School of Mathematics and Statistics, Wuhan University, Wuhan, Hubei, China.
Genetics. 2011 May;188(1):189-95. doi: 10.1534/genetics.110.125542. Epub 2011 Mar 8.
The Collaborative Cross (CC) is a renewable mouse resource that mimics the genetic diversity in humans. The recombinant inbred intercrosses (RIX) generated from CC recombinant inbred (RI) lines share similar genetic structures to those of F(2) individuals. In contrast to F(2) mice, genotypes of RIX can be inferred from the genotypes of their RI parents and can be produced repeatedly. Also, RIX mice do not typically share the same degree of relatedness. This unbalanced genetic relatedness requires careful statistical modeling to avoid a large number of false positive findings. For complex traits, mapping multiple genes simultaneously is arguably more powerful than mapping one gene at a time. In this article, we describe how we have developed a Bayesian quantitative trait locus (QTL) mapping method that simultaneously deals with the special genetic architecture of RIX and maps multiple genes. The performance of the proposed method is evaluated by extensive simulations. In addition, for a given set of RI lines, there are numerous ways to generate RIX samples. To provide a general guideline on future RIX studies, we compare several RIX designs through simulations.
协作交叉 (CC) 是一种可再生的小鼠资源,可模拟人类的遗传多样性。从 CC 重组近交系 (RI) 系产生的重组近交系间杂交 (RIX) 具有与 F2 个体相似的遗传结构。与 F2 小鼠不同,RIX 的基因型可以从其 RI 亲本的基因型推断出来,并可以重复产生。此外,RIX 小鼠通常没有相同程度的亲缘关系。这种不平衡的遗传亲缘关系需要仔细的统计建模,以避免大量的假阳性发现。对于复杂性状,同时映射多个基因的效果可能比一次映射一个基因的效果更好。在本文中,我们描述了如何开发一种贝叶斯数量性状基因座 (QTL) 映射方法,该方法可同时处理 RIX 的特殊遗传结构并映射多个基因。通过广泛的模拟评估了所提出方法的性能。此外,对于给定的一组 RI 系,有多种方法可以生成 RIX 样本。为了为未来的 RIX 研究提供一般指导,我们通过模拟比较了几种 RIX 设计。