Klitz W, Maiers M, Spellman S, Baxter-Lowe L A, Schmeckpeper B, Williams T M, Fernandez-Viña M
Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Tissue Antigens. 2003 Oct;62(4):296-307. doi: 10.1034/j.1399-0039.2003.00103.x.
A collaborative study involving a large sample of European Americans was typed for the histocompatibility loci of the HLA DR-DQ region and subjected to intensive typing validation measures in order to accurately determine haplotype composition and frequency. The resulting tables have immediate application to HLA typing and allogeneic transplantation. The loci within the DR-DQ region are especially valuable for such an undertaking because of their tight linkage and high linkage disequilibrium. The 3798 haplotypes, derived from 1899 unrelated individuals, had a total of 75 distinct DRB1-DQA1-DQB1 haplotypes. The frequency distribution of the haplotypes was right skewed with haplotypes occurring at a frequency of less than 1% numbering 59 and yet constituting less than 12% of the total sample. Given DRB1 typing, it was possible to infer the exact DQA1 and DQB1 composition of a haplotype with high confidence (>90% likelihood) in 21 of the 35 high-resolution DRB1 alleles present in the sample. Of the DRB1 alleles without high reliability for DQ haplotype inference, only *0401, *0701 and *1302 were common, the remaining 11 DRB1 alleles constituting less than 5% of the total sample. This approach failed for the 13 serologically equivalent DR alleles in which only 33% of DQ haplotypes could be reliably inferred. The 36 DQA1-DQB1 haplotypes present in the total sample conformed to the known pattern of permissible heterodimers. Four DQA1-DQB1 haplotypes, all rare, are reported here for the first time. The haplotype frequency tables are suitable as a reference standard for HLA typing of the DR and DQ loci in European Americans.
一项涉及大量欧裔美国人的合作研究对HLA DR - DQ区域的组织相容性位点进行了分型，并采取了严格的分型验证措施，以准确确定单倍型组成和频率。所得表格可直接应用于HLA分型和同种异体移植。DR - DQ区域内的位点对于此类工作特别有价值，因为它们紧密连锁且连锁不平衡程度高。从1899名无关个体中获得的3798个单倍型共有75种不同的DRB1 - DQA1 - DQB1单倍型。单倍型的频率分布呈右偏态，频率低于1%的单倍型有59种，但其数量占总样本的比例不到12%。在样本中存在的35个高分辨率DRB1等位基因中的21个中，给定DRB1分型后，能够以高置信度（>90%可能性）推断单倍型的确切DQA1和DQB1组成。在对于DQ单倍型推断可靠性不高的DRB1等位基因中，只有*0401、0701和1302较为常见，其余11个DRB1等位基因占总样本的比例不到5%。对于13个血清学等价的DR等位基因，这种方法不适用，其中只有33%的DQ单倍型能够可靠推断。总样本中存在的36种DQA1 - DQB1单倍型符合已知的允许异二聚体模式。本文首次报道了4种DQA1 - DQB1单倍型，均很罕见。单倍型频率表适合作为欧裔美国人DR和DQ位点HLA分型的参考标准。
