The overall aim of this project is to expand our knowledge of the genetic background of AR in the parasitic nematode Haemonchus contortus. This nematode, which is highly pathogenic for its host, is an ideal model for the study of AR. By identifying relevant genetic regions using a genome-wide approach, we aim to contribute to the development of molecular tools for routine diagnostics. By promoting the inclusion of these tools in future multi-stakeholder farm-specific action plans, the project will contribute to improving animal health and welfare. AR is the result of genetic changes that occur in response to anthelmintic selection. Therefore, the estimates of reduced drug efficacy obtained by the FECRT can only be expected to correlate with the status of the target gene(s) if the molecular tests are reliable. In a recently completed project, we analyzed several genetic markers for AR detection in H. contortus. For this purpose, allele frequencies in several previously known candidate genes were analyzed using the ddPCR technology in larval samples collected before and after treatment. These genes were selected solely on the basis of the knowledge available on drug's mode of action. When we compared the genetic results with the anthelmintic efficacy results obtained by FECRT, we found that there was little agreement. This explains why an unbiased and statistically rigorous method, initially based on Genome-wide Association Studies, must be used for the selection of target genes. The limitation of the candidate gene approach we have used so far is that it is based on very specific and narrow assumptions about the identity of resistance-associated genes. In contrast, Whole Genome Sequencing unconditionally searches for genetic variants, both in the form of single nucleotide polymorphisms (SNPs), small structural variants up to 50bp (indels), and large structural variants (SVs), which include insertions, deletions, inversions, transversions, and Copy Number Variation (CNVs), associated with AR in a large group of phenotypically well-characterized samples. Genome-wide studies therefore do not contain predetermined assumptions, as demonstrated by their successful application in previous studies. Consequently, loci associated with anthelmintic resistance need to be identified using next-generation sequencing platforms on phenotypically well-characterized samples. Tests for routine diagnostics can then be developed and further validated using other molecular methods. Although knowledge of the genetic mechanisms that explain the development of AR in H. contortus has increased in recent years, further research is needed. This is not only important to understand how selection occurs at farm level, but also to verify whether the developed molecular diagnostic tests are reliable on farms. In this project, we aim to increase the knowledge of ivermectin resistance in Swedish populations of H. contortus, as this is the most used drug class against this parasite species. This will be done by identifying genetic variations conferring resistance based on Whole Genome Sequencing, Genome-wide Association Studies, and population genomics methodology. Ultimately, we aim to develop molecular diagnostic tools to detect AR, and contribute to enhanced parasite control strategies.