HLA haplotype frequency analysis reveals large patient benefits from stem cell donor recruitment in Black South African population

Abstract: More than 41 million potential unrelated donors are currently listed in registries worldwide. However, these donors are not evenly distributed. In particular, individuals from sub-Saharan Africa are underrepresented, complicating unrelated donor searches for patients from this region. Here, we analyzed HLA allele and haplotype frequencies as well as resulting matching probabilities of the 4 South African population groups (Black African, Coloured, Indian/Asian, and White) based on a data set (n = 56 961) of potential stem cell donors registered with DKMS. Our large data set of well-typed and -characterized individuals allowed for unprecedentedly accurate results for these population groups. One major finding was that the haplotypic diversity of Black South African and White individuals was almost identical. The cumulative frequencies of the 50 most frequent 5-locus (HLA-A, -B, -C, -DRB1, and -DQB1) haplotypes were 38.9% for the Black African population and 38.5% for the White population. Indian/Asian (27.5%) and especially Coloured populations (20.8%) had lower cumulative frequencies, indicating higher intrapopulation diversity. Consequently, when donors and patients from the same population group were considered, matching probabilities of Black African and White populations were approximately the same and significantly greater than those of Indian/Asian and particularly of Coloured populations. With 1 000 000 registered Black African donors, the probability for Black African patients to find at least 1 fully matched donor would be 80%. Donor recruitment in the Black African population is therefore very promising. For Indian/Asian and Coloured populations, there is at least a good chance of finding a suitable mismatched donor; for example, 51% (92%) for 9/10 (8/10) matched donors at a registry size of 100 000 for the Coloured population.