中国汉族人发作性睡病的遗传变异机制研究

项目名称： 中国汉族人发作性睡病的遗传变异机制研究

项目编号： No.81501145

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 郑厚峰

作者单位： 杭州师范大学

项目金额： 19万元

中文摘要： 发作性睡病是一种慢性非进行性睡眠障碍，是以不可抗拒入睡等为特征的复杂疾病，突然入睡常可造成患者意外死亡。先前的GWAS研究已经发现6个易感基因。本项目拟深入挖掘发作性睡病的分子遗传学机制，首先加大GWAS样本量，做SNP基因分型推演，增加基因组的SNP密度和罕见变异的数量，并探索一种新的数据分析思路，重新做关联分析，定义目标基因，之后我们利用二代测序技术对目标基因外显子进行测序，发现罕见变异。通过该研究期望发现：1）先前GWAS未发现的新的易感基因；2）罕见变异与疾病的关联性；3）基因间交互作用。我们将进一步利用Real-Time PCR研究基因在外周血的mRNA表达，从功能角度证实基因与发作性睡病的关系。我们将估计所有发现的易感基因和变异对疾病遗传的贡献度，并建立疾病预测模型。该项目立项，将发现更多的发作性睡病易感基因和变异，为疾病的诊断、治疗、预防及风险预测提供基础。

中文关键词： 发作性睡病；单核苷酸多肽性；关联分析；二代测序；基因交互作用

英文摘要： Narcolepsy is a chronic and non-progressive neurological disorder, which affects the control of sleep and wakefulness. Sudden sleep can cause accidental death of patients. Previous GWAS have identified 6 susceptible genes for narcolepsy. The aim of this project is to mine deeper to the mechanism for narcolepsy genetics. First of all, we increase the sample size of GWAS, and increase the SNP number by genotype imputation. By re-analyzing GWAS data, we define the target genes, then target sequencing will be carried out to identify the rare variants. Through this study, we hope we can find: 1) new susceptible genes which were not identified by the previous GWAS; 2) association of rare variants and disease; 3) gene interactions. We will further use Real-Time PCR to study the gene expression in peripheral blood, to confirm the relationship between genes and narcolepsy from functional perspective. Finally, we will estimate the contribution of all susceptibility genes and variants to the risk of narcolepsy, and establish the prediction model. This project will identify more narcolepsy susceptibility genes and variants, further clarify the genetic mechanism of the disease, and lay the foundation for clinical diagnosis, treatment, disease prevention and risk prediction.

英文关键词： Narcolepsy;SNP;Association study;Next generation sequencing;Gene interaction