Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKadarmideen, H.-
dc.contributor.authorWatson-Haigh, N.-
dc.contributor.authorAndronicos, N.-
dc.identifier.citationMolecular Biosystems, 2011; 7(1):235-246-
dc.description.abstractThis study reports on the molecular systems biology of gastrointestinal nematode (GIN) infection and potential biomarkers for GIN resistance in sheep. Microarray gene expression data were obtained for 3 different tissues at 4 time points from sheep artificially challenged with two types of nematodes, Haemonchus contortus (HC) and Trichostrongylus colubriformis (TC). We employed an integrated systems biology approach, integrating 3 main methods: standard differential gene expression analyses, weighted gene co-expression network analyses (WGCNA) and quantitative genetic analyses of gene expression traits of key biomarkers. Using standard differential gene expression analyses we identified differentially expressed genes (DE) which responded differently in sheep challenged with HC compared to those challenged with TC. These interaction genes (e.g. MRPL51, SMEK2, CAT, MAPK1IP1 and SLC25A20A) were enriched in Wnt receptor signalling pathway (p = 0.0132) and positive regulation of NFκβ transcription factor activity (p = 0.00208). We report FCER1A, a gene encoding a high-affinity receptor for the Fc region of immunoglobulin E, which is linked to innate immunity to GIN in sheep. Using weighted gene co-expression network analysis (WGCNA) methods, we identified gene modules that were correlated with the length of infection (disease modules). Hub genes (with high intramodular connectivity) were filtered further to identify biomarkers that are related to the length of infection (e.g. CAT, FBX033, COL15A1, IGFBP7, FBLN1 and IgCgamma). The biomarkers we found in HC networks were significantly associated with functions such as T-cell and B-cell regulations, TNF-alpha, interleukin and cytokine production. In TC networks, biomarkers were significantly associated with functions such as protein catabolic process, heat shock protein binding, protein targeting and localization, cytokine receptor binding, TNF receptor binding, apoptosis and IGF binding. These results provide specific gene targets for therapeutic interventions and provide insights into GIN infections in sheep which may be used to infer the same in related host species. This is also the first study to apply the concept of estimating breeding values of animals to expression traits and reveals 11 heritable candidate biomarkers (0.05 to 0.92) that could be used in selection of animals for GIN resistance.-
dc.description.statementofresponsibilityHaja N. Kadarmideen, Nathan S. Watson-Haigh and Nicholas M. Andronicos-
dc.publisherRoyal Society of Chemistry-
dc.rightsThis journal is © Royal Society of Chemistry 2011-
dc.subjectIntestinal Diseases, Parasitic-
dc.subjectSheep Diseases-
dc.subjectOligonucleotide Array Sequence Analysis-
dc.subjectGene Expression Profiling-
dc.subjectSystems Biology-
dc.subjectGene Regulatory Networks-
dc.subjectImmunity, Innate-
dc.titleSystems biology of ovine intestinal parasite resistance: disease gene modules and biomarkers-
dc.typeJournal article-
dc.identifier.orcidWatson-Haigh, N. [0000-0002-7935-6151]-
Appears in Collections:Agriculture, Food and Wine publications
Aurora harvest 2

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.