Genetic variation in the non-coding genome and cardiovascular disease

Our DNA contains instructions on how to build our cardiovascular system. In addition to coding for proteins that contribute to assemble the heart and the vessels, the genome also contain instructions on when and where these proteins are to be made. Thousands of non-coding regions of the genome act like switches to generate the precise patterns of gene expression, which instruct formation of the cardiovascular system. Similar to mutations in coding regions, inherited DNA sequence variants in these regulatory regions cause conditions such as congenital heart disease or risk to develop disease later in life. However they have remained largely unexplored because clinical diagnostic sequencing currently focuses on identifying disease-causing mutations in coding regions. In this project, we will generate, analyze and integrate maps of chromatin landscapes from developmental time courses of mouse and human embryogenesis to identify non-coding regulatory mutations, and characterize their effects both in vitro and in vivo. This study will help clarifying the basis of human cardiovascular pathology and enable a better understanding and diagnostic solutions for currently unexplained genetic disorders.