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Cited by 1,632Genetic Neurodegenerative DiseasesGenetic factors in colorectal cancerGenetics and Neurodevelopmental Disorders

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

Orr, Harry T., Chung, Ming-yi, Banfi, Sandro, Kwiatkowski, Thomas J., Servadio, Antonio, Beaudet, Arthur L., McCall, Alanna E., Duvick, Lisa A., Ranum, Laura P. W., Zoghbi, Huda Y.·1993·Nature Genetics
DOI 10.1038/ng0793-221
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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.

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Metadata

Authors
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.
Affiliations
  • University of Minnesota (US)
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
1993-07
Volume
4
Issue
3
Pages
221-226
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng0793-221
OpenAlex
W2255469197
Cited by
1,632
References
0
Citations by year
2026: 20 · 2025: 24 · 2024: 30 · 2023: 37 · 2022: 45 · 2021: 35 · 2020: 41 · 2019: 27 · 2018: 42 · 2017: 35 · 2016: 23 · 2015: 19 · 2014: 41 · 2013: 50 · 2012: 34
FWCI
40.91
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
spinocerebellar ataxia type 1, CAG repeat expansion, trinucleotide repeat instability, age of onset, chromosome 6, repeat polymorphism, mRNA transcripts, neurodegeneration
MeSH terms
Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 6, Cloning, Molecular, DNA, Female, Humans, Male, Molecular Sequence Data, Oligodeoxyribonucleotides, Pedigree, Repetitive Sequences, Nucleic Acid, Spinocerebellar Degenerations, Transcription, Genetic, Polymerase Chain Reaction

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