Association of SLC11A1 3'UTR (GT)_n Microsatellite Polymorphisms with Resistance to Paratuberculosis in Sheep

Paratuberculosis (Johne's disease) is a chronic enteric infection of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), leading to significant economic losses in livestock production. While the solute carrier family 11 member 1 (SLC11A1) gene has been implicated in resistance to intracellular pathogens in several species, its role in ovine paratuberculosis remains largely uncharacterized. The present study investigated whether polymorphic variation in the SLC11A1 3' untranslated region (3'UTR) (GT)_n microsatellite is associated with resistance or susceptibility to MAP infection in sheep. A total of 138 sheep from three breeds (Karagouniki, Boutsika, and Chios) were genotyped. Gene expression analysis was subsequently performed on a subset of 53 animals, which comprised rigorously phenotyped MAP-resistant (n = 18) and MAP-sensitive (n = 35) individuals from the Karagouniki breed. Four predominant alleles, (GT)₂₁, (GT)₂₂, (GT)₂₃, and (GT)₂₄, were identified. The (GT)₂₁ and (GT)₂₃ alleles were significantly enriched among resistant sheep, while (GT)₂₂ and (GT)₂₄ were more frequent in sensitive animals (χ² = 12.4, p = 0.006; Cramér's V = 0.38). No significant differences in basal SLC11A1 mRNA expression were detected between phenotypic groups. These findings extend previous GWAS results in sheep by providing the first allele-level evidence linking SLC11A1 3'UTR microsatellite polymorphisms to paratuberculosis resistance in sheep. Although limited by sample size and single-breed representation, the results offer a foundation for future functional and genomic selection studies aimed at enhancing disease resilience in small ruminants.