Whole genome sequencing (WGS) technology and analysis is quickly approaching the stage of development where it can become a medically recognized procedure for prognostics as well as diagnostics. Critical to the development of medical-grade whole genome sequencing is the ability to recognize and minimize technological and biological variation in WGS data. The Inova Translational Medicine Institute (ITMI) has completed a study that generated 1500 whole genome sequences in 15 months and recently launched a study that will generate 20,000 WGS over the next two years. The 1500 sequenced genomes were from individuals from 53 countries, representing four major ancestral groups and many minor sub-groups. ITMI used these data to generate a database of ancestral-specific variants. This database can be used to identify single nucleotide variants in patients with a specific ancestral background as ancestral-specific sequences instead of mutations. This ancestral information was applied to the 487 cancer genes identified in the Wellcome Trust Sanger Institute's Cancer Gene Census, in an attempt to identify germline mutations in these genes, in our cohort of 1500 participants. The result of this analysis identifies the incidence and type of germline mutations in various ethnic groups. The ethical question that remains is what to do with incidental finding of this type as medical whole genome sequencing becomes a common tool in the practice of medicine.

Citation Format: Joseph Vockley, Ramaswamy Iyer, Kathi Huddleston, John Niederhuber. Large-scale familial whole genome sequencing to evaluate genetic risk. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA18.

©2012 American Association for Cancer Research.
2012