Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection

Ragheb, MN and Ford, CB and Chase, MR and Lin, PL and Flynn, JAL and Fortune, SM (2013) The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection. BMC Genomics, 14 (1).

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (478kB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

Background: 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. © 2013 Ragheb et al.; licensee BioMed Central Ltd.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ragheb, MN
Ford, CB
Chase, MR
Lin, PLpll7@pitt.eduPLL7
Flynn, JAL
Fortune, SM
Date: 5 March 2013
Date Type: Publication
Journal or Publication Title: BMC Genomics
Volume: 14
Number: 1
DOI or Unique Handle: 10.1186/1471-2164-14-145
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 06 Oct 2016 15:58
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/29752

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item