NDLI: Systems biology of ovine intestinal parasite resistance: disease gene modules and biomarkers.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kadarmideen, Haja N. Watson-Haigh, Nathan S. Andronicos, Nicholas M.
Description	Country affiliation: Australia Author Affiliation: Kadarmideen HN ( Commonwealth Scientific and Industrial Research Organisation, Livestock Industries, Davies Laboratory, PMB PO Aitkenvale, Townsville, QLD 4814, Australia. Haja.Kadarmideen@csiro.au)
Abstract	This 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 NFκß 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.
File Format	HTM / HTML
ISSN	1742206X
Issue Number	1
Volume Number	7
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2011-01-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Intestinal Diseases, Parasitic Genetics Parasitology Systems Biology Animals Gene Expression Profiling Methods Gene Regulatory Networks Haemonchus Pathogenicity Immunity, Innate Oligonucleotide Array Sequence Analysis Sheep Sheep Diseases Trichostrongylus Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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