COBRE in Human Genetics

摘要 常见和罕见的遗传病影响着世界上很大一部分人口。澄清 自然发生的基因变异影响疾病风险的机制需要多学科研究 数量遗传学、种群遗传学、分子遗传学、细胞遗传学和发育遗传学方面的专门知识；统计学、生物信息学 以及细胞培养和动物模型中的功能基因组学。我们建议成立一个中心 生物医学卓越研究奖(Cobre)在人类遗传学领域构成了两家公司之间独特的合作伙伴关系 克莱姆森大学人类遗传学中心和格林伍德遗传中心。在美国的研究 Cobre in Human Genetics将专注于通过以下方式理解遗传、基因组和表观遗传机制 哪些分子遗传变异影响罕见病和常见病。人类遗传学中的科布雷将 支持初级研究人员的四个研究项目，以解决面临的几个突出挑战 现代人类遗传学，包括人类长非编码RNA在人类疾病风险中的作用， 结构变异对疾病表型和基因调控的影响以及动物模型的建立 罕见疾病，并将上下文相关效应纳入预测复杂性状的统计模型 来自大规模遗传变异数据的表型。由初级调查人员牵头的八个试点项目将 为人类遗传学的科布雷贡献更多的研究主题的广度和深度。研究报告 项目负责人将由国家卫生研究院资助的现有外部研究人员以及三个私人投资机构进行指导。这个 研究和试点项目负责人将得到一个行政核心的支持，该核心提供广泛的 职业发展活动。人类遗传学的COBRE将建立内部和外部 咨询委员会，并实施全面评价计划。这些项目将得到一个 最先进的基因组学和生物信息学研究核心将使另外两所克莱姆森大学受益 科布尔斯以及克莱姆森大学和格林伍德遗传中心的其他教职员工。科布里的科布雷 人类遗传学有强大的机构支持，承诺聘请更多的教员来扩大 在此期间支持研究活动的范围，并为研究生提供研究 资助研究项目的助学金。科布雷项目负责人的研究 人类遗传学将为分子遗传变异的机制提供新的知识 影响健康和疾病复杂性状的变异，提高克莱姆森大学的全国声誉 作为人类遗传学的研究和培训中心，并为机构未来的发展奠定了基础 培训补助金和计划项目。科布雷将加强生物医学研究基础设施 克莱姆森大学和增加NIH资助的南卡罗来纳州科学家的数量。

SUMMARY Common and rare genetic diseases affect a large fraction of the world’s population. Elucidating the mechanisms by which naturally occurring genetic variants affect disease risk requires multidisciplinary expertise in quantitative, population, molecular, cellular and developmental genetics; statistics, bioinformatics and computational biology; and functional genomics in cell culture and animal models. We propose a Center of Biomedical Research Excellence (COBRE) in Human Genetics that constitutes a unique partnership between the Clemson University Center for Human Genetics and the Greenwood Genetic Center. Research in the COBRE in Human Genetics will focus on understanding the genetic, genomic, and epigenetic mechanisms by which molecular genetic variation affects rare and common diseases. The COBRE in Human Genetics will support four research projects from junior investigators that tackle several of the outstanding challenges facing modern human genetics, including the roles of human long non-coding RNAs in risk for human disease, the effects of structural variation on disease phenotypes and gene regulation, development of animal models for rare diseases, and incorporating context-dependent effects into statistical models predicting complex trait phenotypes from large scale genetic variation data. Eight Pilot Projects led by junior investigators will contribute additional breadth and depth of research topics to the COBRE in Human Genetics. The Research Project Leaders will be mentored by established external NIH-funded researchers as well as the three PIs. The Research and Pilot Project Leaders will be supported by an Administrative Core that provides a wide range of professional development activities. The COBRE in Human Genetics will establish both Internal and External Advisory Committees and implement a comprehensive Evaluation Plan. The projects will be supported by a state-of-the-art Genomics and Bioinformatics Research Core that will benefit two other Clemson University COBREs as well as other faculty at Clemson University and the Greenwood Genetic Center. The COBRE in Human Genetics has strong institutional support, with commitments to hire additional faculty to expand the scope of the research activities during this period of support, and to provide graduate student research assistantships to support the research projects. The research performed by the Project Leaders of the COBRE in Human Genetics will provide new knowledge of the mechanisms by which molecular genetic variation affects variation in complex traits in health and disease, enhance the national reputation of Clemson University as a research and training center in human genetics, and set the stage for future development of institutional training grants and program projects. This COBRE will strengthen the biomedical research infrastructure of Clemson University and increase the number of NIH-funded scientists in the state of South Carolina.