División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada No. 800, Guadalajara, Jalisco, Mexico.
Blood Cells Mol Dis. 2010 Mar-Apr;44(2):89-94. doi: 10.1016/j.bcmd.2009.10.004. Epub 2009 Nov 10.
Analysis of the 5' and 3' haplotypes (Hps) of the beta-globin gene cluster was performed in 110 beta(A) chromosomes from unrelated Mexican afromestizo individuals in order to determine Hardy-Weinberg equilibrium, allelic frequencies, linkage disequilibrium (LD) and association between the 5' and 3' haplotypes. All sites were found to be in Hardy-Weinberg equilibrium (p>0.05). In the whole beta-cluster, only 12.87% of the pairs of loci exhibited significant LD (22/171) (r(2)>0.33). Within the 5'Hp, three pairs of loci were associated (epsilonHincII/(G)gammaHindIII, epsilonHincII/3'psibetaHincII and (G)gammaHindIII/3'psibetaHincII). In the 3'Hp, 19 pairs of loci showed significant LD and were distributed mostly among the -551, -340, Exon1nt6 and IVS2nt16 polymorphisms. The absence of pairs of loci significantly linked between both 5' and 3' Hps is noteworthy. The allelic combinations of the 40 studied polymorphisms (5 sites in the 5' Hp and 35 sites in the 3' Hp) displayed 69 distinct haplotypes, 22 of them belonging to group A, 27 to B, 18 to C and 2 to D, which denoted the great heterogeneity of our population. Further, 1a7A1, 1a7B1 and 1a1C1 were the most common sequences with 8, 9 and 9 chromosomes each. Association analysis between both 5' and 3' Hps revealed strong coherence with the proposed evolutionary histories for the beta-globin gene polymorphisms. 5'Hp1 (+----), which is considered to be an ancestral haplotype, was the most frequent haplotype found in our population and was linked to 24 different sequences in the 3'Hp, demonstrating great heterogeneity. A similar result was found in the 3' Hps, where older alleles (a17A1 and a7B1) were linked to a higher number of 5'Hps. This is the first time that an analysis of association among the 5' and 3' haplotypes and the LD has been performed with 40 polymorphisms distributed in the beta-globin gene cluster in the Mexican afromestizo population. The poor LD observed between and within the 5' and 3' Hps show that this region is very prone to recombination events.
对来自 110 个无关的墨西哥非洲裔个体的β(A)珠蛋白基因簇的 5' 和 3' 单体型（Hps）进行分析，以确定 Hardy-Weinberg 平衡、等位基因频率、连锁不平衡（LD）以及 5' 和 3' 单体型之间的关联。所有位点均处于 Hardy-Weinberg 平衡（p＞0.05）。在整个β-簇中，只有 12.87%的两个基因座之间存在显著的 LD（22/171）（r(2)＞0.33）。在 5'Hp 内，三个基因座对呈关联状态（epsilonHincII/(G)gammaHindIII、epsilonHincII/3'psibetaHincII 和 (G)gammaHindIII/3'psibetaHincII）。在 3'Hp 中，19 对基因座显示出显著的 LD，主要分布在-551、-340、Exon1nt6 和 IVS2nt16 多态性之间。值得注意的是，两个 5' 和 3' Hps 之间没有显著连锁的基因座对。研究的 40 个多态性（5' Hp 中的 5 个位点和 3' Hp 中的 35 个位点）的等位基因组合显示出 69 种不同的单体型，其中 22 种属于 A 组，27 种属于 B 组，18 种属于 C 组，2 种属于 D 组，这表明我们的群体具有很大的异质性。此外，1a7A1、1a7B1 和 1a1C1 是最常见的序列，分别有 8、9 和 9 条染色体。5' 和 3' Hps 之间的关联分析显示出与β-珠蛋白基因多态性的提议进化历史之间存在很强的一致性。在我们的人群中发现最常见的单体型是被认为是祖先单体型的 5'Hp1（+----），它与 3' Hp 中的 24 个不同序列相连，表现出很大的异质性。在 3' Hps 中也发现了类似的结果，其中较旧的等位基因（a17A1 和 a7B1）与较多的 5' Hps 相连。这是首次在墨西哥非洲裔人群中对β-珠蛋白基因簇中的 40 个多态性进行 5' 和 3' 单体型之间的关联和 LD 分析。在 5' 和 3' Hps 之间和之内观察到的低 LD 表明该区域非常容易发生重组事件。
