Exome-based mapping and variant prioritization for inherited Mendelian disorders.

ABSTRACT: Exome sequencing in families affected by rare genetic disorders has the potential to rapidly identify new disease genes (genes in which mutations cause disease), but the identification of a single causal mutation among thousands of variants remains a significant challenge. We developed a scoring algorithm to prioritize potential causal variants within a family according to segregation with the phenotype, population frequency, predicted effect, and gene expression in the tissue(s) of interest. To narrow the search space in families with multiple affected individuals, we also developed two complementary approaches to exome-based mapping of autosomal-dominant disorders. One approach identifies segments of maximum identity by descent among affected individuals; the other nominates regions on t

SUBMITTER: Koboldt DC 

PROVIDER: S-EPMC3951946 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature