项目名称: 非综合征型唇腭裂易感基因编码和拷贝数变异的研究
项目编号: No.81470727
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 边专
作者单位: 武汉大学
项目金额: 73万元
中文摘要: 唇腭裂是人类最常见的颅颌面出生缺陷,是一组在环境因素和遗传因素相互作用下发生的复杂疾病,非综合征型唇腭裂(NSCL/P)是最常见的类型,虽然已发现一些染色体结构异常和易感基因与NSCL/P相关,但其发病的遗传机制仍然不明。本项目拟对已收集的150个中国汉族人NSCL/P核心家系,开展以下研究工作:①对以往GWAS、Meta分析、动物模型颅颌面表达分析等研究发现的与NSCL/P相关的已知易感基因进行外显子突变筛查;②利用CytoScanTM HD芯片研究NSCL/P相关的拷贝数变异;③运用外显子组测序技术找寻NSCL/P相关的未知易感基因的稀有编码变异;④对新发现的易感基因进行功能分析,研究它们之间的相互作用及突变对功能的影响。通过本项目的研究,将进一步加深我们对非综合征型唇腭裂致病机制的认识,给临床遗传咨询和疾病预防提供依据,对优生优育和提高我国出生人口质量具有重要意义。
中文关键词: 非综合征型唇腭裂;易感基因;编码变异;拷贝数变异
英文摘要: Cleft lip and palate are the most common human cranial-facial birth defects. The interaction between environment and genetic factors contributes to the etiology of this complex disease and non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common type. Although some abnormal chromosomal structure and susceptible genes have been identified to be associated with NSCL/P, the underlying genetic mechanism remains unknown. This project intends to investigate the coding variations and copy number variations of susceptible genes in Chinese Han core family with NSCL/P. The research proposals include: ① Screening exon mutations in already identified susceptible genes associated with NSCL/P; ②Analysis of copy number variation of NSCL/P by using CytoScanTM HD chips; ③ Using exome sequencing to find rare coding variations of NSCL/P unknown susceptibility genes; (4) In vivo and in vitro functional analysis of susceptible genes and dissecting the effects of mutations on gene function. This objective will faciliate our understanding of the pathogenic mechanisms of NSCL/P, providing the basis for genetic counseling and disease prevention, and improving the quality of birth population in our country.
英文关键词: Non-syndromic CL/P;Susceptible genes;Coding variations;Copy number variations