The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection

Article Article scientifique Article The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection eng 2017 author Sanchez-Mazas Alicia 22545 author Černý Viktor author Di Da 663072 author Buhler Stéphane 0000-0001-6675-5287 502714 author Podgorna Eliska 810932 author Chevallier Elodie 779721 author Brunet Lydie 656435 author Weber Stephan Ole Daniel 104311 author Kervaire Barbara Nelly 26220 author Testi Manuela author Andreani Marco author Tiercy Jean-Marie 26423 author Villard Jean 29595 author Nunes Jose Manuel 122321 6238-6252 10.1111/mec.14366 28950417 0962-1083 Human leukocyte antigen (HLA) genes play a key role in the immune response to infectious diseases, some of which are highly prevalent in specific environments, like malaria in sub-Saharan Africa. Former case-control studies showed that one particular HLA-B allele, B*53, was associated with malaria protection in Gambia, but this hypothesis was not tested so far within a population genetics framework. In this study, our objective was to assess whether pathogen-driven selection associated with malaria contributed to shape the HLA-B genetic landscape of Africa. To that aim, we first typed the HLA-A and -B loci in 484 individuals from 11 populations living in different environments across the Sahel, and we analysed these data together with those available for 29 other populations using several approaches including linear modelling on various genetic, geographic and environmental parameters. In addition to relevant signatures of populations' demography and migrations history in the genetic differentiation patterns of both HLA-A and -B loci, we found that the frequencies of three HLA alleles, B*53, B*78 and A*74, were significantly associated with Plasmodium falciparum malaria prevalence, suggesting their increase through pathogen-driven selection in malaria-endemic environments. The two HLA-B alleles were further identified, by high-throughput sequencing, as B*53:01:01 (in putative linkage disequilibrium with one HLA-C allele, C*04:01:01:01) and B*78:01 in all but one individuals tested, making them appropriate candidates to malaria protection. These results highlight the role of environmental factors in the evolution of the HLA polymorphism and open key perspectives for functional studies focusing on HLA peptide-binding properties. Africa South of the Sahara Alleles Disease Resistance/genetics Genetics Population HLA-B Antigens/genetics Humans Linkage Disequilibrium Malaria Falciparum/genetics Dewey 590 Dewey 616 Swiss National Science Foundation Early human settlements in contrasting environments: HLA molecular variation and its link to population expansions and immune adaptation 144180 CH Project funding 23 Institut de génétique et de génomique 0DH 44 Département de génétique et évolution 162 56 Département de médecine 221 false 824 Groupe Sanchez-Mazas 298 Transplantation immunologie et osteoimmunologie 561 1056 Unité d'anthropologie Molecular Ecology 26 22 07c58ee8-6e25-4994-8fdf-6d0a79946133 Article (Published version) Public Sanchez-Mazas-et-al_Molecular-Ecology-2017.pdf 1023452 application/pdf openAccess Centres et instituts / Institut de génétique et de génomique Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Year	Views	Downloads

The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection	Molecular Ecology	2017	649	642
Diversité génétique des loci HLA-A et HLA-B le long de la frange sahélienne : relation avec l'histoire du peuplement et la prévalence de la malaria en Afrique		2015	174	10

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Chevallier, Elodie