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Gametic and somatic tissue–specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1

Nature Genetics volume 10, pages 344–350 (1995)Cite this article

Abstract

Spinocerebellar ataxia type 1 is associated with expansion of an unstable CAG repeat within the SCA1 gene. Male gametic heterogeneity of the expanded repeat is demonstrated using single sperm and low–copy genome analysis. Low–copy genome analysis of peripheral blood also reveals somatic heterogeneity of the expanded SCA1 allele, thus establishing mitotic instability at this locus. Comparative analysis of a large normal allele and a small affected allele suggests a role of midstream CAT interspersions in stabilizing long (CAG)n stretches. Within the brain, tissue–specific mosaicism of the expanded allele is also observed. The differences in SCA1 allele heterogeneity between sperm and blood and within the brain parallels the findings in Huntington disease, suggesting that both disorders share a common mechanism for tissue–specific instability.

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Author information

Authors and Affiliations

  1. National Center for Human Genome Research, National Institutes of Health, Bethesda, MD, 20892, USA

    Samuel S. Chong, Juan Cota & Mark R. Hughes

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Samuel S. Chong, Juan Cota, Mark R. Hughes & Huda Y. Zoghbi

  3. Department of Pediatrics, and Baylor College of Medicine, Houston, Texas, 77030, USA

    Alanna E. McCall & Huda Y. Zoghbi

  4. University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA

    S.H. Subramony

  5. Department of Laboratory Medicine and Pathology, and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, 55455, USA

    Harry T. Orr

  6. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Mark R. Hughes

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  1. Samuel S. Chong
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  7. Huda Y. Zoghbi
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Chong, S., McCall, A., Cota, J. et al. Gametic and somatic tissue–specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1. Nat Genet 10, 344–350 (1995). https://doi.org/10.1038/ng0795-344

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