PIs: Gregory A. Wray, Devjanee Swain-Lenz (Duke University)
Fall 2019 Seed Grant in Innovative Evolutionary Medicine
A central objective of evolutionary medicine is to understand how evolutionary mechanisms operate on the mutations that cause disease. Genes have two parts: the region that encodes a protein and one or more regions that regulate when, where, and under what conditions the gene is expressed. During the past decade, it has become clear that most mutations that cause common diseases do so by influencing gene expression. Unlike genetic mutations in rare diseases that create defective proteins, we cannot currently predict the effect of a mutation that regulates gene expression. One reason is that the relationship between noncoding mutations and gene expression is considerably more complex than in coding regions. Recent technological advances make it possible to directly measure the effects of mutations in thousands of regulatory regions on gene expression, providing the ability to understand this relationship. Most experiments using this technology have been performed in humans and have ignored the evolutionary origins of genetic variation. To better understand how evolutionary mechanisms operate on mutations that influence gene expression, we will use high-throughput technology to measure the function of tens of thousands of cis-regulatory elements in five primate species. We will use novel bioinformatic analyses to identify features that change cis-regulatory function, adding to our knowledge of the genetic basis for disease.
| next >