This study aimed to identify loci underlying variation in parasite resistance, as measured by worm egg count (WEC), in a large multi-breed sheep population using genome-wide association studies (GWAS) and regional heritability mapping (RHM) approaches. A total of 7153 animals with both genotype data and WEC phenotypes were included in this analysis. Strong evidence of association was observed on chromosome 2 by both approaches. However, RHM had a greater power to identify loci than GW AS analysis. RHM identified an additional region at the genomewide significance level on chromosome 6. This region was also previously found to be associated with mastitis resistance and facial eczema susceptibility in sheep, indicating that some pleiotropic effects are possibly affecting a wide range of sheep diseases. Three other regions on chromosome I, 3 and 24 reached the suggestive threshold.

In this study, we estimated the additive genetic variance explained by genomic markers for parasite resistance in a large mixed population of sheep and compared this estimate to the additive genetic variance explained by pedigree. Furthermore, we partitioned the total genetic variance by fitting both of genomic relationship matrix (GRM) and numerator relationship matrix (NRM) simultaneously into a genomic component explained by genomic relationships and a polygenic component explained by pedigree relationships. In this analysis, all the genetic variation explained by pedigree could be captured by the 50K SNP chip markers. When both of GRM and NRM were fitted simultaneously, 73.7% of total genetic variance was explained by genomic effects while the remaining variance (26.3%) was explained by pedigree effects. The proportion of genetic variance explained by genomic effects was further partitioned into 26 chromosomes. A significant relationship was found between chromosome-specific variance and the length of the chromosome (R² = 0.26). This indicates that disease resistance is a largely polygenic trait with a large number of genes involved in the mechanisms of resistance but there are some chromosomal regions that explain a larger proportion of the variation.

Background: This study aimed at identifying genomic regions that underlie genetic variation of worm egg count, as an indicator trait for parasite resistance in a large population of Australian sheep, which was genotyped with the highdensity 600 K Ovine single nucleotide polymorphism array. This study included 7539 sheep from diferent locations across Australia that underwent a feld challenge with mixed gastrointestinal parasite species. Faecal samples were collected and worm egg counts for three strongyle species, i.e. Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus colubriformis were determined. Data were analysed using genome-wide association studies (GWAS) and regional heritability mapping (RHM).
Results: Both RHM and GWAS detected a region on Ovis aries (OAR) chromosome 2 that was highly signifcantly associated with parasite resistance at a genome-wise false discovery rate of 5%. RHM revealed additional signifcant regions on OAR6, 18, and 24. Pathway analysis revealed 13 genes within these signifcant regions (SH3RF1, HERC2, MAP3K, CYFIP1, PTPN1, BIN1, HERC3, HERC5, HERC6, IBSP, SPP1, ISG20, and DET1), which have various roles in innate and acquired immune response mechanisms, as well as cytokine signalling. Other genes involved in haemostasis regulation and mucosal defence were also detected, which are important for protection of sheep against invading parasites.
Conclusions: This study identifed signifcant genomic regions on OAR2, 6, 18, and 24 that are associated with parasite resistance in sheep. RHM was more powerful in detecting regions that afect parasite resistance than GWAS. Our results support the hypothesis that parasite resistance is a complex trait and is determined by a large number of genes with small efects, rather than by a few major genes with large efects.