Homozygosity mapping of the Werner syndrome locus (WRN).
Homozygosity mapping of the Werner syndrome locus (WRN).
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维尔纳综合征基因座 (WRN) 的纯合性作图。
DOI：
10.1006/geno.1994.1548
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发表时间：
1994
期刊：
影响因子：
4.4
通讯作者：
Melaragno,MI
中科院分区：
文献类型：
--
作者：
Nakura,J;Wijsman,EM;Miki,T;Kamino,K;Yu,CE;Oshima,J;Fukuchi,K;Weber,JL;Piussan,C;Melaragno,MI
维尔纳综合征 (WS) 是一种常染色体隐性遗传疾病，其特征是多种与年龄相关的疾病早发。这种疾病的基因座最近被定位到 8p12。我们研究了 27 个混血的 WS 血统，其中 26 个是近亲血统。在其中 24 个家族中，受影响的受试者被诊断为“明确的”WS，而其余 3 个家系中受影响的受试者则被诊断为“可能的”WS。对每个亲属的受影响受试者进行了 13 个短串联重复多态性位点的基因分型。两点连锁分析产生了与 D8S137、D8S339、D8S87、PLAT、D8S165 和 D8S166 连锁的重要证据。在最小重组分数下产生最大 lod 分数的基因座是 D8S339，表明该标记与测试的 WS 基因（WRN 基因座）最接近。 D8S339 对日本和非日本（主要是白种人）家族均给出了显着的 lod 分数（Zmax≥ 3.0），表明单个基因座对两组中的 WS 都有影响。这些标记的多点分析在距离 D8S339 约 0.6 cM 处产生了 17.05 的最大 lod 分数。来自近交谱系受试者的 2 点分析、多点分析和纯合性区域分析的综合证据表明，WRN 基因座位于 D8S131 和 D8S87 之间，在包含 D8S339 的 8.3 cM 区间内。
Werner syndrome (WS) is an autosomal recessive disorder characterized by the early onset of several age-related diseases. The locus for this disease was recently mapped to 8p12. We studied 27 WS kindreds of mixed ethnic origins, 26 of which were consanguineous. In 24 of these families, the affected subject was given the diagnosis of "definite" WS and affected subjects in the remaining 3 pedigrees were given the diagnosis of "probable" WS. Affected subjects from each kindred were genotyped for 13 short tandem repeat polymorphic sites. Two-point linkage analysis yielded significant evidence for linkage to D8S137, D8S339, D8S87, PLAT, D8S165, and D8S166. The locus yielding a maximum lod score at the smallest recombination fraction was D8S339, suggesting that this marker is the closest to the WS gene (WRN locus) of those tested. D8S339 gave significant lod scores (Zmax≥ 3.0) for both Japanese and non-Japanese (mostly Caucasian) families, demonstrating that a single locus is responsible for WS in both groups. Multipoint analysis of these markers yielded a maximum lod score of 17.05 at a distance of approximately 0.6 cM from D8S339. The combined evidence from 2-point analysis, multipoint analysis, and analysis of regions of homozygosity in subjects from inbred pedigrees indicates that the WRN locus is between D8S131 ad D8S87, in an 8.3-cM interval containing D8S339.