Decoding the heart: mining of the regulatory genome

MR Ramialison

Australian Regenerative Medicine Institute, Monash University

1% of Australian babies are born with Congenital Heart Disease (CHD), manifesting as anatomical heart defects that are detrimental for the newborn. Despite its prevalence, the aetiology of more than 80% of CHD cases remains unknown, making diagnosis and evaluation of the risk of the disease inheritance difficult. Our team has a long-standing interest in identifying the specific gene sets required for the formation of a healthy heart based on the principle that perturbations in these genes will impair normal development, resulting in anatomical cardiac defects. Thousands of genes are expressed in the heart at any given time point during development, but which of these genes are critical for heart formation and play a significant role in CHD? To address this, we designed bioinformatic pipelines to identify novel players in three layers of the cardiac gene regulatory network (kernel, downstream effectors and cis-regulatory modules). These bioinformatic pipelines offer the prospect of identifying new genes essential for cardiogenesis, irrespective of their expression pattern.