Summary
Werner's syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werner's syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis.
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Epstein C, Martin G, Schultz AL, Motulsky AG (1966): Werner's syndrome: A review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine45: 177–221
Goto M, Rubenstein M, Weber J, Woods K, Drayna D (1992): Genetic linkage of Werner's syndrome to five markers on chromosome 8. Nature355: 735–738
Kamino K, Nakura J, Kihara K, Ye L, Nagano K, Ohta T, Jinno Y, Niikawa N, Miki T, Ogihara T (1993): Population variation in the dinucleotide repeat polymorphism at the D8S360 locus. Hum Mol Genet2: 1751
Lander ES, Botstein D (1987): Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science236: 1567–1570
Lathrop G, Lalouel J-M, Julier C, Ott J (1984): Multilocus linkage analysis in human: detection of linkage and estimation of recombination. Proc Natl Acad Sci USA81: 3443–3446
Nagano K, Nakura J, Kihara K, Ye L, Kamino K, Mitsuda M, Ohta T, Jinno Y, Niikawa N, Miki T, Ogihara T (1993): Isolation and mapping of microsatellites from a library microdissected from the Werner's syndrome region, 8p11.2–p22. Jpn J Human Genet38: 391–397
Nakura J, Miki T, Nagano K, Kihara K, Ye L, Kamino K, Fujiwara Y, Yoshida S, Murano S, Fukuchi K, Wijsman EM, Martin G, Schellenberg GD, Ogihara T (1993): Close linkage of the gene for Werner's syndrome to ANK1 and D8S87 on the short arm of chromosome 8. Gerontology39 (suppl 1): 11–15
Nakura J, Wijsman EM, Miki T, Kamino K, Yu C-H, Oshima J, Fukuchi K, Weber JL, Piussan C, Melaragno MI, Epstein CJ, Scappaticci S, Fraccaro M, Matsumura T, Murano S, Yoshida S, Fujiwara Y, Saida T, Ogihara T, Martin GM, Schellenberg GD (1994): Homozygosity mapping of the Werner's syndrome locus. Genomics, in press
Polymeropoulos MH, Rath DS, Xiao H, Merril CR (1991): Dinucleotide repeat polymorphism at the human ankyrin gene (ANK1). Nucleic Acids Res19: 969
Schellenberg GD, Martin GM, Wijsman EM, Nakura J, Miki T, Ogihara T (1992): Homozygosity mapping and Werner's syndrome. Lancet338: 1002
Thomas W, Rubenstein M, Goto M, Drayna D (1993): A genetic analysis of the Werner syndrome region on human chromosome 8p. Genomics16: 685–690
Yu C-H, Oshima J, Goddard KAB, Miki T, Nakura J, Ogihara T, Poot M, Hoehn H, Fraccaro M, Piussan C, Martin G, Schellenberg GD, Wijsman EM (1994): Linkage disequilibrium and haplotype studies of chromosome 8p11.1–21.1 markers and Werner syndrome. Am J Hum Genet55: 356–364
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Kihara, K., Nakura, J., Ye, L. et al. Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus. Jap J Human Genet 39, 403–409 (1994). https://doi.org/10.1007/BF01892385
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DOI: https://doi.org/10.1007/BF01892385