Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

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dc.contributor.authorPhelan, Jody E.en_ZA
dc.contributor.authorColl, Francescen_ZA
dc.contributor.authorBergval, Indraen_ZA
dc.contributor.authorAnthony, Richard M.en_ZA
dc.contributor.authorWarren, Roben_ZA
dc.contributor.authorSampson, Samantha L.en_ZA
dc.contributor.authorGey Van Pittius, Nicolaas C.en_ZA
dc.contributor.authorGlynn, Judith R.en_ZA
dc.contributor.authorCrampin, Amelia C.en_ZA
dc.contributor.authorAlves, Adrianaen_ZA
dc.contributor.authorBessa, Theolis B.en_ZA
dc.contributor.authorCampino, Susanaen_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.contributor.authorGrandjean, Louisen_ZA
dc.contributor.authorHasan, Ruminaen_ZA
dc.contributor.authorHasan, Zahraen_ZA
dc.contributor.authorMiranda, Anabelaen_ZA
dc.contributor.authorMoore, Daviden_ZA
dc.contributor.authorPanaiotov, Stefanen_ZA
dc.contributor.authorPerdigao, Joaoen_ZA
dc.contributor.authorPortugal, Isabelen_ZA
dc.contributor.authorSheen, Patriciaen_ZA
dc.contributor.authorDe Oliveira Sousa, Eriveltonen_ZA
dc.contributor.authorStreicher, Elizabeth M.en_ZA
dc.contributor.authorVan Helden, Paul D.en_ZA
dc.contributor.authorViveiros, Miguelen_ZA
dc.contributor.authorHibberd, Martin L.en_ZA
dc.contributor.authorPain, Arnaben_ZA
dc.contributor.authorMcNerney, Ruthen_ZA
dc.contributor.authorClark, Taane G.en_ZA
dc.date.accessioned2017-01-23T07:58:01Z
dc.date.available2017-01-23T07:58:01Z
dc.date.issued2016-02-29
dc.date.updated2016-12-09T12:01:44Z
dc.descriptionCITATION: Phelan, J. E., et al. 2016. Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. BMC Genomics, 17:151, doi:10.1186/s12864-016-2467-y.
dc.descriptionThe original publication is available at http://bmcgenomics.biomedcentral.com
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.versionPublisher's version
dc.format.extent12 pages
dc.identifier.citationPhelan, J. E., et al. 2016. Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. BMC Genomics, 17:151, doi:10.1186/s12864-016-2467-y
dc.identifier.issn1471-2164 (online)
dc.identifier.otherdoi:10.1186/s12864-016-2467-y
dc.identifier.urihttp://hdl.handle.net/10019.1/100495
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Central
dc.rights.holderAuthors retain copyright
dc.subjectMycobacterium tuberculosis -- Vaccinationen_ZA
dc.subjectVaccines -- Designen_ZA
dc.subjectProline-glutamate (PE and PPE)en_ZA
dc.subjectMycobacterium tuberculosis -- Genetic aspectsen_ZA
dc.titleRecombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineagesen_ZA
dc.typeArticle
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