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利用基于连锁不平衡和与一般复杂家系连锁的显性关系系数来提高定位分辨率。

Using dominance relationship coefficients based on linkage disequilibrium and linkage with a general complex pedigree to increase mapping resolution.

作者信息

Lee S H, Van der Werf J H J

机构信息

School of Rural Science and Agriculture and Institute of Genetics and Bioinformatics, University of New England, Armidale, NSW 2351, Australia.

出版信息

Genetics. 2006 Oct;174(2):1009-16. doi: 10.1534/genetics.106.060806. Epub 2006 Sep 1.

Abstract

Dominance (intralocus allelic interactions) plays often an important role in quantitative trait variation. However, few studies about dominance in QTL mapping have been reported in outbred animal or human populations. This is because common dominance effects can be predicted mainly for many full sibs, which do not often occur in outbred or natural populations with a general pedigree. Moreover, incomplete genotypes for such a pedigree make it infeasible to estimate dominance relationship coefficients between individuals. In this study, identity-by-descent (IBD) coefficients are estimated on the basis of population-wide linkage disequilibrium (LD), which makes it possible to track dominance relationships between unrelated founders. Therefore, it is possible to use dominance effects in QTL mapping without full sibs. Incomplete genotypes with a complex pedigree and many markers can be efficiently dealt with by a Markov chain Monte Carlo method for estimating IBD and dominance relationship matrices (D(RM)). It is shown by simulation that the use of D(RM) increases the likelihood ratio at the true QTL position and the mapping accuracy and power with complete dominance, overdominance, and recessive inheritance modes when using 200 genotyped and phenotyped individuals.

摘要

显性(基因座内等位基因相互作用)在数量性状变异中常常起着重要作用。然而,关于远交动物或人群中数量性状基因座(QTL)定位中显性的研究报道较少。这是因为常见的显性效应主要可针对许多全同胞进行预测,而在具有一般系谱的远交或自然群体中这种情况并不常出现。此外,对于这样的系谱,不完整的基因型使得估计个体间的显性关系系数变得不可行。在本研究中,基于全群体的连锁不平衡(LD)估计了同源一致状态(IBD)系数,这使得追踪无关奠基者之间的显性关系成为可能。因此,在没有全同胞的情况下也能够在QTL定位中使用显性效应。具有复杂系谱和许多标记的不完整基因型可以通过马尔可夫链蒙特卡罗方法有效地处理,以估计IBD和显性关系矩阵(D(RM))。模拟结果表明,当使用200个基因型和表型个体时,在完全显性、超显性和隐性遗传模式下,使用D(RM)会增加真实QTL位置的似然比以及定位准确性和功效。

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