Pei J, Choo S Y, Spies T, Strominger J L, Hansen J A
Fred Hutchinson Cancer Research Center, Seattle, WA.
Tissue Antigens. 1991 May;37(5):191-6. doi: 10.1111/j.1399-0039.1991.tb01871.x.
We have studied restriction fragment length polymorphism (RFLP) in the region 300 kb centromeric to the HLA-B locus. Four probes were used: one was genomic DNA derived from the tumor-necrosis factor (TNF)-beta gene, one was a cDNA for the BAT3 gene, and two single-copy genomic probes, R5A and M20A. The order of these markers from HLA-B towards the centromere is M20A, R5A, TNF and BAT3. The BAT3 and TNF-beta probes each detected two allelic bands with Taq I and Nco I digestion, respectively; the R5A and M20A probes each detected three polymorphic allelic bands with BstEII digestion. To determine if these restriction polymorphisms are preferentially associated with certain HLA-B and -DR haplotypes, a total of 153 HLA haplotypes was analyzed. The haplotypes A1, B8, DR3 and A3, B7, DR2 were each associated with a distinct combination of polymorphisms identified at these four sites, thereby demonstrating that the strong linkage disequilibrium characteristic of these haplotypes extends also to this segment of the class III region. In contrast, haplotypes that are not in positive linkage disequilibrium, such as A1,B8,DR4 and A2,B7,DR3, showed no preferential association with any of these polymorphisms. The antigens HLA-B27 and B35 were also found to be in positive linkage disequilibrium with RFLP patterns at three of these sites, and HLA-B14,B35,B44,Bw57 and Bw62 were found preferentially associated with polymorphisms at one or two of these sites, independent of the DR antigen present. These data further demonstrate that genetic linkage disequilibrium in the HLA class III region is complex and variable among different HLA haplotypes.
我们研究了HLA - B基因座着丝粒方向300 kb区域内的限制性片段长度多态性（RFLP）。使用了4种探针：一种是源自肿瘤坏死因子（TNF）-β基因的基因组DNA，一种是BAT3基因的cDNA，以及两种单拷贝基因组探针R5A和M20A。这些标记从HLA - B向 着丝粒的顺序是M20A、R5A、TNF和BAT3。BAT3和TNF - β探针分别用Taq I和Nco I消化检测到两条等位基因带；R5A和M20A探针用BstEII消化各自检测到三条多态性等位基因带。为了确定这些限制性多态性是否优先与某些HLA - B和 - DR单倍型相关，共分析了153种HLA单倍型。单倍型A1、B8、DR3和A3、B7、DR2各自与在这四个位点鉴定出的多态性的独特组合相关，从而证明这些单倍型的强连锁不平衡特征也延伸到了III类区域的这一片段。相比之下，不存在正向连锁不平衡的单倍型，如A1、B8、DR4和A2、B7、DR3，与这些多态性中的任何一种均无优先关联。还发现抗原HLA - B27和B35在其中三个位点与RFLP模式呈正向连锁不平衡，并且发现HLA - B14、B35、B44、Bw57和Bw62优先与其中一个或两个位点的多态性相关，与存在的DR抗原无关。这些数据进一步证明HLA III类区域中的遗传连锁不平衡是复杂的，并且在不同的HLA单倍型之间存在差异。
