Identifying Downs Syndrome Heart Defect Candidate Genes

描述(申请人提供)：与普通人群相比，唐氏综合症(DS)患者患完全性房室间隔缺陷(AVSD)的风险增加了500倍，AVSD是一种严重的先天性心脏缺陷(CHD)，对该人群的发病率和死亡率有显著影响。本研究的目的是使用候选基因方法，在具有完整的房间隔缺损的DS人群中，确定环境暴露和21号染色体上的遗传变异对CHD易感性的影响。具体地说，1)10Mb DS心脏关键区域内的候选基因将通过表征人类胎儿和成人心脏组织中的转录表达而被优先考虑；2)我们目前与AVSD人群的DS将得到扩展，以促进流行病学和关联性研究；3)候选基因中的单核苷酸多态将被分型，以利用为三体人群开发的统计方法进行关联研究。

DESCRIPTION (provided by applicant): Compared to the general population, individuals with Down syndrome (DS) are at a 500-fold increased risk for complete atrioventricular septal defects (AVSDs), a severe form of congenital heart defect (CHD) that significantly impacts morbidity and mortality in this population. The purpose of this study is to identify environmental exposures and genetic variants on chromosome 21 that contribute to CHD susceptibility using a candidate gene approach in a DS population with complete AVSDs. Specifically, 1) candidate genes within the 10Mb DS heart critical region will be prioritized by characterizing transcript expression in human fetal and adult heart tissue, 2) our current DS with AVSD population will be expanded to facilitate epidemiological and association studies, and 3) single nucleotide polymorphisms in candidate genes will be genotyped to conduct an association study utilizing statistical methods developed for use with trisomic populations.