How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians
A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of mul...
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| Published in: | Frontiers in immunology Vol. 11; p. 584950 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
06-11-2020
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | A match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with "ethnicity" or "race") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as "Black" and "Mixed" on average have lower chances of finding matches than those who self-identify as "White" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly 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. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Pierre-Antoine Gourraud, Université de Nantes, France; Abeer Madbouly, Center for International Blood and Marrow Transplant Research (CIBMTR), United States This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology Edited by: Martin Maiers, National Marrow Donor Program, United States |
| ISSN: | 1664-3224 1664-3224 |
| DOI: | 10.3389/fimmu.2020.584950 |