dc.contributor.author | O'FARRELLY, CLIONA | |
dc.date.accessioned | 2008-12-08T12:25:59Z | |
dc.date.available | 2008-12-08T12:25:59Z | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007 | en |
dc.identifier.citation | Meade, KG, Gormley, E, Doyle, MB, Fitzsimons, T, O'Farrelly, C, Costello, E, Keane, J, Zhao, Y, MacHugh, DE ?Innate gene repression associated with Mycobacterium bovis infection in cattle: toward a gene signature of disease? in BMC genomics, 8, 2007, 400 | en |
dc.identifier.issn | 1471-2164 | |
dc.identifier.other | Y | |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/25999 | |
dc.description | PUBLISHED
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | en |
dc.description.abstract | Bovine tuberculosis is an enduring disease of cattle that has significant repercussions
for human health. The advent of high-throughput functional genomics technologies has facilitated
large-scale analyses of the immune response to this disease that may ultimately lead to novel
diagnostics and therapeutic targets. Analysis of mRNA abundance in peripheral blood mononuclear
cells (PBMC) from six Mycobacterium bovis infected cattle and six non-infected controls was
performed. A targeted immunospecific bovine cDNA microarray with duplicated spot features
representing 1,391 genes was used to test the hypothesis that a distinct gene expression profile
may exist in M. bovis infected animals in vivo.
Results: In total, 378 gene features were differentially expressed at the P ? 0.05 level in bovine
tuberculosis (BTB)-infected and control animals, of which 244 were expressed at lower levels
(65%) in the infected group. Lower relative expression of key innate immune genes, including the
Toll-like receptor 2 (TLR2) and TLR4 genes, lack of differential expression of indicator adaptive
immune gene transcripts (IFNG, IL2, IL4), and lower BOLA major histocompatibility complex ? class
I (BOLA) and class II (BOLA-DRA) gene expression was consistent with innate immune gene
repression in the BTB-infected animals. Supervised hierarchical cluster analysis and class prediction
validation identified a panel of 15 genes predictive of disease status and selected gene transcripts
were validated (n = 8 per group) by real time quantitative reverse transcription PCR.
Conclusion: These results suggest that large-scale expression profiling can identify gene signatures
of disease in peripheral blood that can be used to classify animals on the basis of in vivo infection, in
the absence of exogenous antigenic stimulation. | en |
dc.description.sponsorship | We would like to thank the staff at the UCD Lyons Research Farm for
assistance with cattle blood sampling and Grace O'Gorman, Stephen Park
and Emmeline Hill for technical assistance and advice. We also thank
Frances Quigley and staff at the Mycobacteriology Laboratory, CVRL, Backweston
for their assistance in the bacterial culture of M. bovis from infected
cattle and Prof. Paul Coussens of the MSU Centre for Animal Functional
Genomics for advice and provision of BOTL-5 microarrays. This work was
supported by an Investigator Grant from Science Foundation Ireland (Grant
No: SFI/01/F.1/B028) | en |
dc.format.extent | 400 | en |
dc.format.extent | 575910 bytes | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | en |
dc.publisher | BMC | en |
dc.relation.ispartofseries | BMC genomics | en |
dc.relation.ispartofseries | 8 | en |
dc.rights | Y | en |
dc.subject | Biochemistry | en |
dc.title | Innate gene repression associated with Mycobacterium bovis infection in cattle: toward a gene signature of disease. | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Science Foundation Ireland | |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ofarrecl | |
dc.identifier.rssuri | http://www.biomedcentral.com/content/pdf/1471-2164-8-400.pdf | |
dc.identifier.rssuri | doi:10.1186/1471-2164-8-400 | |