Collaborative African Genomics Network (CAfGEN)

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， 特别脆弱。艾滋病毒疾病发展为艾滋病是复杂的;尽管在成人中进行了研究， 主要是西方人群，已经清楚地证明了宿主遗传因素在这一过程中的一致作用。 进展影响撒哈拉以南地区人群疾病进展的宿主遗传因素， 然而，特别是非洲儿童群体，在很大程度上仍然未知。以同样的方式， 结核病（TB）仍然是撒哈拉以南非洲发病率和死亡率的重要原因， 尤其是那些同时感染艾滋病毒的人。因此，迫切需要找到新的和有效的 管理和诊断结核病感染的战略。暴露于M。结核病-病因 结核病病原体-通常导致活动性结核病（ATB）、潜伏性结核感染（LTBI）或无结核病。的 然而，这些结果背后的驱动机制还没有得到很好的理解， 由于其检测不精确，特别是在儿童中。尽管如此，越来越多的证据表明， 宿主基因组因素起着重要作用，可以用于诊断。 先进的基因组技术的可用性提供了一个宝贵的机会， 艾滋病毒和结核病在撒哈拉以南非洲儿童中的宿主遗传学进展，这是在科学 非洲基因组学合作网络（CAfGEN）的核心-H3非洲合作中心 横跨乌干达、博茨瓦纳、斯威士兰和美国的六个机构。前一 尽管面临不可避免的挑战，CAfGEN能够使用下一代测序技术， 鉴定影响儿科HIV进展和TB疾病进展的候选基因; 科学研究，以建立和发展乌干达的基因组学能力、技术和专业知识， 博茨瓦纳;并有效地使当地社区参与解决道德、法律的和社会问题 （ELSI）与基因组学研究有关。 在下一个资助期内，CAfGEN将通过以下方式在这些成就的基础上再接再厉：a）扩大 儿童中的儿科HIV和TB疾病进展，以纳入新人群和新科学; B） 在非洲大陆提供额外的基因组学和生物信息学培训; c）协助六名博士生 接受两年人类遗传学研究生培训的学生， （d）继续采用创新办法， 在非洲，地方社区参与解决与基因组学研究有关的ELSI问题。通过这样做，CAfGEN将 为儿科HIV和HIV-TB疾病进展提供新的重要机制见解， 同时建立一个可持续的、协同的、知识渊博的非洲基因组联盟， 改变非洲大陆卫生的未来--这是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, however, 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 grant 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.