Nakura J, Miki T, Ye L, Mitsuda N, Zhao Y, Kihara K, Yu C E, Oshima J, Fukuchi K I, Wijsman E M, Schellenberg G D, Martin G M, Murano S i, Hashimoto K, Fujiwara Y, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Osaka, 565, Japan.
Genomics. 1996 Aug 15;36(1):130-41. doi: 10.1006/geno.1996.0433.
Werner syndrome (WS) is an autosomal recessive disorder characterized by the premature occurrence of many age-related features. Previously, the WS gene (WRN) was mapped between D8S131 and D8S87, in an 8.3-cM interval. In this study, regions of homozygosity in 36 WS patients from inbred families were searched for by genotyping for 35 dinucleotide repeat polymorphic markers to narrow down the WRN critical region. The region most consistently homozygous in these patients was between the D8S1219/D8S1220 cluster and D8S278, within a 4.4-cM interval. For 16 markers mapped in this interval, 24 WS patients (22 Japanese patients and 2 Caucasian patients) in whom consanguinity failed to be proved were also genotyped, under the assumption that some of these patients might still be from consanguineous marriages. The data were analyzed by Fisher's exact test with a 2 x 2 contingency table for the 22 Japanese patients, excluding the 2 Caucasian patients. The frequencies of homozygosity in the 22 patients at 10 of 16 markers tested were significantly higher than those detected in the general population. Analysis of homozygosity patterns indicated that the region most consistently homozygous was between D8S1445 and D8S278. Thus the WRN locus is most likely between the two markers D8S1445 and D8S278, in a 1.6-cM interval.
沃纳综合征（WS）是一种常染色体隐性疾病，其特征是许多与年龄相关的特征过早出现。此前，WS基因（WRN）被定位在D8S131和D8S87之间，间隔为8.3厘摩。在本研究中，通过对35个二核苷酸重复多态性标记进行基因分型，在36名来自近亲家庭的WS患者中寻找纯合区域，以缩小WRN关键区域。这些患者中最一致出现纯合的区域在D8S1219/D8S1220簇和D8S278之间，间隔为4.4厘摩。对于定位在该区间的16个标记，还对16名无法证明有血缘关系的WS患者（22名日本患者和2名白种人患者）进行了基因分型，假设其中一些患者可能仍来自近亲婚姻。对22名日本患者（不包括2名白种人患者）的数据使用2×2列联表进行Fisher精确检验分析。在检测的16个标记中的10个标记处，这22名患者的纯合频率显著高于在普通人群中检测到的频率。纯合模式分析表明，最一致出现纯合的区域在D8S1445和D8S278之间。因此，WRN基因座最有可能在两个标记D8S1445和D8S278之间，间隔为1.6厘摩。
