Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content.

ABSTRACT: Dynamic expansions of toxic polyglutamine (polyQ)-encoding CAG repeats in ubiquitously expressed, but otherwise unrelated, genes cause a number of late-onset progressive neurodegenerative disorders, including Huntington disease and the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with repeat length, the intergenerational expansion of unstable CAG repeats leads to anticipation, an earlier age-at-onset in successive generations. Crucially, disease associated alleles are also somatically unstable and continue to expand throughout the lifetime of the individual. Interestingly, the inherited polyQ length mediating a specific age-at-onset of symptoms varies markedly between disorders. It is widely assumed that these inter-locus differences in polyQ toxicity are mediate

SUBMITTER: Nestor CE 

PROVIDER: S-EPMC3232215 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature