青海藏族及土族先天性心脏病相关基因突变的研究

高原地区CHD发病率及各亚型构成比与平原地区有所不同。藏族和土族为高原世居民族，先心病的发病率较高，国内外没有进行过高原地区藏族及土族CHD遗传学机制的研究。本课题将完成拥有700例高原少数民族先心病样本，及700例健康对照的图象信息、核心数据库和专业数据库组成的藏族和土族先心病遗传资源库。利用飞行时间质谱技术在高原少数民族先心病患者及对照群体中进行基于先心病的候选基因标签SNP的关联分析研究；对初步筛选到的基因编码区及剪切序列，利用测序的手段，进行突变筛查，利用生物信息学分析，分析突变对蛋白质结构和功能的影响，结合临床资料分析，最终获得先心病易感基因及其对先心病发病的遗传学贡献。该项目对阐明高原先心病的遗传学机制，揭示高原先心病病因有重要意义，并为进一步对先心病患者进行出生前诊断、分子分型及个体化治疗提供支持。

The incidence and constitute of congential heart disease at high altitude are different from the ones at plain. As the long-term inhabitant nationalities, Tibit and Tu have high incidence of CHD. There are not any study about genetic mechanism of CHD in these nationalities at high altitude. First,a CHD genetic resource library of tibiten and tu nation composed with image information, core data base and professional data base will be estabished while anylized 700 sample of high altitude inhabitants and 700 sample of compared group. Second,an association analysis besed on tag of candidate gene labled SNP was porformed in CHD pentients and control group by using flight time mass-spectrum technique. And than, mutation screening of the cording region and shearing sequence of the pro-selected genes will be preformed. Analyzing the impact of the mutation to the structure and function of the proteins, and combining with the clinic information, we will get the predisposing gene of CHD and contribute to the genetic of CHD. This study have very important impact on illuminating the gentic machanism of CHD at high altitude and reviewing the etiologic factors of CHD. This study also will benefit for the clinic dignosis and treatment.