Mapping Novel Disease Genes for Dilated Cardiomyopathy

绘制扩张型心肌病的新疾病基因图谱

• 批准号: 6530307
• 负责人: Timothy Mark OLSON
• 金额: $ 25.29万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530307
• 关键词: biotechnology; clinical research; congestive heart failure; echocardiography; family genetics; gene expression; gene mutation; genetic disorder; genetic markers; genetic polymorphism; genetic screening; genotype; high throughput technology; human genetic material tag; human subject; idiopathic dilated cardiomyopathy; linkage mapping; nucleic acid sequence; pathologic process; polymerase chain reaction; southern blotting

Dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder causing congestive heart failure. Current medical therapy has minimal impact on prognosis and cardiac transplantation is the only definitive treatment for end-stage disease. The molecular and cellular mechanisms underlying DCM are poorly defined, but the importance of single gene defects in disease pathogenesis is becoming increasingly apparent. The objective of this study is to identify novel DCM genes by genetic linkage and mutational analyses. The first aim is to determine the chromosomal location of novel familial DCM genes. This will be accomplished by genome-wide genotyping and genetic linkage analyses in 3 large families with autosomal dominant DCM. Previously identified DCM genes have been excluded in these families. The second aim is to identify mutations in novel genes that cause familial DCM by linkage and sequence analyses of candidate genes mapping to DCM loci. Once novel genes for familial DCM are identified, the third aim will be to determine the role of these genes in a large cohort of unrelated patients with familial and sporadic DCM. High throughput DNA sequence analyses will be performed to identify additional inherited and de novo mutations. The long-term objectives of this work are to gain new insights into molecular mechanisms for heart failure and to improve prediction, prevention, and treatment of DCM.

扩张的心肌病（DCM）是一种可遗传的，遗传上异质性的疾病，导致充血性心力衰竭。 当前的药物治疗对预后的影响最小，心脏移植是终末期疾病的唯一明确治疗方法。 DCM基础的分子和细胞机制的定义很差，但是单基因缺陷在疾病发病机理中的重要性越来越明显。 这项研究的目的是通过遗传连锁和突变分析来鉴定新型的DCM基因。 第一个目的是确定新型家族性DCM基因的染色体位置。 这将通过3个具有常染色体显性DCM的大家族的全基因组基因分型和遗传连锁分析来实现。以前确定的DCM基因已被排除在这些家族中。 第二个目的是鉴定新的基因中的突变，这些突变通过将候选基因映射到DCM基因座的链接和序列分析引起家族性DCM。 一旦确定了家族性DCM的新基因，第三个目的是确定这些基因在大量无关家族和零星DCM的无关患者中的作用。 将进行高吞吐量DNA序列分析，以识别其他遗传和从头突变。 这项工作的长期目标是获得对心力衰竭分子机制的新见解，并改善DCM的预测，预防和治疗。