Multipoint quantitative-trait linkage analysis in general pedigrees
Multipoint quantitative-trait linkage analysis in general pedigrees
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DOI：
10.1086/301844
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发表时间：
1998-05-01
影响因子：
9.8
通讯作者：
Blangero, J
中科院分区：
文献类型：
--
作者：
Almasy, L;Blangero, J
数量性状位点（qtl）的多点连锁分析以前仅限于兄弟姐妹和小家系。在本文中，我们展示了如何在任意大小和复杂性的谱系中使用方差分量链接方法，并开发了多点血统同一性（IBD）概率计算的一般框架。我们将Fulker等人的兄弟对多点映射方法推广到一般相对对。这种多点IBD方法使用基因型位点上遗传相同的等位基因比例来估计每对相对染色体上任意点的IBD共享。我们已经推导出IBD共享的相关性，作为一般谱系中亲属对染色体距离的函数，并提供了一个简单的框架，使这些相关性可以很容易地获得任何由单线血统或多个独立血统相关的亲属对。多点相对对ibd计算后可用于方差成分连锁分析，该分析综合考虑了整个家系的似然性。给出了使用模拟数据的例子，证明了QTL定位的准确性以及使用5-，10-和20-cM标记图进行多点分析所提供的功率增加。一般谱系方差成分和IBD估计方法已经在SOLAR（顺序寡基因连锁分析程序）计算机包中实现。
Multipoint linkage analysis of quantitative-trait loci (QTLs) has previously been restricted to sibships and small pedigrees. In this article, we show how variance-component linkage methods can be used in pedigrees of arbitrary size and complexity, and we develop a general framework for multipoint identity-by-descent (IBD) probability calculations. We extend the sib-pair multipoint mapping approach of Fulker et al. to general relative pairs. This multipoint IBD method uses the proportion of alleles shared identical by descent at genotyped loci to estimate IBD sharing at arbitrary points along a chromosome for each relative pair. We have derived correlations in IBD sharing as a function of chromosomal distance for relative pairs in general pedigrees and provide a simple framework whereby these correlations can be easily obtained for any relative pair related by a single line of descent or by multiple independent lines of descent. Once calculated, the multipoint relative-pair IBDs can be utilized in variance-component linkage analysis, which considers the likelihood of the entire pedigree jointly. Examples are given that use simulated data, demonstrating both the accuracy of QTL localization and the increase in power provided by multipoint analysis with 5-, 10-, and 20-cM marker maps. The general pedigree variance component and IBD estimation methods have been implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package.