Exome sequencing the expert view.docVIP

Biesecker et al. Genome Biology 2011,12:128 /2011/12/9/128 OPINION Exome sequencing: the expert view Leslie G Biesecker *, Kevin V Shianna and Jim C Mullikin 1 2 3 samples analyzed by whole exome sequencing (WES) or one by whole genome sequencing (WGS)?’ Our current, fully loaded price for a WGS is six times that of a WES assay – a ratio that has changed surprisingly little in the past 2 years. Which study one should use depends on the biomedical question that is being asked. If it is primarily a genotype-phenotype question, and the putative variant is high penetrance, then it is crucial to increase our statistical power by increasing our N, so exomes provide a big advantage here. If the question is di?erent, it could be that a smaller number of WGS interrogations would be more e?ective. WES and WGS are tools – one has to Abstract To complement our special issue on exome sequencing, Genome Biology asked several leaders in the eld for their views on this new approach. Leslie G Biesecker (LGB), Jim C Mullikin (JM) and Kevin V Shianna (KVS) discuss the reasons for the popularity of exome sequencing and its contribution to genomics. How can exome sequencing contribute to our understanding of the dynamic nature of the genome? LGB, JCM: Exomes are ideal to help us understand high- select the optimal tool considering the biomedical penetrance allelic variation and its relationship to phenotype. Because exomes focus on exons, which include coding regions of genes, and because most high- question and the available resources. KVS: e lower cost of exome sequencing is probably the primary driver for its increased use, but a related and penetrance (Mendelian or nearly so) variation is equally important factor is how much longer it takes to mediated by non-synonymous, fram