Iakoubova O A, Dushkin H, Beier D R
Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genomics. 1995 Mar 1;26(1):107-14. doi: 10.1016/0888-7543(95)80088-4.
We have used a novel method of chromosomal exclusion to map the recessive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J) F1jck/ + mice. The severity of polycystic kidney disease (PKD) in the intercross progeny was significantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affects expression of jck. Two regions--one from DBA/2J on chromosome 10 and a second from C57BL/6J on chromosome 1--are associated with inheritance of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease severity, with a maximal QTL analysis lod score of 16.8, was unexpected; this result suggests that inheritance of both this locus and at least one DBA/2J locus results in the more severe phenotype, presumably as a consequence of a direct or indirect interaction between their protein products.
我们采用了一种新的染色体排除方法，通过 (C57BL/6J×DBA/2J) F1jck/+ 小鼠之间的杂交，将隐性突变少年多囊肾 (jck) 定位到小鼠的11号染色体上。杂交后代中多囊肾病 (PKD) 的严重程度比亲代C57BL/6J品系中的明显更具变异性，这表明从DBA/2J引入的一个或多个修饰基因座会影响jck的表达。两个区域——一个来自10号染色体上的DBA/2J，另一个来自1号染色体上的C57BL/6J——与更严重的PKD表型的遗传相关。一个与C57BL/6J相关的基因座的遗传与疾病严重程度之间存在高度显著的关联，最大QTL分析lod分数为16.8，这一发现出乎意料；该结果表明，这个基因座和至少一个DBA/2J基因座的遗传都会导致更严重的表型，可能是由于它们的蛋白质产物之间直接或间接相互作用的结果。
