Identifying a Gene for Canine Cardiomyopathy

鉴定犬心肌病基因

• 批准号: 6755173
• 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
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-10 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6755173
• 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

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）导致人群中与心脏病和卒中相关的显著发病率、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。 在某些犬种中，扩张型心肌病是一种相对常见的致命疾病。最近对500只爱尔兰猎狼犬（IW）的研究发现，24%患有DCM; 88%的这些受影响的狗也患有AF。DCM/AF表型似乎是作为常染色体显性性状遗传的。我们从一个IW大家族中收集了AF和进行性DCM分离的DNA和临床数据。我们的假设是，在一个单一的基因突变导致DCM/AF在IW，我们建议定位该基因的连锁分析，并使用定位克隆和候选基因分析的工具来确定该基因。 人DCM最常见的遗传原因之一是核纤层蛋白A/C基因突变。在此类患者中由核纤层蛋白A/C突变引起的表型也包括传导系统疾病，因此类似于IW中的DCM/AF表型。在初步研究中，我们已经排除核纤层蛋白A/C作为IW缺陷的位点。因此，我们提出的工作提供了一个理想的机会，以确定一个新的DCM/AF疾病基因。如果成功的话，这可能会提高对人类DCM和AF机制的认识。