Characterization of DNA methylation in Malawian clinical isolates.

Victor Ndhlovu; Anmol Kiran; Derek J. Sloan; Wilson Mandala; Marriott Nliwasa; Dean B. Everett; Benjamin Kumwenda; Mphatso Mwapasa; Nadia Kontogianni; Mercy Kamdolozi; Elizabeth Corbett; Maxine Caws; Gerry Davies

doi:10.7717/peerj.10432

Characterization of DNA methylation in Malawian clinical isolates.

Victor Ndhlovu, Anmol Kiran, Derek J. Sloan, Wilson Mandala, Marriott Nliwasa, Dean B. Everett, Benjamin Kumwenda, Mphatso Mwapasa, Nadia Kontogianni, Mercy Kamdolozi, Elizabeth Corbett, Maxine Caws, Gerry Davies

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Background

Although strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in are not well understood but epigenetic variation is thought to contribute. At present the methylome of has not been completely characterized.

Methods

We completed methylomes of 18 () clinical isolates from Malawi representing the largest number of 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 . For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the gene of Indo-oceanic lineage of . Additionally, we report a novel missense mutation G454A (G152S) in the gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCG 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 locus in L6 isolates. We confirm that methylation in is lineage specific although some unresolved issues still remain.

Original language	English
Article number	e10432
Pages (from-to)	e10432
Journal	PeerJ
Volume	8
DOIs	https://doi.org/10.7717/peerj.10432
Publication status	Published - 16 Dec 2020

Keywords

DNA methylation
Malawian Mtb clinical isolates
Motif
Mycobacterium tuberculosis
Single Molecule Real Time Sequencing

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10.7717/peerj.10432Licence: CC BY

DNA methylation malawi - MCawsFinal published version, 1.8 MBLicence: CC BY

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title = "Characterization of DNA methylation in Malawian clinical isolates.",

abstract = "BackgroundAlthough strains exhibit genomic homology of >99\%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in are not well understood but epigenetic variation is thought to contribute. At present the methylome of has not been completely characterized.MethodsWe completed methylomes of 18 () clinical isolates from Malawi representing the largest number of genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date.ResultsWe replicate and confirm four methylation disrupting mutations in 4 lineages of . For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the gene of Indo-oceanic lineage of . Additionally, we report a novel missense mutation G454A (G152S) in the gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCG 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 locus in L6 isolates. We confirm that methylation in is lineage specific although some unresolved issues still remain.",

keywords = "DNA methylation, Malawian Mtb clinical isolates, Motif, Mycobacterium tuberculosis, Single Molecule Real Time Sequencing",

author = "Victor Ndhlovu and Anmol Kiran and Sloan, \{Derek J.\} and Wilson Mandala and Marriott Nliwasa and Everett, \{Dean B.\} and Benjamin Kumwenda and Mphatso Mwapasa and Nadia Kontogianni and Mercy Kamdolozi and Elizabeth Corbett and Maxine Caws and Gerry Davies",

year = "2020",

month = dec,

day = "16",

doi = "10.7717/peerj.10432",

language = "English",

volume = "8",

pages = "e10432",

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TY - JOUR

T1 - Characterization of DNA methylation in Malawian clinical isolates.

AU - Ndhlovu, Victor

AU - Kiran, Anmol

AU - Sloan, Derek J.

AU - Mandala, Wilson

AU - Nliwasa, Marriott

AU - Everett, Dean B.

AU - Kumwenda, Benjamin

AU - Mwapasa, Mphatso

AU - Kontogianni, Nadia

AU - Kamdolozi, Mercy

AU - Corbett, Elizabeth

AU - Caws, Maxine

AU - Davies, Gerry

PY - 2020/12/16

Y1 - 2020/12/16

N2 - BackgroundAlthough strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in are not well understood but epigenetic variation is thought to contribute. At present the methylome of has not been completely characterized.MethodsWe completed methylomes of 18 () clinical isolates from Malawi representing the largest number of genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date.ResultsWe replicate and confirm four methylation disrupting mutations in 4 lineages of . For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the gene of Indo-oceanic lineage of . Additionally, we report a novel missense mutation G454A (G152S) in the gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCG 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 locus in L6 isolates. We confirm that methylation in is lineage specific although some unresolved issues still remain.

AB - BackgroundAlthough strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in are not well understood but epigenetic variation is thought to contribute. At present the methylome of has not been completely characterized.MethodsWe completed methylomes of 18 () clinical isolates from Malawi representing the largest number of genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date.ResultsWe replicate and confirm four methylation disrupting mutations in 4 lineages of . For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the gene of Indo-oceanic lineage of . Additionally, we report a novel missense mutation G454A (G152S) in the gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCCG 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 locus in L6 isolates. We confirm that methylation in is lineage specific although some unresolved issues still remain.

KW - DNA methylation

KW - Malawian Mtb clinical isolates

KW - Motif

KW - Mycobacterium tuberculosis

KW - Single Molecule Real Time Sequencing

U2 - 10.7717/peerj.10432

DO - 10.7717/peerj.10432

M3 - Article

SN - 2167-8359

VL - 8

SP - e10432

JO - PeerJ

JF - PeerJ

M1 - e10432

ER -

Characterization of DNA methylation in Malawian clinical isolates.

Abstract

Keywords

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