A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group

Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.

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, IT15, 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 4p16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 4
  • Cloning, Molecular
  • Exons
  • Gene Expression
  • Genes
  • Humans
  • Huntington Disease / genetics*
  • Molecular Sequence Data
  • Mutation
  • Oligodeoxyribonucleotides / chemistry
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA, Messenger / genetics
  • Repetitive Sequences, Nucleic Acid
  • Restriction Mapping

Substances

  • Oligodeoxyribonucleotides
  • RNA, Messenger

Associated data

  • GENBANK/L09219
  • GENBANK/L09220
  • GENBANK/L09221
  • GENBANK/L09222
  • GENBANK/L09223
  • GENBANK/L09224
  • GENBANK/L09225
  • GENBANK/L11016
  • GENBANK/L12392
  • GENBANK/L33709