Population Structure and Implications on the Genetic Architecture of HIV-1 Phenotypes Within Southern Africa

Abstract

The interesting history of Southern Africa has put the region in the spotlight for population medical genetics. Major events including the Bantu expansion and European colonialism have imprinted unique genetic signatures within autochthonous populations of Southern Africa, this resulting in differential allele frequencies across the region. This genetic structure has potential implications on susceptibility and resistance to infectious diseases such as human immunodeficiency virus (HIV) infection. Southern Africa is the region affected worst by HIV. Here, we discuss advances made in genome-wide association studies (GWAS) of HIV-1 in the past 12 years and dissect population diversity within Southern Africa. Our findings accentuate that a plethora of factors such as migration, language and culture, admixture, and natural selection have profiled the genetics of the people of Southern Africa. Genetic structure has been observed among the Khoe-San, among Bantu speakers, and between the Khoe-San, Coloureds, and Bantu speakers. Moreover, Southern African populations have complex admixture scenarios. Few GWAS of HIV-1 have been conducted in Southern Africa, with only one of these identifying two novel variants (HCG22rs2535307 and CCNG1kgp22385164) significantly associated with HIV-1 acquisition and progression. High genetic diversity, multi-wave genetic mixture and low linkage disequilibrium of Southern African populations constitute a challenge in identifying genetic variants with modest risk or protective effect against HIV-1. We therefore posit that it is compelling to assess genome-wide contribution of ancestry to HIV-1 infection. We further suggest robust methods that can pin-point population-specific variants that may contribute to the control of HIV-1 in Southern Africa.

Whole Genome Sequencing-based Characterization of Human Genome Variation and Mutation Burden in Botswana

“…Major events such as the "Bantu expansion" and Eurasian migration into Southern Africa have shaped the genetic landscape of the region. These events have led to varying degrees of admixture of the migrant groups and indigenous population (14,(25)(26)(27)(28)(29)(30)(31). These previous findings are congruent with the current study that reports a 3-way admixture of Niger-Congo (65.9%), Khoe-San (32.9%) and European (1.1%) populations observed in the Botswana population (Figure 7 and Table 3).…”

“…Major events such as the "Bantu expansion" and Eurasian migration into Southern Africa have shaped the genetic landscape of the region. These events have led to varying degrees of admixture of the migrant groups and indigenous population (14,(25)(26)(27)(28)(29)(30)(31). Given the complex genetic architecture and high disease burden in Southern Africa, it is important to characterize the genetic variation within the region in order to understand the biology of disease (14,27,32).…”

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“…The severe COVID-19 outbreaks in South Africa compared to the rest of Africa cannot be ascribed to differences in ethnicity (so-called genetic differences), age demographics, health burdens, economic activities, molecular diagnostic capacity, or social-political factors ( Mbow et al, 2020 ). Botswana, which borders South Africa and lies at the edge of the South Atlantic Anomaly, has not experienced a severe COVID-19 outbreak, despite shared ethnic-cultural groups (predominately, Bantu tribes), similar age demographic (median age 24–27), underling health burdens (i.e., HIV/AIDS, Tuberculosis and obesity) and economic development/activities (i.e., mining and tourism) with South Africa ( Lurie and Williams, 2014 ; Thami and Chimusa, 2019 ; Langen, 2005 ). Additionally, the disproportionate severity of COVID-19 outbreaks in South Africa emerged despite the early and stringent governmental interventions to enforce the germ theory-derived public health measures (i.e., social distancing, the wearing of facemasks) ( Mbow et al, 2020 ; Mehtar et al, 2020 ).…”

Past and current biological factors affecting malaria in the low transmission setting of Botswana: A review

“…In Botswana, the peculiar genetic admixture between these two populations clusters specific genotypes more than other Southern African countries (Retshabile et al, 2018). In particular, this genetic structure has potential implications on susceptibility and resistance to infectious diseases and treatment outcomes (Retshabile et al, 2018;Tawe et al, 2018aTawe et al, , 2018bThami and Chimusa, 2019).…”