Zhao Honghua, Rothschild Max F, Fernando Rohan L, Dekkers Jack C M
Department of Animal Science, 225C Kildee Hall, Iowa State University, Ames, Iowa, 50011, USA.
Mamm Genome. 2003 Jul;14(7):472-82. doi: 10.1007/s00335-002-2215-y.
In recent years, several F(2) crosses between outbred lines of livestock have been developed to identify quantitative trait loci (QTL). These populations are valuable for further genetic analysis, including positional candidate gene loci (CGL). Analysis of CGL in F(2) populations is, however, hindered by extensive between-breed linkage disequilibrium (LD). The objectives here were to develop and evaluate three tests for CGL in simulated F(2) breed-cross populations. 1) A standard association test, based on the fixed effect of CGL genotype. This test was significant for CGL at considerable distances from the QTL. 2) A marker-assisted association test, based on a test at the CGL of the fixed effect of CGL genotype in a breed-cross QTL interval mapping model. This removed the impact of between-breed LD, but was not powerful in detecting CGL closely linked to the QTL, unless the CGL was the QTL. 3) An F-drop test, comparing F ratios for a QTL at the CGL with and without the CGL included as fixed effect. It had low power to distinguish close from distant CGL. Power to distinguish two CGL within 10 cM from the QTL was limited and little improved by including QTL effects associated with markers to remove between-breed LD, although the power was greater when one of the CGL was the causative mutation. Therefore, while we conclude that candidate gene tests in QTL mapping populations must be interpreted with caution, we now have a clearer picture of the value of candidate gene tests in these populations.
近年来，已经培育出了几种家畜远交系之间的F(2)杂交种，以确定数量性状位点（QTL）。这些群体对于进一步的遗传分析很有价值，包括定位候选基因位点（CGL）。然而，F(2)群体中CGL的分析受到品种间广泛连锁不平衡（LD）的阻碍。本文的目的是开发和评估三种用于模拟F(2)品种杂交群体中CGL的检验方法。1）一种基于CGL基因型固定效应的标准关联检验。该检验对于距离QTL相当远的CGL具有显著性。2）一种标记辅助关联检验，基于在品种杂交QTL区间定位模型中对CGL基因型固定效应在CGL处的检验。这消除了品种间LD的影响，但在检测与QTL紧密连锁的CGL时效力不强，除非CGL就是QTL。3）一种F值下降检验，比较在有和没有将CGL作为固定效应纳入的情况下，CGL处QTL的F比率。它区分紧密和远距离CGL的效力较低。区分距QTL 10 cM以内的两个CGL的效力有限，并且通过纳入与标记相关的QTL效应以消除品种间LD几乎没有得到改善，尽管当其中一个CGL是致病突变时效力更大。因此，虽然我们得出结论，QTL定位群体中的候选基因检验必须谨慎解释，但我们现在对这些群体中候选基因检验的价值有了更清晰的认识。
