Abstract
Background: Lack of HLA data in southern African populations hampers disease association studies and our understanding of genetic diversity in these populations. We aimed to determine HLA diversity in South African populations using high resolution HLA ∼A, ∼B, ∼C, ∼DRB1, ∼DQA1 and ∼DQB1 data, from 3005 previously typed individuals. Methods: We determined allele and haplotype frequencies, deviations from Hardy-Weinberg equilibrium (HWE), linkage disequilibrium (LD) and neutrality test. South African HLA class I data was additionally compared to other global populations using non-metrical multidimensional scaling (NMDS), genetic distances and principal component analysis (PCA). Results: All loci strongly (p < 0.0001) deviated from HWE, coupled with excessive heterozygosity in most loci. Two of the three most frequent alleles, HLA ∼DQA1*05:02 (0.2584) and HLA ∼C*17:01 (0.1488) were previously reported in South African populations at lower frequencies. NMDS showed genetic distinctness of South African populations. Phylogenetic analysis and PCA clustered our current dataset with previous South African studies. Additionally, South Africans seem to be related to other sub-Saharan populations using HLA class I allele frequencies. Discussion and Conclusion: Despite the retrospective nature of the study, data missingness, the imbalance of sample sizes for each locus and haplotype pairs, and induced methodological difficulties, this study provides a unique and large HLA dataset of South Africans, which might be a useful resource to support anthropological studies, disease association studies, population based vaccine development and donor recruitment programs. We additionally provide simulated high resolution HLA class I data to augment the mixed resolution typing results generated from this study.
Highlights
The human leukocyte antigen (HLA) gene region is considered to be one of the most polymorphic regions in the human genome (Mungall et al, 2003; Wong et al, 2013)
We previously described allele and haplotype frequencies from the South African Bone Marrow Registry (SABMR) (Tshabalala et al, 2018) in an effort to understand HLA diversity in South Africans
There was profound data missingness which we attempted to address in our quest to highlight HLA diversity from South African populations
Summary
The human leukocyte antigen (HLA) gene region is considered to be one of the most polymorphic regions in the human genome (Mungall et al, 2003; Wong et al, 2013). Despite the growing documented evidence of genetic diversity in Africans (Chen et al, 1995; Zietkiewicz et al, 1997; Jorde et al, 2000; Prugnolle et al, 2005; Disotell, 2012), there remains an information gap on HLA diversity in these populations (reviewed in Tshabalala et al (2015)). This lack of HLA data hampers disease association studies (reviewed in Dyer et al (2013), population-specific vaccine development (Gourraud et al, 2015) and programs aimed at donor recruitment into registries (Edinur et al, 2016). We aimed to determine HLA diversity in South African populations using high resolution HLA ~A, ~B, ~C, ~DRB1, ~DQA1 and ~DQB1 data, from 3005 previously typed individuals
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