Genetic Susceptibility to Biliary Atresia

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): This is a proposal to identify genetic susceptibility factors for biliary atresia (BA). BA is a devastating pediatric disease associated with medical complications related to a rapidly developing biliary cirrhosis that accounts for 50% of all pediatric liver transplantations. The etiology of BA is unknown, although it is proposed to be multi-factorial, with potential infectious, environmental, inflammatory and genetic causes. In the proposed study, we will test the hypothesis that there is an underlying genetic susceptibility to BA. We will identify susceptibility genes for BA using a large, well-characterized cohort of patients that has been identified through an NIDDK sponsored research consortium. We will conduct a genome-wide association study, testing for association of genetic variation (both single nucleotide polymorphisms and copy number variants) to identify genes or genomic regions associated with BA disease susceptibility. We will perform exome sequencing of a family with two affected and one unaffected sibling, and three additional unrelated BA patients. We will follow up on regions and genes identified, via next generation sequencing to identify causal variants. This proposal will build upon the resources of a large multi-center consortium and our own cutting-edge genomic and bioinformatic facilities. We anticipate that our studies will contribute new knowledge about the biologic pathogenesis of BA and will lead to the development of rationale therapeutics and diagnostics.