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

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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 B
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
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.accessioned2016-05-25T07:43:07Z
dc.date.available2016-05-25T07:43:07Z
dc.date.issued2016-02-29
dc.date.updated2016-05-19T09:14:06Z
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.en_ZA
dc.identifier.apacitationPhelan, J. E., Coll, F., Bergval, I., Anthony, R. M., Warren, R., Sampson, S. L., ... Clark, T. G. (2016). Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. <i>BMC Genomics</i>, http://hdl.handle.net/11427/19844en_ZA
dc.identifier.chicagocitationPhelan, Jody E, Francesc Coll, Indra Bergval, Richard M Anthony, Rob Warren, Samantha L Sampson, Nicolaas C Gey van Pittius, et al "Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages." <i>BMC Genomics</i> (2016) http://hdl.handle.net/11427/19844en_ZA
dc.identifier.citationPhelan, J. E., Coll, F., Bergval, I., Anthony, R. M., Warren, R., Sampson, S. L., ... & Bessa, T. B. (2016). Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. BMC genomics, 17(1), 151.en_ZA
dc.identifier.issnBMC Genomicsen_ZA
dc.identifier.ris TY - Journal Article AU - Phelan, Jody E AU - Coll, Francesc AU - Bergval, Indra AU - Anthony, Richard M AU - Warren, Rob AU - Sampson, Samantha L AU - Gey van Pittius, Nicolaas C AU - Glynn, Judith R AU - Crampin, Amelia C AU - Alves, Adriana AU - Bessa, Theolis B AU - Campino, Susana AU - Dheda, Keertan AU - Grandjean, Louis AU - Hasan, Rumina AU - Hasan, Zahra AU - Miranda, Anabela AU - Moore, David AU - Panaiotov, Stefan AU - Perdigao, Joao AU - Portugal, Isabel AU - Sheen, Patricia AU - de Oliveira Sousa, Erivelton AU - Streicher, Elizabeth M AU - van Helden, Paul D AU - Viveiros, Miguel AU - Hibberd, Martin L AU - Pain, Arnab AU - McNerney, Ruth AU - Clark, Taane G AB - Background: 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. DA - 2016-02-29 DB - OpenUCT DO - 10.1186/s12864-016-2467-y DP - University of Cape Town J1 - BMC Genomics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 SM - BMC Genomics T1 - Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages TI - Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages UR - http://hdl.handle.net/11427/19844 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s12864-016-2467-y
dc.identifier.urihttp://hdl.handle.net/11427/19844
dc.identifier.vancouvercitationPhelan JE, Coll F, Bergval I, Anthony RM, Warren R, Sampson SL, et al. Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages. BMC Genomics. 2016; http://hdl.handle.net/11427/19844.en_ZA
dc.languageengen_ZA
dc.language.rfc3066en
dc.publisherBioMed Centralen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)*
dc.rights.holderPhelan et al.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_ZA
dc.sourceBMC Genomicsen_ZA
dc.source.urihttp://bmcgenomics.biomedcentral.com/
dc.titleRecombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineagesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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