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.
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SCA1 is caused by expansion of a CAG repeat encoding a glutamine tract in the protein ATXN1.
“spinocerebellar ataxia type 1 (SCA1), a disease caused by a polyglutamine expansion in the protein ATAXIN1 (ATXN1).”
From Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1 (2013) · cites this paper as Orr et al., 1993
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- 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
- Published
- 1993-07
- Volume
- 4
- Issue
- 3
- Pages
- 221-226
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- 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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