Olorin: combining gene flow with exome sequencing in large family studies of complex disease

摘要

>Motivation: The existence of families with many individuals affected by the same complex disease has long suggested the possibility of rare alleles of high penetrance. In contrast to Mendelian diseases, however, linkage studies have identified very few reproducibly linked loci in diseases such as diabetes and autism. Genome-wide association studies have had greater success with such diseases, but these results explain neither the extreme disease load nor the within-family linkage peaks, of some large pedigrees. Combining linkage information with exome or genome sequencing from large complex disease pedigrees might finally identify family-specific, high-penetrance mutations.>Results: Olorin is a tool>, which integrates gene flow within families with next generation sequencing data to enable the analysis of complex disease pedigrees. Users can interactively filter and prioritize variants based on haplotype sharing across selected individuals >and other measures of importance, including predicted functional consequence and population frequency.>Availability: >Contact: