染色体20q12区域遗传变异与中国人群非综合征型唇腭裂遗传机制的研究

项目名称： 染色体20q12区域遗传变异与中国人群非综合征型唇腭裂遗传机制的研究

项目编号： No.81200808

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 潘永初

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 非综合征型唇腭裂（简称NSOC）是一类严重危害儿童身心健康的出生缺陷，在我国高发。其病因和具体发病机制仍未阐明。最近，Beaty等学者开展的一项NSOC全基因组关联研究发现位于染色体20q12区域的 rs13041247是NSOC易感位点，本课题组的研究也证实该位点为中国人群NSOC易感位点。但是目前尚未在中国人群中对此区域进行其他位点的筛选及功能学研究。本课题在前期研究的基础上，通过生物信息学确定该区域候选SNPs，拟在大样本的病例-对照研究中，探讨该区域SNPs与中国人群NSOC发病风险的关系，分析评价基因型-临床表型相关性以及基因-环境交互作用。在此基础上，采用一系列细胞分子生物学手段进一步探讨SNPs的功能学效应，阐明染色体20q12区域SNPs参与NSOC发生发展的可能生物学机制，为寻找与NSOC发病相关的生物学标志物，开展早期筛检，实施切实有效的预防措施，控制发病提供科学依据。

中文关键词： 非综合征型唇腭裂；MAFB；单核苷酸多态性；病例对照研究；

英文摘要： Non-syndromic orofacial clefts (NSOC) are kinds of birth defects harmful to the physical and mental health of children, with a high incidence in China. Its etiology and pathogenesis is not yet clarified. Recently, a genome-wide association studies conducted by Beaty and his colleague found that rs13041247, located on chromosome 20q12 was a NSOC susceptibility loci, which was also confirmed in our study. However, none research has been performed on the screening and functional analysis of this area in Chinese populations. On the basis of our preliminary studies, we firstly employ bioinformatics to pick out the candidate SNPs in the region and then design a large sample size of case-control study to explore the associations between the genetic variations in the region and NSOC susceptibility, inluding genotype-phenotypes correlation and gene-environment interaction. Then, a series of cellular and molecular biology methods was further applied to explore their functional effects, aimming to clarify the possible biological mechanisms of SNPs in the development of NSOC. Therefore, the project will be helpful to the finding of biological markers of NSOC, as well as early screening and prevention.

英文关键词： Non-syndromic orofacial clefts；MAFB；single nucleotide polymorphism；case-control study；