Natural genetic variation determines susceptibility to aggregation or toxicity in a C. elegans model for polyglutamine disease

摘要

BackgroundMonogenic gain-of-function protein aggregation diseases, including Huntington’s disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. This difference in phenotypic expression of proteotoxic mutations is proposed to be due, at least in part, to the variability in genetic background. To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model.