High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci
High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci
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DOI：
10.1034/j.1399-0039.2000.560502.x
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发表时间：
2000-11-01
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影响因子：
--
通讯作者：
Erlich, HA
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文献类型：
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作者：
Bugawan, TL;Klitz, W;Erlich, HA
人类6号染色体(6p21.3)短臂上的人类白细胞抗原(6p21.3)区域含有人类基因组中最具多态性的编码序列。多态I类基因座人群样本的高分辨率DNA-HLA分型。HLAA-A、-B和-C最近才变得可行。这里。我们报告了基于欧洲血统的家庭样本(CEPH资料库)的分子人类白细胞抗原分型。这显示出非常高的多态。有20个A等位基因。在248个单倍型样本中，38个B等位基因和19个C等位基因。总体而言。等位基因频率分布始终比过去选择性中性的预期更均匀(观察到的纯合性统计较低)，这表明有平衡选择的历史。II类基因座也是如此。DRB1.这些样品中的DQA1和DQB1。DPA1和DPB1基因座也不存在。他们的等位基因频率分布更加偏斜(在中性模型下观察到的纯合性统计比预期的更高)。尽管连锁不平衡是整个人类白细胞抗原区域的一个显著特征。只有19%的8个基因座单倍型被多次抽样。一些B等位基因的相对年龄可以从B-C单倍型关联模式中推断出来。我们认为，观察到的连锁不平衡模式反映了几乎所有HLA等位基因的选择操作。
The HLA region on the short arm of chromosome 6 (6p21.3) contains the most polymorphic coding sequences in the human genome. High-resolution DNA-based HLA typing of population samples of the poly morphic class I loci. HLAA-A, -B, and -C has only recently become feasible. Here. we report molecular HLA typing on family-based samples of European origin (the CEPH repository). which demonstrated very high poly morphism. with 20 A alleles. 38 B alleles and 19 C alleles in the sample of 248 independent haplotypes. in general. allele frequency distributions are consistently more even (lower observed homozygosity statistic) than expected from a past of selective neutrality suggesting a history of balancing selection. This was also true for the class II loci. DRB1. DQA1 and DQB1 in these samples. bur nor for the DPA1 and DPB1 loci. whose allelle frequency distributions were more skewed (higher observed homozygosity statistics than expected under a neutral model. Although linkage disequilibrium Is a prominent feature across the HLA region. only 19% of the eight locus haplotypes were sampled more than once. The relative age of some of the B alleles could be inferred from the pattern of B-C haplotypic associations. We suggest that the observed patterns of linkage disequilibrium reflect the operation of selection on nearly all HLA alleles.