How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians

Abstract

associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.

How HLA diversity is apportioned: influence of selection and relevance to transplantation

“…Given that matching for transplantation requires identity over multiple HLA loci, the higher haplotypic Would increasing the proportion of individuals with African ancestry in the registries increase the chances of patients with a greater African ancestry finding a compatible donor? Nunes et al [47] showed that individuals with a higher proportion of African ancestry in the MHC on average find proportionally more donors identified as 'Black' or 'Mixed' (figure 6b). This suggests that, for individuals with greater African ancestry, an increase in the proportion of donors with African ancestry will contribute to their chances of finding a compatible donor.…”

“…What are the consequences of the large differences in allele frequencies between geographic regions (figure 5) to the chances of finding a matching donor in a repository? Nunes et al [47] quantified how an individual's ancestry influences their chances of finding a matching donor in REDOME, the Brazilian bone-marrow donor registry. Surveying over 8000 admixed individuals, they showed that those who self-identify as 'Black' have a reduction in their chances of finding a matching donor, with respect to those who self-identify as 'White'.…”

“…Surveying over 8000 admixed individuals, they showed that those who self-identify as 'Black' have a reduction in their chances of finding a matching donor, with respect to those who self-identify as 'White'. Nunes et al [47] also explored the effects of two forms of identifying the individual's genetic ancestry: genomewide ancestry and ancestry specific to the MHC region. In both cases, greater African ancestry was associated with decreased chances of finding a match in REDOME (figure 6).…”

“…the northeast of the country) in an effort to reduce the disparity in access to compatible donors. Nunes et al's [47] analysis of ancestry and matching underscores the importance of genetic diversity in medical research and public policies, and points out the importance of finding an appropriate way to describe HLA diversity.…”

Increasing access to allogeneic hematopoietic cell transplant: an international perspective

“…7 In a recent study of the Brazilian UD reg is try (REDOME), this proba bil ity was <10% for sickle cell dis ease patients. 8 In addi tion, access to searching for and using UD grafts is lim ited by financial issues even in dif fer ent areas of high-income countries (HICs). In the US, Paulson et al found that patients with leu kemia from poorer areas were less likely to undergo UD allo-HCT com pared to patients from wealth ier countries.…”