Advanced genetic and genomic technologies promise to transform our understanding and approach to human health and disease. Such genomic analyses are now common in Western populations of European descent. Studies of host genetic factors underlying long-term non-progressors of HIV infection have led to new therapies through the identification of loci that are important to in vivo control of virus pathogenicity. Similar stdies of host genetic factors influencing active TB infection have also identified important loci that could significantly impact the future development of more effective therapeutic and prophylactic strategies. Most of these studies were undertaken in non-African, adult populations, although there are more than 2 million new cases of HIV and HIV-TB in Sub-Saharan Africa every year, including more than half a million in children. HIV-infected children - who differ from their adult counterparts in their route of acquisition, clinical course, and pathophysiology - have been conspicuously absent, although they potentially have more to ultimately contribute and gain from therapeutic advances. The Collaborative African Genomics Network (CAfGEN) aims to redress this scientific imbalance by integrating genetic and genomics technologies to probe host factors that are important to the progression of HIV and HIV-TB infection in sub-Saharan African children. The network will incorporate five sites - the Botswana and the Uganda Children's Clinical Centers of Excellence will provide clinical expertise for patient recruitment; Makerere University and the University of Botswana will provide local molecular genetic expertise; and Baylor College of Medicine will provide access to genomics expertise and resources that will ultimately be transitioned to African researchers and institutions in a sustainable manner. The CAfGEN research agenda includes the recruitment of prospective and retrospective cohorts of HIV and HIV-TB infected children; the development of core genomic facilities for sample processing and storage; candidate gene re-sequencing, HLA allelotyping and whole-exome sequencing of patients at the extremes of HIV disease progression; and integrated genomic analyses of active TB progression and associated clinical outcomes using expression quantitative trait loci. These projects will be undertaken through an extensive training and career development plan that will also see significant upgrades in local genomics infrastructure, in so doing, CAfGEN will create a unique, highly synergistic African alliance that can contribute novel and important mechanistic insights to pediatric HIV and HIV-TB disease progression while establishing sustainable genomics technology, expertise, and capacity on the African continent.

Public Health Relevance

HIV/AIDS, tuberculosis and a variety of other diseases disproportionately affect the citizens of Africa. Through a collaborative network of institutions i Africa and the USA we plan to establish genomic technology, expertise, and capability in Africa so that African scientists can effectively use these tools to address serious health concerns, and so that these efforts will be sustainable.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHG1-HGR-P (M2))
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Srinivasan, Sudha
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Botswana Baylor Child/Clincal Center/Excell
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Retshabile, Gaone; Mlotshwa, Busisiwe C; Williams, Lesedi et al. (2018) Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana. Am J Hum Genet 102:731-743
Mlotshwa, Busisiwe C; Mwesigwa, Savannah; Mboowa, Gerald et al. (2017) The collaborative African genomics network training program: a trainee perspective on training the next generation of African scientists. Genet Med 19:826-833
Mokone, Gaonyadiwe G; Kebaetse, Maikutlo; Wright, John et al. (2014) Establishing a new medical school: Botswana's experience. Acad Med 89:S83-7
H3Africa Consortium (see original citation for additional authors) (2014) Research capacity. Enabling the genomic revolution in Africa. Science 344:1346-8