Identification of Disease Genes for Atrial Fibrillation

心房颤动疾病基因的鉴定

• 批准号: 7534019
• 负责人: Timothy Mark OLSON
• 金额: $ 28.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-20 至 2010-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534019
• 关键词: African; Aging; Arrhythmia; Atrial Fibrillation; Candidate Disease Gene; Cardiac; Chromosome Mapping; Chromosomes, Human, Pair 1; Defect; Disease; Epidemic; European; Family; Frequencies; Genes; Genetic; Haplotypes; Inherited; Ion Channel; Lead; Location; Maps; Membrane Proteins; Molecular; Morbidity - disease rate; Mutation; Mutation Spectra; Nuclear Envelope; Pathogenesis; Patients; Physiological; Population; Prevention; Recruitment Activity; Reporting; Sodium Channel; Syndrome; Testing; Work; base; cohort; gene discovery; genetic linkage analysis; genome-wide linkage; improved; insight; mortality; novel; socioeconomics

Atrial fibrillation (AF) is the most common sustained arrhythmia, reaching epidemic proportions in the aging U.S. population and resulting in significant morbidity, mortality, and socioeconomic burden. Preliminary studies indicate that idiopathic or lone AF is familial in at least 15% of patients, highlighting the importance of genetic factors in the pathogenesis of this disorder. The overall objective of this study is to identify genes for AF by linkage and mutational analyses. The first aim is to determine the chromosomal location of AF genes by genome-wide linkage analyses. Mapping studies will be carried out in 4 large families with autosomal dominant AF in which linkage to known loci for AF have been excluded. The second aim is to identify mutations in candidate genes for AF based on chromosomal location, cardiac expression, and physiological rationale. Novel genes, once identified, will be screened for additional inherited and de novo mutations in a cohort of 154 unrelated patients with familial and sporadic AF. The third aim is to determine the frequency and spectrum of heritable ion channel and nuclear membrane defects in racially-diverse cohorts with lone AF. The long-term objectives of this work are to gain new insights into molecular mechanisms of arrhythmogenesis and to improve prediction, prevention, and treatment of AF.

心房颤动（AF）是最常见的持续性心律失常，在衰老中达到流行病 美国人口，导致大量发病率，死亡率和社会经济负担。初步的 研究表明，在至少15％的患者中，特发性或唯一的AF是家族性的，强调了重要性 该疾病发病机理中的遗传因素。这项研究的总体目的是确定 通过连锁和突变分析的AF基因。第一个目的是确定染色体位置 通过全基因组链接分析的AF基因的AF基因。将在4个大家庭中进行映射研究 常染色体显性AF，其中排除了与已知基因座的链接。第二个目标是 基于染色体位置，心脏表达和 生理原理。一旦确定的新基因将被筛选以进行其他继承和从头开始 154例家族性和零星AF患者的队列中的突变。第三个目的是确定 种族多样性中可遗传离子通道和核膜缺陷的频率和光谱 与唯一AF的队列。这项工作的长期目标是获得对分子的新见解 心律失常的机制并改善AF的预测，预防和治疗。