The sequencing of the complete human genome in 2001 was a remarkable achievement. For the first time, researchers could pore over a consensus sequence of an average human, describing many of the genes that make us tick. Differences from this consensus are thought to contribute to the pantheon of human variation that makes each of us uniquely ourselves, from our eye or hair color, to our height and shape and even our likelihood of developing various diseases.
But interpreting exactly which, and how, each of those differences bring about these outcomes has been difficult, particularly when the genetic differences occur not in the coding regions of genes, but instead in the surrounding regulatory regions that control their expression.
Furthermore, some genes are expressed only in particular tissue types and not others, making them challenging to study.
In 2010, scientists from around the country banded together at the urging of the National Institutes of Health to better understand how variations in an individual’s DNA sequence affect whether, where, how and when specific genes are expressed in tissues throughout the body. The collaborative effort, known as the Genotype-Tissue Expression, or GTEx project, aims to learn at the most basic level how and why individuals differ. The knowledge is likely to transform our understanding of disease and eventually change the way medicine is practiced, researchers believe.
“We’ve known for years that certain genetic variants confer increased risk for a variety of diseases,” said Stephen Montgomery, PhD, assistant professor of pathology and of genetics at the Stanford University School of Medicine, “but until now we didn’t know in which tissues these variants exerted their effects. As genes vary in their levels of expression or activity among the many tissues of the human body, we’ve now been able to identify where variants exert their effects and connect this variation to complex human traits and diseases.”
The project is supported by the National Institute of Health’s Common Fund, which is meant to address challenging, high-priority biomedical problems outside the scope of any one institute alone, but that, when solved, will benefit researchers throughout the field. Researchers from 30 institutions across the country and around the world collaborated as part of the GTEx consortium over the past seven years.