Fellowship: Identifying genes that prevent mitochondrial DNA deletions: a targete

奖学金：识别防止线粒体 DNA 缺失的基因：目标

• 批准号: 8255121
• 负责人: Katie Anne Clark
• 金额: $ 4.92万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8255121
• 关键词: Age; Aging; Animal Model; Animals; Area; Caenorhabditis elegans; Candidate Disease Gene; Cardiac; Cells; DNA Damage; DNA biosynthesis; Deletion Mutation; Diagnosis; Disease; Fellowship; Fertility; Functional disorder; Gene Targeting; Generations; Genes; Genetic; Genome; Goals; Health; Human; Individual; Mitochondria; Mitochondrial DNA; Mitochondrial Diseases; Mitochondrial Myopathies; Modeling; Molecular; Nematoda; Pathway interactions; Play; Prevention; Process; RNA Interference; Research; Role; Screening procedure; System; Testing; base; experience; human disease; mitochondrial DNA mutation; mitochondrial genome; mutant; prevent; research study

DESCRIPTION (provided by applicant): In humans, both aging diseases such as cardiac dysfunction are associated with the formation of large deletion mutations in the mitochondrial genome (mtDNA). Despite the prominent role of large mtDNA deletions in human aging and disease, the exact molecular mechanism of mtDNA deletion formation remains unknown. I propose to use the model nematode, Caenorhabditis elegans, as a system to genetically screen for genes that are associated with the formation or accumulation of large mtDNA deletion mutations. The identification of the gene(s) responsible for preventing the formation or accumulation of mtDNA deletions would open up fundamentally new scientific avenues for dissecting the genetic pathways associated with mtDNA deletion formation. Genes identified by this study can be considered as new gene targets for human disease for both diagnosis and treatment. PUBLIC HEALTH RELEVANCE: Mitochondria are the "powerhouses" that create energy in cells. Damage to the mitochondria is associated with both aging and disease in humans. This goal of this research is to use the well-characterized model animal Caenorhabdidits elegans to identify the gene(s) involved in the formation of mitochondrial DNA damage in human disease.

描述（由申请人提供）：在人类中，两种衰老疾病如心功能障碍都与线粒体基因组（mtDNA）中大缺失突变的形成有关。尽管线粒体DNA大片段缺失在人类衰老和疾病中起着重要作用，但其确切的分子机制仍不清楚。我建议使用的模式线虫，秀丽隐杆线虫，作为一个系统来遗传筛选与大的mtDNA缺失突变的形成或积累相关的基因。确定负责防止mtDNA缺失形成或积累的基因将为解剖与mtDNA缺失形成相关的遗传途径开辟全新的科学途径。本研究发现的基因可作为人类疾病诊断和治疗的新基因靶点。 公共卫生相关性：线粒体是在细胞中产生能量的“发电站”。线粒体的损伤与人类的衰老和疾病有关。本研究的目的是使用特征良好的模式动物秀丽隐杆线虫来鉴定参与人类疾病中线粒体DNA损伤形成的基因。