title: Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
authors.forename: M Y
authors.initials: MY
authors.lastname: Chung
authors.forename: S
authors.initials: S
authors.lastname: Banfi
authors.forename: T J
authors.initials: TJ
authors.lastname: Kwiatkowski
authors.forename: A
authors.initials: A
authors.lastname: Servadio
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: A E
authors.initials: AE
authors.lastname: McCall
authors.forename: L A
authors.initials: LA
authors.lastname: Duvick
authors.forename: L P
authors.initials: LP
authors.lastname: Ranum
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA