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 <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP), leading to significant economic losses in livestock production. While the <i>solute carrier family 11 member 1</i> (<i>SLC11A1</i>) 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 <i>SLC11A1</i> 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, <i>p</i> = 0.006; Cramér's V = 0.38). No significant differences in basal <i>SLC11A1</i> mRNA expression were detected between phenotypic groups. These findings extend previous GWAS results in sheep by providing the first allele-level evidence linking <i>SLC11A1</i> 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.