Human Genetics

, Volume 100, Issue 1, pp 123–130

Mutation and haplotype analyses of the Werner’s syndrome gene based on its genomic structure: genetic epidemiology in the Japanese population

  • Takehisa Matsumoto
  • Osamu Imamura
  • Yukako Yamabe
  • Junro Kuromitsu
  • Yoshiki Tokutake
  • Akira Shimamoto
  • Noriyuki Suzuki
  • Misako Satoh
  • Saori Kitao
  • Koji Ichikawa
  • Hiroshi Kataoka
  • Kahori Sugawara
  • Winston Thomas
  • Brian Mason
  • Zenta Tsuchihashi
  • D. Drayna
  • Minoru Sugawara
  • Masanobu Sugimoto
  • Y. Furuichi
  • Makoto Goto
Original investigation

DOI: 10.1007/s004390050477

Cite this article as:
Matsumoto, T., Imamura, O., Yamabe, Y. et al. Hum Genet (1997) 100: 123. doi:10.1007/s004390050477

Abstract

The correlation between mutations in the Werner’s syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6–10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Takehisa Matsumoto
    • 1
  • Osamu Imamura
    • 1
  • Yukako Yamabe
    • 1
  • Junro Kuromitsu
    • 1
  • Yoshiki Tokutake
    • 1
  • Akira Shimamoto
    • 1
  • Noriyuki Suzuki
    • 1
  • Misako Satoh
    • 1
  • Saori Kitao
    • 1
  • Koji Ichikawa
    • 1
  • Hiroshi Kataoka
    • 1
  • Kahori Sugawara
    • 1
  • Winston Thomas
    • 2
  • Brian Mason
    • 2
  • Zenta Tsuchihashi
    • 2
  • D. Drayna
    • 2
  • Minoru Sugawara
    • 1
  • Masanobu Sugimoto
    • 1
  • Y. Furuichi
    • 1
  • Makoto Goto
    • 3
  1. 1.AGENE Research Institute, 200 Kajiwara, Kamakura, Kanagawa 247, Japan Tel.: +81-467-46-9590; Fax: +81-467-48-6595JP
  2. 2.Mercator Genetics Inc., 4040 Campbell Avenue, Menlo Park, CA 94025, USAUS
  3. 3.Department of Rheumatology, Tokyo Metropolitan Otsuka Hospital, 2-8-1, Minami-Otsuka, Toshima-ku, Tokyo 170, JapanJP