Mutation and haplotype analyses of the Werner's syndrome gene based on its genomic structure: Genetic epidemiology in the Japanese population
Mutation and haplotype analyses of the Werner's syndrome gene based on its genomic structure: Genetic epidemiology in the Japanese population
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DOI：
10.1007/s004390050477
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发表时间：
1997-07-01
期刊：
影响因子：
5.3
通讯作者：
Goto, M
中科院分区：
文献类型：
--
作者：
Matsumoto, T;Imamura, O;Goto, M
在日本患者中研究了沃纳综合征（WRN）基因突变与周围标记单倍型之间的相关性。我们已经阐明了WRN解旋酶的基因组结构，并发现了五个额外的突变，命名为突变6-10。突变4和6被认为是两个主要的突变在这个群体中，这些突变分别占50.8%和17.5%，在126个明显无关的染色体的样本。几乎所有突变4纯合子的患者在WRN基因周围都有一个单倍型，这与他们来自单一祖先的观点一致。在WRN基因的鉴定中显示的这一重要优势表明，日本人为克隆其他疾病基因提供了独特的人群。在19个位点上观察到保守的单倍型，估计WRN基因周围的距离超过1.4 Mbp。这种单倍型在随机的日本个体中是罕见的。出乎意料的是，所有9名突变6纯合的患者在这19个标记中的18个标记处共享与该单倍型相同的单倍型。这些结果表明，突变4和6独立出现在几乎相同的罕见单倍型。其余突变（1、5、7、8、9和10）很少发生，并且各自与不同的单倍型相关。
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.