Practical Applications of the Bioinformatics Toolbox for Narrowing Quantitative Trait Loci
Practical Applications of the Bioinformatics Toolbox for Narrowing Quantitative Trait Loci
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DOI：
10.1534/genetics.108.090175
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发表时间：
2008-12-01
期刊：
影响因子：
3.3
通讯作者：
Paigen, Beverly
中科院分区：
文献类型：
--
作者：
Burgess-Herbert, Sarah L.;Cox, Allison;Paigen, Beverly
剖析复杂性状中涉及的基因可能会受到多种因素的干扰，包括基因间广泛的上位性相互作用、表观遗传调节因子的参与以及性状的可变表达性。虽然数量性状基因座（QTL）分析已经成为定位复杂性状的染色体区域的有力工具，但系统地鉴定致病基因仍然具有挑战性。在这里，通过其应用于小鼠血浆高密度脂蛋白胆固醇（HDL）水平，我们展示了一种利用比较基因组学和生物信息学技术缩小QTL的策略。我们展示了在多个杂交中检测到的QTL如何进行组合交叉分析和单倍型块分析;来自一个物种的QTL如何映射到另一个物种的一致区域;以及如何将单倍型组与其表型相关联的全基因组扫描可用于优先考虑窄化区域。然后，我们说明了如何将这些缩小QTL的个别方法系统地整合到小鼠12号和15号染色体上，从而显著减少候选基因的数量，通常从数百个到2000个。
Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable expressivity of traits. Although quantitative trait locus (QTL) analysis has been a powerful tool for localizing the chromosomal regions Underlying complex traits, systematically identifying the causal genes remains challenging. Here, through its application to plasma levels of high-density lipoprotein cholesterol (HDL) in mice, we demonstrate a strategy for narrowing QTL that Utilizes comparative genomics and bioinformatics techniqnes. We show how QTL detected in multiple crosses are subjected to both combined cross analysis and haplotype block analysis; how QTL from one species are mapped to the concordant regions in another species; and how genomewide scans associating haplotype groups with their phenotypes can be used to prioritize the narrowed regions. Then we illustrate how these individual methods for narrowing QTL can be systematically integrated for mouse chromosomes 12 and 15, resulting in a significantly reduced number of candidate genes, often from hundreds to