Zhang Min, Montooth Kristi L, Wells Martin T, Clark Andrew G, Zhang Dabao
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA.
Genetics. 2005 Apr;169(4):2305-18. doi: 10.1534/genetics.104.034181. Epub 2004 Nov 1.
We developed a classification approach to multiple quantitative trait loci (QTL) mapping built upon a Bayesian framework that incorporates the important prior information that most genotypic markers are not cotransmitted with a QTL or their QTL effects are negligible. The genetic effect of each marker is modeled using a three-component mixture prior with a class for markers having negligible effects and separate classes for markers having positive or negative effects on the trait. The posterior probability of a marker's classification provides a natural statistic for evaluating credibility of identified QTL. This approach performs well, especially with a large number of markers but a relatively small sample size. A heat map to visualize the results is proposed so as to allow investigators to be more or less conservative when identifying QTL. We validated the method using a well-characterized data set for barley heading values from the North American Barley Genome Mapping Project. Application of the method to a new data set revealed sex-specific QTL underlying differences in glucose-6-phosphate dehydrogenase enzyme activity between two Drosophila species. A simulation study demonstrated the power of this approach across levels of trait heritability and when marker data were sparse.
我们基于贝叶斯框架开发了一种用于多数量性状基因座(QTL)定位的分类方法,该框架纳入了重要的先验信息,即大多数基因型标记不会与QTL共同传递,或者其QTL效应可忽略不计。使用具有三个分量的混合先验对每个标记的遗传效应进行建模,其中一类是效应可忽略不计的标记,另外两类分别是对性状有正向或负向效应的标记。标记分类的后验概率为评估已识别QTL的可信度提供了一个自然的统计量。这种方法表现良好,尤其是在标记数量众多但样本量相对较小的情况下。我们提出了一个热图来可视化结果,以便研究人员在识别QTL时可以或多或少地保持保守。我们使用来自北美大麦基因组图谱项目的一个特征明确的大麦抽穗期数据集验证了该方法。将该方法应用于一个新数据集,揭示了两个果蝇物种之间6-磷酸葡萄糖脱氢酶活性差异背后的性别特异性QTL。一项模拟研究证明了该方法在不同性状遗传力水平以及标记数据稀疏时的功效。