Systems genetics analysis reveals gene modules and heritable biomarkers for sheep intestinal parasite resistance

Abstract

Systems genetics methods were applied to microarray gene expression profiling data from a sheep gastrointestinal nematode (GIN) challenge experiment that was designed to detect genes associated with resistance to GIN. Analyses went beyond just detecting and annotating differentially expressed (DE) genes. This included detection of co-expressed (CE) gene modules associated with the duration of infection, essential hub genes, functional enrichment and pathway analyses. Results revealed that DE genes were highly enriched in functions such as cell-mediated and humoral immunological response to GIN. Further, heritabilities were estimated for expression phenotypes of such candidate biomarkers (range 0.05 to 0.9 with high s.e.) indicating their potential for expression-assisted selection. Hence, the systems genetics method is a key step in identifying biologically relevant and heritable genes/biomarkers amongst several sets of DE genes. This approach would provide specific targets for breeding and therapeutic interventions.