Frisch A, Frydman M, Blau O, Narinsky R, Morduchowicz G, Boner G, Bachner L, Steinherz R
Laboratory of Biochemical Genetics, Felsenstein Medical Research Center, Petah Tikva, Israel.
Isr J Med Sci. 1992 Oct;28(10):700-5.
A large Jewish family from Tashkent (Uzbekistan) was studied for linkage of autosomal dominant polycystic kidney disease (ADPKD) to molecular markers on the short arm of chromosome 16. A restriction fragment length polymorphism (RFLP) analysis was performed on 28 family members, including 9 ADPKD diagnosed patients in 3 consecutive generations. A specific haplotype was found to segregate with the disease in eight of the nine affected individuals. The peak lod scores for linkage between the disease phenotype and the five informative flanking markers were: 3'HVR 1.70 at theta = 0.08; GGG1 1.18 at theta = 0.001; CMM65 1.50 at theta = 0.001; 26-6 0.86 at theta = 0.001 and 218EP6 1.39 at theta = 0.001. A particular haplotype of these markers segregated with the disease phenotype. The peak lod score of this haplotype was 3.046. Homogeneity test, comparing this family to 40 PKD European families, showed that the conditional probability that it belongs to the same group is 1.000. Taken together, these findings show that the defective gene in this Jewish family from Uzbekistan is PKD1. To our knowledge, this is the first ADPKD family in Israel in whom linkage studies were performed and one of the few originating from populations outside the Western world.
对一个来自塔什干（乌兹别克斯坦）的大型犹太家庭进行了研究，以确定常染色体显性遗传性多囊肾病（ADPKD）与16号染色体短臂上分子标记的连锁关系。对28名家庭成员进行了限制性片段长度多态性（RFLP）分析，其中包括连续三代中的9名被诊断为ADPKD的患者。在9名受影响个体中的8名中，发现一种特定的单倍型与疾病共分离。疾病表型与五个信息性侧翼标记之间连锁的最高lod分数为：在θ = 0.08时，3'HVR为1.70；在θ = 0.001时，GGG1为1.18；在θ = 0.001时，CMM65为1.50；在θ = 0.001时，26 - 6为0.86；在θ = 0.001时，218EP6为1.39。这些标记的一种特定单倍型与疾病表型共分离。该单倍型的最高lod分数为3.046。将这个家庭与40个欧洲多囊肾病家庭进行同质性测试，结果表明它属于同一组的条件概率为1.000。综上所述，这些发现表明，这个来自乌兹别克斯坦的犹太家庭中的缺陷基因是PKD1。据我们所知，这是以色列第一个进行连锁研究的ADPKD家庭，也是少数几个来自西方世界以外人群的家庭之一。
