先天性心脏病（CHD）是一类最常见的出生缺陷，但目前已知的遗传变异仅能解释其中一小部分病例，且主要聚焦于蛋白编码基因。基因组非编码区尤其是长链非编码RNA（lncRNA）已被证明在胚胎发育、器官形成等过程中发挥重要的调控作用，但lncRNA与CHD的关系还鲜有报道。本课题组的前期研究结果显示，通过序列变异分析可发现与CHD致病基因表达有关的lncRNA。本研究拟依据现有的lncRNA及CHD致病基因相关信息，筛选与CHD相关的候选lncRNA；通过对500例CHD患者及500例正常对照样本进行高通量靶向测序，结合生物信息学分析及共表达实验筛选与CHD相关的lncRNA；通过敲减/过表达相关lncRNA，以揭示其导致CHD发生的机制。本项目将从序列变异角度出发，研究与CHD相关的lncRNA，将有助于发现新的CHD分子标志物，为其早期分子诊断与干预提供新的理论依据。

Congenital heart disease (CHD) represents the most common birth defects. However, the identified genetic variants, which are mainly composed of protein coding genes, could only explain a small fraction of all CHD cases. Recently, the noncoding regions, especially the long noncoding RNA (lncRNA) have been proven to play important regulatory roles in processes such as embryonic development and organogenesis, etc. However, few investigation of relationship between lncRNA and CHD has been reported. Our previously study revealed that sequence variants-based approach could help finding CHD-related lncRNA. To systematically reveal the association of lncRNA and CHD, we intend to select candidate CHD lncRNA genes based on perform high throughput target sequencing for 500 clinically characterized patients with CHD and 500 normal controls，and combinate with co-expression analysis using cell models to identify CHD associated lncRNAs; Furthermore, regulatory mechanism would also be investigated by knock-down or over-expression CHD associated lncRNA. The project would from the variants point of view, reveal the role of lncRNA in the pathogenesis of CHD, help to find new biomarker of CHD and provide the basis for the early molecular diagnosis and intervention of CHD.