Lee J K, Thomas D C
Department of Health Evaluation Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Am J Hum Genet. 2000 Nov;67(5):1232-50. doi: 10.1016/S0002-9297(07)62953-X. Epub 2000 Oct 13.
Markov chain-Monte Carlo (MCMC) techniques for multipoint mapping of quantitative trait loci have been developed on nuclear-family and extended-pedigree data. These methods are based on repeated sampling-peeling and gene dropping of genotype vectors and random sampling of each of the model parameters from their full conditional distributions, given phenotypes, markers, and other model parameters. We further refine such approaches by improving the efficiency of the marker haplotype-updating algorithm and by adopting a new proposal for adding loci. Incorporating these refinements, we have performed an extensive simulation study on simulated nuclear-family data, varying the number of trait loci, family size, displacement, and other segregation parameters. Our simulation studies show that our MCMC algorithm identifies the locations of the true trait loci and estimates their segregation parameters well-provided that the total number of sibship pairs in the pedigree data is reasonably large, heritability of each individual trait locus is not too low, and the loci are not too close together. Our MCMC algorithm was shown to be significantly more efficient than LOKI (Heath 1997) in our simulation study using nuclear-family data.
用于数量性状基因座多点定位的马尔可夫链蒙特卡罗(MCMC)技术已基于核心家系和扩展家系数据得到发展。这些方法基于对基因型向量的重复抽样-剥离和基因分型,以及在给定表型、标记和其他模型参数的情况下,从其完全条件分布中对每个模型参数进行随机抽样。我们通过提高标记单倍型更新算法的效率以及采用添加基因座的新提议,进一步完善了此类方法。纳入这些改进后,我们对模拟的核心家系数据进行了广泛的模拟研究,改变了性状基因座的数量、家系大小、位移和其他分离参数。我们的模拟研究表明,只要系谱数据中同胞对的总数足够大,每个个体性状基因座的遗传力不太低,且基因座不太靠近,我们的MCMC算法就能很好地识别真实性状基因座的位置并估计其分离参数。在我们使用核心家系数据的模拟研究中,我们的MCMC算法被证明比LOKI(Heath,1997)效率显著更高。