Whole-genome sequencing of rare disease patients in a national healthcare system

In my talk, I will describe three recently completed research projects I have led or co-led. Firstly, I will describe a genetic association method for rare Mendelian diseases called BeviMed. Secondly, I will present the results of the analyses of whole-genome sequencing (WGS) data for 13,037 participants in an NIHR-funded study, of whom 9,802 had a rare disease. Briefly, we provided a genetic diagnosis to 1,138 patients, we identified 99 BeviMed associations between genes and rare diseases, we showed that rare alleles can explain the presence of some UK Biobank participants in the tails of a quantitative red blood cell trait, and we reported 4 novel non-coding variants which cause disease through the disruption of transcription. Finally, I will describe our analysis of mitochondrial DNA sequences, generated as a by-product of WGS, suggesting that mitochondrial DNA is under selective forces exerted by the nuclear genome.