Doherty D G, Vaughan R W, Donaldson P T, Mowat A P
Department of Child Health, King's College Hospital and School of Medicine and Dentistry, London, England.
Hum Immunol. 1992 May;34(1):53-63. doi: 10.1016/0198-8859(92)90085-2.
A precise method for comprehensive HLA DQA and DQB genotyping using gene amplification and hybridization with sequence-specific oligonucleotide (SSO) probes is described. Twenty-four SSO probes were used to detect all DQ allotypes defined by nucleotide sequence variation in the second exons of the DQ genes, using a standard set of conditions for all probes at each locus. Five hundred individuals were genotyped for 8 DQA1 and 16 DQB1 alleles by using this method and for 33 alleles of the DRB1, DRB3, DRB4, and DRB5 genes by using previously described SSO probes. The 4-locus DQB1-DQA1-DRB1-DRB3/4/5 haplotypes present were characterized on the basis of known linkage disequilibrium between class II alleles. Fifty-two different haplotypes that have previously been described were further characterized at the nucleotide sequence level and two novel haplotypes were identified. The distributions of these alleles and haplotypes in 177 randomly selected healthy Caucasoid controls from the United Kingdom are reported. These results identify further haplotypic diversity in the HLA class II region, even though strong linkage disequilibrium exists between the DR and DQ gene loci.
描述了一种使用基因扩增和与序列特异性寡核苷酸（SSO）探针杂交进行全面HLA DQA和DQB基因分型的精确方法。使用24个SSO探针检测由DQ基因第二外显子中的核苷酸序列变异定义的所有DQ同种异型，在每个位点对所有探针使用一组标准条件。通过使用该方法对500个人进行了8个DQA1和16个DQB1等位基因的基因分型，并通过使用先前描述的SSO探针对DRB1、DRB3、DRB4和DRB5基因的33个等位基因进行了基因分型。基于II类等位基因之间已知的连锁不平衡，对存在的4位点DQB1-DQA1-DRB1-DRB3/4/5单倍型进行了表征。对先前描述的52种不同单倍型在核苷酸序列水平上进行了进一步表征，并鉴定出两种新的单倍型。报告了这些等位基因和单倍型在来自英国的177名随机选择的健康白种人对照中的分布情况。这些结果确定了HLA II类区域中进一步的单倍型多样性，尽管DR和DQ基因座之间存在强连锁不平衡。
