人类淋巴母细胞系中基因与DNA甲基化上位效应对基因表达作用的研究

项目名称： 人类淋巴母细胞系中基因与DNA甲基化上位效应对基因表达作用的研究

项目编号： No.31471212

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘贇

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 表观遗传修饰（如DNA甲基化）可以同时受到遗传及环境因素的影响，进而调控个体表型的可塑性。我们的前期工作发现DNA甲基化可以受到基因的调控，进而导致类风湿性关节炎的发生。但是目前的研究工作仍然没能发现那些不受DNA序列调控的，导致疾病发生的表观遗传修饰改变。这可能归因于传统的关联分析忽视了基因型与表观遗传修饰之间的相互作用对疾病表型的影响，即上位效应。本项目计划以国际千人基因组计划的淋巴母细胞系为研究对象，通过整合已有的基因变异与表达数据和本项目产生的DNA甲基化谱，研究DNA甲基化与基因序列相互作用对基因表达的调控机制，揭示表观遗传上位效应的模式和规律，发现一批同时受到遗传及表观遗传调控的重要功能基因。通过整合遗传学和表观遗传学的新角度，探索出一条认知人类复杂疾病产生机理机制的崭新道路。

中文关键词： DNA甲基化；表观遗传学；基因组；基因表达

英文摘要： Epigenetic modifications such as DNA methylation can integrate both genetic and environmental cues and are critical for phenotypic plasticity. Our previous work shows that DNA methylation can mediate genetic risk for rheumatoid arthritis. However, our works, as well as others, still failed to identify any epigenetic changes unrelated to the DNA sequence itself that may lead to diseases. One potential reason is the role of epistasis in which disease susceptibility is controlled by the interaction between genetic and epigenetic variants. In this case, the associations between epigenetic modifications and phenotype are marginal significant and are neglected through a conventional genome-wide approach. In this project, we propose to study potential epistatic interactions between genetic variants and DNA methylation on gene expression in human lymphoblastoid cell lines (LCLs) from 1000 Genomes Project. This project bears substantial significance to reveal the role of epigenetic epistasis on gene expression and human common diseases. Through integrating both genetic and epigenetic information, this will help us towards development of new predictive, preventive and therapeutic strategies.

英文关键词： DNA Methylation;Epigenetics;Genomics;Gene Expression