Weighted single-step genome-wide association study and functional enrichment analyses for gastrointestinal nematode resistance traits in Santa Ines sheep

This study aimed to identify genomic regions, pathways, and putative candidate genes associated with resistance to gastrointestinal nematode in Santa Ines sheep. The phenotypic information comprised 5529 records from 1703 naturally infected animals. After genomic data quality control, 37,511 SNPs from 589 animals were available. The weighted single-step approach for genome-wide association study was performed to estimate the SNP effects and variances accounted by 10-SNP sliding windows. Confirming the polygenic nature of the studied traits, 20, 22, 21, and 19 genomic windows that explained more than 0.5% of the additive genetic variance were identified for fecal egg counts (FEC), Famacha (c) (FAM), packed cell volume (PCV), and total plasma protein (TPP), respectively. A total of 81, 122, 106, and 101 protein-coding genes were found in windows associated with FEC, FAM, PCV, and TPP, respectively. Several protein-coding genes related to the immune system and inflammatory response functions were identified within those genomic regions, such as ADCY9, ADRB2, BRAF, CADM1, CCL20, CD70, CREBBP, FNBP1, HTR4, IL16, IL22, IL26, MAPK8, NDFIP1, NLRC3, PAK5, PLCB1, PLCB4, ROCK1, TEK, TNFRSF12A, and VAV1. Functional enrichment analysis by DAVID tool also revealed many significant (P < 0.05) pathways and Gene Ontology terms that could be related to resistance to gastrointestinal nematode in Santa Ines sheep, such as chemokine signaling pathway (oas04062), cAMP signaling pathway (oas04024), cGMP-PKG signaling pathway (Oas04022), platelet activation (Oas04611), Rap1 signaling pathway (oas04015), and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705). These results contribute to improving the knowledge of the genetic architecture of resistance to gastrointestinal nematode in Santa Ines sheep.