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Identifying a Gene for Canine Cardiomyopathy

鉴定犬心肌病基因

基本信息

批准号：
6910844
负责人：
PETRA M JAKOBS
金额：
$ 18.88万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-10 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6910844
关键词：
atrial fibrillation autosomal dominant trait congestive heart failure disease /disorder model dogs gene mutation genetic screening genetic strain human data linkage mapping ventricular hypertrophy

项目摘要

DESCRIPTION (provided by applicant): Atrial fibrillation (AF) causes significant morbidity, disability, and mortality related to heart disease and stroke in the human population. Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation and systolic contractile dysfunction and is an important cause of heart failure. In some canine breeds, DCM is a relatively common, lethal disease. A recent study of 500 Irish Wolfhounds (IW) found that 24% had DCM; 88% of these affected dogs also had AF. The DCM/AF phenotype appears to be inherited as an autosomal dominant trait. We have collected DNA and clinical data from a large family of IW in which AF and progressive DCM is segregating. Our hypothesis is that a mutation in a single gene causes DCM/AF in IW, and we propose to map this gene by linkage analysis and to use the tools of positional cloning and candidate gene analysis to identify the gene. One of the most common genetic causes of human DCM is mutation in the lamin A/C gene. The phenotype caused by lamin A/C mutations in such patients also includes conduction system disease and therefore resembles the DCM/AF phenotype in IW. In preliminary studies, we have excluded lamin A/C as the locus of the defect in IW. Hence our proposed work presents an ideal opportunity to identify a novel DCM/AF disease gene. If successful, this may lead to improved knowledge of the mechanisms of DCM and AF in humans.

描述(由申请人提供)：房颤(AF)在人类人群中会导致与心脏病和中风相关的显著发病率、残疾和死亡率。扩张型心肌病(DCM)以心室扩张和收缩功能障碍为特征，是心力衰竭的重要原因。在一些犬种中，扩张性心肌炎是一种相对常见的致命疾病。最近一项对500只爱尔兰猎狼犬(IW)的研究发现，24%的狗患有扩张型心肌炎；这些受影响的狗中有88%还患有房颤。DCM/AF表型似乎是遗传的常染色体显性性状。我们收集了一个IW大家族的DNA和临床数据，在这个家族中，房颤和进行性DCM是分开的。我们的假设是单个基因的突变导致了IW的DCM/AF，我们建议通过连锁分析来定位该基因，并使用位置克隆和候选基因分析的工具来鉴定该基因。人类弥漫性心肌病最常见的遗传原因之一是层蛋白A/C基因突变。在这类患者中，由lamin A/C突变引起的表型也包括传导系统疾病，因此与IW中的DCM/AF表型相似。在初步研究中，我们排除了层蛋白A/C作为IW缺陷的部位。因此，我们提出的工作为鉴定新的DCM/AF疾病基因提供了一个理想的机会。如果成功，这可能会提高对人类扩张性心肌病和房颤机制的了解。