A case-control genome-wide association study of estimated breeding values for resistance to gastrointestinal nematodes in two local dairy sheep breeds

In sheep, gastrointestinal nematodes (GINs) can cause disease, reduced feed intake, and nutritional deficiencies. To counteract GINs, anthelmintics are widely used although it is well known they may enter the environment impacting ecosystems. In addition, anthelmintics resistance has rapidly developed and consequently, alternative approaches are crucial for profitable and sustainable sheep production. The occurrence of resistant individuals is mainly due to their intrinsic genetic diversity; therefore, the implementation of breeding plans for resistant animals may provide a promising strategy to reduce the use of anthelmintics. This study is aimed at identifying genomic regions involved in sheep resistance to GINs. To do this, faecal samples were collected from 642 Comisana and 323 Massese sheep over 3 years to assess Faecal Egg Counts, and Estimated Breeding Values (EBVs) for GIN resistance were estimated by a repeatability animal model. Then, EBVs in the 99.95th and 0.05th percentiles were used to identify the most and least "genetically resistant" individuals to GINs, using genotyped individuals with the Illumina OvineSNP50 beadchip. A genome-wide case-control analysis was performed retaining the most significant single nucleotide polymorphisms (SNPs) with a threshold of 0.005% for the false discovery rate. Genes and Quantitative Trait Loci overlapping significant SNPs were annotated and enriched respectively while genes have been also enriched for functional pathways. As a result, 13 genes on 12 chromosomes and 10 genes on 11 different chromosomes were identified in the Comisana and Massese breed, respectively. Among these, genes involved in the physiology or pathology of the gastrointestinal tract, in adaptive processes and in production traits, were detected. The enrichment analysis highlighted 36 significant pathways in the Comisana breed and 21 in the Massese breed. Many of these pathways were involved in the regulation of the immune response, drug metabolism and detoxification, and vitamin metabolism. Interestingly, pathways involved in vitamin and drug metabolism were also identified in previous research and have shown to play an active role in GIN resistance. In this study, we took advantage of the use of EBVs as a metric for GIN resistance in a case-control genome-wide framework and successfully identified several genomic regions that might be involved in the trait. The presence of overlapping functional pathways related to different genes in the two breeds seems to reinforce the idea of the polygenicity of this trait, and further studies are needed in order to make selection schemes an effective tool to contrast GINs.