences in an individual’s genomic make-up can affect gene activity and contribute to disease. The new resource will enable scientists to examine the underlying genomics of many different human tissues and cells at the same time, and promises to open new avenues to the study and understanding of human biology.
GTEx investigators reported initial findings from a two-year pilot study in several papers. These efforts provide new insights into how genomic variants – inherited spelling differences in the DNA code – control how, when, and how much genes are turned on and off in different tissues, and can predispose people to diseases such as cancer, heart disease, and diabetes.

“GTEx was designed to sample as many tissues as possible from a large number of individuals in order to understand the causal effects of genes and variants, and which tissues contribute to predisposition to disease,” said Emmanouil Dermitzakis, Ph.D., professor of genetics at the University of Geneva Faculty of Medicine, Switzerland, and a corresponding author. “The number of tissues examined in GTEx provides an unprecedented depth of genomic variation. It gives us unique insights into how people differ in gene expression in tissues and organs.”

NIH launched the GTEx Project in 2010 to create a data resource and tissue bank for scientists to study how genomic variants may affect gene activity and disease susceptibility. Investigators are collecting more than 30 tissue types from autopsy and organ donations in addition to tissue transplant programs. The DNA and RNA from those samples are then analysed using cutting-edge genomic methods. The project will eventually include tissue samples from about 900 deceased donors.

“GTEx will be a great resource for understanding human biological function, and will have many practical applications in areas such as drug development,” said NHGRI Program Director Simona Volpi, Pharm.D., Ph.D. “Scientists studying asthma or kidney cancer, for example, will be interested in understanding how specific variants influence the biological function of the lung, kidney, and other organs.” Broad Institute