H3Africa Kidney Disease Research Network

据估计，在撒哈拉以南非洲，每年有50多万人死于终末期肾病，另有5000万人患有透析前慢性肾病。先进的基于基因组的分析策略，如非裔美国人的混合连锁不平衡作图(MALD)，已经确定了单基因变异(例如Myh9和AP0L1)与肾脏疾病之间的强烈关联。此外，近20个基因变异与儿童肾病综合征有关。这些在阐明肾脏疾病病因方面的遗传进展大多发生在撒哈拉以南非洲以外，那里缺乏遗传专家，人类基因组研究的基础设施就像撒哈拉沙漠本身一样稀少。在这项申请中，我们建议通过一个由五个非洲国家(POP)10个机构的研究人员组成的合作研究网络，迅速提高在撒哈拉以南非洲进行肾脏疾病基因组研究的能力。3.62亿个(埃塞俄比亚、加纳、肯尼亚、尼日利亚和南非)和四个北美机构。该网络将实现以下七个目标：(1)8,000个肾脏疾病病例和对照的表型(1：1)；(2)开展四个遗传研究项目，研究受影响家庭中的单基因突变肾脏疾病、人群中与肾脏疾病有关的单基因的遗传变异和全基因组关联研究；(3)在非洲建立两个低资本密集度、坚固和可持续的基因组研究实验室；(4)为驻非洲的基因组研究人员实施定制的六轨培训和职业发展计划；(5)建立和维护一个将与H3非洲生物信息库赠款(RFA-RM-11-011)无缝协调的全网生物样品储存库；(6)建立和维护一个将有效地与H3非洲生物信息学网络(RFA-RM-11-010)相结合的全网络数据管理和生物信息学设施；(7)与H3非洲联盟和NIH计划科学家/工作人员合作和协调该网络的活动。本申请由加纳大学提交，密歇根大学提供大量机构支持。

It is estimated more than 500,000 individuals succumb to end stage renal disease annually in sub-Saharan Africa with an additional 50 million people suffering from pre-dialysis chronic kidney disease. Advanced genome-based analysis strategies, such as Mapping by Admixture Linkage Disequilibrium (MALD) in African Americans, have identified a strong association between single gene variants (e.g., MYH9 and AP0L1) and kidney disease. In addition, nearly 20 genetic variants have been linked to childhood onset nephrotic syndrome. Most of these genetic advances in elucidating the etiology of kidney disease have occurred outside sub-Saharan Africa where there is a shortage of genetic experts and the infrastructure for human genomic research is as sparse as the Sahara Desert itself. In this application, we propose to rapidly increase the capacity to conduct genomic studies of kidney disease in sub-Saharan Africa through a collaborative research network comprised of investigators based at 10 institutions in five African countries - pop. 362 million (Ethiopia, Ghana, Kenya, Nigeria and South Africa) and four North American institutions. The Network will accomplish the following seven objectives: (1) phenotype 8,000 kidney disease cases and controls (1:1); (2) conduct four genetic research projects addressing single gene mutation kidney disorders in affected families, genetic variants of single genes associated with kidney diseases in the populations and genome wide association studies; (3) establish two low-capital intensity, rugged and sustainable genomics research laboratories in Africa; (4) implement a customized six-track training and career development plan for African-based genomic researchers; (5) establish and maintain a Network-wide biospecimen repository that will harmonize seamlessly with the H3Africa Biorepository Grants (RFA-RM-11-011); (6) establish and maintain a Network-wide data management and bioinformatics facility that will effectively integrate with the H3Africa Bioinformatics Network (RFA-RM-11-010) and (7) cooperate and coordinate the activities of this Network with the H3Africa Consortium and the NIH Program Scientists/Staff. This application is submitted by the University of Ghana with substantial institutional support from the University of Michigan.