一项对35个成年发病型多囊肾病家庭的基因连锁异质性研究。

A study of genetic linkage heterogeneity in 35 adult-onset polycystic kidney disease families.

作者信息

Wright A F, Teague P W, Pound S E, Pignatelli P M, Macnicol A M, Carothers A D, De Mey R J, Allan P L, Watson M L

机构信息

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

出版信息

Hum Genet. 1993 Jan;90(5):569-71. doi: 10.1007/BF00217461.

DOI:10.1007/BF00217461

PMID:8428756

Abstract

A genetic heterogeneity analysis of 35 kindreds with adult-onset polycystic kidney disease (ADPKD) was carried out using the D16S85, D16S84, D16S125 and D16S94 loci that are closely linked to the PKD1 locus on chromosome 16. The results show that the likelihood of two ADPKD loci is 2,514.9 times greater than for a single locus (P < 0.0001). The maximum likelihood lod score is 27.38 under heterogeneity with PKD1 lying 4.9 cM proximal to D16S85 (in males). At least 3% of kindreds are unlinked to PKD1, since the 95% confidence limits of alpha, the proportion of families linked to PKD1, are 0.54-0.97. Only 2 out of 35 kindreds (5.7%) show statistically significant evidence of non-linkage to PKD1, with conditional probabilities of 0.987 and 0.993 that the disease locus is unlinked. This confirms the existence of a small subgroup of ADPKD kindreds that are unlinked to PKD1 and provides a firm basis for genetic counselling of this population on the basis of DNA probes.

摘要

利用与16号染色体上PKD1基因座紧密连锁的D16S85、D16S84、D16S125和D16S94基因座，对35个成年发病型多囊肾病（ADPKD）家系进行了遗传异质性分析。结果显示，两个ADPKD基因座的可能性比单个基因座大2514.9倍（P < 0.0001）。在异质性情况下，最大似然连锁值为27.38，PKD1位于D16S85近端4.9 cM处（男性）。至少3%的家系与PKD1不连锁，因为与PKD1连锁的家系比例α的95%置信区间为0.54 - 0.97。35个家系中只有2个（5.7%）显示出与PKD1不连锁的统计学显著证据，疾病基因座不连锁的条件概率分别为0.987和0.993。这证实了存在一小部分与PKD1不连锁的ADPKD家系，并为基于DNA探针的该人群遗传咨询提供了坚实基础。