Further diversification of the HLA-B locus in Central American Amerindians: new B*39 and B*51 alleles in the Kuna of Panama.
Further diversification of the HLA-B locus in Central American Amerindians: new B*39 and B*51 alleles in the Kuna of Panama.
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DOI：
10.1111/j.1399-0039.1997.tb02868.x
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发表时间：
1997-09
期刊：
影响因子：
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通讯作者：
K. K. Iwanaga-K.;M. Eberle;C. Kolman;E. Bermingham;D. Watkins
中科院分区：
文献类型：
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作者：
K. K. Iwanaga-K.;M. Eberle;C. Kolman;E. Bermingham;D. Watkins
在南美印第安人中发现了几个新的HLA-B等位基因。相比之下，分析的MHC I类等位基因的北美本土人口揭示了一些新的HLA-B等位基因。这表明HLA-B基因座在南美人群中正在迅速进化。在这里，我们描述了HLA-B基因座等位基因存在于一个中美洲部落，巴拿马的库纳人的个人。使用基于序列的分型技术，分离等位基因的变性梯度凝胶电泳（DGGE），然后直接测序，我们确定了HLA-B等位基因从8个库纳。库纳人中存在的两个HLA-B等位基因此前已在其他南美洲美洲印第安人群体中描述过;一个等位基因已在墨西哥裔美国人中得到描述。我们在Kuna中鉴定了两个新的HLA-B等位基因，HLA-B * 3911和HLA-B * 5110。HLA-B * 3911与HLA-B * 3905的区别仅在于外显子3中的单个核苷酸取代。该取代导致α 2结构域中第156位残基处的亮氨酸被精氨酸取代。这种变化可能会影响由该分子结合的肽的库。HLA-B * 5110与其他HLA-B * 51等位基因的显著不同之处在于，它是最少216个核苷酸的异常大的基因座内重组事件的结果。这种重组导致等位基因是部分HLA-B * 51和部分HLA-B * 40。因此，更戏剧性的重组事件也可能在美洲印第安人HLA-B基因座的快速进化中发挥作用。
Several new HLA-B locus alleles have been discovered in South American Amerindians. By contrast, analysis of the MHC class I alleles of North American native populations has revealed few new HLA-B alleles. This suggests that the HLA-B locus is evolving rapidly in South American populations. Here we describe the HLA-B locus alleles present in individuals from a Central American tribe, the Kuna of Panama. Using a sequence-based typing technique that separates alleles by denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing, we determined the HLA-B alleles from eight Kunas. Two of the HLA-B alleles present in the Kuna have been previously described in other South American Amerindian populations; one allele has been characterized in a Mexican-American. We characterized two new HLA-B alleles in the Kuna, HLA-B*3911 and HLA-B*5110. HLA-B*3911 differed from HLA-B*3905 by only a single nucleotide substitution in exon 3. This substitution resulted in an amino acid replacement of leucine by arginine at residue 156 in the alpha 2 domain. Such a change may affect the repertoire of peptides that are bound by this molecule. HLA-B*5110 differed significantly from other HLA-B*51 alleles in that it is the result of an unusually large intra-locus recombination event of minimally 216 nucleotides. This recombination results in an allele that is part HLA-B*51 and part HLA-B*40. Thus, more dramatic recombination events may also play a role in the rapid evolution of the HLA-B locus in Amerindians.