Model Development for Causative Candidate Gene Discovery for Parasite Resistance in Sheep

Results of parasite resistance QTL studies in sheep have been quite variable, even when the phenotypes that were the basis of studies were similar.  This variability has hindered the identification of candidate genes and genetic markers for selection.  A meta-analysis was performed in order to find individual candidate genes that may be causative for host resistance to internal parasites.  The objective of this project was to develop an unbiased model for selection of candidate genes involved in disease mechanisms.  Data from QTL regions were collected from published projects in sheep, cattle, mice, and human.  Genes from QTL and gene expression (GE) projects were assigned weights, normalized between 1 and 2 and multiplied across projects.  Weights for QTL data were defined as the distance to the closest QTL peak, and weights for GE data were based on the log of the fold change. The weights for each gene were combined to assess a collective weight to determine a specific gene’s relative importance for host resistance to internal parasites.  Some potential candidate genes that were identified using this methodology were ARHGEF12, VAPA, CD3G, and RALBP1.  Each of these genes were found in pathways previously associated with parasite resistance and present in significant gene ontology (GO) function enrichment clusters.  The data suggests that the use of the mathematical model for the selection of candidate genes may improve the discovery of genes associated with host resistance to internal parasites.