Aerobic Running Capacity QTL's and Cardiac Performance

有氧跑步能力 QTL 和心脏性能

• 批准号: 6621698
• 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/6621698
• 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(申请人提供)：使用有氧运动跑步机测试 在临床上评估心血管健康状况、心血管储备，并作为 总体健康状况的一般测试。我们的长期目标是识别基因 与有氧运动能力的遗传差异有关。我们 11个品系近交系跑台有氧跑能力的评价与观察 COP和DA菌株的有氧跑能力相差3倍， 2)有氧跑成绩与运动成绩呈极显著正相关(r=0.86 离体心功能(朗宁多夫-尼利)。考虑到这种巨大的差异 在有氧能力方面，我们建议识别包含 观察到的有氧跑能力差异的基因 COP和DA大鼠，通过构建同源菌株对其进行鉴定 联合使用差异基因表达的强候选基因 基因图谱。 假设1：有氧跑步能力是一种可遗传的多基因性状。这个 COP和DA近交系的有氧运动能力相差3倍 大鼠品系为鉴定染色体区域提供了合适的底物 含有导致有氧跑步遗传差异的基因 能力；即有氧跑能力数量性状基因座(QTL)。 假设2：影响有氧跑能力QTL的基因(S)可能 在关键器官中差异表达，如左心室。基因(S) 负责有氧跑步能力的QTL效应应映射到 携带特定QTL的染色体区域。拥有这些的基因 特征将是更好的候选基因，至少是 部分是特定的有氧运动能力QTL。具体目标1：确定 含有与需氧菌株差异相关基因的染色体区域 运力区间作图。我们将对目前存在的老鼠进行基因分型 尾巴的有氧跑能力表型分布。特定的 目的2：通过导入染色体区域产生新的同源菌株 含高(或低)有氧能力QTL等位基因(S)(特异系AIM 1) 低(或高)产能近交系大鼠品系。这些同源菌株将是 使用跑步机负荷试验进行表型鉴定，以确认是否存在需氧菌 运行量QTL。具体目标3：识别基因 不同有氧运动大鼠(关键器官)的差异表达 能力，即COP和DA品系。映射的差异表达基因 接近有氧跑步能力的QTL将是该基因的优势候选基因(S) 负责特定有氧跑能力的QTL。