Luo Jia, Tian Wei, Pan FengHua, Liu XueXiang, Li LiXin
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan, People's Republic of China.
Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan, People's Republic of China.
Hum Immunol. 2014 Apr;75(4):383-8. doi: 10.1016/j.humimm.2013.12.010. Epub 2013 Dec 27.
In this study, the 5'promoter region of MHC class I chain-related gene A (MICA) was investigated in 104 healthy, unrelated Han individuals recruited from northern China, using PCR-sequencing method. Twelve variable sites were detected, which were in very strong linkage disequilibrium with each other. Twelve different MICA 5'promoter haplotypes were identified, among which Promoter-7 predominated (0.5529). Twenty-six extended haplotypes incorporating MICA 5'promoter and MICA exons 2-5 were observed in this population, 9 of which were in significant linkage disequilibrium (LD). Phylogenetic analysis of 5'promoter refined MICA sub-lineage structure previously constructed according to MICA coding and 3'untranslated regions. Ewens-Watterson homozygosity statistics at MICA 5'promoter region were consistent with neutral expectations. None of the five variable sites detected within the minimal promoter of MICA gene was located in the putative binding sites for transcription factor. Our study provided for the first time the sequence information about 5'promoter of MICA gene at a human population level. The data will facilitate the understanding of regulation of MICA gene expression, which represents a promising pathway for immune intervention against cancer, autoimmune disorders and infections.
在本研究中，采用聚合酶链反应测序法，对来自中国北方的104名健康、无亲缘关系的汉族个体的MHC I类链相关基因A（MICA）的5'启动子区域进行了研究。检测到12个可变位点，它们之间存在很强的连锁不平衡。鉴定出12种不同的MICA 5'启动子单倍型，其中启动子-7占主导地位（0.5529）。在该人群中观察到26种包含MICA 5'启动子和MICA外显子2-5的扩展单倍型，其中9种存在显著的连锁不平衡（LD）。对5'启动子的系统发育分析完善了先前根据MICA编码区和3'非翻译区构建的MICA亚系结构。MICA 5'启动子区域的Ewens-Watterson纯合性统计与中性预期一致。在MICA基因最小启动子内检测到的5个可变位点均不在转录因子的假定结合位点内。我们的研究首次在人群水平上提供了MICA基因5'启动子的序列信息。这些数据将有助于理解MICA基因表达的调控，这是针对癌症、自身免疫性疾病和感染进行免疫干预的一条有前景的途径。
