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Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT

Nature Genetics volume 14, pages 277–284 (1996)Cite this article

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded GAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids — with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

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Authors and Affiliations

  1. Departments of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951, Japan

    K. Sanpei, H. Takano, S. Igarashi, T. Sato, M. Oyake, Y. Ishida, T. Ikeuchi, R. Koide, M. Saito, A. Sato, I. Eguchi, H. Tanaka & S. Tsuji

  2. Department of Neurology, Hokkaido University School of Medicine, Kita-ku, Sapporo, 060, Japan

    H. Sasaki & K. Tashiro

  3. First Department of Pathology, Hokkaido University School of Medicine, Kita-ku, Sapporo, 060, Japan

    A. Wakisaka

  4. Department of Psychiatry, Niigata University School of Medicine, 1-757 Asahimachi, Niigata, 951, Japan

    T. Tanaka

  5. Department of Neurology, Jichi Medical School, Minamikawachi, Tochigi, 329-04, Japan

    S. Hanyu, Y. Takiyama & M. Nishizawa

  6. Department of Neurology, Teikyo University School of Medicine, Ichihara Hospital, 3426-3 Anesaki, Ichihara, 299-01, Japan

    N. Shimizu

  7. Segawa Neurological Clinic for Children, Kanda Surugadai 2-8, Chiyoda-ku, Tokyo, 101, Japan

    Y. Nomura & M. Segawa

  8. Department of Neurology and Psychiatry, Kanagawa Rehabilitation Center, 516 Nanasawa, Atsugi, Kanagawa, 243-01, Japan

    K. Iwabuchi

  9. Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, 951, Japan

    H. Takahashi

Authors
  1. K. Sanpei
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  2. H. Takano
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Sanpei, K., Takano, H., Igarashi, S. et al. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet 14, 277–284 (1996). https://doi.org/10.1038/ng1196-277

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