Human Genetics and Clinical Research Core

suwmary项目（见说明）：遗传学和基因组学方法在确定人类健康和疾病背后的新生物学方面成效显著。在O'Brien中心的支持下，外显子组测序技术的发展极大地加速了过去5年的进步。外显子组测序是一种快速、廉价地对基因组中所有蛋白质编码基因进行测序的方法。疾病基因发现的成功需要临床医生、基础科学家和生物统计学家之间的多种技能和有效合作。必要的工具包括临床医学方面的专业知识，监管环境方面的知识，以允许制定适当的HIC方案，研究设计方面的专业知识，以确保研究得到充分的支持，技术专业知识，以确保基于实验室的方法保持在该领域的前沿，以及一流的结果生物统计分析，以确保发现是有效和稳健的。耶鲁在这些领域都发展了专业知识，因此耶鲁的研究人员一直站在这一努力的最前沿，在孟德尔病和不同学科的复杂特征的基因发现方面处于领先地位。在过去的5年里，由耶鲁大学奥布莱恩中心培养的项目已经导致了一系列肾脏疾病的新疾病基因的发现，还有许多来自NIDDK社区的主要研究人员正在进行的发现项目。该核心将继续为发现路径上的所有步骤提供关键基础设施支持，包括HIC协议的开发、患者招募、工具生产和下一代DNA测序和其他大型数据集的分析。这一核心将为学生、研究员和教师提供有效的培训，并将有助于吸引新的研究人员参与转化研究。

PROJECT SUIWMARY (See instructions): Genetic and genomic approaches have been highly productive in identifying new biology that underlies human health and disease. Advances in the last 5 years have been dramatically accelerated by the development, with support of the O'Brien Center, of exome sequencing, a method for rapiidly and inexpensively sequencing all the protein-coding genes in the genome. Success in disease gene discovery requires diverse skill sets and effective collaborations among clinicians, basic scientists, and biostatisticians. Necessary tools include expertise in clinical medicine, knowledge of the regulatory environment to permit development of appropriate HIC protocols, expertise in study design to ensure that studies are adequately powered, technological expertise to ensure that lab-based approaches remain at the cutting edge of the field, and first-rate biostatistical analysis of results to ensure that findings are valid and robust. Yale has developed expertise in each of these areas and as a consequence Yale investigators have been at the forefront of this endeavor with leaders in gene finding for Mendelian disease and complex traits across diverse disciplines. In the last 5 years, projects fostered by the Yale O'Brien center have led to discovery of new disease genes for a wide array of kidney diseases, with many more discovery projects underway with leading investigators from the NIDDK community. This core will continue to provide key infrastructure support for all steps along the path to discovery, including development of HIC protocols, patient recruitment, tools production and analysis of next generation DNA sequencing and other large data sets. This core will provide effective training for students, fellows and faculty and will help engage new investigators in translational research.