HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales
HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales
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DOI：
10.1159/000019057
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Thomas, M
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文献类型：
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作者：
Darke, C;Guttridge, MG;Thomas, M
在正常人群中HLA-A、B、DR和DQ表型、基因和单倍型频率（HF）的准确估计在例如疾病易感性研究、血小板输注支持和移植中是重要的。HLA群体遗传学研究已经在许多群体中进行，然而，没有在威尔士人口中进行过重大研究。作为我们常规HLA-A和B分型的验证过程的一部分，使用序列特异性引物（PCR-SSP），我们检查了1,798名正常的，无关的高加索人献血者生活在威尔士，并招募到威尔士骨髓供体登记处（WBMDR）。通过血清学（HLA-A、B）和低分辨率的PCR-SSP（HLA-A、B、DR、DQ）进行分型，从而产生特别严格的HLA特异性分配水平。HLA-A、B血清学与PCR-SSP的特异性分配存在4个差异：（1）2例HLA-A2血清学未被PCR-SSP检出，为一个新的HLA-A2等位基因- A*0224;（2）1例PCR-SSP检测HLA-B*15不与血清学反应，且在随后的样本中仍不能被血清学检测到，（3）1例血清学HLA-B45经PCR-SSP鉴定为HLA-B*5002。Hardy-Weinberg分析和纯合子分析结果显示拟合优度良好（p > 0.05）。对于所有四个基因座，表型分布和鉴定的纯合子的数量。所鉴定的18种HLA-A、34 -B、15 -DR和8 -DQ特异性的表型和基因频率以及HLA-A/B、B/DR、DR/ DQ和HLA-A/B/DR和B/DR/ DQ的两个和三个位点HF、连锁不平衡和相关值基本上是典型的北方欧洲人群。HLA-A2、B44、DR 4和DQ 2是出现频率最高的表型，HLA-A2403、A34、A74、B42、B75、B2708、B48、B67和B703仅出现一次。没有A36、A43、A69、A80、B46、B54、B59、B73、B76、B77、B7801、B8101或DR 18特异性的例子。DR 17、DQ 2和A1、B8、DR 17是出现频率最高的两位点和三位点单倍型。在87.0%（1,564）的受试者中鉴定出不同的HLA-A、B、DR表型。当考虑HLA-DQ时，在89.1%（1，602）的受试者中鉴定出不同的四个位点表型。该频率信息将有益于作为疾病易感性研究的高质量参考对照，并计算在患者的大家庭中识别骨髓供体的机会。该过程成功验证了我们的HLA-A和-B PCR-SSP分型程序，结果表明，以前仅通过血清学分型的WBMDR面板供体的特异性分配水平准确。
Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele - A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05). for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/ DQ and HLA-A/B/DR and B/DR/ DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and Al, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient's extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.