SCOR-MOLECULAR GENETICS OF HYPERTENSION

申请建议更新爱荷华大学心血管中心高血压分子遗传学专业研究中心（SCOR）。会议的主题是“人类和实验动物中遗传性高血压的分子和生理机制”。在过去的18个月里，我们一直在计划为6个项目和一个科学核心提供资金。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（爱荷华州的瓦尔·谢菲尔德、本托·苏亚雷斯和柯特·西格蒙德，俄亥俄州的约翰·拉普）；分子生物学家（彼得·斯奈德和约翰·恩格尔哈特）；遗传流行病学家和生物统计学家（特鲁迪·伯恩斯）；和领先的高血压生理学家（Allyn Mark, John Stokes, Robin Davisson， Gerald DiBona和Joseph Hill）共同追求高血压分子遗传学SCOR的三大目标。该提案的优势包括：(1)研究两个不同的人群，包括肥胖和血压的马斯卡廷人口研究中的核心家庭；以及来自以色列南部同质人群的贝都因人家庭，他们的肥胖发病率很高；(2)领先的人类和大鼠分子遗传学实验室，能够进行高通量基因鉴定、cDNA测序以及cDNA微阵列的生成和分析；(3)盐敏感性高血压大鼠遗传模型中染色体数量性状位点、生理和细胞中间表型以及候选基因的协同追求；(4)对编码上皮钠通道的基因的遗传变异后果的功能数据的追求；(5)利用转基因小鼠、组织特异性敲除小鼠和突变小鼠品系，检测组织特异性肾素-血管紧张素系统在高血压和心肌肥厚中的作用，研究肥胖致高血压的根本机制。这些研究人员在我们的SCOR内以及与其他机构研究高血压遗传学的研究人员建立了充满活力的合作关系。这个由爱荷华州SCOR领先的分子遗传学家和高血压生理学家组成的联盟有望继续为推进高血压分子遗传学的知识做出重大贡献。

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.