High Resolution Class I HLA -A, -B, and -C Diversity in Eastern and Southern African Populations

Africa remains significantly underrepresented in high-resolution Human Leukocyte Antigen (HLA) data, despite being one of the most genetically diverse regions in the world. This critical gap in genetic information poses a substantial barrier to HLA-based research on the continent. In this study, Class I HLA data from Eastern and Southern African populations were analysed to assess genetic diversity across the region. We examined allele and haplotype frequency distributions, deviations from Hardy-Weinberg Equilibrium (HWE), linkage disequilibrium (LD), and conducted neutrality tests of homozygosity across various populations. Additionally, the African HLA data were compared to those of Caucasian and African American populations using the Jaccard index and multidimensional scaling (MDS) methods. The study revealed that South African populations exhibited 50.4% more genetic diversity within the Class I HLA region compared to other African populations. Zambia showed an estimated 36.5% genetic diversity, with Kenya, Rwanda and Uganda showing 35.7%, 34.2%, and 31.1%, respectively. Furthermore, an analysis of in-country diversity among diferent tribes indicated an average Class I HLA diversity of 25.7% in Kenya, 17% in Rwanda, 2.8% in South Africa, 13.6% in Uganda, and 6.5% in Zambia. The study also highlighted the genetic distinctness of Caucasian and African American populations compared to African populations. Notably, the diferential frequencies of disease- promoting and disease-preventing HLA alleles across these populations emphasize the urgent need to generate high-quality HLA data for all regions of Africa and its major ethnic groups. Such eforts will be crucial in enhancing healthcare outcomes across the continent. Author SummaryThis study investigated the diversity of class I HLA in the eastern and southern regions of the African continent using a population genetics approach. Analysis of HLA data at both country and tribal levels revealed significant genetic diferences and the unique characteristics of these populations compared to Caucasian and African American populations in the United States. The diferential frequencies of disease-promoting and disease-preventing HLA alleles across these populations suggest that large-scale vaccine administration may be inefective without a thorough understanding of the HLA composition of each population. This study highlights the urgent need to generate high-quality HLA data across all regions of Africa and its major ethnic groups. Such comprehensive data collection is essential for optimizing vaccine design, deepening our understanding of HLA-disease associations, and ultimately improving healthcare outcomes across the continent.