Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels
Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels
复制标题
DOI：
10.1086/323612
复制
发表时间：
2001-10-01
影响因子：
9.8
通讯作者：
Di Rienzo, A
中科院分区：
文献类型：
--
作者：
Frisse, L;Hudson, RR;Di Rienzo, A
为了描述人类群体中的连锁不平衡（LD）水平，我们分析了来自非洲人、亚洲人和欧洲人三个主要种族群体样本中的10个独立的非编码片段。描述性统计表明，非洲样品中的LD衰减速度比非非洲样品快得多。在平衡模型的假设下，我们估计了存在基因转换的种群交叉参数(4N(e)r（bp)，其中N-e为有效种群大小，r（bp）为相邻碱基对之间的每代交叉率）。在非洲样本中，LD和多态性水平导致对有效种群规模的类似估计，正如在平衡模型下所期望的那样。相反，在两个非非洲样本中，LD水平表明的有效种群规模比多态性水平所暗示的要小。这一观察结果与非非洲样本等位基因频率谱中平衡模型的显著偏离相一致。除了排除非非洲人口处于平衡状态的可能性外，这些结果表明这些群体的人口统计历史（时间和空间）不同。有趣的是，非洲样本符合基于多态性和发散水平以及频谱的平衡模型的期望。对于该样本，在平均长度为500 bp的基因束中，基因转换与交叉率的估计比率为7.3，这表明基因转换可能比以前认为的更频繁。这些发现表明，与非非洲人群相比，疾病相关的研究将需要更密集的非洲人群多态性位点图谱。
To characterize linkage disequilibrium (LD) levels in human populations, we have analyzed 10 independent noncoding segments in three population samples from the major ethnic groups-that is, Africans, Asians, and Europeans. Descriptive statistics show that LD decays much faster in the African samples than in the non-African ones. With the assumption of an equilibrium model, we estimated the population crossing-over parameter (4N(e)r(bp), where N-e is the effective population size and r(bp) is the crossing-over rate per generation between adjacent base pairs) in the presence of gene conversion. In the African sample, LD and polymorphism levels lead to similar estimates of effective population size, as expected under an equilibrium model. Conversely, in both non-African samples, LD levels suggest a smaller effective population size than that implied by polymorphism levels. This observation is paralleled by significant departures from an equilibrium model in the spectrum of allele frequencies of the non-African samples. Besides ruling out the possibility that non-African populations are at equilibrium, these results suggest different demographic history (temporal and spatial) of these groups. Interestingly, the African sample fits the expectations of an equilibrium model based on polymorphism and divergence levels and on frequency spectrum. For this sample, the estimated ratio of gene conversion to crossing-over rates is 7.3 for a mean tract length of 500 bp, suggesting that gene conversion may be more frequent than previously thought. These findings imply that disease-association studies will require a much denser map of polymorphic sites in African than in non-African populations.