Genomics Training and Career Development for African Scientists

项目摘要 艾滋病毒/艾滋病仍然是撒哈拉以南非洲发病率和死亡率的主要原因，尤其是儿童 很脆弱。艾滋病毒疾病向艾滋病的发展是复杂的。尽管对成人的研究，主要是西方的 种群已经清楚地证明了宿主遗传因素在这一进程中的一致作用，宿主 影响撒哈拉以南地区人群疾病进展的遗传因素，特别是非洲儿科人群 人口，在很大程度上仍然是未知的。同样，结核病(TB)仍然是导致 撒哈拉以南非洲的发病率和死亡率，特别是在感染艾滋病毒的人中。因此，有一种 迫切需要找到新的有效战略来管理和诊断结核病感染。暴露于M。 结核病--结核病的病原体--通常会导致活动性肺结核(ATB)、潜伏期结核病 感染(LTBI)，或无结核病。然而，这些结果背后的驱动机制并不是很清楚， 使得用于检测它们的诊断方法不准确，特别是在儿童中。尽管如此，还是有 越来越多的证据表明，宿主基因组因素发挥着突出的作用，并可以诊断利用。 先进基因组技术的出现为研究寄主提供了宝贵的机会。 撒哈拉以南地区儿童中艾滋病毒和结核病疾病进展的遗传学，这是 非洲基因组合作网络(CAfGEN)--一个横跨六个国家的H3非洲合作中心 乌干达、博茨瓦纳、斯威士兰和美国的机构。在前一次颁奖期间，尽管 不可避免的挑战，CAfGEN能够使用下一代测序来识别候选基因 影响儿童艾滋病毒和结核病的进展；利用科学研究建立和 在乌干达和博茨瓦纳发展基因组学能力、技术和专业知识；并有效地与当地 解决与基因组学研究有关的伦理、法律和社会问题(ELSI)。 在下一个赠款期间，CAfGEN将在这些成就的基础上，a)扩大对 儿童艾滋病毒和结核病的儿科进展，包括新的人口和新的科学；b)提供 在非洲大陆进行额外的基因组学和生物信息学培训；c)帮助六名博士生 接受了两年的人类遗传学研究生培训，以过渡到独立的研究人员在他们的 母国；和d)继续使用创新办法，使当地社区参与 解决与非洲基因组研究有关的ELSI问题。通过这样做，CAfGEN将贡献新的和 对儿科HIV和HIV-TB疾病进展的重要机械性见解，同时创建可持续的、 协同、知识丰富的非洲基因组联盟能够改变非洲人的健康未来 非洲大陆--H3非洲倡议的最终目标。

Project Summary HIV/AIDS remains a major cause of morbidity and mortality in sub-Saharan Africa and children are particularly vulnerable. The progression of HIV disease to AIDS is complex. Although studies in adult, mostly Western populations have clearly demonstrated a consistent role for host genetic factors in this progression, the host genetic factors influencing disease progression in sub-Saharan populations, and in particular, pediatric African populations, remains largely unknown. In the same way, tuberculosis (TB) remains a significant cause of morbidity and mortality in sub-Saharan Africa, particularly in those co-infected with HIV. Hence there is a pressing need to find new and effective strategies for managing and diagnosing TB infections. Exposure to M. tuberculosis – the causative agent of TB – typically results in either active TB disease (ATB), latent TB infection (LTBI), or no TB. The driving mechanisms behind these outcomes, however, are not well understood, making the diagnostics employed for their detection imprecise, particularly in children. Nonetheless, there is growing evidence that host genomic factors play a prominent role, and can be diagnostically exploited. The availability of advanced genomic technologies presents a valuable opportunity to investigate the host genetics of HIV and TB disease progression in sub-Saharan children, and this is at the scientific core of the Collaborative African Genomics Network (CAfGEN) – an H3Africa Collaborative Center spanning six institutions in Uganda, Botswana, Swaziland, and the United States. During the previous award period, despite unavoidable challenges, CAfGEN was able to use next-generation sequencing to identify candidate genes influencing pediatric HIV progression and TB disease progression; leverage scientific studies to establish and develop genomics capacity, technology, and expertise in Uganda and Botswana; and effectively engage local communities in addressing ethical, legal and social issues (ELSI) related to genomics research. In the next grant period CAfGEN will build on these achievements by a) expanding genomics studies of pediatric HIV and TB disease progression in children to include new populations and new science; b) providing additional genomics and bioinformatics training on the continent; c) assisting the six PhD students who received two-years of graduate training in human genetics to transition into independent investigators in their home countries; and d) continuing the use of innovative approaches to engage local communities in addressing ELSI related to genomics research in Africa. In so doing, CAfGEN will contribute novel and important mechanistic insights to pediatric HIV and HIV-TB disease progression, whilst creating a sustainable, synergistic, knowledgeable African genomic alliance capable of transforming the future of health on the African continent – the ultimate goal of the H3Africa Initiative.