BRWD3基因单核苷酸多态性和秦巴山区精神发育迟滞相关性研究

发布时间：2018-09-04 15:09

【摘要】：精神发育迟滞(Mental retardation, MR)是精神类疾病中最为常见的症状之一,也是导致病患终身残疾的重要原因,长期困扰人类社会的健康发展,也影响着我国的国民素质。其主要特征表现为情感、智力以及社会适应行为障碍,致病因素包括环境和遗传因素。目前,对精神发育迟滞尚缺乏有效治疗手段。精神发育迟滞的研究一直以来多采用传统的遗传学策略研究,目前已经筛选到400多个基因与MR关联,如FMR1、PAK3、DLG3等。BRWD3是新发现的X-连锁精神发育迟滞的候选基因,该基因编码8个WD40结构域和2个溴基域。这两个保守结构域突变与X-连锁精神发育迟滞关联。为分析该基因与秦巴山区MR是否存在关联性,本课题采用病例-对照样本进行关联分析,对分布于BRWD3基因上的8个SNP位点做了基因分型,并进行关联分析,实验结果显示,单位点分析后SNP位点rs12689192(A/C)和rs7049509(A/T)的核苷酸多态性和MR存在阳性关系,随后通过进一步的单倍型分析,四个单倍型区块存在显著性差异(Global P=0.00588021、Global P=0.000177345、 Global P=0.0084852、Global P=0.00130286)。论文首次发现BRWD3基因和秦巴山区汉族人MR存在相关性；该基因可能以染色质乙酰化桥接分子参与染色质结构修饰或者重塑,也可能经JAK/STATA信号途径参与学习、记忆过程以及神经系统发育调节。突变致病机制有待进一步深入研究。
[Abstract]:Mental retardation (Mental retardation, MR) is one of the most common symptoms of mental diseases and an important cause of lifelong disability. It has long troubled the healthy development of human society and affected the quality of our country. Its main characteristics are affective, intellectual and social adaptive behavioral disorders, and the pathogenic factors include environmental and genetic factors. At present, there is a lack of effective treatment for mental retardation. More than 400 genes have been screened for association with MR, such as FMR1,PAK3,DLG3 et al. BRWD3 is a newly discovered candidate gene for X- linked mental retardation. The gene encodes 8 WD40 domains and 2 bromine domains. These two conserved domain mutations are associated with X-linked mental retardation. In order to analyze the relationship between the gene and MR in Qinling and Bashan Mountains, we used the case-control sample to carry on the association analysis, did the genotyping of 8 SNP loci distributed on the BRWD3 gene, and carried on the association analysis, the experimental results showed that, The nucleotide polymorphisms of SNP locus rs12689192 (A / C) and rs7049509 (A / T) were positively correlated with MR after unit point analysis. By further haplotype analysis, there were significant differences among the four haplotype blocks (Global P0. 00588021, GPA 0. 000177345, Global P0. 0084852 Global P0. 00130286). It is the first time that BRWD3 gene is associated with MR of Han nationality in Qinba Mountain area. The gene may be involved in chromatin structural modification or remodeling by acetylated chromatin bridging molecules, and may also participate in learning through JAK/STATA signaling pathway. Memory processes and regulation of nervous system development. The pathogenesis of mutation needs further study.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.94

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