Discovering genomic regions associated with parasite resistance in Australian sheep breeds

Worm egg count (WEC) is a commonly used method for estimating the number of adult parasite worms in sheep, enabling monitoring and prompt treatment. Furthermore, breeding programs have integrated WEC into their breeding objectives to select sheep with increased resistance to parasite infestations. At the genomic level, the precise identification of quantitative trait loci (QTL) regions associated with parasite resistance may be used to improve the accuracy of genomic prediction for WEC in sheep. The aim of this study was to identify genomic regions and genes associated with WEC in Australian sheep. Genotypes (61,566 SNPs) and WEC phenotypes recorded at weaning were available for a total of 14,383 sheep, provided by Sheep Genetics from the Combined LAMBPLAN database. The major breeds represented were Poll Dorset, Coopworth, White Suffolk, Ultrawhite, Commercial Shedders, and Commercial Maternals. WEC records were cube root transformed and adjusted phenotypes were obtained as the residuals of the animal model fitted in ASReml v4.2 with age*sex interaction, age of dam, birth-rear type, and contemporary groups (defined by flock, sex, stage, year of birth, and date of measurement) as fixed effects. PLINK was used for quality control, filtering out SNPs with minor allele frequency < 0.01. The remaining SNPs were imputed to HD and then to the sequence level in Beagle using the Run2 dataset as reference. A genome-wide association analysis for WEC was performed using the mixed linear model-based association (MLMA) method in GCTA, fitting the genomic relationship matrix and adjusted phenotypes. QTL regions were defined as a 100 kb window from the significant SNPs (−log10(P-value) ≥ 7.3), while candidate genes (−log10(P-value) ≥ 5) were annotated on that region using the Oar_v3.1 reference genome. The pathways and Gene Ontology (GO) terms associated with candidate genes were investigated using DAVID. These preliminary results show the polygenic nature of WEC by identifying a single QTL region on chromosome 23, encompassing NPC1, ANKRD29, RIOK3, LAMA3, TTC39C, TMEM241, CABLES1, and ENSOARG00000007938. Using the suggestive threshold, 25 additional regions with small effects were identified, containing 494 candidate genes. These genes are involved in 53 GO terms and one pathway. Among the enriched GO terms, membrane, pheromone receptor activity, and G protein-coupled receptor activity were the most significant. In addition, terms such as adaptive immune response, immune response, and immune system process were significantly represented. These results suggest a complex mechanism underlying WEC, which could be used to improve genomic prediction accuracy and develop new management strategies to enhance parasite resistance in sheep. Nevertheless, parasite resistance in sheep at different ages might be driven by various mechanisms, highlighting the importance of further research to evaluate additional production age groups.