GWAS analysis of coccidiosis resistance in Portuguese Merino sheep

Abstract

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. Coccidiosis is a parasitic disease caused by protozoa of the genus Eimeria. Although coccidial infection is often asymptomatic in sheep, both clinical and subclinical forms of the disease can result considerable production losses, mainly in young lambs. Current control of coccidiosis in sheep mainly relies on anticoccidial drugs. However, emergence of drug-resistant strains has reduced treatment efficacy and capacity to control outbreaks. Studies aiming to identify genetic markers for use in selection programs toward increasing genetic resistance to coccidiosis are lacking and have yet to be performed in Portuguese Merino sheep. From an initial population of 1,022 sheep having known phenotypic characteristics, 206 and 202 distinct animals were genotyped using 50K and 600K Single Nucleotide Polymorphism (SNP) arrays, respectively. Once the 50K array was imputed using the 600K as reference, an association analysis was performed using GCTA for fecal oocyst counts. We identified 12 SNPs significantly associated with resistance by using a chromosome-wide significance threshold. The significant SNPs were related to Ccser1, Thsd4, Eci1, Tnfrsf12a, Znf200, Chrm3 and Slc20a2 genes. In addition, we identified 80 candidate genes located in the proximity of the significant SNPs using predefined confidence regions (100 Kb upstream and downstream). The GeneMANIA Cytoscape plugin was used to construct a network with the most related genes to the 80 candidate genes. The functional analysis of the network revealed a significant enrichment in relation to transport vesicle. Given the role that extracellular vesicles plays in the parasite-host interactions, 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.