非综合征型单纯腭裂（NSCPO）是由遗传和环境因素共同作用所导致。既往研究发现低频/罕见遗传变异与欧美人群NSCPO发病相关。然而，这些遗传变异及其与环境的交互作用在中国人群NSCPO发病中的作用和机制仍不清楚。本课题组前期通过对418例NSCPO病例和健康对照的全外显子测序发现多个可能与该疾病发生相关的、特异性的低频/罕见遗传变异和基因。本研究拟进一步：1、在新收集的病例-对照、核心家系等人群中，利用靶向捕获测序技术对前期识别出的低频/罕见遗传变异进行验证。2、采用Logistic回归等方法，评估低频/罕见遗传变异与孕期吸烟、饮酒等环境危险因素的交互作用对NSCPO发病的影响。3、运用表达数量性状基因座分析、荧光素酶报告基因、斑马鱼实验等方法研究候选低频/罕见遗传变异位点的功能学意义。本研究旨在阐明低频/罕见遗传变异在中国人群NSCPO发病中的作用，并为其防控提供更多依据。

Non-syndromic cleft palate only (NSCPO) is caused by a combination of genetic and environmental factors. Previous studies have found that low/rare frequency genetic variants were associated with the pathogenesis of NSCPO in Caucasians. However, the role of low/rare frequency genetic variants and their interactions with environment in the pathogenesis of NSCPO in Chinese population remain unclear. Multiple specific low/rare frequency genetic variants and genes were found associated with the pathogenesis of NSCPO via whole exome sequencing in 418 NSCPO cases and controls in our previous study. Therefore, this study intends to: 1. use target sequencing technology in a large sample of case-control, nuclear family to validate low/rare frequency genetic variants; 2. use logistic regression and other statistical analysis methods to evaluate the influence of the interaction between low/rare frequency genetic variants and environmental risk factors; 3. perform expressing quantitative trait locus analysis, luciferase reporter assay and zebrafish experiment to explore the function of candidate low/rare frequency genetic variants. The purpose of this study was to reveal the pathogenesis of NSCPO and provide more evidence for its prevention and control.