A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes

Academic Article

Abstract

  • The Huntington's disease (HD) gene has been mapped in 4p16.3 but has eluded identification. We have used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect. A new gene, 1715, isolated using cloned trapped exons from the target area contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from all 75 disease families examined, comprising a variety of ethnic backgrounds and 4p 16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted ≈348 kd protein that is widely expressed but unrelated to any known gene. Thus, the HD mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype. © 1993.
  • Digital Object Identifier (doi)

    Author List

  • MacDonald ME; Ambrose CM; Duyao MP; Myers RH; Lin C; Srinidhi L; Barnes G; Taylor SA; James M; Groot N
  • Start Page

  • 971
  • End Page

  • 983
  • Volume

  • 72
  • Issue

  • 6