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Early human settlements in contrasting environments: HLA molecular variation and its link to population expansions and immune adaptation

Applicant Sanchez-Mazas Alicia
Number 144180
Funding scheme Project funding (Div. I-III)
Research institution Unité d'anthropologie Département de génétique et évolution Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Genetics
Start/End 01.12.2012 - 31.05.2016
Approved amount 379'100.00
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Keywords (10)

molecular evolution; immune adaptation; HLA; human evolution; population genetics; demographic expansions; natural selection; joint asymmetric selection; disease associations; malaria

Lay Summary (French)

Lead
La diversité actuelle des gènes responsables de notre immunité (HLA) dépasse celle de tout autre gène, ce qui est généralement expliqué par une meilleure protection des populations face aux maladies. Notre étude contribue à clarifier les mécanismes selon lesquels cette diversité varie toutefois entre populations de diverses régions géographiques.
Lay summary

La diversité génétique des populations peut varier dans le temps et l’espace sous l’effet de facteurs démographiques (isolements, expansions,..) et/ou environnementaux (sélection naturelle). Dans ce projet, notre objectif était de mieux caractériser l’importance relative de ces facteurs pour les gènes HLA, qui présentent une variabilité considérable chez l’humain. Pour ce faire, nous avons d’abord enrichi les données génétiques HLA en séquençant l’ADN d’environ 3’500 individus de populations vivant dans des environnements contrastés, puis nous avons testé divers modèles évolutifs en tenant compte de paramètres géographiques, démographiques et environnementaux.

Nos résultats suggèrent que, dans certains cas, un effet protecteur vis-à-vis de maladies très endémiques, comme la malaria dans certaines régions d’Afrique, a conduit à modifier localement le profil génétique des populations, pour un gène HLA donné. Cependant, notre conclusion majeure est que toutes les populations auraient un potentiel immunitaire semblable pour combattre les maladies grâce à l'effet conjoint de plusieurs gènes HLA, ce qui nous a amenés à proposer un nouveau mécanisme évolutif. Ces résultats motivent des analyses encore plus détaillées de la diversité moléculaire HLA.

Notre projet s’inscrit à l’interface de la recherche fondamentale en biologie, avec l’évolution des gènes HLA, et d’enjeux sociétaux tels que la compréhension des résistances aux maladies.

Direct link to Lay Summary Last update: 13.09.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Genetic history of the African Sahelian populations
Černý Viktor, Kulichová Iva, Poloni Estella S., Nunes José Manuel, Pereira Luisa, Mayor Anne, Sanchez-Mazas Alicia (2018), Genetic history of the African Sahelian populations, in HLA, 91(3), 153-166.
Mandenka from Senegal
Goeury Thomas, Creary Lisa E., Fernandez-Viña Marcelo A., Tiercy Jean-Marie, Nunes José Manuel, Sanchez-Mazas Alicia (2018), Mandenka from Senegal, in HLA, 91, 148-150.
Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa
Goeury Thomas, Creary Lisa. E., Brunet Lydie, Galan Maxime, Pasquier Maeva, Kervaire Barbara, Langaney André, Tiercy Jean-Marie, Fernández-Viña Marcelo A., Nunes José Manuel, Sanchez-Mazas Alicia (2018), Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well-documented population from sub-Saharan Africa, in HLA, 91(1), 36-51.
The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection
Sanchez-Mazas Alicia, Černý Viktor, Di Da, Buhler Stéphane, Podgorná Eliška, Chevallier Elodie, Brunet Lydie, Weber Stephan, Kervaire Barbara, Testi Manuela, Andreani Marco, Tiercy Jean-Marie, Villard Jean, Nunes José Manuel (2017), The HLA-B landscape of Africa: Signatures of pathogen-driven selection and molecular identification of candidate alleles to malaria protection, in Molecular Ecology, 26(22), 6238-6252.
Common and well-documented HLA alleles over all of Europe and within European sub-regions: A catalogue from the European Federation for Immunogenetics SAN CHEZ-MAZAS et al .
Sanchez-Mazas A., Nunes José Manuel, Middleton Derek, Sauter Jürgen, Buhler Stéphane, McCabe Antony, Hofmann Jan, Baier Daniel M., Schmidt Alexander H., Nicoloso Grazia, Andreani Marco, Grubic Zorana, Tiercy Jean-Marie, Fleischhauer Katharina (2017), Common and well-documented HLA alleles over all of Europe and within European sub-regions: A catalogue from the European Federation for Immunogenetics SAN CHEZ-MAZAS et al ., in HLA, 89(2), 104-113.
The HLA-A, -B and -DRB1 polymorphism in a large dataset of South Brazil bone marrow donors from Rio Grande do SulHLA-A, -B and -DRB1 genetic diversity in Southern Brazil
Boquett Juliano A., Nunes José Manuel, Buhler Stéphane, de Oliveira Marcelo Z., Jobim Luis F., Jobim Mariana, Fagundes Nelson J. R., Schüler-Faccini Lavinia, Sanchez-Mazas Alicia (2017), The HLA-A, -B and -DRB1 polymorphism in a large dataset of South Brazil bone marrow donors from Rio Grande do SulHLA-A, -B and -DRB1 genetic diversity in Southern Brazil, in HLA, 89(1), 29-38.
Mapping the HLA diversity of the Iberian Peninsula
Romòn Iñigo, Montes Carmen, Ligeiro Dario, Trindade Hélder, Sanchez-Mazas Alicia, Nunes José Manuel, Buhler Stéphane (2016), Mapping the HLA diversity of the Iberian Peninsula, in Human Immunology, 77(10), 832-840.
HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection
Buhler Stéphane, Nunes José Manuel, Sanchez-Mazas Alicia (2016), HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection, in Immunogenetics, 68(6-7), 401-416.
Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages under Selection
Currat Mathias, Gerbault Pascale, Di Da, Nunes José M., Sanchez-Mazas Alicia (2016), Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages under Selection, in Evolutionary Bioinformatics, 11s2, EBO.S33488-EBO.S33488.
Using UNIFORMAT and GENE[RATE] to Analyze Data with Ambiguities in Population Genetics
Nunes José Manuel (2016), Using UNIFORMAT and GENE[RATE] to Analyze Data with Ambiguities in Population Genetics, in Evolutionary Bioinformatics, 11s2, EBO.S32415-EBO.S32415.
Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection.
Currat Mathias, Gerbault Pascale, Di Da, Nunes José M, Sanchez-Mazas Alicia (2016), Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection., in Evolutionary bioinformatics online, 11(Suppl 2), 27-39.
HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection.
Buhler Stéphane, Nunes José Manuel, Sanchez-Mazas Alicia (2016), HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection., in Immunogenetics, 68(6-7), 401-16.
Using uniformat and gene[rate] to Analyze Data with Ambiguities in Population Genetics.
Nunes José Manuel (2016), Using uniformat and gene[rate] to Analyze Data with Ambiguities in Population Genetics., in Evolutionary Bioinformatics Online, (S2), 19-26.
Computer simulation of human leukocyte antigen genes supports two main routes of colonization by human populations in East Asia
Di Da, Sanchez-Mazas Alicia, Currat Mathias (2015), Computer simulation of human leukocyte antigen genes supports two main routes of colonization by human populations in East Asia, in BMC Evolutionary Biology, 15(1), 240-240.
HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
dos Santos Francisco Rodrigo, Buhler Stéphane, Nunes José Manuel, Bitarello Bárbara Domingues, França Gustavo Starvaggi, Meyer Diogo, Sanchez-Mazas Alicia (2015), HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms, in Immunogenetics, 67(11-12), 651-663.
HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West AfricaHLA-phased haplotypes in Nigerians
Testi Manuela, Battarra Mariarosa, Lucarelli Guido, Isgro Antonella, Morrone Aldo, Akinyanju Olu, Wakama Tambi, Nunes José Manuel, Andreani Marco, Sanchez-Mazas Alicia (2015), HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West AfricaHLA-phased haplotypes in Nigerians, in Tissue Antigens, 86(4), 285-292.
HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central EuropeHLA genetic diversity in Hungary
Inotai Dora, Szilvasi Anikó, Benko Sára, Boros-Major Anita, Illes Zsuzsanna, Bors András, Kiss K. P., Rajczy Katalin, Gelle-Hossó Adrienn, Buhler Stéphane, Nunes José Manuel, Sanchez-Mazas Alicia, Tordai Attila (2015), HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central EuropeHLA genetic diversity in Hungary, in Tissue Antigens, 86(2), 115-121.
HLA-A, B and DRB1 genetic heterogeneity in Quebec
Buhler Stéphane, Nunes José Manuel, Sanchez-Mazas Alicia, Richard Lucie (2015), HLA-A, B and DRB1 genetic heterogeneity in Quebec, in International Journal of Immunogenetics, 42(2), 69-77.
Computer simulation of human leukocyte antigen genes supports two main routes of colonization by human populations in East Asia.
Di Da, Sanchez-Mazas Alicia, Currat Mathias (2015), Computer simulation of human leukocyte antigen genes supports two main routes of colonization by human populations in East Asia., in BMC evolutionary biology, 15, 240-240.
HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe.
Inotai D, Szilvasi A, Benko S, Boros-Major A, Illes Z, Bors A, Kiss K P, Rajczy K, Gelle-Hossó A, Buhler S, Nunes J M, Sanchez-Mazas A, Tordai A (2015), HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe., in Tissue antigens, 86(2), 115-21.
HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms.
Dos Santos Francisco Rodrigo, Buhler Stéphane, Nunes José Manuel, Bitarello Bárbara Domingues, França Gustavo Starvaggi, Meyer Diogo, Sanchez-Mazas Alicia (2015), HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms., in Immunogenetics, 67(11-12), 651-63.
HLA-A, B and DRB1 genetic heterogeneity in Quebec.
Buhler S, Nunes J M, Sanchez-Mazas A, Richard L (2015), HLA-A, B and DRB1 genetic heterogeneity in Quebec., in International journal of immunogenetics, 42(2), 69-77.
HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West Africa.
Testi M, Battarra M, Lucarelli G, Isgro A, Morrone A, Akinyanju O, Wakama T, Nunes J M, Andreani M, Sanchez-Mazas A (2015), HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West Africa., in Tissue antigens, 86(4), 285-92.
Modes d'analyse de la variabilité des fréquences des polymorphismes génétiques dans les populations humaines
Sanchez-Mazas Alicia, Nunes José Manuel (2015), Modes d'analyse de la variabilité des fréquences des polymorphismes génétiques dans les populations humaines, in Bailly Pascal (ed.), John Libbey Eurotext, Paris, 341-359.
A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation
Sanchez-Mazas Alicia, Buhler Stéphane, Nunes José Manuel (2014), A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation, in Human Heredity, 76(3-4), 162-177.
The HLA-net G ENE[RATE ] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas
Nunes José Manuel, Buhler Stéphane, Roessli David, Sanchez-Mazas Alicia (2014), The HLA-net G ENE[RATE ] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas, in Tissue Antigens, 83(5), 307-323.
NO to obsolete definitions: YES to blanksLetter to the Editor
Nunes José Manuel, Buhler Stéphane, Sanchez-Mazas Alicia (2014), NO to obsolete definitions: YES to blanksLetter to the Editor, in Tissue Antigens, 83(2), 119-120.
HLA variation reveals genetic continuity rather than population group structure in East Asia.
Di Da, Sanchez-Mazas Alicia (2014), HLA variation reveals genetic continuity rather than population group structure in East Asia., in Immunogenetics, 66(3), 153-160.
Human Heredity Vol. 76, No. 3-4, 2013: Genetic diversity in European populations: evolutionary evidence and medical implications
Sanchez-Mazas Alicia (ed.) (2014), Human Heredity Vol. 76, No. 3-4, 2013: Genetic diversity in European populations: evolutionary evidence and medical implications, Karger, Basel:Switzerland.
The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas.
Nunes J M, Buhler S, Roessli D, Sanchez-Mazas A, Sanchez-Mazas A (2014), The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas., in Tissue antigens, 83(5), 307-23.
The Relevance of HLA Sequencing in Population Genetics Studies
Sanchez-Mazas Alicia, Meyer Diogo (2014), The Relevance of HLA Sequencing in Population Genetics Studies, in Journal of Immunology Research, 2014, 1-12.
The relevance of HLA sequencing in population genetics studies.
Sanchez-Mazas Alicia, Meyer Diogo (2014), The relevance of HLA sequencing in population genetics studies., in Journal of immunology research, 2014, 971818-971818.
Common and well-documented HLA alleles: 2012 update to the CWD catalogueCWD 2.0.0 catalogue
Mack S. J., Cano P., Hollenbach J. A., He J., Hurley C. K., Middleton D., Moraes M. E., Pereira S. E., Kempenich J. H., Reed E. F., Setterholm M., Smith A. G., Tilanus M. G., Torres M., Varney M. D., Voorter C. E. M., Fischer G. F., Fleischhauer K., Goodridge D., Klitz W., Little A.-M., Maiers M., Marsh S. G. E., Müller C. R., Noreen H., RozemullerE.H., Sanchez-MazasA., SenitzerD., TrachtenbergE., Fernandez-VinaMarcelo (2013), Common and well-documented HLA alleles: 2012 update to the CWD catalogueCWD 2.0.0 catalogue, in Tissue Antigens, 81(4), 194-203.
A new HLA map of Europe: Regional genetic variation and its implication for peopling history, disease-association studies and tissue transplantation.
Sanchez-Mazas Alicia, Buhler Stéphane, Nunes José Manuel (2013), A new HLA map of Europe: Regional genetic variation and its implication for peopling history, disease-association studies and tissue transplantation., in Human heredity, 76(3-4), 162-77.
Does NGS typing highlight our understanding of HLA population diversity? Some good reasons to say yes and a few to say be careful
Sanchez-Mazas Alicia, Nunes José Manuel, Does NGS typing highlight our understanding of HLA population diversity? Some good reasons to say yes and a few to say be careful, in Human Immunology.

Collaboration

Group / person Country
Types of collaboration
Dr Maxime GALAN/Centre de Biologie pour la Gestion des Populations/Montpellier France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dr Jean-Michel DUGOUJON/Laboratoire d'Anthropologie Moléculaire/Université Paul Sabatier/Toulouse France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Diogo MEYER/University of São Paulo, São Paulo Brazil (South America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Zorana GRUBIC/University Hospital Center Zagreb Croatia (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Marcelo FERNANDEZ-VINA/Stanford University School of Medicine, Palo Alto, California United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Marco ANDREANI/IME Foundation, Policlinico Università Tor Vergata, Rome Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
DKMS, German Bone Marrow Center, Tübingen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr Jean-Marie TIERCY/Transplantation Immunology lab/HUG Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Walter REITH/Dpt Pathologie et Immunologie, Faculté de médecine/UNIGE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Katharina FLEISHHAUER/University Hospital Essen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Jean VILLARD/Geneva University Hospitals, Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Derek MIDDLETON/Royal Liverpool & Broadgreen University Hospital Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr Jacques CHIARONI/Etablissement Français du Sang (EFS)/Marseille France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dr Viktor CERNY/Laboratoire d'Archéogénétique, Institut d'Anthropologie/Prague Czech Republic (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Gottfried FISCHER/Université de Vienne Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Lavinia SCHUELER-FACCINI/ Universidade Federal do Rio Grande do Sul, Porto Alegre Brazil (South America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Hacène BROUK/University of Badji Mokhtar d'Annaba Algeria (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SMBE 2018, 50th Anniversary of the Neutral Theory of Molecular Evolution, Yokohama (Japan) Talk given at a conference Differences in peptide-binding affinities among alleles: a key to understand the complex patterns of natural selection on HLA genes 08.07.2018 Yokohama, Japan Nunes José Manuel; Di Da; Sanchez-Mazas Alicia;
SMBE 2018, 50th Anniversary of the Neutral Theory of Molecular Evolution, Yokohama (Japan) Talk given at a conference Evolution of adaptive immunity and MHC genes 08.07.2018 Yokohama, Japan Nunes José Manuel; Di Da; Sanchez-Mazas Alicia;
32th European Immunogenetics and Histocompatibility Conference Talk given at a conference Open Meeting of the EFI Population Genetics Working Group 09.05.2018 Venice Lido, Italy Sanchez-Mazas Alicia; Di Da; Nunes José Manuel;
32th European Immunogenetics and Histocompatibility Conference, Venice Lido, Italy Talk given at a conference The distribution of human leukocyte antigen A and B genes in populations is strongly shaped by their functional relationships 09.05.2018 Venice Lido, Italy Di Da; Sanchez-Mazas Alicia; Nunes José Manuel;
32th European Immunogenetics and Histocompatibility Conference, Venice Lido, Italy Poster Markov Chain modelling brings new clues on HLA evolutionary history 09.05.2018 Venice Lido, Italy Sanchez-Mazas Alicia; Nunes José Manuel;
32th European Immunogenetics and Histocompatibility Conference, Venice Lido, Italy Poster Confirmed or well-determined (CWD) HLA haplotypes in Europe: A preliminary catalogue of the EFI Population Genetics Working Group 09.05.2018 Venice Lido, Italy Nunes José Manuel; Bühler Stéphane; Sanchez-Mazas Alicia;
31th European Immunogenetics and Histocompatibility Conference, Mannheim, Germany Talk given at a conference The influence of HLA resolution level on population comparisons strongly depends on loci and geographic ranges 30.05.2017 Mannheim, Germany Nunes José Manuel; Di Da; Sanchez-Mazas Alicia;
31th European Immunogenetics and Histocompatibility Conference, Mannheim, Germany Poster CWD-viewer: a tool to visualize and inspect EFI and other CWD catalogues 30.05.2017 Mannheim, Germany Nunes José Manuel; Sanchez-Mazas Alicia;
31th European Immunogenetics and Histocompatibility Conference, Mannheim, Germany Talk given at a conference The use of entropy to describe HLA molecular information 30.05.2017 Mannheim, Germany Sanchez-Mazas Alicia; Nunes José Manuel;
31th European Immunogenetics and Histocompatibility Conference Talk given at a conference Open Meeting of the EFI Population Genetics Working Group 30.05.2017 Mannheim, Germany Di Da; Sanchez-Mazas Alicia; Bühler Stéphane; Nunes José Manuel;
31th European Immunogenetics and Histocompatibility Conference, Mannheim, Germany Talk given at a conference Heterogeneity of HLA–A and –B genetic profiles in relation to P.falciparum malaria prevalence and populations’ demography in Africa 30.05.2017 Mannheim, Germany Sanchez-Mazas Alicia; Nunes José Manuel; Bühler Stéphane; Brunet Lydie;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference Common and well-documented (CWD) HLA alleles in Europe: a catalogue characterized by regional variation 11.05.2016 Kos, Greece Bühler Stéphane; Nunes José Manuel; Sanchez-Mazas Alicia;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference From SSO to NGS in HLA population studies: the case of Mandenka (Senegal) 11.05.2016 Kos, Greece Brunet Lydie; Sanchez-Mazas Alicia; Nunes José Manuel;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference HLA Next Generation Sequencing in U.S. populations of European and African ancestry 11.05.2016 Kos, Greece Sanchez-Mazas Alicia; Nunes José Manuel;
30th European Immunogenetics and Histocompatibility Conference Poster A 24 years follow-up of HLA molecular characterization of a single population: the HLA class II profile of the African Mandenka, from PCR-SSO typing to 454 and Miseq high-throughput sequencing 11.05.2016 Kos, Greece Sanchez-Mazas Alicia; Nunes José Manuel; Brunet Lydie;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference HLA-DQA1 and DQB1 high-throughput sequencing of more than 1,500 individuals from 26 African populations: a molecular population genetics approach 11.05.2016 Kos, Greece Brunet Lydie; Nunes José Manuel; Sanchez-Mazas Alicia;
30th European Immunogenetics and Histocompatibility Conference Poster Next generation sequencing reveals HLA genomic and haplotype diversity in an US population of Northern European ancestry 11.05.2016 Kos, Greece Sanchez-Mazas Alicia; Nunes José Manuel;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference Using donor registries to map the HLA genetic landscape of the Iberian Peninsula 11.05.2016 Kos, Greece Bühler Stéphane; Nunes José Manuel; Sanchez-Mazas Alicia;
30th European Immunogenetics and Histocompatibility Conference Poster SELECTOR: forward-in-time, spatially explicit modelling software to simulate HLA lineages 11.05.2016 Kos, Greece Currat Mathias; Sanchez-Mazas Alicia; Di Da; Nunes José Manuel;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference Open meeting of the EFI Population Genetics Working Group 11.05.2016 Kos, Greece Bühler Stéphane; Nunes José Manuel; Sanchez-Mazas Alicia; Di Da;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference Deciphering HLA class I functional diversity in populations worldwide: specific signals found at HLA-C 11.05.2016 Kos, Greece Nunes José Manuel; Sanchez-Mazas Alicia; Bühler Stéphane;
30th European Immunogenetics and Histocompatibility Conference Talk given at a conference Population Genetics at EFI 11.05.2016 Kos, Greece Nunes José Manuel; Sanchez-Mazas Alicia;
Invited talk at McDonald Institute for Archaeological Research, University of Cambridge Individual talk Multiple dispersal model of modern human settlement in East Asia 26.10.2015 Cambridge, Great Britain and Northern Ireland Di Da;
29th European Immunogenetics and Histocompatibility Conference Talk given at a conference Common and well-documented HLA-A alleles reported in Europe: a pilot study from the EFI Population Genetics Working Group 26.04.2015 Geneva, Switzerland Bühler Stéphane; Nunes José Manuel; Sanchez-Mazas Alicia;
29th European Immunogenetics and Histocompatibility Conference Talk given at a conference Open meeting of the EFI Population Genetics Working Group 26.04.2015 Geneva, Switzerland Nunes José Manuel; Di Da; Sanchez-Mazas Alicia; Bühler Stéphane;
29th European Immunogenetics and Histocompatibility Conference Talk given at a conference Contrasted levels of linkage disequilibrium in Europeans and Africans revealed by precise estimations of HLA 5-locus phased haplotypes 26.04.2015 Geneva, Switzerland Sanchez-Mazas Alicia; Nunes José Manuel;
29th European Immunogenetics and Histocompatibility Conference Talk given at a conference To bind or not to bind, that is the function: an analysis of HLA class I functional diversity in 46 human populations 26.04.2015 Geneva, Switzerland Nunes José Manuel; Sanchez-Mazas Alicia; Bühler Stéphane;
29th European Immunogenetics and Histocompatibility Conference Poster Mapping the HLA molecular diversity of the Iberian Peninsula: a study of two registry panels totalling 125,000 individuals 26.04.2015 Geneva, Switzerland Bühler Stéphane; Nunes José Manuel; Sanchez-Mazas Alicia;
29th European Immunogenetics and Histocompatibility Conference Poster Particular evolutionary strategy of HLA-DQ genes in East Asian populations 24.04.2015 Geneva, Switzerland Di Da; Sanchez-Mazas Alicia;
Conference "Migrations and Transfers in Prehistory: Asian and Oceanic Ethnolinguistic Phylogeography” Talk given at a conference Multiple dispersal model of modern human settlement in East Asia supported by statistical analyses and computer simulations of HLA genes 28.07.2014 Bern, Switzerland Di Da;
28th European Immunogenetics and Histocompatibility Conference Poster HLA antigen distribution comparisons between the Hungarian population and the Gypsy minority as well as surrounding European and other Gypsy cohorts 25.06.2014 Stockholm, Sweden Nunes José Manuel; Bühler Stéphane; Sanchez-Mazas Alicia;
28th European Immunogenetics and Histocompatibility Conference Poster Computer simulation of HLA genes supports two main routes of colonization by human populations in East Asia 25.06.2014 Stockholm, Sweden Currat Mathias; Di Da; Sanchez-Mazas Alicia;
28th European Immunogenetics and Histocompatibility Conference Talk given at a conference Worldwide distribution and population differentiation of HLA-A and HLA-B supertypes: functionality, natural selection and adaptation to local pathogens 25.06.2014 Stockholm, Sweden Nunes José Manuel; Bühler Stéphane; Sanchez-Mazas Alicia;
28th European Immunogenetics and Histocompatibility Conference Talk given at a conference HLA-net now: Immunogenetics for all 25.06.2014 Stockholm, Sweden Bühler Stéphane; Sanchez-Mazas Alicia; Nunes José Manuel;
28th European Immunogenetics and Histocompatibility Conference Talk given at a conference Open meeting of the EFI Population Genetics Working Group 25.06.2014 Stockholm, Sweden Nunes José Manuel; Bühler Stéphane; Sanchez-Mazas Alicia; Di Da;
28th European Immunogenetics and Histocompatibility Conference Talk given at a conference Shared MHC molecular diversity patterns between chimpanzees and humans 25.06.2014 Stockholm, Sweden Sanchez-Mazas Alicia; Nunes José Manuel;
28th European Immunogenetics and Histocompatibility Conference Poster Demographic history and malaria prevalence : how independent causes may explain the HLA molecular profile of African populations in Nigeria 25.06.2014 Stockholm, Sweden Sanchez-Mazas Alicia;
28th European Immunogenetics and Histocompatibility Conference Talk given at a conference The regional genetic diversity of HLA in Europe: a comprehensive map drawn from 145 population samples 25.06.2014 Stockholm, Sweden Nunes José Manuel; Sanchez-Mazas Alicia; Bühler Stéphane;
Joint Meeting of 37th Asia-Pacific Histocompatibility and Immunogenetics Association (APHIA) and 2nd Hong Kong Society of Histocompatibilty and Immunogenetics (HKSHI) Talk given at a conference Role of different evolutionary forces in shaping the HLA genetic diversity in East Asia 31.07.2013 Hong Kong, China Currat Mathias; Di Da; Sanchez-Mazas Alicia;
27th annual EFI European Immunogenetics and Histocompatibility Conference Poster Distribution of HLA-A, -B and -DRB1 antigens at low resolution in the Hungarian and minority Gypsy populations 11.05.2013 Maastricht, Netherlands Bühler Stéphane; Sanchez-Mazas Alicia; Nunes José Manuel;
Genetic diversity and origins of Europeans Talk given at a conference Investigating European genetic history through computer simulations 15.01.2013 Geneva, Switzerland Currat Mathias;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Range dynamics and genetic diversity : focusing on Homo sapiens / Séminaire du département de Biologie, University of Fribourg Talk 30.04.2013 Fribourg, Switzerland Currat Mathias;
Investigating European genetic history through computer simulations / Séminaire de recherche du département d’archéologie Talk 13.03.2013 Durham, Great Britain and Northern Ireland Currat Mathias;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Détroit de Gibraltar: lieu de passage ou barrière aux migrations préhistoriques? / CGA Geneva Western Switzerland 2015
Media relations: radio, television Le rôle capital des gènes HLA RTS CQFD Western Switzerland 2014

Associated projects

Number Title Start Funding scheme
186511 Africa: 300'000 years of human diversity 01.04.2019 Agora
127465 Early human settlements in East Asia: HLA molecular variation, population expansions and linguistic differentiations 01.11.2009 Project funding (Div. I-III)
127465 Early human settlements in East Asia: HLA molecular variation, population expansions and linguistic differentiations 01.11.2009 Project funding (Div. I-III)

Abstract

We investigated HLA molecular diversity in a large set of human populations to better understand the evolutionary mechanisms affecting different HLA genes in relation to both populations’ history and the role of these genes in the immune response. To that aim, we typed (mostly through 454 and MiSeq NGS) about 3,500 individuals from populations living in contrasting environments and analysed them (by developing several additional computer tools implemented in the Gene[rate] and Selector programs) with existing data in models including distinct geographic, demographic and environmental parameters, and through peptide-binding predictions.Although clear signals of populations’ demographic history and geographic expansions are detected at all loci, pathogen-driven positive selection depending on specific environments appears to have left significant signatures on the patterns of HLA variation, like heterogeneous distributions, in Africa, of alleles B*53:01:01, B*78 and A*74 and the class II haplotype DRB1*13:04-DQA1*05:05:01-DQB1*03:19 through a putative protection to P. falciparum malaria and, possibly, to O. volvulus onchocerciasis, respectively. Weaker evidence of heterozygous advantage is observed when HLA variation is modeled in relation to pathogen richness or latitude, indicating that a uniform model of overdominant selection is more likely than an environment-specific one. A major finding is that all populations exhibit an equivalent amount of functional HLA diversity in terms of peptide-binding potential when several HLA genes are considered simultaneously. This led us to propose a new evolutionary model of joint divergent asymmetric selection explaining that some populations may exhibit a low HLA diversity at some loci, contrary to the general observation. However, HLA-A would evolve more neutrally than HLA-B by being more affected by genetic drift and less by selection at the level of its peptide-binding pockets’ variation (supertypes). Complementary analyses comparing relative levels of MHC diversity at different loci between humans and chimpanzees reveal that they are conserved through time.Overall, this project not only enhances our understanding of human genetic diversity in relation to population expansions and adaptation to contrasting environments; it also provides key knowledge on the evolution of the main genes of our immune system. By doing so, it will contribute to define differential susceptibilities of populations to environmental factors and foster research towards population-based individualized medicine.
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