PMID- 28950417 OWN - NLM STAT- MEDLINE DCOM- 20180222 LR - 20180222 IS - 1365-294X (Electronic) IS - 0962-1083 (Linking) VI - 26 IP - 22 DP - 2017 Nov TI - The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection. PG - 6238-6252 LID - 10.1111/mec.14366 [doi] AB - 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. CI - (c) 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd. FAU - Sanchez-Mazas, Alicia AU - Sanchez-Mazas A AUID- ORCID: 0000-0002-7714-2432 AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. FAU - Cerny, Viktor AU - Cerny V AD - Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic. FAU - Di, Da AU - Di D AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. FAU - Buhler, Stephane AU - Buhler S AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. AD - Department of Genetic and Laboratory Medicine, Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility (UIT/LNRH), Geneva University Hospitals, Geneva, Switzerland. FAU - Podgorna, Eliska AU - Podgorna E AD - Department of the Archaeology of Landscape and Archaeobiology, Archaeogenetics Laboratory, Institute of Archaeology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic. FAU - Chevallier, Elodie AU - Chevallier E AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. FAU - Brunet, Lydie AU - Brunet L AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. AD - Department of Genetic and Laboratory Medicine, Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility (UIT/LNRH), Geneva University Hospitals, Geneva, Switzerland. FAU - Weber, Stephan AU - Weber S AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. FAU - Kervaire, Barbara AU - Kervaire B AD - Department of Genetic and Laboratory Medicine, Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility (UIT/LNRH), Geneva University Hospitals, Geneva, Switzerland. FAU - Testi, Manuela AU - Testi M AD - Laboratory of Immunogenetics and Transplant Biology, IME Foundation, Policlinic of the University of Tor Vergata, Rome, Italy. FAU - Andreani, Marco AU - Andreani M AD - Laboratory of Immunogenetics and Transplant Biology, IME Foundation, Policlinic of the University of Tor Vergata, Rome, Italy. FAU - Tiercy, Jean-Marie AU - Tiercy JM AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. AD - Department of Genetic and Laboratory Medicine, Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility (UIT/LNRH), Geneva University Hospitals, Geneva, Switzerland. FAU - Villard, Jean AU - Villard J AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. AD - Department of Genetic and Laboratory Medicine, Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility (UIT/LNRH), Geneva University Hospitals, Geneva, Switzerland. FAU - Nunes, Jose Manuel AU - Nunes JM AD - Department of Genetics and Evolution - Anthropology Unit, Laboratory of Anthropology, Genetics and Peopling History (AGP), University of Geneva, Geneva, Switzerland. AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. LA - eng PT - Journal Article DEP - 20171016 PL - England TA - Mol Ecol JT - Molecular ecology JID - 9214478 RN - 0 (HLA-B Antigens) SB - IM MH - Africa South of the Sahara MH - Alleles MH - Disease Resistance/*genetics MH - *Genetics, Population MH - HLA-B Antigens/*genetics MH - Humans MH - Linkage Disequilibrium MH - Malaria, Falciparum/*genetics OTO - NOTNLM OT - African populations OT - HLA polymorphism and disease associations OT - geographic patterns OT - human population genetics OT - malaria protection OT - pathogen-driven selection EDAT- 2017/09/28 06:00 MHDA- 2018/02/23 06:00 CRDT- 2017/09/27 06:00 PHST- 2016/06/10 00:00 [received] PHST- 2017/09/11 00:00 [accepted] PHST- 2017/09/28 06:00 [pubmed] PHST- 2018/02/23 06:00 [medline] PHST- 2017/09/27 06:00 [entrez] AID - 10.1111/mec.14366 [doi] PST - ppublish SO - Mol Ecol. 2017 Nov;26(22):6238-6252. doi: 10.1111/mec.14366. Epub 2017 Oct 16.