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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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Research works printed but not linked: 40

  1. Schut, J.W. Hereditary ataxia: clinical study through six generations. Arch. Neurol. Psychiat. 63, 535–567 (1954). · DOI
  2. Currier, R.D., Glover, G., Jackson, J.F. & Tipton, A.C. Spinocerebellar ataxia: study of a large kindred. Neurology 22, 1040–1043 (1972). · DOI
  3. Nino, H.E., Noreen, H.J. & Dubey, D.P. A family with hereditary ataxia: HLA typing. Neurology 30, 12–20 (1980). · DOI
  4. Zoghbi, H.Y. et al. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred. Ann. Neurol. 23, 580–584 (1988). · DOI
  5. Greenfield, J.G. The spino-cerebellar degenerations (Charles C. Thomas, Springfield, Illinois, 1954).
  6. Haines, J.L., Schut, L.J. & Weitkamp, L.R. Spinocerebellar ataxia in large kindred: age at onset, reproduction, and genetic linkage studies. Neurology 34, 1542–1548 (1984). · DOI
  7. Brook, J.D. et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68, 799–808 (1992). · DOI
  8. Bruner, H.G. et al. Reverse mutation in myotonic dystrophy. New Engl. J. Med. 328, 476–480 (1993). · DOI
  9. Buxton, J. et al. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 355, 547–548 (1992). · DOI
  10. Fu, Y.-H. et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255, 1256–1259 (1992). · DOI
  11. Harley, H.G. et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 355, 545–546 (1992). · DOI
  12. Harley, H.G. et al. Unstable DNA sequence in myotonic dystrophy. Lancet 339, 1125–1128 (1992). · DOI
  13. Kremer, E.J. et al. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science 252, 1711–1714 (1991). · DOI
  14. Mahadevan, M. et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255, 1253–1255 (1992). · DOI
  15. La Spada, A.R., Wilson, E.M., Lubahn, D.B., Harding, A.E. & Fishbeck, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991). · DOI
  16. Yakura, H., Wakisaka, A., Fujimoto, S. & Itakura, K. Hereditary ataxia and HLA genotypes. New Engl. J. Med. 291, 154–155 (1974).
  17. Jackson, J.F., Currier, R.D., Terasaki, P.I. & Morton, N.E. Spinocerebellar ataxia and HLA linkage: risk prediction by HLA typing. New Engl. J. Med. 296, 1138–1141 (1977). · DOI
  18. Ranum, L.P.W. et al. Localization of the autosomal dominant, HLA-linked spinocerebellar ataxia (SCA1) locus in two kindreds within an 8cM subregion of chromosome 6p. Am. J. hum. Genet. 49, 31–41 (1991).
  19. Kwiatkowski, T.J. Jr. et al. The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps centromeric to D6S89 and shows no recombination, in nine large kindreds, with a dinudeotide repeat at the AM10 locus. Am. J. hum. Genet. (in the press).
  20. La Spada, A.R. et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nature Genet. 2, 301–304 (1992). · DOI
  21. Coutinho, P. & Andrade, C. Autosomal dominant system degeneration in Portuguese families of the Azores. Neurology 28, 703–709 (1978). · DOI
  22. Takiyama, Y. et al. The gene for Machado-Joseph disease maps to human chromosome 14q. Nature Genet. 4, 300–304 (1993). · DOI
  23. Harding, A.E. Genetic aspects of autosomal dominant late onset cerebellar ataxia. J. med. Genet. 18, 436–441 (1981). · DOI
  24. Orozco, G. et al. Dominantly inherited olivopontocerebellar atrophy from eastern Cuba: clinical, neuropathological, and biochemical findings. J. neurol. Sci. 93, 27–50 (1989). · DOI
  25. Gispert, S. et al. Chromosomal assignment of the second (Cuban) locus for autosomal dominant cerebellar atrophy (SCA2) to human chromosome 12q23–24.1. Nature Genet. 4, 295–299 (1993). · DOI
  26. Richards, R.I. et al. Evidence of founder chromosomes in fragile X syndrome. Nature Genet. 1, 257–260 (1992). · DOI
  27. Harley, H.G. et al. Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker. Am. J. hum. Genet 49, 68–75 (1991).
  28. Quigley, C.A. et al. Complete deletion of the androgen receptor gene: definion of the null phenotype of the androgen insensitivity syndrome and determination of carrier status. J. clin. endocrinol. Metab. 74, 927–933 (1992). · DOI
  29. Trifiro, M. et al. The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene. Molec. cell. endocrinol. 75, 37–47 (1991). · DOI
  30. Wharton, K.A., Johansen, K.M., Xu, T. & Artavanis-Tsakonas, S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43, 567–581 (1985). · DOI
  31. Vaessin, H. et al. prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila. Cell 67, 941–953 (1991). · DOI
  32. Bellen, H.J., Kooyer, S., D'Evelyn, D. & Pearlman, J. The Drosophila Couch potato protein is expressed in nuclei of peripheral neuronal precursors and shows homology to RNA-binding proteins. Genes Dev. 6, 2125–2136 (1992). · DOI
  33. Courey, A.J., Holtzman, D.A., Jackson, S.P. & Tjian, R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 59, 827–836 (1989). · DOI
  34. Benson, M. & Pirrotta, V. The Drosophila zeste protein binds cooperatively to sites in many gene regulatory regions: implications for transvection and gene regulation. EMBO J. 7, 3907–3915 (1988). · DOI
  35. Rich, S.S., Wilkie, P., Schut, L., Vance, G. & Orr, H.T. Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6. Am. J. hum. Genet. 41, 524–531 (1987).
  36. Zoghbi, H.Y., Daiger, S.P., McCall, A., O'Brien, W.E. & Beaudet, A.L. Extensive DNA polymorphism at the factor Xllla (F13a) locus and linkage to HLA. Am. J. hum. Genet. 42, 877–883 (1988).
  37. Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular Cloning: A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, 1989).
  38. Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992). · DOI
  39. Albertsen, H.M. et al. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc. natn. Acad. Sci. U.S.A. 87, 4256–4260 (1990). · DOI
  40. Brownstein, B.H. et al. Isolation of single-copy human genes from a library of yeast artificial chromosome clones. Science 244, 1348–1351 (1989). · DOI

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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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