Immunogenetics Research Group, Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan, People's Republic of China.
Hum Immunol. 2013 Jun;74(6):746-50. doi: 10.1016/j.humimm.2013.01.028. Epub 2013 Feb 1.
In this study, the 3'untranslated region (3'UTR) of MHC class I chain-related gene B (MICB) were investigated in 104 healthy, unrelated Han individuals recruited from northern China, using PCR-sequencing method. Seven polymorphic sites were detected including a 2-bp deletion/insertion, a 6-bp deletion/insertion and 5 SNPs. Seven different 3'UTR alleles were identified with frequencies ranging from 0.0048 to 0.7981. MICB(∗)005:02, the most frequent allele in this population, exhibited significant linkage disequilibrium (LD) with UTR1; MICB(∗)004:01, which was also relatively common in this population, showed strong LD with both UTR2 and UTR3 alleles. Analysis for targets of miRNAs revealed that miRNA hsa-miR-4768-5p, whose seed region binds to positions 82-88 of MICB 3'UTR, encompasses the +11800 A/G polymorphism. Ewens-Watterson homozygosity statistics at MICB coding and 3'UTR regions were consistent with neutral expectations. Phylogenetic analysis demonstrated the existence of two main MICB lineages. Our results provided for the first time the data of genetic variation in the 3'UTR of MICB gene in human populations. The findings are valuable for future studies of the mechanisms underlying MICB post-transcriptional regulation, the potential role of regulatory region of MICB gene in disease susceptibility in related ethnic groups, and will inform studies of evolution of the MHC gene complex.
本研究采用 PCR-测序法，对 104 名来自中国北方的健康、无关汉族个体的 MHC Ⅰ类链相关基因 B（MICB）的 3'非翻译区（3'UTR）进行了研究。共检测到 7 个多态性位点，包括 2 个碱基缺失/插入、6 个碱基缺失/插入和 5 个 SNP。鉴定出 7 种不同的 3'UTR 等位基因，其频率范围为 0.0048 至 0.7981。该人群中最常见的等位基因 MICB(∗)005:02 与 UTR1 表现出显著的连锁不平衡（LD）；在该人群中也相对常见的 MICB(∗)004:01 与 UTR2 和 UTR3 等位基因均表现出强 LD。miRNA 靶标分析表明，miRNA hsa-miR-4768-5p 的种子区与 MICB 3'UTR 的 82-88 位结合，包含+11800 A/G 多态性。MICB 编码区和 3'UTR 区域的 Ewens-Watterson 同质性统计与中性预期一致。系统发生分析表明，MICB 存在两个主要的谱系。本研究首次提供了人类群体 MICB 基因 3'UTR 遗传变异的数据。这些发现对于研究 MICB 转录后调控的机制、MICB 基因调控区在相关族群疾病易感性中的潜在作用以及 MHC 基因复合体进化的研究具有重要价值。
