Wang Jing, Koehler Kenneth J, Dekkers Jack C M
Department of Animal Science and Center for Integrated Animal Genomics, Iowa State University, Ames, Iowa 50011, USA.
Genet Sel Evol. 2007 Nov-Dec;39(6):685-709. doi: 10.1186/1297-9686-39-6-685. Epub 2007 Dec 6.
Selective DNA pooling is an efficient method to identify chromosomal regions that harbor quantitative trait loci (QTL) by comparing marker allele frequencies in pooled DNA from phenotypically extreme individuals. Currently used single marker analysis methods can detect linkage of markers to a QTL but do not provide separate estimates of QTL position and effect, nor do they utilize the joint information from multiple markers. In this study, two interval mapping methods for analysis of selective DNA pooling data were developed and evaluated. One was based on least squares regression (LS-pool) and the other on approximate maximum likelihood (ML-pool). Both methods simultaneously utilize information from multiple markers and multiple families and can be applied to different family structures (half-sib, F2 cross and backcross). The results from these two interval mapping methods were compared with results from single marker analysis by simulation. The results indicate that both LS-pool and ML-pool provided greater power to detect the QTL than single marker analysis. They also provide separate estimates of QTL location and effect. With large family sizes, both LS-pool and ML-pool provided similar power and estimates of QTL location and effect as selective genotyping. With small family sizes, however, the LS-pool method resulted in severely biased estimates of QTL location for distal QTL but this bias was reduced with the ML-pool.
选择性DNA池化是一种通过比较来自表型极端个体的池化DNA中的标记等位基因频率来鉴定含有数量性状位点(QTL)的染色体区域的有效方法。目前使用的单标记分析方法可以检测标记与QTL的连锁,但不能提供QTL位置和效应的单独估计,也不能利用多个标记的联合信息。在本研究中,开发并评估了两种用于分析选择性DNA池化数据的区间作图方法。一种基于最小二乘回归(LS-pool),另一种基于近似最大似然(ML-pool)。两种方法都同时利用多个标记和多个家系的信息,并且可以应用于不同的家系结构(半同胞、F2杂交和回交)。通过模拟将这两种区间作图方法的结果与单标记分析的结果进行了比较。结果表明,LS-pool和ML-pool检测QTL的能力均比单标记分析更强。它们还提供了QTL位置和效应的单独估计。在大家庭规模下,LS-pool和ML-pool提供的检测QTL的能力以及QTL位置和效应的估计与选择性基因分型相似。然而,在小家庭规模下,LS-pool方法对远端QTL的QTL位置估计产生严重偏差,但ML-pool可减少这种偏差。