Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level.
Identifieur interne : 000123 ( PubMed/Checkpoint ); précédent : 000122; suivant : 000124Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level.
Auteurs : Johanna Rhodes [Royaume-Uni] ; Christopher A. Desjardins [États-Unis] ; Sean M. Sykes [États-Unis] ; Mathew A. Beale [Royaume-Uni] ; Mathieu Vanhove [Royaume-Uni] ; Sharadha Sakthikumar [États-Unis] ; Yuan Chen [États-Unis] ; Sharvari Gujja [États-Unis] ; Sakina Saif [États-Unis] ; Anuradha Chowdhary [Inde] ; Daniel John Lawson [Royaume-Uni] ; Vinicius Ponzio [Brésil] ; Arnaldo Lopes Colombo [Brésil] ; Wieland Meyer [Australie] ; David M. Engelthaler [États-Unis] ; Ferry Hagen [Pays-Bas] ; Maria Teresa Illnait-Zaragozi [Cuba] ; Alexandre Alanio [France] ; Jo-Marie Vreulink [Afrique du Sud] ; Joseph Heitman [États-Unis] ; John R. Perfect [États-Unis] ; Anastasia P. Litvintseva [États-Unis] ; Tihana Bicanic [Royaume-Uni] ; Thomas S. Harrison [Royaume-Uni] ; Matthew C. Fisher [Royaume-Uni] ; Christina A. Cuomo [Royaume-Uni]Source :
- Genetics [ 1943-2631 ] ; 2017.
Abstract
Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them. While most isolates of C. neoformans var. grubii belong to one of three major lineages (VNI, VNII, and VNB), some haploid isolates show hybrid ancestry including some that appear to have recently interbred, based on the detection of large blocks of each ancestry across each chromosome. Many isolates display evidence of aneuploidy, which was detected for all chromosomes. In diploid isolates of C. neoformans var. grubii (serotype AA) and of hybrids with C. neoformans var. neoformans (serotype AD) such aneuploidies have resulted in loss of heterozygosity, where a chromosomal region is represented by the genotype of only one parental isolate. Phylogenetic and population genomic analyses of isolates from Brazil reveal that the previously "African" VNB lineage occurs naturally in the South American environment. This suggests migration of the VNB lineage between Africa and South America prior to its diversification, supported by finding ancestral recombination events between isolates from different lineages and regions. The results provide evidence of substantial population structure, with all lineages showing multi-continental distributions; demonstrating the highly dispersive nature of this pathogen.
DOI: 10.1534/genetics.117.203836
PubMed: 28679543
Affiliations:
- Afrique du Sud, Australie, Brésil, Cuba, France, Inde, Pays-Bas, Royaume-Uni, États-Unis
- Arizona, Caroline du Nord, Gueldre, Massachusetts, Nouvelle-Galles du Sud, État de São Paulo, Île-de-France
- Nimègue, Paris, Sydney, São Paulo
- Université de Sydney, Université de São Paulo
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Nord</region></placeName><wicri:cityArea>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Gujja, Sharvari" sort="Gujja, Sharvari" uniqKey="Gujja S" first="Sharvari" last="Gujja">Sharvari Gujja</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Saif, Sakina" sort="Saif, Sakina" uniqKey="Saif S" first="Sakina" last="Saif">Sakina Saif</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Chowdhary, Anuradha" sort="Chowdhary, Anuradha" uniqKey="Chowdhary A" first="Anuradha" last="Chowdhary">Anuradha Chowdhary</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, 110007, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, 110007</wicri:regionArea><wicri:noRegion>110007</wicri:noRegion></affiliation></author><author><name sortKey="Lawson, Daniel John" sort="Lawson, Daniel John" uniqKey="Lawson D" first="Daniel John" last="Lawson">Daniel John Lawson</name><affiliation wicri:level="1"><nlm:affiliation>Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, BS8 1TH, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, BS8 1TH</wicri:regionArea><wicri:noRegion>BS8 1TH</wicri:noRegion></affiliation></author><author><name sortKey="Ponzio, Vinicius" sort="Ponzio, Vinicius" uniqKey="Ponzio V" first="Vinicius" last="Ponzio">Vinicius Ponzio</name><affiliation wicri:level="4"><nlm:affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Division of Infectious Diseases, Federal University of São Paulo, 04039-032</wicri:regionArea><orgName type="university">Université de São Paulo</orgName><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Colombo, Arnaldo Lopes" sort="Colombo, Arnaldo Lopes" uniqKey="Colombo A" first="Arnaldo Lopes" last="Colombo">Arnaldo Lopes Colombo</name><affiliation wicri:level="4"><nlm:affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Division of Infectious Diseases, Federal University of São Paulo, 04039-032</wicri:regionArea><orgName type="university">Université de São Paulo</orgName><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Meyer, Wieland" sort="Meyer, Wieland" uniqKey="Meyer W" first="Wieland" last="Meyer">Wieland Meyer</name><affiliation wicri:level="4"><nlm:affiliation>Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Institute for Medical Research, 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Institute for Medical Research, 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Engelthaler, David M" sort="Engelthaler, David M" uniqKey="Engelthaler D" first="David M" last="Engelthaler">David M. Engelthaler</name><affiliation wicri:level="2"><nlm:affiliation>TGen North, Translational Genomics Research Institute, Flagstaff, Arizona 86005.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Arizona</region></placeName><wicri:cityArea>TGen North, Translational Genomics Research Institute, Flagstaff</wicri:cityArea></affiliation></author><author><name sortKey="Hagen, Ferry" sort="Hagen, Ferry" uniqKey="Hagen F" first="Ferry" last="Hagen">Ferry Hagen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Illnait Zaragozi, Maria Teresa" sort="Illnait Zaragozi, Maria Teresa" uniqKey="Illnait Zaragozi M" first="Maria Teresa" last="Illnait-Zaragozi">Maria Teresa Illnait-Zaragozi</name><affiliation wicri:level="1"><nlm:affiliation>Departamento Bacteriología-Micologia, Centro de Investigación, Diagnóstico y Referencia, Instituto de Medicina Tropical Pedro Kourí, La Habana, 601, Cuba.</nlm:affiliation><country xml:lang="fr">Cuba</country><wicri:regionArea>Departamento Bacteriología-Micologia, Centro de Investigación, Diagnóstico y Referencia, Instituto de Medicina Tropical Pedro Kourí, La Habana, 601</wicri:regionArea><wicri:noRegion>601</wicri:noRegion></affiliation></author><author><name sortKey="Alanio, Alexandre" sort="Alanio, Alexandre" uniqKey="Alanio A" first="Alexandre" last="Alanio">Alexandre Alanio</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Paris, 75010, France; Université Paris Diderot, Sorbonne Paris Cité, 75010, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de la Recherche Scientifique, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Paris, 75010, France; Université Paris Diderot, Sorbonne Paris Cité, 75010, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de la Recherche Scientifique, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Vreulink, Jo Marie" sort="Vreulink, Jo Marie" uniqKey="Vreulink J" first="Jo-Marie" last="Vreulink">Jo-Marie Vreulink</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Stellenbosch University, 7600, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Microbiology, Stellenbosch University, 7600</wicri:regionArea><wicri:noRegion>7600</wicri:noRegion></affiliation></author><author><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Perfect, John R" sort="Perfect, John R" uniqKey="Perfect J" first="John R" last="Perfect">John R. Perfect</name><affiliation wicri:level="2"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Litvintseva, Anastasia P" sort="Litvintseva, Anastasia P" uniqKey="Litvintseva A" first="Anastasia P" last="Litvintseva">Anastasia P. Litvintseva</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bicanic, Tihana" sort="Bicanic, Tihana" uniqKey="Bicanic T" first="Tihana" last="Bicanic">Tihana Bicanic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, St. George's University London, WC1E 6BT</wicri:regionArea><wicri:noRegion>WC1E 6BT</wicri:noRegion></affiliation></author><author><name sortKey="Harrison, Thomas S" sort="Harrison, Thomas S" uniqKey="Harrison T" first="Thomas S" last="Harrison">Thomas S. Harrison</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, St. George's University London, WC1E 6BT</wicri:regionArea><wicri:noRegion>WC1E 6BT</wicri:noRegion></affiliation></author><author><name sortKey="Fisher, Matthew C" sort="Fisher, Matthew C" uniqKey="Fisher M" first="Matthew C" last="Fisher">Matthew C. Fisher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</nlm:affiliation><country wicri:rule="url">Royaume-Uni</country><wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG</wicri:regionArea><wicri:noRegion>W2 1PG</wicri:noRegion></affiliation></author><author><name sortKey="Cuomo, Christina A" sort="Cuomo, Christina A" uniqKey="Cuomo C" first="Christina A" last="Cuomo">Christina A. Cuomo</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142 matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</nlm:affiliation><country wicri:rule="url">Royaume-Uni</country><wicri:regionArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:regionArea><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28679543</idno><idno type="pmid">28679543</idno><idno type="doi">10.1534/genetics.117.203836</idno><idno type="wicri:Area/PubMed/Corpus">000637</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000637</idno><idno type="wicri:Area/PubMed/Curation">000635</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000635</idno><idno type="wicri:Area/PubMed/Checkpoint">000635</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000635</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level.</title><author><name sortKey="Rhodes, Johanna" sort="Rhodes, Johanna" uniqKey="Rhodes J" first="Johanna" last="Rhodes">Johanna Rhodes</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG</wicri:regionArea><wicri:noRegion>W2 1PG</wicri:noRegion></affiliation></author><author><name sortKey="Desjardins, Christopher A" sort="Desjardins, Christopher A" uniqKey="Desjardins C" first="Christopher A" last="Desjardins">Christopher A. Desjardins</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Sykes, Sean M" sort="Sykes, Sean M" uniqKey="Sykes S" first="Sean M" last="Sykes">Sean M. Sykes</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Beale, Mathew A" sort="Beale, Mathew A" uniqKey="Beale M" first="Mathew A" last="Beale">Mathew A. Beale</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG</wicri:regionArea><wicri:noRegion>W2 1PG</wicri:noRegion></affiliation></author><author><name sortKey="Vanhove, Mathieu" sort="Vanhove, Mathieu" uniqKey="Vanhove M" first="Mathieu" last="Vanhove">Mathieu Vanhove</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG</wicri:regionArea><wicri:noRegion>W2 1PG</wicri:noRegion></affiliation></author><author><name sortKey="Sakthikumar, Sharadha" sort="Sakthikumar, Sharadha" uniqKey="Sakthikumar S" first="Sharadha" last="Sakthikumar">Sharadha Sakthikumar</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Chen, Yuan" sort="Chen, Yuan" uniqKey="Chen Y" first="Yuan" last="Chen">Yuan Chen</name><affiliation wicri:level="2"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Gujja, Sharvari" sort="Gujja, Sharvari" uniqKey="Gujja S" first="Sharvari" last="Gujja">Sharvari Gujja</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Saif, Sakina" sort="Saif, Sakina" uniqKey="Saif S" first="Sakina" last="Saif">Sakina Saif</name><affiliation wicri:level="2"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Chowdhary, Anuradha" sort="Chowdhary, Anuradha" uniqKey="Chowdhary A" first="Anuradha" last="Chowdhary">Anuradha Chowdhary</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, 110007, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, 110007</wicri:regionArea><wicri:noRegion>110007</wicri:noRegion></affiliation></author><author><name sortKey="Lawson, Daniel John" sort="Lawson, Daniel John" uniqKey="Lawson D" first="Daniel John" last="Lawson">Daniel John Lawson</name><affiliation wicri:level="1"><nlm:affiliation>Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, BS8 1TH, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, BS8 1TH</wicri:regionArea><wicri:noRegion>BS8 1TH</wicri:noRegion></affiliation></author><author><name sortKey="Ponzio, Vinicius" sort="Ponzio, Vinicius" uniqKey="Ponzio V" first="Vinicius" last="Ponzio">Vinicius Ponzio</name><affiliation wicri:level="4"><nlm:affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Division of Infectious Diseases, Federal University of São Paulo, 04039-032</wicri:regionArea><orgName type="university">Université de São Paulo</orgName><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Colombo, Arnaldo Lopes" sort="Colombo, Arnaldo Lopes" uniqKey="Colombo A" first="Arnaldo Lopes" last="Colombo">Arnaldo Lopes Colombo</name><affiliation wicri:level="4"><nlm:affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Division of Infectious Diseases, Federal University of São Paulo, 04039-032</wicri:regionArea><orgName type="university">Université de São Paulo</orgName><placeName><settlement type="city">São Paulo</settlement><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Meyer, Wieland" sort="Meyer, Wieland" uniqKey="Meyer W" first="Wieland" last="Meyer">Wieland Meyer</name><affiliation wicri:level="4"><nlm:affiliation>Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Institute for Medical Research, 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Institute for Medical Research, 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Engelthaler, David M" sort="Engelthaler, David M" uniqKey="Engelthaler D" first="David M" last="Engelthaler">David M. Engelthaler</name><affiliation wicri:level="2"><nlm:affiliation>TGen North, Translational Genomics Research Institute, Flagstaff, Arizona 86005.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Arizona</region></placeName><wicri:cityArea>TGen North, Translational Genomics Research Institute, Flagstaff</wicri:cityArea></affiliation></author><author><name sortKey="Hagen, Ferry" sort="Hagen, Ferry" uniqKey="Hagen F" first="Ferry" last="Hagen">Ferry Hagen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen</wicri:regionArea><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Illnait Zaragozi, Maria Teresa" sort="Illnait Zaragozi, Maria Teresa" uniqKey="Illnait Zaragozi M" first="Maria Teresa" last="Illnait-Zaragozi">Maria Teresa Illnait-Zaragozi</name><affiliation wicri:level="1"><nlm:affiliation>Departamento Bacteriología-Micologia, Centro de Investigación, Diagnóstico y Referencia, Instituto de Medicina Tropical Pedro Kourí, La Habana, 601, Cuba.</nlm:affiliation><country xml:lang="fr">Cuba</country><wicri:regionArea>Departamento Bacteriología-Micologia, Centro de Investigación, Diagnóstico y Referencia, Instituto de Medicina Tropical Pedro Kourí, La Habana, 601</wicri:regionArea><wicri:noRegion>601</wicri:noRegion></affiliation></author><author><name sortKey="Alanio, Alexandre" sort="Alanio, Alexandre" uniqKey="Alanio A" first="Alexandre" last="Alanio">Alexandre Alanio</name><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Paris, 75010, France; Université Paris Diderot, Sorbonne Paris Cité, 75010, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de la Recherche Scientifique, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Paris, 75010, France; Université Paris Diderot, Sorbonne Paris Cité, 75010, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de la Recherche Scientifique, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, 75015, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Vreulink, Jo Marie" sort="Vreulink, Jo Marie" uniqKey="Vreulink J" first="Jo-Marie" last="Vreulink">Jo-Marie Vreulink</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Stellenbosch University, 7600, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>Department of Microbiology, Stellenbosch University, 7600</wicri:regionArea><wicri:noRegion>7600</wicri:noRegion></affiliation></author><author><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Perfect, John R" sort="Perfect, John R" uniqKey="Perfect J" first="John R" last="Perfect">John R. Perfect</name><affiliation wicri:level="2"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Litvintseva, Anastasia P" sort="Litvintseva, Anastasia P" uniqKey="Litvintseva A" first="Anastasia P" last="Litvintseva">Anastasia P. Litvintseva</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bicanic, Tihana" sort="Bicanic, Tihana" uniqKey="Bicanic T" first="Tihana" last="Bicanic">Tihana Bicanic</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, St. George's University London, WC1E 6BT</wicri:regionArea><wicri:noRegion>WC1E 6BT</wicri:noRegion></affiliation></author><author><name sortKey="Harrison, Thomas S" sort="Harrison, Thomas S" uniqKey="Harrison T" first="Thomas S" last="Harrison">Thomas S. Harrison</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Infection and Immunity, St. George's University London, WC1E 6BT</wicri:regionArea><wicri:noRegion>WC1E 6BT</wicri:noRegion></affiliation></author><author><name sortKey="Fisher, Matthew C" sort="Fisher, Matthew C" uniqKey="Fisher M" first="Matthew C" last="Fisher">Matthew C. Fisher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</nlm:affiliation><country wicri:rule="url">Royaume-Uni</country><wicri:regionArea>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG</wicri:regionArea><wicri:noRegion>W2 1PG</wicri:noRegion></affiliation></author><author><name sortKey="Cuomo, Christina A" sort="Cuomo, Christina A" uniqKey="Cuomo C" first="Christina A" last="Cuomo">Christina A. Cuomo</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142 matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</nlm:affiliation><country wicri:rule="url">Royaume-Uni</country><wicri:regionArea>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge</wicri:regionArea><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author></analytic><series><title level="j">Genetics</title><idno type="eISSN">1943-2631</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them. While most isolates of C. neoformans var. grubii belong to one of three major lineages (VNI, VNII, and VNB), some haploid isolates show hybrid ancestry including some that appear to have recently interbred, based on the detection of large blocks of each ancestry across each chromosome. Many isolates display evidence of aneuploidy, which was detected for all chromosomes. In diploid isolates of C. neoformans var. grubii (serotype AA) and of hybrids with C. neoformans var. neoformans (serotype AD) such aneuploidies have resulted in loss of heterozygosity, where a chromosomal region is represented by the genotype of only one parental isolate. Phylogenetic and population genomic analyses of isolates from Brazil reveal that the previously "African" VNB lineage occurs naturally in the South American environment. This suggests migration of the VNB lineage between Africa and South America prior to its diversification, supported by finding ancestral recombination events between isolates from different lineages and regions. The results provide evidence of substantial population structure, with all lineages showing multi-continental distributions; demonstrating the highly dispersive nature of this pathogen.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">28679543</PMID><DateCreated><Year>2017</Year><Month>07</Month><Day>06</Day></DateCreated><DateRevised><Year>2017</Year><Month>09</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1943-2631</ISSN><JournalIssue CitedMedium="Internet"><Volume>207</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Genetics</Title><ISOAbbreviation>Genetics</ISOAbbreviation></Journal><ArticleTitle>Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level.</ArticleTitle><Pagination><MedlinePgn>327-346</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1534/genetics.117.203836</ELocationID><Abstract><AbstractText>Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them. While most isolates of C. neoformans var. grubii belong to one of three major lineages (VNI, VNII, and VNB), some haploid isolates show hybrid ancestry including some that appear to have recently interbred, based on the detection of large blocks of each ancestry across each chromosome. Many isolates display evidence of aneuploidy, which was detected for all chromosomes. In diploid isolates of C. neoformans var. grubii (serotype AA) and of hybrids with C. neoformans var. neoformans (serotype AD) such aneuploidies have resulted in loss of heterozygosity, where a chromosomal region is represented by the genotype of only one parental isolate. Phylogenetic and population genomic analyses of isolates from Brazil reveal that the previously "African" VNB lineage occurs naturally in the South American environment. This suggests migration of the VNB lineage between Africa and South America prior to its diversification, supported by finding ancestral recombination events between isolates from different lineages and regions. The results provide evidence of substantial population structure, with all lineages showing multi-continental distributions; demonstrating the highly dispersive nature of this pathogen.</AbstractText><CopyrightInformation>Copyright © 2017 Rhodes et al.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rhodes</LastName><ForeName>Johanna</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-1338-7860</Identifier><AffiliationInfo><Affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Desjardins</LastName><ForeName>Christopher A</ForeName><Initials>CA</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-3160-4734</Identifier><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sykes</LastName><ForeName>Sean M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beale</LastName><ForeName>Mathew A</ForeName><Initials>MA</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-4740-3187</Identifier><AffiliationInfo><Affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Infection Genomics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vanhove</LastName><ForeName>Mathieu</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sakthikumar</LastName><ForeName>Sharadha</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gujja</LastName><ForeName>Sharvari</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saif</LastName><ForeName>Sakina</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chowdhary</LastName><ForeName>Anuradha</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-2028-7462</Identifier><AffiliationInfo><Affiliation>Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, 110007, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lawson</LastName><ForeName>Daniel John</ForeName><Initials>DJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5311-6213</Identifier><AffiliationInfo><Affiliation>Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, BS8 1TH, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ponzio</LastName><ForeName>Vinicius</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colombo</LastName><ForeName>Arnaldo Lopes</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Federal University of São Paulo, 04039-032, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meyer</LastName><ForeName>Wieland</ForeName><Initials>W</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-9933-8340</Identifier><AffiliationInfo><Affiliation>Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead Institute for Medical Research, 2145, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Mycology Laboratory, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, 21040-360, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Engelthaler</LastName><ForeName>David M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>TGen North, Translational Genomics Research Institute, Flagstaff, Arizona 86005.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hagen</LastName><ForeName>Ferry</ForeName><Initials>F</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5622-1916</Identifier><AffiliationInfo><Affiliation>Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre of Expertise in Mycology, Radboudumc/Canisius-Wilhelmina Hospital, 6532SZ Nijmegen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Illnait-Zaragozi</LastName><ForeName>Maria Teresa</ForeName><Initials>MT</Initials><AffiliationInfo><Affiliation>Departamento Bacteriología-Micologia, Centro de Investigación, Diagnóstico y Referencia, Instituto de Medicina Tropical Pedro Kourí, La Habana, 601, Cuba.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alanio</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-9726-3082</Identifier><AffiliationInfo><Affiliation>Laboratoire de Parasitologie-Mycologie, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal Paris, 75010, France; Université Paris Diderot, Sorbonne Paris Cité, 75010, Paris, France; Unité de Mycologie Moléculaire, Institut Pasteur, Centre National de la Recherche Scientifique, Centre National de Référence Mycoses Invasives et Antifongiques, URA3012, 75015, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vreulink</LastName><ForeName>Jo-Marie</ForeName><Initials>JM</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-5446-1396</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Stellenbosch University, 7600, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heitman</LastName><ForeName>Joseph</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-6369-5995</Identifier><AffiliationInfo><Affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perfect</LastName><ForeName>John R</ForeName><Initials>JR</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0019-8638</Identifier><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Litvintseva</LastName><ForeName>Anastasia P</ForeName><Initials>AP</Initials><AffiliationInfo><Affiliation>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bicanic</LastName><ForeName>Tihana</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harrison</LastName><ForeName>Thomas S</ForeName><Initials>TS</Initials><AffiliationInfo><Affiliation>Institute of Infection and Immunity, St. George's University London, WC1E 6BT, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fisher</LastName><ForeName>Matthew C</ForeName><Initials>MC</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-1862-6402</Identifier><AffiliationInfo><Affiliation>Department of Infectious Disease Epidemiology, Imperial College London, W2 1PG, United Kingdom matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cuomo</LastName><ForeName>Christina A</ForeName><Initials>CA</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-5778-960X</Identifier><AffiliationInfo><Affiliation>Infectious Disease and Microbiome Program, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142 matthew.fisher@imperial.ac.uk cuomo@broadinstitute.org.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R37 AI039115</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI073896</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI093257</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U54 HG003067</GrantID><Acronym>HG</Acronym><Agency>NHGRI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI039115</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI050113</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>U19 AI110818</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>07</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Genetics</MedlineTA><NlmUniqueID>0374636</NlmUniqueID><ISSNLinking>0016-6731</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Genome Res. 2015 Mar;25(3):413-25</RefSource><PMID Version="1">25504520</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Infect Dis. 2008 Jul 1;47(1):123-30</RefSource><PMID Version="1">18505387</PMID></CommentsCorrections><CommentsCorrections 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PubStatus="medline"><Year>2017</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>7</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28679543</ArticleId><ArticleId IdType="pii">genetics.117.203836</ArticleId><ArticleId IdType="doi">10.1534/genetics.117.203836</ArticleId><ArticleId IdType="pmc">PMC5586382</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Afrique du Sud</li><li>Australie</li><li>Brésil</li><li>Cuba</li><li>France</li><li>Inde</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Arizona</li><li>Caroline du Nord</li><li>Gueldre</li><li>Massachusetts</li><li>Nouvelle-Galles du Sud</li><li>État de São Paulo</li><li>Île-de-France</li></region><settlement><li>Nimègue</li><li>Paris</li><li>Sydney</li><li>São Paulo</li></settlement><orgName><li>Université de Sydney</li><li>Université de São Paulo</li></orgName></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Rhodes, Johanna" sort="Rhodes, Johanna" uniqKey="Rhodes J" first="Johanna" last="Rhodes">Johanna Rhodes</name></noRegion><name sortKey="Beale, Mathew A" sort="Beale, Mathew A" uniqKey="Beale M" first="Mathew A" last="Beale">Mathew A. Beale</name><name sortKey="Bicanic, Tihana" sort="Bicanic, Tihana" uniqKey="Bicanic T" first="Tihana" last="Bicanic">Tihana Bicanic</name><name sortKey="Cuomo, Christina A" sort="Cuomo, Christina A" uniqKey="Cuomo C" first="Christina A" last="Cuomo">Christina A. Cuomo</name><name sortKey="Fisher, Matthew C" sort="Fisher, Matthew C" uniqKey="Fisher M" first="Matthew C" last="Fisher">Matthew C. Fisher</name><name sortKey="Harrison, Thomas S" sort="Harrison, Thomas S" uniqKey="Harrison T" first="Thomas S" last="Harrison">Thomas S. Harrison</name><name sortKey="Lawson, Daniel John" sort="Lawson, Daniel John" uniqKey="Lawson D" first="Daniel John" last="Lawson">Daniel John Lawson</name><name sortKey="Vanhove, Mathieu" sort="Vanhove, Mathieu" uniqKey="Vanhove M" first="Mathieu" last="Vanhove">Mathieu Vanhove</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Desjardins, Christopher A" sort="Desjardins, Christopher A" uniqKey="Desjardins C" first="Christopher A" last="Desjardins">Christopher A. Desjardins</name></region><name sortKey="Chen, Yuan" sort="Chen, Yuan" uniqKey="Chen Y" first="Yuan" last="Chen">Yuan Chen</name><name sortKey="Engelthaler, David M" sort="Engelthaler, David M" uniqKey="Engelthaler D" first="David M" last="Engelthaler">David M. Engelthaler</name><name sortKey="Gujja, Sharvari" sort="Gujja, Sharvari" uniqKey="Gujja S" first="Sharvari" last="Gujja">Sharvari Gujja</name><name sortKey="Heitman, Joseph" sort="Heitman, Joseph" uniqKey="Heitman J" first="Joseph" last="Heitman">Joseph Heitman</name><name sortKey="Litvintseva, Anastasia P" sort="Litvintseva, Anastasia P" uniqKey="Litvintseva A" first="Anastasia P" last="Litvintseva">Anastasia P. Litvintseva</name><name sortKey="Perfect, John R" sort="Perfect, John R" uniqKey="Perfect J" first="John R" last="Perfect">John R. Perfect</name><name sortKey="Saif, Sakina" sort="Saif, Sakina" uniqKey="Saif S" first="Sakina" last="Saif">Sakina Saif</name><name sortKey="Sakthikumar, Sharadha" sort="Sakthikumar, Sharadha" uniqKey="Sakthikumar S" first="Sharadha" last="Sakthikumar">Sharadha Sakthikumar</name><name sortKey="Sykes, Sean M" sort="Sykes, Sean M" uniqKey="Sykes S" first="Sean M" last="Sykes">Sean M. Sykes</name></country><country name="Inde"><noRegion><name sortKey="Chowdhary, Anuradha" sort="Chowdhary, Anuradha" uniqKey="Chowdhary A" first="Anuradha" last="Chowdhary">Anuradha Chowdhary</name></noRegion></country><country name="Brésil"><region name="État de São Paulo"><name sortKey="Ponzio, Vinicius" sort="Ponzio, Vinicius" uniqKey="Ponzio V" first="Vinicius" last="Ponzio">Vinicius Ponzio</name></region><name sortKey="Colombo, Arnaldo Lopes" sort="Colombo, Arnaldo Lopes" uniqKey="Colombo A" first="Arnaldo Lopes" last="Colombo">Arnaldo Lopes Colombo</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Meyer, Wieland" sort="Meyer, Wieland" uniqKey="Meyer W" first="Wieland" last="Meyer">Wieland Meyer</name></region></country><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Hagen, Ferry" sort="Hagen, Ferry" uniqKey="Hagen F" first="Ferry" last="Hagen">Ferry Hagen</name></region></country><country name="Cuba"><noRegion><name sortKey="Illnait Zaragozi, Maria Teresa" sort="Illnait Zaragozi, Maria Teresa" uniqKey="Illnait Zaragozi M" first="Maria Teresa" last="Illnait-Zaragozi">Maria Teresa Illnait-Zaragozi</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Alanio, Alexandre" sort="Alanio, Alexandre" uniqKey="Alanio A" first="Alexandre" last="Alanio">Alexandre Alanio</name></region></country><country name="Afrique du Sud"><noRegion><name sortKey="Vreulink, Jo Marie" sort="Vreulink, Jo Marie" uniqKey="Vreulink J" first="Jo-Marie" last="Vreulink">Jo-Marie Vreulink</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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