SCOR-MOLECULAR GENETICS OF HYPERTENSION

该申请建议在爱荷华州大学心血管中心更新高血压分子遗传学专业研究中心(SCOR)。总的主题是“人类和实验动物遗传性高血压的分子和生理学机制”。在过去的18个月里，我们一直在计划这一倡议，以资助6个项目和1个科学核心。该中心汇集了一批研究人员，其中包括杰出的分子遗传学家(爱荷华州的Val Shefffield、Bento Soares和Curt Sigmund以及俄亥俄州的John Rapp)；分子生物学家(Peter Snyder和John Engelhardt)；遗传流行病学家和生物统计学家(Trudy Burns)；以及领先的高血压生理学家(Allyn Mark、John Stokes、Robin Davisson、Gerald DiBona和Joseph Hill)，以追求高血压分子遗传学SCOR的三个广泛目标。该建议的优势包括：(1)研究两个不同的人类群体，包括来自马斯卡廷人群肥胖和血压研究的核心家庭；以及来自以色列南部肥胖症高发人群的贝都因人家庭；(2)领先的人和大鼠分子遗传学实验室，具有高通量基因识别、cDNA测序以及cDNA微阵列生成和分析的能力；(3)在遗传性盐敏感型高血压大鼠模型中协调追求染色体数量性状基因座、生理和细胞中间表型以及候选基因；(4)寻求关于上皮性钠通道基因遗传变异后果的功能数据；以及(5)利用转基因小鼠、组织特异性基因敲除小鼠和突变小鼠品系来测试组织特异性肾素-血管紧张素系统在高血压和心肌肥厚中的作用，并研究肥胖性高血压的基本机制。这些研究人员在我们的SCOR内部以及与其他机构研究高血压遗传学的研究人员之间建立了充满活力的合作。爱荷华州SCOR的领先分子遗传学家和高血压生理学家的这一联盟有望继续为推进高血压的分子遗传学知识做出实质性贡献。

The application proposes to renew a Specialized Center of Research (SCOR) in the Molecular Genetics of Hypertension in the University of Iowa Cardiovascular Center. The overall theme is "Molecular and Physiologic Mechanisms of Genetic Hypertension in Humans and Experimental Animals." This initiative, which we have been planning for the past 18 months to fund 6 projects and one scientific core. The center brings together a cadre of investigators including outstanding molecular geneticists (Val Sheffield, Bento Soares and Curt Sigmund at Iowa and John Rapp in Ohio); molecular biologists (Peter Snyder and John Engelhardt); a genetic epidemiologist and biostatistician (Trudy Burns); and leading hypertension physiologists (Allyn Mark, John Stokes, Robin Davisson, Gerald DiBona, and Joseph Hill) to pursue the three broad goals of the Hypertension Molecular Genetics SCOR. The strengths of the proposal include: (1) study of two distinctive human populations including nuclear families from the Muscatine population study of obesity and blood pressure; and Bedouin families from a homogenous population in Southern Israel with a high incidence of obesity; (2) a leading human and rat molecular genetics laboratory with capability for high throughput gene identification, sequencing of cDNAs, and generation and analysis of cDNA microarrays; (3) coordinated pursuit of chromosomal quantitative trait loci, physiologic and cellular intermediate phenotypes, and candidate genes in rat models of genetically salt-sensitive hypertension; (4) pursuit of functional data on the consequences of genetic variation in genes encoding the epithelial sodium channel; and (5) use of transgenic mice, tissue-specific knockout mice and mutant mouse strains to test the role of tissue-specific renin- angiotensin systems in hypertension and cardiac hypertrophy, and to study fundamental mechanisms in obesity-induced hypertension. These investigators have established vibrant collaborations within our SCOR and with investigators studying the genetics of hypertension at other institutions. This coalition of leading molecular geneticists and hypertension physiologists in the Iowa SCOR holds promise for continued substantial contribution to advancing knowledge of the molecular genetics of hypertension.