基于层次化系统模型研究复杂疾病表型的遗传调控机制

项目名称： 基于层次化系统模型研究复杂疾病表型的遗传调控机制

项目编号： No.31200998

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 张帆

作者单位： 哈尔滨医科大学

项目金额： 20万元

中文摘要： 遗传因素在疾病发生和发展中的作用机制一直是科学研究的前沿和热点，对于复杂疾病的诊断和治疗具有重要指导意义。这里我们提出层次化的系统模型来研究从基因型到疾病等复杂表型的遗传调控问题。通过整合SNP基因型谱、基因表达谱、分子互作网络和疾病表型数据等多层面信息，来构建遗传变异->基因表达变异->分子间互作改变->通路或网络扰动->细胞功能失调->表型变异的层次化系统模型。基于模式生物进行模型有效性的验证，并构建包括多个物种和组织的整合数据分析平台，为人类常见疾病等复杂表型的遗传调控机制研究提供有益的探索和启示，并给予一定的数据和方法支持。

中文关键词： 遗传扰动；表观遗传调控；复杂疾病；层次化系统；网络扰动

英文摘要： Understanding the hereditary basis of disease susceptibility is alongstanding goal of genetics research, and it is essential for diagnosis and therapy of complex diseases. Here we propose a hierarchical system model to study the mechanistic links from the measured genotypes to the observed complex phenotypes. By integrating SNPgenotype profiling, gene expression, molecular network and disease phenotype data, we constructed the model and apply it to dissect how genetic variations may affect phenotype through a series of hierarchical levels, with genetic variation at the base of this hierarchy affecting higher processes, such as gene expression change, molecular interactions rearrangement, pathway and network reorganization, and cell function disordering. We then assessed the effectiveness of our model based on model organisms, and implemented an integrative data analysis platform, including data from multiple species and tissues. This comprehensive model provides insight into genetic regulation mechanism of common diseases and supports complex phenotype research in both data and analysis methodologies.

英文关键词： genetic perturbation；epigenetic regulation；complex disease；hierarchical system；network perturbation