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

ABSTRACT:

Background

Monogenic 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.

Results

Introgression of polyQ40 into three wild genetic backgrounds uncovered wide variation in onset of aggregation and corresponding toxicity, as well as alteration in the

SUBMITTER: Gidalevitz T 

PROVIDER: S-EPMC3816611 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature