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定位有序性状的多个数量性状基因座。

Mapping multiple quantitative trait Loci for ordinal traits.

作者信息

Yi Nengjun, Xu Shizhong, George Varghese, Allison David B

机构信息

Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.

出版信息

Behav Genet. 2004 Jan;34(1):3-15. doi: 10.1023/B:BEGE.0000009473.43185.43.

Abstract

Many complex traits in humans and other organisms show ordinal phenotypic variation but do not follow a simple Mendelian pattern of inheritance. These ordinal traits are presumably determined by many factors, including genetic and environmental components. Several statistical approaches to mapping quantitative trait loci (QTL) for such traits have been developed based on a single-QTL model. However, statistical methods for mapping multiple QTL are not well studied as continuous traits. In this paper, we propose a Bayesian method implemented via the Markov chain Monte Carlo (MCMC) algorithm to map multiple QTL for ordinal traits in experimental crosses. We model the ordinal traits under the multiple threshold model, which assumes a latent continuous variable underlying the ordinal phenotypes. The ordinal phenotype and the latent continuous variable are linked through some fixed but unknown thresholds. We adopt a standardized threshold model, which has several attractive features. An efficient sampling scheme is developed to jointly generate the threshold values and the values of latent variable. With the simulated latent variable, the posterior distributions of other unknowns, for example, the number, locations, genetic effects, and genotypes of QTL, can be computed using existing algorithms for normally distributed traits. To this end, we provide a unified approach to mapping multiple QTL for continuous, binary, and ordinal traits. Utility and flexibility of the method are demonstrated using simulated data.

摘要

人类和其他生物体中的许多复杂性状表现出有序的表型变异,但并不遵循简单的孟德尔遗传模式。这些有序性状可能由许多因素决定,包括遗传和环境成分。基于单基因座模型,已经开发了几种用于定位此类性状的数量性状基因座(QTL)的统计方法。然而,作为连续性状,用于定位多个QTL的统计方法尚未得到充分研究。在本文中,我们提出了一种通过马尔可夫链蒙特卡罗(MCMC)算法实现的贝叶斯方法,用于在实验杂交中定位有序性状的多个QTL。我们在多阈值模型下对有序性状进行建模,该模型假设有序表型背后存在一个潜在的连续变量。有序表型和潜在连续变量通过一些固定但未知的阈值联系起来。我们采用标准化阈值模型,该模型具有几个吸引人的特点。开发了一种有效的抽样方案,以联合生成阈值和潜在变量的值。利用模拟的潜在变量,可以使用现有的正态分布性状算法计算其他未知量的后验分布,例如QTL的数量、位置、遗传效应和基因型。为此,我们提供了一种统一的方法来定位连续、二元和有序性状的多个QTL。使用模拟数据证明了该方法的实用性和灵活性。

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