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Extended multipoint identity-by-descent analysis of human quantitative traits: efficiency power and modeling considerations.

机译:对人类定量特征的扩展多点逐血身份分析:效率功能和建模注意事项。

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摘要

Goldgar introduced a novel marker-based method for partitioning the variation of a quantitative trait into specific chromosomal regions. Unlike traditional linkage mapping methods, Goldgar's method does not require the estimation of statistical quantities characterizing each locus thought to influence the trait under scrutiny (e.g., allele frequencies, penetrances, etc.). Goldgar's method is thus more flexible and less model dependent than many traditional marker-based genetic analysis techniques. Unfortunately, however, many of the properties of Goldgar's method have not been investigated. In this paper, the utility of an extended version of Goldgar's approach is studied in settings in which sibships are taken as the sampling unit of interest. The extensions discussed resolve around the incorporation of a wider variety of effects and factors into Goldgar's basic model. Analytic studies pertaining to power, sample-size requirements, and estimation procedures for the proposed extended version of Goldgar's method are described. Hypothesis-testing strategies are also discussed. The results of the analytic studies indicate that, although an extended sib-pair version of Goldgar's variance-partitioning approach to modeling the chromosomal determinants of a quantitative trait will be useful only for traits with high heritabilities or when fine-scale genetic maps can be employed. Goldgar's technique as a whole has promise, as it can be made relatively robust statistically, refined through some simple and intuitive extensions, and can be easily adapted to work with more complex sampling units. Further extensions of Goldgar's methods are proposed, and areas in need of additional research are discussed.
机译:Goldgar引入了一种新的基于标记的方法,用于将定量性状的变异划分为特定的染色体区域。与传统的连锁作图方法不同,Goldgar的方法不需要估计表征每个基因座的统计量,这些基因座在仔细检查下会影响性状(例如等位基因频率,外显率等)。因此,与许多传统的基于标记的遗传分析技术相比,Goldgar的方法更灵活,模型依赖性更小。但是,不幸的是,尚未研究Goldgar方法的许多特性。在本文中,研究了Goldgar方法的扩展版本的效用,在这种环境中,以同居关系为目标采样单位。讨论的扩展解决了将各种影响和因素纳入Goldgar的基本模型的问题。描述了有关拟议的Goldgar方法扩展版本的功效,样本量要求和估算程序的分析研究。还讨论了假设检验策略。分析研究的结果表明,尽管Goldgar方差划分方法的同胞对扩展版本对定量性状的染色体决定因素进行建模,但仅对具有高遗传力的性状或可使用精细的遗传图谱有用。 。 Goldgar的技术总体上很有希望,因为它可以在统计上变得相对可靠,可以通过一些简单直观的扩展进行完善,并且可以轻松地应用于更复杂的采样单元。提出了Goldgar方法的进一步扩展,并讨论了需要进一步研究的领域。

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