The Non-coding Genome and Cardiovascular Disease

The genetic bases of cardiovascular disease are well established in many instances throughout the studied pedigrees and populations despite a wild spectrum of phenotypes. The map of the genes and subsequently their variants that potentially affect these phenotypes is still however very primitive and the pieces of the puzzle not well connected. One of the main reasons behind this paucity in knowledge is pertaining to the fact that only 1% of the human genome that code for a protein is being considered important whereas the 99% remaining non-coding DNA sequences are neglected. With the emerging world of small RNA molecules (miRNAs and lncRNAs), it is of utmost importance to include these and other genomic sequences in any global analysis assessing the genotype/phenotype paradigm of cardiovascular disease. Next generation sequencing (NGS) has helped in many venues to put the pieces of the puzzle together, and with the steady decrease in the cost of human genome sequencing, we hope that more insight into the basis of these diseases will be gained. In addition, the unraveling of these black boxes in the genome will pave the way towards a better understanding of the evolutionary paths that govern organogenesis in general and adaptation of humans to the environment on the planet. In the following series of articles, we will try to explore the current challenges presenting to the cardiovascular genetics field in general in terms of successful and failed attempt to map genetic variants, and to explore potential hits found in studies using GWAS, homozygosity mapping, and whole genome sequencing (WGS). We will also explore the potential roles of these non-coding RNAs in developing therapeutic strategies to mitigate pathological cardiac remodeling and to ameliorate cardiovascular disease.