Identifying Downs Syndrome Heart Defect Candidate Genes

识别唐氏综合症心脏缺陷候选基因

• 批准号: 6741226
• 负责人: LORA J BEAN
• 金额: $ 4.64万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741226
• 关键词: Downs syndrome; animal tissue; biotechnology; cardiovascular disorder risk; case history; child (0-11); chromosome 21; clinical research; comorbidity; congenital heart disorder; congenital heart septum defect; environmental exposure; family genetics; gene environment interaction; gene expression; genetic registry /resource /referral center; genetic susceptibility; genotype; human subject; linkage mapping; polymerase chain reaction; postdoctoral investigator; quantitative trait loci; single nucleotide polymorphism; statistics /biometry

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.

描述（由申请人提供）：与一般人群相比，唐氏综合征（DS）患者发生完全性房室间隔缺损（AVSD）的风险增加500倍，AVSD是一种严重的先天性心脏病（CHD），对该人群的发病率和死亡率有显著影响。本研究的目的是在具有完全AVSD的DS人群中使用候选基因方法来识别导致CHD易感性的环境暴露和21号染色体上的遗传变异。具体而言，1）将通过表征人胎儿和成人心脏组织中的转录本表达来优先考虑10 Mb DS心脏关键区域内的候选基因，2）我们目前的DS伴AVSD人群将扩大，以促进流行病学和相关性研究，和3）候选基因中的单核苷酸多态性将被基因分型，以利用开发用于以下的统计方法进行关联研究：三体群体