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dc.contributor.authorRagheb, Mark N
dc.contributor.authorFord, Christopher Burton
dc.contributor.authorChase, Michael Richard
dc.contributor.authorLin, Philana Ling
dc.contributor.authorFlynn, JoAnne L
dc.contributor.authorFortune, Sarah Merritt
dc.date.accessioned2013-12-11T17:59:03Z
dc.date.issued2013
dc.identifier.citationRagheb, Mark N, Christopher B Ford, Michael R Chase, Philana Ling Lin, JoAnne L Flynn, and Sarah M Fortune. 2013. The mutation rate of mycobacterial repetitive unit loci in strains of m. tuberculosis from cynomolgus macaque infection. BMC Genomics 14: 145.en_US
dc.identifier.issn1471-2164en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11365875
dc.description.abstractBackground: Mycobacterial interspersed repetitive units (MIRUs) are minisatellites within the Mycobacterium tuberculosis (Mtb) genome. Copy number variation (CNV) in MIRU loci is used for epidemiological typing, making the rate of variation important for tracking the transmission of Mtb strains. In this study, we developed and assessed a whole-genome sequencing (WGS) approach to detect MIRU CNV in Mtb. We applied this methodology to a panel of Mtb strains isolated from the macaque model of tuberculosis (TB), the animal model that best mimics human disease. From these data, we have estimated the rate of MIRU variation in the host environment, providing a benchmark rate for future epidemiologic work. Results: We assessed variation at the 24 MIRU loci used for typing in a set of Mtb strains isolated from infected cynomolgus macaques. We previously performed WGS of these strains and here have applied both read depth (RD) and paired-end mapping (PEM) metrics to identify putative copy number variants. To assess the relative power of these approaches, all MIRU loci were resequenced using Sanger sequencing. We detected two insertion/deletion events both of which could be identified as candidates by PEM criteria. With these data, we estimate a MIRU mutation rate of 2.70 × 10-03 (95% CI: 3.30 × 10-04- 9.80 × 10-03) per locus, per year. Conclusion: Our results represent the first experimental estimate of the MIRU mutation rate in Mtb. This rate is comparable to the highest previous estimates gathered from epidemiologic data and meta-analyses. Our findings allow for a more rigorous interpretation of data gathered from MIRU typing.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2164-14-145en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635867/pdf/en_US
dash.licenseLAA
dc.subjectMycobacterial interspersed repetitive unitsen_US
dc.subjectMIRUen_US
dc.subjectMolecular epidemiologyen_US
dc.subjectCopy number variationen_US
dc.subjectWhole-genome sequencingen_US
dc.subjectRead depthen_US
dc.subjectPaired-end mappingen_US
dc.subjectMutation rateen_US
dc.titleThe mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infectionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Genomicsen_US
dash.depositing.authorFord, Christopher Burton
dc.date.available2013-12-11T17:59:03Z
dc.identifier.doi10.1186/1471-2164-14-145*
dash.contributor.affiliatedFord, Christopher Burton
dash.contributor.affiliatedChase, Michael
dash.contributor.affiliatedFortune, Sarah


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