Gao Guimin, Hoeschele Ina
Virginia Bioinformatics Institute and Department of Statistics, Virginia Tech, Blacksburg, Virginia 24061, USA.
Genetics. 2005 Sep;171(1):365-76. doi: 10.1534/genetics.104.040337. Epub 2005 Jun 18.
Identity-by-descent (IBD) matrix calculation is an important step in quantitative trait loci (QTL) analysis using variance component models. To calculate IBD matrices efficiently for large pedigrees with large numbers of loci, an approximation method based on the reconstruction of haplotype configurations for the pedigrees is proposed. The method uses a subset of haplotype configurations with high likelihoods identified by a haplotyping method. The new method is compared with a Markov chain Monte Carlo (MCMC) method (Loki) in terms of QTL mapping performance on simulated pedigrees. Both methods yield almost identical results for the estimation of QTL positions and variance parameters, while the new method is much more computationally efficient than the MCMC approach for large pedigrees and large numbers of loci. The proposed method is also compared with an exact method (Merlin) in small simulated pedigrees, where both methods produce nearly identical estimates of position-specific kinship coefficients. The new method can be used for fine mapping with joint linkage disequilibrium and linkage analysis, which improves the power and accuracy of QTL mapping.
基于家系的同源性（IBD）矩阵计算是使用方差成分模型进行数量性状基因座（QTL）分析的重要步骤。为了有效地计算具有大量基因座的大型家系的IBD矩阵，提出了一种基于家系单倍型构型重建的近似方法。该方法使用通过单倍型分型方法识别出的高似然性单倍型构型子集。在模拟家系的QTL定位性能方面，将该新方法与马尔可夫链蒙特卡罗（MCMC）方法（Loki）进行了比较。对于QTL位置和方差参数的估计，两种方法产生的结果几乎相同，而对于大型家系和大量基因座，新方法在计算上比MCMC方法高效得多。在小型模拟家系中，还将该方法与精确方法（Merlin）进行了比较，两种方法在特定位置亲缘系数的估计上产生几乎相同的结果。新方法可用于联合连锁不平衡和连锁分析的精细定位，提高了QTL定位的功效和准确性。
