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Population Structure in Admixed Populations: Effect of Admixture Dynamics on the Pattern of Linkage Disequilibrium

机译:混合人口中的人口结构:混合动力学对连锁不平衡模式的影响

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摘要

Gene flow between genetically distinct populations creates linkage disequilibrium (admixture linkage disequilibrium [ALD]) among all loci (linked and unlinked) that have different allele frequencies in the founding populations. We have explored the distribution of ALD by using computer simulation of two extreme models of admixture: the hybrid-isolation (HI) model, in which admixture occurs in a single generation, and the continuous-gene-flow (CGF) model, in which admixture occurs at a steady rate in every generation. Linkage disequilibrium patterns in African American population samples from Jackson, MS, and from coastal South Carolina resemble patterns observed in the simulated CGF populations, in two respects. First, significant association between two loci (FY and AT3) separated by 22 cM was detected in both samples. The retention of ALD over relatively large (>10 cM) chromosomal segments is characteristic of a CGF pattern of admixture but not of an HI pattern. Second, significant associations were also detected between many pairs of unlinked loci, as observed in the CGF simulation results but not in the simulated HI populations. Such a high rate of association between unlinked markers in these populations could result in false-positive linkage signals in an admixture-mapping study. However, we demonstrate that by conditioning on parental admixture, we can distinguish between true linkage and association resulting from shared ancestry. Therefore, populations with a CGF history of admixture not only are appropriate for admixture mapping but also have greater power for detection of linkage disequilibrium over large chromosomal regions than do populations that have experienced a pattern of admixture more similar to the HI model, if methods are employed that detect and adjust for disequilibrium caused by continuous admixture.
机译:遗传上不同的种群之间的基因流会在创始种群中具有不同等位基因频率的所有基因座(连锁和非连锁)之间造成连锁不平衡(混合连锁不平衡[ALD])。我们通过计算机模拟了两种极端的混合物模型,探索了ALD的分布:混合隔离(HI)模型(其中混合物是单代发生的)和连续基因流(CGF)模型,其中每一代都以稳定的速度发生混合。从两个方面来看,来自密西西比州杰克逊和南卡罗来纳州沿海地区的非裔美国人样本中的连锁不平衡模式类似于在模拟CGF人群中观察到的模式。首先,在两个样品中均检测到两个基因座(FY和AT3)之间的显着关联,两者之间的间隔为22 cM。 ALD在相对较大(> 10 cM)染色体片段上的保留是混合物的CGF模式的特征,而不是HI模式的特征。其次,正如在CGF模拟结果中观察到的,但在模拟HI群体中未观察到的,在许多对未链接基因座之间也检测到显着的关联。在这些人群中,未连锁标记之间的如此高的缔合率可能会导致混合物映射研究中的假阳性连锁信号。但是,我们证明,通过对父母混合物的调节,我们可以区分真正的联系和共同祖先所产生的联系。因此,具有CGF混合史的种群不仅适用于混合物作图,而且与那些经历了与HI模型更相似的混合模式的种群相比,具有更大的检测大染色体区域连锁不平衡的能力。用于检测和调整由连续混合引起的不平衡。

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