Clinical PhD Programme at Imperial College London: 'Gene and variant discovery of inherited cardiac conditions'. (360G-Wellcome-092854_Z_10_Z)

Heart failure is a major cause of morbidity and mortality in humans. A substantial proportion of dilated heart failure results from idiopathic dilated cardiomyopathy (IDC) which is characterised by left ventricular dilatation and systolic dysfunction after known causes have been excluded. IDC may be familial in up to 50% of cases and over 40 causative genes have been identified, however a cause is found in only 20-30% of cases. The goal of my research is to increase understanding of heart failure pathogenesis using IDC as a model and to contribute to the development of more effective, specific and safer treatments. I plan to harness the power of new target enrichment technologies coupled with new high throughput sequencing technologies to investigate candidate genes and for whole exome studies that would not be feasible using conventional sequencing in large cohorts of well phenotyped patients. Direct sequencing of exomes has been shown to be an elegant and efficient way of searching for the causative gene for monogenic disorders. I will prioritise large pedigrees with severe or early onset disease for investigation as cohorts with extreme phenotypes are likely to be enriched for rare variants consequently increasing the likelihood of their discovery.