HLA DRB 1 , DQA 1 , DQB 1 and DPB 1 polymorphisms in Namibian Khoi and San and in the Xhosa and South African mixed-ancestry populations

The human leukocyte antigen (HLA) system, located within the major histocompatibility complex (MHC) on chromosome 6, is highly polymorphic and represents one of the most intensely studied regions of the human genome. HLA molecules bind peptide antigens, which they present to T cells and thus shape the T-cell repertoire. HLA antigens play a key role in allograft rejection and disease susceptibility. HLA-DRB1, -DQA1 and -DQB1 alleles are inherited together in closely associated haplotypes, which are found repeatedly and in characteristic patterns in different populations. This linkage disequilibrium between the HLA genes has been used to characterize population differentiation. The present-day Namibian San and Khoi represent original southern African populations and have currently been reduced to very small numbers consisting of communities of approximately 50–100 people. On the basis of linguistic, cultural and genetic studies, the Khoi and San are thought to share a common ancestry and to be direct descendants of an early humanoid African population from which all other ethnic populations are derived. This founding population is believed to have lived around 100 000 years ago, at which time they diverged into different ethnic groups. The Khoi and San are thought to have diverged at least 10 000 years ago. African blacks, originating from West Africa, are postulated to represent an early migratory wave of the founding population. Xhosa are derived from this population; they migrated to southeast Africa during the past 1000 years. Some later admixture with the San is also assumed to have taken place. The C4, BF (properdin factor B) and DPB (vitamin D binding protein) polymorphisms and HLA associations have confirmed that: 1) the Khoi and San are closely related; 2) the Khoi share some characteristics with Caucasoids that are not shared with Xhosa; and 3) the combined Khoisan group shares more similarities with Xhosa than with Caucasoids. The founding populations of the South African mixed-ancestry (so-called Cape coloured) population are the Khoi and western Europeans, with an admixture of Xhosa and southeast Asian genes. Using DNA typing techniques, HLA alleles have been best characterized in Caucasoids, Gambians and Malawians, Zimbabweans and African-Americans. Gambians and African-Americans showed a far greater allelic diversity than Caucasoids. Studies in South American Indians showed a similar trend to allelic diversification. Many new alleles may have been generated recently in these populations, which arose while the people lived in tropical rain-forests for extended periods. These tropical conditions, with abundant vegetation and animal life, which promote the presence of a large diversity of viral, bacterial and parasitological pathogens, could favour the retention of allelic diversity within the HLA system. By contrast, the habitat of the Khoi has been limited to southwestern Africa, encompassing a semi-desert and Mediterranean climate, while the habitat of the San was limited to the harsh Kalahari semi-desert and desert. Recently, studies have been conducted on isolated populations living in dry, harsh climates. A study in five different Siberian populations showed limited variability at the allelic level, but selected HLA alleles were present in very high frequencies. However, there was high variability at the DRB1, DQA1, DQB1 haplotype level. In the Chinese Kazak and Han populations, who live in northwestern China in the vicinity of the Gobi desert, the same phenomenon occurred. The DRB1, DQA1, DQB1 haplotype repertoire was limited while other haplotypes tended to predominate. Information on the molecular biology of the highly polymorphic HLA system in the Khoi, San and Xhosa may reveal clues about the divergence of modern Homo sapiens into the various ethnic groups. We report on the HLA allelic specificities and frequencies, as well as the DRB1, DQA1, DQB1 and DRB1, DQB1, DPB1 haplotype frequencies in Namibian Khoi and San, and in the South African Xhosa and the mixed-ancestry populations.