Authors

S R Doyle⁴; J Cotton⁴; U Chaudhry²; N D Sargison²; D Bartley¹; K Maitland³; L Matthews³; M Berriman⁴; B Mable³; C Britton³; R Laing³; E Devaney³;  ¹ Moredun Research institute, UK;  ² The Royal (Dick) School of Veterinary Studies and the Roslin Institute, The University of Edinburgh, UK;  ³ University of Glasgow , UK;  ⁴ Wellcome Trust Sanger Institute, UK

Discussion

Gastrointestinal nematodes are responsible for significant health and economic burdens in human and animal hosts worldwide. Haemonchus contortus is a major pathogen of ruminants, and is the focus of significant anthelmintic control to minimise parasite burden and reduce disease, which includes anemia, lethargy, weight loss, and death. Perhaps not surprisingly, drug resistance is widespread, and isolates resistant to all major classes of anthelmintics (including multi-drug resistant strains) have been described. We have exploited and built upon the available genomics resources for H. contortus by undertaking a genome-wide approach toward understanding the mechanisms of anthelmintic resistance, and aim to identify genetic markers to diagnose drug resistance in the field. A genetic cross between the drug-susceptible ISE (used in WTSI genome assembly) and the multi-drug (benzimidazole, levamisole, & ivermectin) resistant UGA/2004 strains was performed, from which a F1 genetic linkage map was constructed. The F2 progeny of the cross were subsequently used to disconnect and dissect the genetic basis for each of the individual drug classes via a bulk segregant analysis of pre- and post-drug treatment. We will discuss the expected (and some unexpected) outcomes of the genetic cross, provide evidence for drug selection throughout the genome, and outline how we propose to use this information to monitor the evolution and spread of drug resistance in the field.