Renal Genomics Core

慢性肾脏疾病（CKD）、高血压（HTN）和心血管疾病（CVD）风险之间的流行病学联系已经确立，但导致这些风险放大的具体机制尚不清楚。这些疾病的遗传基础是显而易见的，但致病基因机制尚未确定。最近的大型全基因组关联/连锁（GWAS/GWLS）研究已经确定了多个与CKD、CVD或HTN风险相关的基因座。该核心将促进旨在了解CKD、CVD和HTN各自遗传机制的研究，和/或探索它们共同的遗传风险途径。由于无法获得所需的基础设施和资源，而且也无法获得研究设计、遗传流行病学和对成功发现至关重要的分析方法方面的专业知识，研究人员往往无法利用这些进展。肾基因组学核心（RGC）将利用人类遗传学中心和人类基因组变异中心现有的一流机构资源，为那些对探索这些问题的遗传基础感兴趣的研究人员减少关键核心服务的障碍。我们的目标是：1)建立一个研究前咨询服务，作为对开展心脏-肾脏遗传研究感兴趣的研究者的切入点。协助研究设计和与研究者协调研究方案，包括功效分析、人类受试者IRB准备、编程和信息学。2)提供DNA分离和储存、组织库和DNA分配的标准化服务。3)协助开展分子遗传学研究。获得GWAS/GWLS和全基因组/外显子组测序的技术能力和专业知识。研资局将进行有针对性的桑格测序，以进行基因鉴定、原始结果数据管理、质量控制、统计和生物信息学分析，并结合统计和基因组学方法的最新进展。研资局将为用户提供全面的基因组学服务，不论其经验水平如何，均可有效利用。获得强大的工具将促进对CVD和HTN中肾脏复杂相互作用的遗传结构的理解。

Epidemiological links between chronic kidney disease (CKD), hypertension (HTN), and risk for cardiovascular disease (CVD) are established, specific mechanisms responsible for these amplified risks are not clear. A genetic basis for each of these maladies is apparent, but causative gene mechanisms have not been identified. Recent large genome-wide association/linkage (GWAS/GWLS) studies have identified multiple loci associated with risk for CKD, CVD or HTN. This Core will facilitate studies aimed at understanding the genetic mechanisms of CKD, CVD, and HTN individually, and/or exploring their shared pathways of genetic risk. Researchers are often unable to take advantage of these advances due to lack of access to required infrastructure and resources and also lack access to expertise in study design, genetic epidemiology and analytical approaches critical for successful discovery. The Renal Genomics Core (RGC) will capitalize on superb existing institutional resources at the Center for Human Genetics and the Center for Human Genome Variation, reducing barriers to critical core services for researcher who are interested in exploring the genetic basis of these problems. We aim to: 1) Establish a pre-study consultation service as an entry point for investigators interested in carrying out cardio-renal genetic studies. Assistance in study design and coordination of study protocols with investigators, including power analyses, human subjects IRB preparation, programming and informatics will be provided. 2)Provide a standardized service for DNA isolation and storage, tissue banking and DNA allocation. 3)Provide assistance in carrying out molecular genetic studies. Access to technical capabilities and expertise for GWAS/GWLS and whole-genome/-exome sequencing. The RGC will carry out followup targeted Sanger sequencing for gene identification, raw results data management, quality control, statistical and bioinformatic analysis incorporating the latest advances in statistical and genomic methodology. RGC will provide users with comprehensive genomics services that can be effectively utilized regardless of level of experience. Access to powerful tools will promote advances in understanding the genetic architecture of the complex interactions of the kidney in CVD and HTN.