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Exploring the Zoonotic Potential of Mycobacterium avium Subspecies paratuberculosis through Comparative Genomics.

Wynne, JW; Bull, TJ; Seemann, T; Bulach, DM; Wagner, J; Kirkwood, CD; Michalski, WP (2011) Exploring the Zoonotic Potential of Mycobacterium avium Subspecies paratuberculosis through Comparative Genomics. PLOS ONE, 6 (7). e22171. ISSN 1932-6203
SGUL Authors: Bull, Timothy John

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A comparative genomics approach was utilised to compare the genomes of Mycobacterium avium subspecies paratuberculosis (MAP) isolated from early onset paediatric Crohn's disease (CD) patients as well as Johne's diseased animals. Draft genome sequences were produced for MAP isolates derived from four CD patients, one ulcerative colitis (UC) patient, and two non-inflammatory bowel disease (IBD) control individuals using Illumina sequencing, complemented by comparative genome hybridisation (CGH). MAP isolates derived from two bovine and one ovine host were also subjected to whole genome sequencing and CGH. All seven human derived MAP isolates were highly genetically similar and clustered together with one bovine type isolate following phylogenetic analysis. Three other sequenced isolates (including the reference bovine derived isolate K10) were genetically distinct. The human isolates contained two large tandem duplications, the organisations of which were confirmed by PCR. Designated vGI-17 and vGI-18 these duplications spanned 63 and 109 open reading frames, respectively. PCR screening of over 30 additional MAP isolates (3 human derived, 27 animal derived and one environmental isolate) confirmed that vGI-17 and vGI-18 are common across many isolates. Quantitative real-time PCR of vGI-17 demonstrated that the proportion of cells containing the vGI-17 duplication varied between 0.01 to 15% amongst isolates with human isolates containing a higher proportion of vGI-17 compared to most animal isolates. These findings suggest these duplications are transient genomic rearrangements. We hypothesise that the over-representation of vGI-17 in human derived MAP strains may enhance their ability to infect or persist within a human host by increasing genome redundancy and conferring crude regulation of protein expression across biologically important regions.

Item Type: Article
Additional Information: ©2011 Wynne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Base Sequence, Cattle, Child, Comparative Genomic Hybridization, Crohn Disease, Disease Transmission, Infectious, Gene Duplication, Genome, Bacterial, High-Throughput Nucleotide Sequencing, Humans, Molecular Sequence Data, Mycobacterium avium subsp. paratuberculosis, Paratuberculosis, Phylogeny, Polymorphism, Single Nucleotide, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, RESTRICTION ENDONUCLEASE ANALYSIS, CROHNS-DISEASE, MOLECULAR EPIDEMIOLOGY, SUSCEPTIBILITY LOCI, UNITED-KINGDOM, TUBERCULOSIS, SEQUENCE, STRAINS, IDENTIFICATION, POLYMORPHISMS
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
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22 July 2011Published
Web of Science ID: WOS:000293097300018
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