Tian W, Li L-X, Wang F, Luo Q-Z, Yan M-Y, Yu P, Guo S-S, Cao Y
Department of Immunology, Central South University Xiang-Ya School of Medicine,Changsha, Hunan, China.
Int J Immunogenet. 2006 Aug;33(4):241-5. doi: 10.1111/j.1744-313X.2006.00605.x.
Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICADel) were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B46, -B60, -B13, and -B15, and MICAA5, MICAA5.1 and MICAA4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B13 and MICAA4, HLA-B38 and MICAA9, HLA-B58 and MICAA9, HLA-B46 and MICAA5, HLA-B51 and MICAA6, HLA-B52 and MICAA6, and HLA-B60 and MICAA5.1, were observed. HLA-B48 was linked to MICAA5, MICAA5.1 and MICADel. HLA-B5801-MICAA10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor-recipient HLA matching in clinical transplantation and HLA-linked disease association.
主要组织相容性复合体（MHC）I类链相关基因A（MICA）位于HLA - B着丝粒方向46 kb处，编码一种应激诱导蛋白。MICA等位基因变异被认为与疾病易感性以及对移植的免疫反应有关。本研究旨在调查中国南方汉族人群中人类白细胞抗原（HLA）- B与MICA基因第5外显子中的（GCT）(n)短串联重复序列（MICA - STR）之间的单倍型多样性和连锁不平衡。在中国南方湖南省收集了58个随机选择的核心家庭，共183名成员，包括85个无关的亲代样本。通过聚合酶链反应 - 序列特异性引物（PCR - SSP）进行HLA - B基因分型，对显示新的HLA - B - MICA - STR连锁的样本通过高分辨率PCR - SSP进一步进行HLA - B等位基因变异分型。通过荧光PCR - 大小测序和PCR - SSP检测MICA - STR等位基因变异和MICA基因缺失（MICADel）。通过家系分离分析确定单倍型。对85个无关亲代样本的数据进行统计分析。在85个无关亲代样本中观察到19种HLA - B特异性和7种MICA - STR等位基因变体，其中最主要的分别是HLA - B46、- B60、- B13和- B15，以及MICAA5、MICAA5.1和MICAA4。HLA - B、MICA - STR位点的基因型分布符合Hardy - Weinberg平衡。明确确定了所有85个无关亲代样本的HLA - B - MICA - STR单倍型相位，其中包含30种HLA - B、MICA - STR单倍型组合，其中9种在文献中尚未报道。观察到某些HLA - B与MICA - STR等位基因之间存在显著的正连锁不平衡，包括HLA - B13与MICAA4、HLA - B38与MICAA9、HLA - B58与MICAA9、HLA - B46与MICAA5、HLA - B51与MICAA6、HLA - B52与MICAA6以及HLA - B60与MICAA5.1。HLA - B48与MICAA5、MICAA5.1和MICADel连锁。在一个家庭中发现了HLA - B5801 - MICAA10连锁。我们的数据表明，中国南方汉族人群中MICA - STR与HLA - B之间存在高度的单倍型多样性和强烈的连锁不平衡，这些数据将为未来的人类学研究、临床移植中供体 - 受体HLA匹配以及HLA相关疾病关联研究提供参考。
