Department of Epidemiology and Health Policy Research, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2007 Aug 15;2(8):e732. doi: 10.1371/journal.pone.0000732.
The ultimate goal of genetic mapping of quantitative trait loci (QTL) is the positional cloning of genes involved in any agriculturally or medically important phenotype. However, only a small portion (< or = 1%) of the QTL detected have been characterized at the molecular level, despite the report of hundreds of thousands of QTL for different traits and populations.
METHODS/RESULTS: We develop a statistical model for detecting and characterizing the nucleotide structure and organization of haplotypes that underlie QTL responsible for a quantitative trait in an F2 pedigree. The discovery of such haplotypes by the new model will facilitate the molecular cloning of a QTL. Our model is founded on population genetic properties of genes that are segregating in a pedigree, constructed with the mixture-based maximum likelihood context and implemented with the EM algorithm. The closed forms have been derived to estimate the linkage and linkage disequilibria among different molecular markers, such as single nucleotide polymorphisms, and quantitative genetic effects of haplotypes constructed by non-alleles of these markers. Results from the analysis of a real example in mouse have validated the usefulness and utilization of the model proposed.
The model is flexible to be extended to model a complex network of genetic regulation that includes the interactions between different haplotypes and between haplotypes and environments.
数量性状基因座（QTL）遗传作图的最终目标是对涉及任何农业或医学重要表型的基因进行定位克隆。然而，尽管报告了数十万种不同性状和群体的 QTL，但只有一小部分（<=1%）被在分子水平上进行了特征描述。
方法/结果：我们开发了一种统计模型，用于检测和描述构成 F2 家系中负责数量性状的 QTL 的核苷酸结构和单倍型组织。通过新模型发现的这些单倍型将有助于 QTL 的分子克隆。我们的模型基于在系谱中分离的基因的群体遗传特性，以基于混合物的最大似然为基础构建，并使用 EM 算法实现。已经推导出了封闭形式来估计不同分子标记（如单核苷酸多态性）之间的连锁和连锁不平衡，以及由这些标记的非等位基因构建的单倍型的数量遗传效应。对老鼠实际例子的分析结果验证了所提出模型的有用性和可利用性。
该模型具有灵活性，可以扩展到包括不同单倍型之间以及单倍型与环境之间相互作用的复杂遗传调控网络模型。
