Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations
Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations
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DOI：
10.1034/j.1399-0039.2001.057005424.x
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发表时间：
2001-05-01
期刊：
影响因子：
--
通讯作者：
Klitz, W
中科院分区：
文献类型：
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作者：
Begovich, AB;Moonsamy, PV;Klitz, W
为了了解控制人类白细胞抗原-DP分子遗传多样性进化的因素，采用聚合酶链式反应(PCR)方法对编码该异二聚体的DPA1和DPB1基因座的遗传变异进行了研究，这些群体来自15个不同的群体，包括非洲人、亚洲人、美洲印第安人、印度人和欧洲人。这些不同种族的样本代表了各种种群亚结构，包括规模较小、与世隔绝的人群，以及可能受到钦佩的较大人群。在87种不同的DP单倍型上发现了10个DPA1和39个DPB1等位基因，其中34个等位基因在至少一个群体中处于显著正连锁不平衡状态。一些单倍型存在于所有民族，而另一些单倍型仅限于单一种族或群体。所有15个群体均存在DPA1和DPB1之间的正向全球连锁不平衡(W-n)。非洲种群的W-n值最低，而美洲印第安人种群的W-n值接近绝对不平衡。使用Ewens-Watterson纯合统计量的归一化偏差F对单倍型分布的分析表明，编码功能性异源二聚体的DP单倍型受到的平衡选择程度比HLA区域内的其他座位低得多。最后，邻接树分析证明了单倍型多样性在推断不同种群之间的关系方面的能力。
In order to understand the forces governing the evolution of the genetic diversity in the HLA-DP molecule, polymerase chain reaction (PCR)based methods were used to characterize genetic variation at the DPA1 and DPB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including individuals of African, Asian, Amerindian, Indian and European origin. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger, presumably admired populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in significant positive linkage disequilibrium in at least one population. Some haplotypes were found in all ethnic groups while others were confined to a single ethnic group or population. Strong positive global linkage disequilibrium (W-n) between DPA1 and DPB1 was present in all 15 populations. The African populations displayed the lowest values of W-n whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses demonstrate the power of haplotype diversity for inferring the relationships between the different populations.