Estimating multilocus linkage disequilibria
Estimating multilocus linkage disequilibria
复制标题
DOI：
10.1046/j.1365-2540.2000.00683.x
复制
发表时间：
2000-03-01
期刊：
影响因子：
3.8
通讯作者：
Barton, NH
中科院分区：
文献类型：
--
作者：
Barton, NH
一个二倍体群体在每n个位点上分离两个等位基因的状态可以用2（2n）个基因型频率来描述，或者用等位基因频率来描述，或者用不同阶的多位点瞬间或累积量来描述。这些连锁不平衡的测量通常无法确定，因为人们无法判断一个基因是来自母亲还是父亲的配子，而且即使从大样本中也无法估计如此大量的参数。因此，必须简化假设。本文列出了估计多位点基因型频率的方法，这些频率适用于非连锁的中性位点，以及最终由两个源种群混合而成的种群。在这样一个杂交群体中，所有的多位点关联主要取决于来自母系基因组的基因座数量和来自父系基因组的基因座数量。基因座之间的等位基因频率可能不同，每个基因座对多基因座关联的贡献可以通过该基因座源群体之间等位基因频率的差异来衡量（δ p小于或等于1）。例如，描述来自母系基因组的基因i、j、k和来自父系基因组的基因i、l之间关联的累积量是kappa(i,j,k,i*l*), = δ p(i)(2) δ p(j) δ p(k) δ p(l) kappa（3,2）。种群状态由n个等位基因频率描述；N次散度，p；由累积量对称矩阵kappa(J，K) (J=0，…， n， K=0，…, n)。给出了这些累积量在短期和长期迁移下的表达式。描述了两种估计累积量的方法：一种基于多元矩的简单方法和一种使用Metropolis算法的极大似然法。在两个或四个基因座的模拟测试中，这两种方法都表现良好。
The state of a diploid population segregating for two alleles at each of n loci is described by 2(2n) genotype frequencies, or equivalently, by allele frequencies and by multilocus moments or cumulants of various orders. These measures of linkage disequilibrium cannot usually be determined, both because one cannot tell whether a gene came from the maternal or paternal gamete, and because such a large number of parameters cannot be estimated even from large samples. Simplifying assumptions must therefore be made. This paper sets out methods for estimating multilocus genotype frequencies which are appropriate for unlinked neutral loci, and for populations that are ultimately derived by mixing of two source populations. In such a hybrid population, all multilocus associations depend primarily on the number of loci involved that derive from the maternal genome, and the number derived from the paternal genome. Allele frequencies may differ across loci, and the contribution of each locus to multilocus associations may be scaled by the difference in allele frequency between source populations for that locus (delta p less than or equal to 1). For example, the cumulant describing the association between genes i, j, k from the maternal genome, and genes i, l from the paternal genome is kappa(i,j,k,i*l*), = delta p(i)(2) delta p(j) delta p(k) delta p(l) kappa(3,2). The state of the population is described by n allele frequencies; n divergences, delta p; and by a symmetric matrix of cumulants, kappa(J,K) (J=0 ,..., n, K=0 ,..., n). Expressions for these cumulants under short- and long-range migration are given. Two methods for estimating the cumulants are described: a simple method based on multivariate moments, and a maximum likelihood procedure, which uses the Metropolis algorithm. Both methods perform well when tested against simulations with two or four loci.