Brem Rachel B, Storey John D, Whittle Jacqueline, Kruglyak Leonid
Program in Computational Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M2-B876, Seattle, Washington 98109, USA.
Nature. 2005 Aug 4;436(7051):701-3. doi: 10.1038/nature03865.
Interactions between polymorphisms at different quantitative trait loci (QTLs) are thought to contribute to the genetics of many traits, and can markedly affect the power of genetic studies to detect QTLs. Interacting loci have been identified in many organisms. However, the prevalence of interactions, and the nucleotide changes underlying them, are largely unknown. Here we search for naturally occurring genetic interactions in a large set of quantitative phenotypes--the levels of all transcripts in a cross between two strains of Saccharomyces cerevisiae. For each transcript, we searched for secondary loci interacting with primary QTLs detected by their individual effects. Such locus pairs were estimated to be involved in the inheritance of 57% of transcripts; statistically significant pairs were identified for 225 transcripts. Among these, 67% of secondary loci had individual effects too small to be significant in a genome-wide scan. Engineered polymorphisms in isogenic strains confirmed an interaction between the mating-type locus MAT and the pheromone response gene GPA1. Our results indicate that genetic interactions are widespread in the genetics of transcript levels, and that many QTLs will be missed by single-locus tests but can be detected by two-stage tests that allow for interactions.
不同数量性状基因座（QTL）上的多态性之间的相互作用被认为对许多性状的遗传有贡献，并且会显著影响检测QTL的遗传学研究的效能。在许多生物体中都已鉴定出相互作用的基因座。然而，相互作用的普遍性以及其背后的核苷酸变化在很大程度上尚不清楚。在这里，我们在一大组数量表型中寻找自然发生的遗传相互作用——酿酒酵母两个菌株杂交后代中所有转录本的水平。对于每个转录本，我们寻找与通过其个体效应检测到的主要QTL相互作用的次要基因座。据估计，这样的基因座对参与了57%的转录本的遗传；为225个转录本鉴定出了具有统计学意义的基因座对。其中，67%的次要基因座的个体效应太小，在全基因组扫描中不显著。同基因菌株中的工程多态性证实了交配型基因座MAT和信息素反应基因GPA1之间的相互作用。我们的结果表明，遗传相互作用在转录本水平的遗传学中广泛存在，并且许多QTL会被单基因座检测遗漏，但可以通过考虑相互作用的两阶段检测来检测。
