Claudin and Rab proteins are key molecular components involved in coccidiosis resistance in Portuguese Merino sheep

Although coccidial infection is often asymptomatic in sheep, both clinical and subclinical forms of the disease are linked to considerable production losses, mainly in young lambs. Studies aiming to identify genetic markers for use in selection programs towards increasing genetic resistance to coccidiosis are lacking and have yet to be performed in Portuguese Merino sheep. The purpose of this study was to identify genomic regions associated with resistance to coccidiosis by conducting a genome-wide association study (GWAS) in Portuguese Merino sheep.

From an initial population of 1,022 sheep having known phenotypic characteristics, 206 and 202 distinct animals were genotyped using 50 K and 600 K Single Nucleotide Polymorphism (SNP) arrays, respectively. After the 50 K array was imputed using a 600 K array as reference, an association analysis was performed for faecal oocyst counts (FOC). We identified 12 SNPs that were significantly associated with resistance by using a chromosome-wide significance threshold. The significant SNPs were related to Ccser1, Thsd4, Eci1, Tnfrsf12a, Chrm3 and Slc20a2 genes. We identified 80 candidate genes located in the proximity of the significant SNPs using the defined confidence regions. Two types of gene set enrichment analyses were performed. Enrichment based on the set of candidate genes, identified the terms virus receptor activity and exogenous protein binding to be enriched, both due to two claudins, CLDN6 and CLDN9. Enrichment based on gene interactions, showed enrichment of terms related to transport vesicles, mainly due to the presence of Rab proteins.

Given the role that Rab and Claudins play in host-parasite relationships, these results suggest the existence of reliable markers associated with resistance to coccidiosis. These markers should be explored in future studies to further validate their use in marker assisted selection, with the goal of enhancing sustainability of the breed conservation-management program.