A Comprehensive Haplotype-Targeting Strategy for Allele-Specific HTT Suppression in Huntington Disease.

ABSTRACT: Huntington disease (HD) is a fatal neurodegenerative disorder caused by a gain-of-function mutation in HTT. Suppression of mutant HTT has emerged as a leading therapeutic strategy for HD, with allele-selective approaches targeting HTT SNPs now in clinical trials. Haplotypes associated with the HD mutation (A1, A2, A3a) represent panels of allele-specific gene silencing targets for efficient treatment of individuals with HD of Northern European and indigenous South American ancestry. Here we extend comprehensive haplotype analysis of the HD mutation to key populations of Southern European, South Asian, Middle Eastern, and admixed African ancestry. In each of these populations, the HD mutation occurs predominantly on the A2 HTT haplotype. Analysis of HD haplotypes across all affected populat

SUBMITTER: Kay C 

PROVIDER: S-EPMC6904807 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature