Polymorphism, recombination, and linkage disequilibrium within the HLA class II region.
Polymorphism, recombination, and linkage disequilibrium within the HLA class II region.
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DOI：
10.4049/jimmunol.148.1.249
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发表时间：
1992-01
影响因子：
4.4
通讯作者：
A. Begovich;G. McClure;V. Suraj;R. Helmuth;N. Fildes;T. Bugawan;H. Erlich;W. Klitz
中科院分区：
文献类型：
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作者：
A. Begovich;G. McClure;V. Suraj;R. Helmuth;N. Fildes;T. Bugawan;H. Erlich;W. Klitz
已对由 502 名个体组成的 39 个 CEPH（人类多态性研究中心）家族进行了 HLA II 类基因 DRB1、DQA1、DQB1 和 DPB1 分型，使用非放射性序列特异性寡核苷酸探针分析聚合酶链式反应扩增的 DNA。该群体由 266 条独立染色体组成，包含 27 个 DRB1、7 个 DQA1、12 个 DQB1 和 17 个 DPB1 等位基因。使用纯合性统计分析等位基因频率的分布，表明过去的选择压力，表明平衡选择作用于 DRB1、DQA1 和 DQB1 位点。然而，DPB1 等位基因的分布表明了不同的进化历史。家族数据可以估计重组率和明确的单倍型分配。 DRB1、DQA1 和 DQB1 之间未发现重组体；然而，在 DQB1 和 DPB1 之间检测到重组体，导致估计的重组分数大于或等于 0.008 +/- 0.004。在该群体中仅发现 33 个不同的 DRB1-DQA1-DQB1 单倍型，这说明了这些位点等位基因的极端非随机单倍型关联。其中一些单倍型对于高加索人群来说是不寻常的（以前未报告过），很可能是由于 DR 和 DQ 亚区域之间过去的重组事件造成的。使用这些数据和这些样本的可用血清学 HLA-A 和 HLA-B 类型检查整个 HLA 区域的不平衡表明，这些基因座之间的整体不平衡随着重组分数的增加而下降，在最远间隔接近统计无显着性，HLA-A 到 HLA-DP。DR-DQ 单倍型与 DPB1 和 B 连锁不平衡被注意到，最后，某些 II 类的进化起源解决了单倍型。
Thirty-nine CEPH (Centre d'Etude du Polymorphisme Humain) families, comprised of 502 individuals, have been typed for the HLA class II genes DRB1, DQA1, DQB1, and DPB1 using nonradioactive sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA. This population, which consists of 266 independent chromosomes, contains 27 DRB1, 7 DQA1, 12 DQB1, and 17 DPB1 alleles. Analysis of the distribution of allele frequencies using the homozygosity statistic, which gives an indication of past selection pressures, suggests that balancing selection has acted on the DRB1, DQA1, and DQB1 loci. The distribution of DPB1 alleles, however, suggests a different evolutionary past. Family data permits the estimation of recombination rates and the unambiguous assignment of haplotypes. No recombinants were found between DRB1, DQA1, and DQB1; however, recombinants were detected between DQB1 and DPB1, resulting in an estimated recombination fraction of greater than or equal to 0.008 +/- 0.004. Only 33 distinct DRB1-DQA1-DQB1 haplotypes were found in this population which illustrates the extreme nonrandom haplotypic association of alleles at these loci. A few of these haplotypes are unusual (previously unreported) for a Caucasian population and most likely result from past recombination events between the DR and DQ subregions. Examination of disequilibrium across the HLA region using these data and the available serologic HLA-A and HLA-B types of these samples shows that global disequilibrium between these loci declines with the recombination fraction, approaching statistic nonsignificance at the most distant interval, HLA-A to HLA-DP.DR-DQ haplotypes in linkage disequilibrium with DPB1 and B are noted and, finally, the evolutionary origin of certain class II haplotypes is addressed.