Werner's Syndrome: Background


Werner's Syndrome (WS) is a very rare autosomal recessive disease characterized by the early onset of several age-related disease such as diabetes mellitus, esteoporosis (Martin, 1978). The locus for this disease was mapped to chromosome 8p11-12 (Goto et al. 1992; Nakura et al. 1993). WRN, the WS syndrome gene, is tightly linked with D8S339 that was initially thought to be located in the about 7cM interval between D8S87 and ankyrin 1 (ANK1). Later reports from both linkage analysis (Nakura et al. 1994) and linkage disequilibrium analysis (Goddard et al. 1996) revealed that D8S339 is telometric to D8S87, within the 8.3 cM interval between D8S137 and D8S87.

The WRN gene was cloned by positional cloning in 1996 (Yu et al. 1996). For those who are curious, it turned out to be a mutated gene which encodes both a 3'->5' helicase (enzyme that splits the double-helix structure of DNA so that single-stranded DNA can serve as template for DNA synthesis) and a 3'->5' exonuclease (enzyme that can cut DNA from the end).

References

  1. Schellenberg GD, Martin GM, Wijsman EM, Nakura J, Miki T, Ogihara T (1992) Homozygosity mapping and Werner's syndrome. Lancet 339:1002.
  2. Nakura J, Miki T, Nagano K, Kihara K, Ye L, Kamino K, Fujiwara Y, Yoshida S, Murano S, Fukuchi K, et al (1993) Close linkage of the gene for Werner's syndrome to ANK1 and D8S87 on the short arm of chromosome 8. Gerontology 39 Suppl 1:11-5.
    3. (Abstract).
  3. Nakura J, Wijsman EM, Miki T, Kamino K, Yu CE, Oshima J, Fukuchi K, Weber JL, Piussan C, Melaragno MI (1994) Homozygosity mapping of the Werner syndrome locus (WRN). Genomics 23:600-8. (Abstract)
  4. Goddard KA, Yu CE, Oshima J, Miki T, Nakura J, Piussan C, Martin GM, Schellenberg GD, Wijsman EM (1996) Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers. Am J Hum Genet 58:1286-302.(Abstract).
  5. Nakura J, Miki T, Ye L, Mitsuda N, Zhao Y, Kihara K, Yu CE, Oshima J, Fukuchi KI, Wijsman EM, Schellenberg GD, Martin GM, Murano Si, Hashimoto K, Fujiwara Y, Ogihara T (1996) Narrowing the position of the Werner syndrome locus by homozygosity analysis-extension of homozygosity analysis. Genomics 36:130-41. (Full Text).
  6. Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD (1996) Positional cloning of the Werner's syndrome gene. Science 272:258-62. (Abstract)
Last modified: Tue Nov 21 19:01:48 PST 2000