Haas J P, Kimura A, Andreas A, Hochberger M, Keller E, Brünnler G, Bettinotti M P, Nevinny-Stickel C, Hildebrandt B, Sierp G
Immunogenetics Laboratory, Ludwig-Maximilians University Children's Polyclinic, Munich, Germany.
Hum Immunol. 1994 Jan;39(1):31-40. doi: 10.1016/0198-8859(94)90098-1.
Polymorphism in the URR of the MHC class II DQA1 gene defines ten different alleles named QAP. Oligotyping for the alleles of DRB1, QAP, DQA1, and DQB1 have been performed in 210 unrelated healthy controls from Germany. Moreover, 83 HTCs from the Tenth IHWS have been tested. Four point loci haplotypes (DRB1, QAP, DQA1, and DQB1) have been analyzed in the unrelated healthy population sample. Computer analysis of the linkage disequilibria leads to the conclusion that QAP alleles are in strong linkage disequilibrium with alleles either the DQA1 or the DRB1 locus. One typical ("common") haplotype was found to be associated with each DRB1 allele in the majority (86%) of the tested persons. Apart from that, 25 other less frequent ("unusual") haplotypes, with an overall frequency of 14% have been defined. Some of these "unusual" MHC class II haplotypes were found to differ only in the regulatory alleles of DQA1 (QAP alleles) while they are identical for the alleles coding for structural elements (DRB1, DQA1, and DQB1). Most of the "unusual" haplotypes were found to carry HLA-DQ6. Assuming that "unusual" (= rare) haplotypes have arisen from "common" (= frequent) haplotypes by point mutation and recombination, we propose the existence of three recombination sites in the MHC DR-DQ region: one between DRB1 and QAP, the second between QAP and DQA1, and the third between DQA1 and DQB1.
MHC Ⅱ类 DQA1 基因上游调控区（URR）的多态性定义了 10 种不同的等位基因，命名为 QAP。对来自德国的 210 名无亲缘关系的健康对照进行了 DRB1、QAP、DQA1 和 DQB1 等位基因的寡核苷酸分型。此外，还对第十届国际人类白细胞抗原研讨会（IHWS）的 83 份造血干细胞（HTC）进行了检测。在无亲缘关系的健康人群样本中分析了四点基因座单倍型（DRB1、QAP、DQA1 和 DQB1）。对连锁不平衡的计算机分析得出结论，QAP 等位基因与 DQA1 或 DRB1 基因座的等位基因处于强连锁不平衡状态。在大多数（86%）受测者中，发现每种 DRB1 等位基因都与一种典型的（“常见的”）单倍型相关。除此之外，还定义了 25 种其他频率较低的（“不常见的”）单倍型，总频率为 14%。发现其中一些“不常见的”MHC Ⅱ类单倍型仅在 DQA1 的调控等位基因（QAP 等位基因）上有所不同，而编码结构元件的等位基因（DRB1、DQA1 和 DQB1）则相同。发现大多数“不常见的”单倍型携带 HLA-DQ6。假设“不常见的”（=罕见的）单倍型是由“常见的”（=频繁的）单倍型通过点突变和重组产生的，我们提出 MHC DR-DQ 区域存在三个重组位点：一个在 DRB1 和 QAP 之间，第二个在 QAP 和 DQA1 之间，第三个在 DQA1 和 DQB1 之间。
