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Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I

Nature Genetics volume 5, pages 254–258 (1993)Cite this article

Abstract

Spinocerebellar ataxia type I (SCAI) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat on chromosome 6p. Normal alleles range from 19–36 repeats while SCA1 alleles contain 43–81 repeats. We now show that in 63% of paternal transmissions, an increase in repeat number is observed, whereas 69% of maternal transmissions showed no change or a decrease in repeat number. Sequence analysis of the repeat from 126 chromosomes reveals an interrupted repeat configuration in 98% of the unexpanded alleles but a contiguous repeat (CAG)n configuration in 30 expanded alleles from seven SCA1 families. This indicates that the repeat instability in SCA1 is more complex than a simple variation in repeat number and that the loss of an interruption predisposes the SCA1 (CAG)n to expansion.

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Authors and Affiliations

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

    Ming-yi Chung, Laura P.W. Ranum, Lisa A. Duvick & Harry T. Orr

  2. Department of Pediatrics, and Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Antonio Servadio & Huda Y. Zoghbi

Authors
  1. Ming-yi Chung
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  2. Laura P.W. Ranum
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  3. Lisa A. Duvick
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  4. Antonio Servadio
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  5. Huda Y. Zoghbi
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  6. Harry T. Orr
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Chung, My., Ranum, L., Duvick, L. et al. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet 5, 254–258 (1993). https://doi.org/10.1038/ng1193-254

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