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dc.contributor.authorNdhlovu, Victor
dc.contributor.authorKiran, Anmol
dc.contributor.authorSloan, Derek J.
dc.contributor.authorMandala, Wilson
dc.contributor.authorNliwasa, Marriott
dc.contributor.authorEverett, Dean B.
dc.contributor.authorKumwenda, Benjamin
dc.contributor.authorMwapasa, Mphatso
dc.contributor.authorKontogianni, Konstantina
dc.contributor.authorKamdolozi, Mercy
dc.contributor.authorCorbett, Elizabeth
dc.contributor.authorCaws, Maxine
dc.contributor.authorDavies, Gerry
dc.identifier.citationNdhlovu , V , Kiran , A , Sloan , D J , Mandala , W , Nliwasa , M , Everett , D B , Kumwenda , B , Mwapasa , M , Kontogianni , K , Kamdolozi , M , Corbett , E , Caws , M & Davies , G 2020 , ' Characterization of DNA methylation in Malawian Mycobacterium tuberculosis clinical isolates ' , PeerJ , vol. 8 , e10432 .
dc.identifier.otherORCID: /0000-0002-7888-5449/work/87404420
dc.descriptionFunding: This work was supported by the Helse Nord Tuberculosis Initiative (No.095).en
dc.description.abstractBackground. Although Mycobacterium tuberculosis (Mtb) strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in Mtb are not well understood but epigenetic variation is thought to contribute. At present the methylome of Mtb has not been completely characterized. Methods. We completed methylomes of 18 Mycobacterium tuberculosis (Mtb) clinical isolates from Malawi representing the largest number of Mtb genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date. Results. We replicate and confirm four methylation disrupting mutations in 4 lineages of Mtb. For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the MamB gene of Indo-oceanic lineage of Mtb. Additionally, we report a novel missense mutation G454A (G152S) in the MamA gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCAG motif but partial loss in a partner motif. Through a genomic and methylome comparative analysis with a global sample of sixteen, we report previously unknown mutations affecting the pks15/1 locus in L6 isolates. We confirm that methylation in Mtb is lineage specific although some unresolved issues still remain.
dc.subjectDNA methylationen
dc.subjectMalawian Mtb clinical isolatesen
dc.subjectMycobacterium tuberculosisen
dc.subjectSingle Molecule Real Time Sequencingen
dc.subjectQH426 Geneticsen
dc.subjectQR Microbiologyen
dc.subjectAgricultural and Biological Sciences(all)en
dc.subjectBiochemistry, Genetics and Molecular Biology(all)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleCharacterization of DNA methylation in Malawian Mycobacterium tuberculosis clinical isolatesen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Infection and Global Health Divisionen
dc.description.statusPeer revieweden

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