Microarray analysis of selection lines from outbred populations to identify genes involved with nematode parasite resistance in sheep

Gastrointestinal nematodes infect sheep grazing contaminated pastures. Traditionally, these have been controlled with anthelmintic drenching. The selection of animals resistant to nematodes is an alternative to complete reliance on drugs, but the genetic basis of host resistance is poorly understood. Using a 10,204 bovine cDNA microarray, we have examined differences in gene expression between genetically resistant and susceptible lambs previously field challenged with larval nematodes. Northern blot analysis for a selection of genes validated the data obtained from the microarrays. The results identified over one hundred genes that were differentially expressed based on conservative criteria. The microarray results were further analyzed to identify promoter motifs common to the differentially expressed genes. Motifs identified in upregulated gene promoters were primarily restricted to those promoters; however, motifs identified in downregulated gene promoters were also found in the promoters of upregulated genes but not in the promoters of genes whose expression was unaltered. Protein Annotators' Assistant was used for lexical analysis of the differentially expressed genes, and Gene Ontology was used to look for metabolic and cell signaling pathways associated with parasite resistance. Two pathways represented by genes differentially expressed in resistant animals were those involved with the development of an acquired immune response and those related to the structure of the intestine smooth muscle. Genes involved in these processes appear from our analysis to be key genetic determinants of parasite resistance.