Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1

Nat Genet. 1993 Jul;4(3):221-6. doi: 10.1038/ng0793-221.


Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder characterized by neurodegeneration of the cerebellum, spinal cord and brainstem. A 1.2-Megabase stretch of DNA from the short arm of chromosome 6 containing the SCA1 locus was isolated in a yeast artificial chromosome contig and subcloned into cosmids. A highly polymorphic CAG repeat was identified in this region and was found to be unstable and expanded in individuals with SCA1. There is a direct correlation between the size of the (CAG)n repeat expansion and the age-of-onset of SCA1, with larger alleles occurring in juvenile cases. We also show that the repeat is present in a 10 kilobase mRNA transcript. SCA1 is therefore the fifth genetic disorder to display a mutational mechanism involving an unstable trinucleotide repeat.

Publication types

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

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6
  • Cloning, Molecular
  • DNA / genetics
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / genetics
  • Pedigree
  • Polymerase Chain Reaction
  • Repetitive Sequences, Nucleic Acid*
  • Spinocerebellar Degenerations / genetics*
  • Transcription, Genetic


  • Oligodeoxyribonucleotides
  • DNA