项目名称: 基于同卵双生非共患孤独症的表观遗传修饰及验证研究
项目编号: No.81202221
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 预防医学、地方病学、职业病学、放射医学
项目作者: 梁爽
作者单位: 哈尔滨医科大学
项目金额: 23万元
中文摘要: 孤独症是一种成因十分复杂的神经发育障碍性疾病,病因不明。目前已有的遗传学研究结果仅能解释孤独症病因的10-20%,而越来越多的证据显示表观遗传学可能在孤独症的病因学研究中发挥重要作用。双生子研究一直是遗传学与表型研究中的重要方法,本研究选取表观遗传学研究最有代表性的样本-同卵双生非共患孤独症患儿,利用最新的全基因组甲基化芯片技术,寻找可能导致表型差异的DNA甲基化异常修饰位点或片段,分析其与不同基因甲基化改变的相关性,以及探讨多个相关基因、多个相关甲基化片段之间的关联性,筛选孤独症发生相关的甲基化异常修饰,并在大样本的家系、病例-对照研究中采用bisulfite测序方法进行验证,以解释同卵双生子在遗传物质基础和结构均相同的情况下所出现的表型差异,并从DNA甲基化的角度探讨孤独症的可能的致病原因,为深入开展孤独症的病因学研究提供重要依据。
中文关键词: 孤独症;甲基化;差异位点;同卵双生非共患双胞胎;ESR2
英文摘要: Autism is a very complex neuro-developmental disorder, remains unclear etiology.Nowadays,the genome studys have shown that genetic contribution to the etiology of autism can reach only 10-20%,and more and more study shows epigenetics would be very important for autism etiology.Twins study is always the important way for study between genetics and phenotype.This study selects the best sample for epigenetics- monozgtic twins discordant for autism to screen the abnormal methylation modification by the newest genome-wide methylation chip, which can cause MZ twins with diverse phenotypes,to analysis the relation and association with other genes methylation.And then, we will identify the abnormal modication loci in a lagre sample of trios and case-control by bisulfite sequencing. Furthermore, we will identify the epigenetic abnomal modication loci,and find out the potential reason of different phenotypes between two MZ twins who have the same genetic materials and structure,and explore the etiology of autism at the DNA methylation level.Finally,we can provide a new target evidence for the molecular diagnosis of autism.
英文关键词: autism;methylation;different loci;monozygotic discordant twins;ESR2