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

Harry T. Orr, Ming yi Chung, Sandro Banfi, Thomas J. Kwiatkowski, Antonio Servadio, Arthur L. Beaudet, Alanna E. McCall, Lisa A. Duvick, Laura P.W. Ranum, Huda Y. Zoghbi

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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.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNature Genetics
Volume4
Issue number3
DOIs
StatePublished - Jul 1993

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    Orr, H. T., Chung, M. Y., Banfi, S., Kwiatkowski, T. J., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., & Zoghbi, H. Y. (1993). Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genetics, 4(3), 221-226. https://doi.org/10.1038/ng0793-221