Renal Genomics Core

慢性肾脏疾病(CKD)、高血压(HTN)和心血管疾病风险(CVD)之间的流行病学联系已经建立，但导致这些放大风险的具体机制尚不清楚。这些疾病的遗传基础都很明显，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)研究已经发现了与CKD、CVD或HTN风险相关的多个基因座。这一核心将促进旨在了解CKD、CVD和HTN各自的遗传机制和/或探索它们共同的遗传风险途径的研究。研究人员往往无法利用这些进展，因为无法获得必要的基础设施和资源，也无法获得对成功发现至关重要的研究设计、遗传流行病学和分析方法方面的专门知识。肾脏基因组核心中心(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，为有兴趣探索这些问题的遗传基础的研究人员减少关键核心服务的障碍。我们的目标是：1)建立研究前咨询服务，作为有兴趣开展心肾遗传学研究的研究人员的切入点。将在研究设计和与调查人员协调研究方案方面提供协助，包括电力分析、人体受试者IRB准备、编程和信息学。2)为DNA分离和存储、组织银行和DNA分配提供标准化服务。3)协助开展分子遗传学研究。获得技术能力和专业知识，用于全球气候变化分析/全球地球观测系统和全基因组/外显子组测序。研资局将进行后续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方法的最新进展。RGC将为用户提供全面的基因组学服务，无论用户的体验水平如何，都可以有效地利用这些服务。获得强大的工具将促进在理解CVD和HTN肾脏复杂相互作用的遗传结构方面的进展。

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.