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dc.contributor.authorPhelan, Jody E.
dc.contributor.authorColl, Francesc
dc.contributor.authorBergval, Indra
dc.contributor.authorAnthony, Richard M.
dc.contributor.authorWarren, Rob
dc.contributor.authorSampson, Samantha L.
dc.contributor.authorGey van Pittius, Nicolaas C.
dc.contributor.authorGlynn, Judith R.
dc.contributor.authorCrampin, Amelia C.
dc.contributor.authorAlves, Adriana
dc.contributor.authorBessa, Theolis Barbosa
dc.contributor.authorCampino, Susana
dc.contributor.authorDheda, Keertan
dc.contributor.authorGrandjean, Louis
dc.contributor.authorHasan, Rumina
dc.contributor.authorHasan, Zahra
dc.contributor.authorMiranda, Anabela
dc.contributor.authorMoore, David J.
dc.contributor.authorPanaiotov, Stefan
dc.contributor.authorPerdigao, Joao
dc.contributor.authorPortugal, Isabel
dc.contributor.authorSheen, Patricia
dc.contributor.authorde Oliveira Sousa, Erivelton
dc.contributor.authorStreicher, Elizabeth M.
dc.contributor.authorvan Helden, Paul D.
dc.contributor.authorViveiros, Miguel
dc.contributor.authorHibberd, Martin L.
dc.contributor.authorPain, Arnab
dc.contributor.authorMcNerney, Ruth
dc.contributor.authorClark, Taane G.
dc.date.accessioned2016-03-02T06:30:36Z
dc.date.available2016-03-02T06:30:36Z
dc.date.issued2016-02-29
dc.identifier.citationRecombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages 2016, 17 (1) BMC Genomics
dc.identifier.issn1471-2164
dc.identifier.pmid26923687
dc.identifier.doi10.1186/s12864-016-2467-y
dc.identifier.urihttp://hdl.handle.net/10754/600452
dc.description.abstractBackground Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies. Results To elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules. Conclusions This, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development.
dc.description.sponsorshipJP is supported by a Biotechnology and Biological Sciences Research Council UK PhD studentship. FC was the recipient of a Bloomsbury Research Fund PhD studentship. SLS receives funding from the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (UID 86539). AP is supported by the KAUST faculty baseline research fund (KAUST-BRF). TGC receives funding from the Medical Research Council UK (grant numbers MR/K000551/1, MR/M01360X/1, MR/N010469/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.urlhttp://www.biomedcentral.com/1471-2164/17/151
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
dc.titleRecombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalBMC Genomics
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT London, UK
dc.contributor.institutionKIT Biomedical Research, Royal Tropical Institute, Amsterdam, Netherlands
dc.contributor.institutionDepartment of Science and Technology and National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, and Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa
dc.contributor.institutionFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK
dc.contributor.institutionKaronga Prevention Study, Lilongwe, Malawi
dc.contributor.institutionNational Mycobacterium Reference Laboratory, Porto, Portugal
dc.contributor.institutionCentro de Pesquisas Goncalo Moniz, Fundacao Oswaldo Cruz Bahia R, Salvador, Bahia, Brazil
dc.contributor.institutionDepartment of Medicine, Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, University of Cape Town, Cape Town, Western Cape, South Africa
dc.contributor.institutionInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, Western Cape, South Africa
dc.contributor.institutionLaboratorio de Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
dc.contributor.institutionDepartment of Pathology and Laboratory Medicine, The Aga Khan University, Stadium Road, Karachi, Pakistan
dc.contributor.institutionNational Center of Infectious and Parasitic Diseases, 1504 Sofia, Bulgaria
dc.contributor.institutionUniversidade de Lisboa, Lisbon, Portugal
dc.contributor.institutionGrupo de Micobactérias, Unidade de Microbiologia Médica, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa (IHMT/UNL), Lisbon, Portugal
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personPain, Arnab
dc.relation.issupplementedbyDOI:10.6084/m9.figshare.c.3645272
refterms.dateFOA2018-06-13T10:33:33Z
display.relations<b> Is Supplemented By:</b> <br/> <ul><li><i>[Dataset]</i> <br/> Phelan, J., Coll, F., Bergval, I., Anthony, R., Warren, R., Sampson, S., … Taane Clark. (2016). Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. Figshare. https://doi.org/10.6084/m9.figshare.c.3645272. DOI: <a href="https://doi.org/10.6084/m9.figshare.c.3645272">10.6084/m9.figshare.c.3645272</a> HANDLE: <a href="http://hdl.handle.net/10754/624142">10754/624142</a></li></ul>
dc.date.published-online2016-02-29
dc.date.published-print2016-12


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