Gould K A, Luongo C, Moser A R, McNeley M K, Borenstein N, Shedlovsky A, Dove W F, Hong K, Dietrich W F, Lander E S
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.
Genetics. 1996 Dec;144(4):1777-85. doi: 10.1093/genetics/144.4.1777.
As genetic mapping of quantitative trait loci (QTL) becomes routine, the challenge is to identify the underlying genes. This paper develops rigorous genetic tests for evaluation of candidate genes for a QTL, involving determination of allelic status in inbred strains and fine-structure genetic mapping. For the Mom1 modifier of intestinal adenomas caused by ApcMin, these tests are used to evaluate two candidate genes: Pla2g2a, a secretory phospholipase, and Rap1GAP, a GTPase activating protein. Rap1GAP passes the first test but is excluded by a single fine-structure recombinant. Pla2g2a passes both tests and is a strong candidate for Mom1. Significantly, we also find that ApcMin-induced adenomas remain heterozygous for the Mom1 region, consistent with Mom1 acting outside the tumor lineage and encoding a secreted product.
随着数量性状基因座（QTL）的遗传定位变得常规化，面临的挑战是鉴定潜在基因。本文开发了严格的遗传学测试来评估QTL的候选基因，包括确定近交系中的等位基因状态和精细结构遗传定位。对于由ApcMin引起的肠道腺瘤的Mom1修饰基因，这些测试用于评估两个候选基因：分泌型磷脂酶Pla2g2a和GTP酶激活蛋白Rap1GAP。Rap1GAP通过了第一项测试，但被一个单一的精细结构重组体排除。Pla2g2a通过了两项测试，是Mom1的有力候选基因。值得注意的是，我们还发现ApcMin诱导的腺瘤在Mom1区域保持杂合状态，这与Mom1在肿瘤谱系外起作用并编码一种分泌产物一致。
