Browsing by Author "Mlotshwa, Busisiwe C."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    The Collaborative African Genomics Network (CAfGEN): Applying Genomic technologies to probe host factors important to the progression of HIV and HIV-tuberculosis infection in sub-Saharan Africa [version 1; referees: awaiting peer review]
    (AAS open research, 2018) Mboowa, Gerald; Mwesigwa, Savannah; Katagirya, Eric; Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Kekitiinwa, Adeodata; Kateete, David; Wampande, Eddie; Wayengera, Misaki; Nsangi Kintu, Betty; Kisitu, Grace P.; Kyobe, Samuel; Brown, Chester W.; Hanchard, Neil A.; Mardon, Graeme; Joloba, Moses; Anabwani, Gabriel; Pettitt, Ed; Tsimako-Johnstone, Masego; Kasvosve, Ishmael; Maplanka, Koketso; Mpoloka, Sununguko W.; Hlatshwayo, Makhosazana; Matshaba, Mogomotsi
    The Human Heredity and Health in Africa consortium (H3Africa) was conceived to facilitate the application of genomics technologies to improve health across Africa. Here, we describe how the Collaborative African Genomics Network (CAfGEN) of the H3Africa consortium is using genomics to probe host genetic factors important to the progression of HIV and HIV-tuberculosis (TB) coinfection in sub-Saharan Africa. Methods: CAfGEN is an H3Africa collaborative centre comprising expertise from the University of Botswana; Makerere University; Baylor College of v
  • Thumbnail Image
    Item
    The collaborative African genomics network training program: a trainee perspective on training the next generation of African scientists
    (Genetics in Medicine, 2017) Mlotshwa, Busisiwe C.; Mwesigwa, Savannah; Mboowa, Gerald; Williams, Lesedi; Retshabile, Gaone; Kekitiinwa, Adeodata; Wayengera, Misaki; Kyobe, Samuel; Brown, Chester W.; Hanchard, Neil A.; Mardon, Graeme; Joloba, Moses; Anabwani, Gabriel; Mpoloka, Sununguko W.
    The Collaborative African Genomics Network (CAf- GEN) aims to establish sustainable genomics research programs in Botswana and Uganda through long-term training of PhD students from these countries at Baylor College of Medicine. Here, we present an overview of the CAfGEN PhD training program alongside trainees’ perspectives on their involvement. Background: Historically, collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs), or North–South collaborations, have been criticized for the lack of a mutually beneficial distribution of resources and research findings, often undermining LMICs. CAfGEN plans to address this imbalance in the genomics field through a program of technology and expertise transfer to the participating LMICs. Methods: An overview of the training program is presented. Trainees from the CAfGEN project summarized their experiences, looking specifically at the training model, benefits of the program, challenges encountered relating to the cultural transition, and program outcomes after the first 2 years. Conclusion: Collaborative training programs like CAfGEN will not only help establish sustainable long-term research initiatives in LMICs but also foster stronger North–South and South–South networks. The CAfGEN model offers a framework for the development of training programs aimed at genomics education for those for whom genomics is not their “first language.”
  • Thumbnail Image
    Item
    Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations
    (Frontiers in Genetics, 2021) Kyobe, Samuel; Mwesigwa, Savannah; Kisitu, Grace P.; Farirai, John; Katagirya, Eric; Mirembe, Angella N.; Ketumile, Lesego; Wayengera, Misaki; Ashaba Katabazi, Fred; Kigozi, Edgar; Wampande, Edward M.; Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Morapedi, Koketso; Kasvosve, Ishmael; Kyosiimire-Lugemwa, Jacqueline; Nsangi, Betty; Tsimako-Johnstone, Masego; Brown, Chester W.; Joloba, Moses; Anabwani, Gabriel; Bhekumusa, Lukhele; Mpoloka, Sununguko W.; Mardon, Graeme; Matshaba, Mogomotsi; Kekitiinwa, Adeodata; Hanchard, Neil A.
    Human leucocyte antigen (HLA) class I molecules present endogenously processed antigens to T-cells and have been linked to differences in HIV-1 disease progression. HLA allelotypes show considerable geographical and inter-individual variation, as does the rate of progression of HIV-1 disease, with long-term non-progression (LTNP) of disease having most evidence of an underlying genetic contribution. However, most genetic analyses of LTNP have occurred in adults of European ancestry, limiting the potential transferability of observed associations to diverse populations who carry the burden of disease. This is particularly true of HIV-1 infected children. Here, using exome sequencing (ES) to infer HLA allelotypes, we determine associations with HIV- 1 LTNP in two diverse African pediatric populations. We performed a case-control association study of 394 LTNPs and 420 rapid progressors retrospectively identified from electronic medical records of pediatric HIV-1 populations in Uganda and Botswana. We utilized high-depth ES to perform high-resolution HLA allelotyping and assessed evidence of association between HLA class I alleles and LTNP. Sixteen HLA alleles and haplotypes had significantly different frequencies between Uganda and Botswana, with allelic differences being more prominent in HLA-A compared to HLA-B and C allelotypes. Three HLA allelotypes showed association with LTNP, including a novel association in HLA-C (HLA-B 57:03, aOR 3.21, Pc = 0.0259; B 58:01, aOR 1.89, Pc = 0.033; C 03:02, aOR 4.74, Pc = 0.033). Together, these alleles convey an estimated population attributable risk (PAR) of non-progression of 16.5%. We also observed novel haplotype associations with HLA-B 57:03-C 07:01 (aOR 5.40, Pc = 0.025) and HLA-B 58:01- C 03:02 (aOR 4.88, Pc = 0.011) with a PAR of 9.8%, as well as a previously unreported independent additive effect and heterozygote advantage of HLA-C 03:02 with B 58:01 (aOR 4.15, Pc = 0.005) that appears to limit disease progression, despite weak LD (r2 = 0.18) between these alleles. These associations remained irrespective of gender or country. In one of the largest studies of HIV in Africa, we find evidence of a protective effect of canonical HLA-B alleles and a novel HLA-C association that appears to augment existing HIV-1 control alleles in pediatric populations. Our findings outline the value of using multi-ethnic populations in genetic studies and offer a novel HIV-1 association of relevance to ongoing vaccine studies.
  • Thumbnail Image
    Item
    Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana
    (The American Journal of Human Genetics, 2018) Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Mwesigwa, Savannah; Mboowa, Gerald; Huang, Zhuoyi; Rustagi, Navin; Swaminathan, Shanker; Katagirya, Eric; Kyobe, Samuel; Wayengera, Misaki; Kisitu, Grace P.; Kateete, David P.; Wampande, Eddie M.; Maplanka, Koketso; Kasvosve, Ishmael; Pettitt, Edward D.; Matshaba, Mogomotsi; Nsangi, Betty; Marape, Marape; Tsimako-Johnstone, Masego; Brown, Chester W.; Yu, Fuli; Kekitiinwa, Adeodata; Joloba, Moses; Mpoloka, Sununguko W.; Mardon, Graeme; Anabwani, Gabriel; Hanchard, Neil A.
    Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa.We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana—a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%–25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p ¼ 2.2 3 10 16) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (<1%) pathogenic and damaging variants. Batswana clustered with other Southern African populations, but distinctly from 1000 Genomes African populations, and had limited evidence for admixture with extra-continental ancestries. We also observed a surprising lack of genetic substructure in Botswana, despite multiple tribal ethnicities and language groups, alongside a higher degree of relatedness than purported founder populations from the 1000 Genomes project. Our observations reveal a complex, but distinct, ancestral history and genomic architecture among Batswana and suggest that disease mapping within similar Southern African populations will require a deeper repository of genetic variation and allelic dependencies than presently exists.