Aerobic Running Capacity QTL's and Cardiac Performance

有氧跑步能力 QTL 和心脏性能

• 批准号: 6688265
• 负责人: GEORGE T CICILA
• 金额: $ 29.4万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688265
• 关键词: aerobic exercise; aerobiosis; cardiovascular function; gait; gene expression; genetic mapping; laboratory rat; microarray technology; nucleic acid probes; quantitative trait loci

DESCRIPTION (provided by applicant): An aerobic exercise treadmill test is used clinically to assess cardiovascular fitness, cardiovascular reserves, and as a general test of overall health status. Our long-term goal is to identify genes associated with heritable differences in aerobic exercise capacity. We evaluated treadmill aerobic running capacity in 11 inbred strains and observed a 3-fold difference in aerobic running capacity between COP and DA strains and 2) a strong correlation (r=0.86) between aerobic running performance and isolated heart performance (Langendorff-Neely). Given this large differential in aerobic capacity, we propose to identify chromosomal regions containing genes responsible for differences in aerobic running capacity observed between COP and DA rats, confirm them by constructing congenic strains, and identify strong candidate genes using differential gene expression in conjunction with gene mapping. Hypothesis 1: Aerobic running capacity is a heritable polygenic trait. The 3-fold difference in aerobic exercise capacity between the COP and DA inbred strains of rats provides a suitable substrate to identify chromosomal regions containing the genes responsible for inherited differences in aerobic running capacity; i.e. aerobic running capacity Quantitative Trait Loci (QTLs). Hypothesis 2: Gene(s) underlying the observed aerobic running capacity QTLs may be differentially-expressed in key organs, such as the left ventricle. Gene(s) responsible for an aerobic running capacity QTLs effect should map to the chromosomal region carrying the particular QTL. Genes possessing these characteristics will be superior candidates as genes responsible for, at least in part, a specific aerobic exercise capacity QTL. Specific Aim 1: to identify chromosomal regions containing genes linked to strain differences in aerobic running capacity by interval mapping. We will genotype rats present in the tails of the distribution of the aerobic running capacity phenotype. Specific Aim 2: To produce novel congenic strains by introgressing chromosomal regions containing high (or low) aerobic capacity QTL allele(s) (SPECIFIC AIM 1) into the (low (or high)) capacity inbred rat strain. These congenic strains will be phenotyped using a treadmill stress test to confirm the presence of an aerobic running capacity QTL. Specific Aim 3: To identify genes differentially-expressed in (key organs of) rats differing in aerobic running capacity, i.e., the COP and DA strains. Differentially-expressed genes that map near aerobic running capacity QTLs will be superior candidates for the gene(s) responsible for specific aerobic running capacity QTL.

描述（由申请人提供）：使用有氧运动平板试验 临床上评估心血管健康，心血管储备，并作为一个 全面健康状况的一般测试。我们的长期目标是确定基因 与有氧运动能力的遗传差异有关。我们 评价了11个近交系的跑台有氧运动能力， COP和DA菌株之间有氧运动能力的3倍差异， 2)有氧跑步成绩与运动成绩之间有很强的相关性（r=0.86）， 离体心脏性能（Langendorff-Neely）。考虑到这个巨大的差异 在有氧能力，我们建议确定染色体区域， 基因负责的差异，在有氧运动能力的观察， COP和DA大鼠，通过构建同源品系进行确认，并鉴定 使用差异基因表达结合 基因定位 假设1：有氧跑步能力是一个可遗传的多基因性状。的 3-COP和DA近交系之间有氧运动能力的倍数差异 大鼠品系提供了一种合适的基质来鉴定染色体区域 含有导致有氧跑步遗传差异的基因 能力;即有氧跑步能力数量性状基因座（QTL）。 假设2：所观察到的有氧跑步能力QTL的潜在基因可能 在关键器官如左心室中有差异表达。基因 负责有氧跑能力的QTL效应应该映射到 携带特定QTL的染色体区域。拥有这些基因的 这些特征将是上级候选者，因为基因至少负责 一个特定的有氧运动能力QTL。具体目标1：确定 含有与需氧菌菌株差异相关基因的染色体区域 运行能力区间映射。我们将基因分型大鼠目前在 有氧跑能力表型分布呈尾部分布。具体 目的2：通过染色体区域渐渗产生新的同源菌株 含有高（或低）有氧能力QTL等位基因（特异性AIM 1）的基因， （低（或高））能力近交系大鼠品系。这些同源菌株将是 使用跑步机压力测试进行表型分析，以确认有氧代谢的存在。 运行能力QTL。具体目标3：识别基因 在有氧运动不同的大鼠（的关键器官）中差异表达 能力，即，COP和DA菌株。差异表达基因 接近有氧跑能力的QTL将是该基因的上级候选者 负责特定有氧跑能力的QTL。