A genome-wide in vitro bacterial-infection screen reveals human variation in the host response associated with inflammatory disease.

ABSTRACT: Recent progress in cataloguing common genetic variation has made possible genome-wide studies that are beginning to elucidate the causes and consequences of our genetic differences. Approaches that provide a mechanistic understanding of how genetic variants function to alter disease susceptibility and why they were substrates of natural selection would complement other approaches to human-genome analysis. Here we use a novel cell-based screen of bacterial infection to identify human variation in Salmonella-induced cell death. A loss-of-function allele of CARD8, a reported inhibitor of the proinflammatory protease caspase-1, was associated with increased cell death in vitro (p = 0.013). The validity of this association was demonstrated through overexpression of alternative alleles and RNA i

SUBMITTER: Ko DC 

PROVIDER: S-EPMC2725265 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature