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

Autor(es):Mostrar menos -

Nunes, Kelly ^[1] ; Aguiar, Vitor R. C. ^[1] ; Silva, Marcio ^[2] ; Sena, Alexandre C. ^[2] ; de Oliveira, Danielli C. M. ^[3] ; Dinardo, Carla L. ^[4] ; Kehdy, Fernanda S. G. ^[5] ; Tarazona-Santos, Eduardo ^[6] ; Rocha, Vanderson G. ^{[4, 7]} ; Carneiro-Proietti, Anna Barbara F. ^[8] ; Loureiro, Paula ^{[8, 9]} ; Flor-Park, Miriam V. ^[10] ; Maximo, Claudia ^[11] ; Kelly, Shannon ^{[12, 13]} ; Custer, Brian ^{[14, 12]} ; Weir, Bruce S. ^[15] ; Sabino, Ester C. ^[16] ; Porto, Luis Cristovao ^[17] ; Meyer, Diogo ^[1]

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sao Paulo, Inst Biosci, Lab Evolutionary Genet, Sao Paulo - Brazil

^[2] Univ Estado Rio De Janeiro, Inst Matemat & Estat, Rio De Janeiro - Brazil

^[3] Minist Saude, Inst Nacl Canc, Registro Nacl Doadores Voluntarios Medula Ossea R, Rio De Janeiro - Brazil

^[4] Fundacao Pro Sangue, Hemoctr Sao Paulo, Sao Paulo - Brazil

^[5] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro - Brazil

^[6] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Genet Ecol & Evolucao, Belo Horizonte, MG - Brazil

^[7] Univ Sao Paulo, Hosp Clin, Serv Hematol Hemoterapia & Terapia Celular, Fac Med, Sao Paulo - Brazil

^[8] Fundacao HEMOMINAS, Belo Horizonte, MG - Brazil

^[9] Fundacao Hematol & Hemoterapia Pernambuco, HEMOPE, Recife, PE - Brazil

^[10] Univ Sao Paulo, Inst Crianca, Hosp Clin, Fac Med, Sao Paulo - Brazil

^[11] Fundacao Hemorio, Rio De Janeiro - Brazil

^[12] Vitalant Res Inst, Epidemiol, San Francisco, CA - USA

^[13] Univ Calif San Francisco, Benioff Childrens Hosp Oakland, Oakland, CA - USA

^[14] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 - USA

^[15] Univ Washington, Dept Biostat, Seattle, WA 98195 - USA

^[16] Univ Sao Paulo, Inst Med Trop, Dept Molestias Infecciosas & Parasitarias, Fac Med, Sao Paulo - Brazil

^[17] Univ Estado Rio de Janeiro, Lab Histocompatibilidade & Criopreservac, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, NOV 6 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 12/18010-0 - Seleção balanceadora no genoma humano: detecção, causas e consequências
• Beneficiário: Diogo Meyer
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/09950-9 - Evolução de genes HLA: diferenciação populacional e sinais de seleção recente em populações nativas e miscigenadas do Brasil
• Beneficiário: Kelly Nunes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado