Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
Genetics. 2009 Oct;183(2):709-21. doi: 10.1534/genetics.109.104190. Epub 2009 Jul 20.
We assume that quantitative measurements on a considered trait and unphased genotype data at certain marker loci are available on a sample of individuals from a background population. Our goal is to map quantitative trait loci by using a Bayesian model that performs, and makes use of, probabilistic reconstructions of the recent unobserved genealogical history (a pedigree and a gene flow at the marker loci) of the sampled individuals. This work extends variance component-based linkage analysis to settings where the unobserved pedigrees are considered as latent variables. In addition to the measured trait values and unphased genotype data at the marker loci, the method requires as an input estimates of the population allele frequencies and of a marker map, as well as some parameters related to the population size and the mating behavior. Given such data, the posterior distribution of the trait parameters (the number, the locations, and the relative variance contributions of the trait loci) is studied by using the reversible-jump Markov chain Monte Carlo methodology. We also introduce two shortcuts related to the trait parameters that allow us to do analytic integration, instead of stochastic sampling, in some parts of the algorithm. The method is tested on two simulated data sets. Comparisons with traditional variance component linkage analysis and association analysis demonstrate the benefits of our approach in a gene mapping context.
我们假设在背景人群的个体样本中可获得某个特征的定量测量值和未相位基因型数据在某些标记基因座上。我们的目标是通过使用贝叶斯模型来定位数量性状基因座,该模型执行并利用对采样个体最近未观察到的系谱历史(谱系和标记基因座处的基因流动)的概率重建。这项工作将基于方差分量的连锁分析扩展到未观察到的系谱被视为潜在变量的情况。除了标记基因座上的测量特征值和未相位基因型数据外,该方法还需要作为输入估计群体等位基因频率和标记图谱,以及与群体大小和交配行为有关的一些参数。给定这些数据,通过使用可逆跳跃马尔可夫链蒙特卡罗方法来研究特征参数(数量、位置和特征基因座的相对方差贡献)的后验分布。我们还引入了两个与特征参数相关的快捷方式,允许我们在算法的某些部分进行分析积分,而不是随机采样。该方法在两个模拟数据集上进行了测试。与传统的方差分量连锁分析和关联分析的比较表明了我们的方法在基因映射背景下的优势。