Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I

Nat Genet. 1993 Nov;5(3):254-8. doi: 10.1038/ng1193-254.


Spinocerebellar ataxia type I (SCAI) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat on chromosome 6p. Normal alleles range from 19-36 repeats while SCA1 alleles contain 43-81 repeats. We now show that in 63% of paternal transmissions, an increase in repeat number is observed, whereas 69% of maternal transmissions showed no change or a decrease in repeat number. Sequence analysis of the repeat from 126 chromosomes reveals an interrupted repeat configuration in 98% of the unexpanded alleles but a contiguous repeat (CAG)n configuration in 30 expanded alleles from seven SCA1 families. This indicates that the repeat instability in SCA1 is more complex than a simple variation in repeat number and that the loss of an interruption predisposes the SCA1 (CAG)n to expansion.

Publication types

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

MeSH terms

  • Base Sequence
  • Cell Line
  • Chromosomes, Human, Pair 6
  • DNA
  • DNA Primers
  • Genes, Dominant
  • Genetic Variation
  • Humans
  • Molecular Sequence Data
  • Repetitive Sequences, Nucleic Acid*
  • Spinocerebellar Degenerations / genetics*


  • DNA Primers
  • DNA