先心病是发病率最高的出生缺陷病种，遗传因素和环境因素均可致病。我们前期根据本实验室CNV检测数据，检索文献及DECIPHER数据库发现5q35.2-35.3可能是先心病的易感区域，然而目前尚无该区域致病基因鉴定的研究。我们前期通过eQTL分析，整合基因表达及表观调控等生物信息学分析数据，筛选出候选基因HIGD2A，进一步通过生物信息学预测和预实验初步证实HIGD2A基因启动子区SNP rs3172921所在区域可能是AP-2α调控其表达的作用靶点。本项目拟进一步通过分子生物学-细胞生物学-实验动物学的研究路线，从功能鉴定到机能验证，从细胞模型到动物模型，围绕HIGD2A基因功能及表达调控展开一系列研究，阐述HIGD2A基因参与心脏发育的过程及其异常表达导致先心病的致病机理，为先心病的预防和诊断奠定一定的理论基础，也为类似遗传病的基因鉴定、精准诊断和治疗提供一个新思路。

CHD (Congenital Heart Disease) is the most common type of birth defect. Causes of CHD are often partitioned into genetic and environmental categories. Previously, Based on the CNV test data from our laboratory, as well as results from literature and the DECIPHER database, 5q35.2-35.3 was considered to be a susceptible chromosomal region for CHD. However, none pathogenic genes within this region was identified so far. With eQTL (expression Quantitative Trait Loci) analysis to integrate bioinformatics analysis data such as gene expression and epigenetic regulation, HIGD2A was screened as an candidate gene of CHD. It was further confirmed by bioinformatics prediction and preliminary experiments that SNP rs3172921 located in the promoter of HIGD2A may be the target of AP-2α, which modulating the transcription of HIGD2A. This project aims to deeply elucidate the function of HIGD2A gene in cardiac development and pathogenesis of CHD through a series of researches in cell model to animal model according to the route of molecular biology-cell biology-experimental zoology. The results would lay a certain theoretical foundation for the prevention and diagnosis of CHD, and also provide a new idea for the genetic identification, accurate diagnosis and treatment of similar genetic diseases.