The First Report of Genetic Polymorphisms of the Equine SPRN Gene in Outbred Horses, Jeju and Halla Horses

SIMPLE SUMMARY: Prion disease is a fatal neurodegenerative disease caused by the accumulation of pathogenic prion protein (PrP(Sc)) in various mammalian hosts. However, to date, prion disease has not been reported in horses. Since the Sho protein encoded by the shadow of the prion protein gene (SPRN) plays an essential role in the progression of prion diseases, we investigated the genetic characteristics of the equine SPRN gene in horses. We found four single nucleotide polymorphisms (SNPs) of the equine SPRN gene and significant different distributions among three horse breeds including Jeju, Halla and Thoroughbred horses. Although the polymorphisms affect the property of mRNA of the equine SPRN gene, it did not affect the sequence and structure of Sho protein. Since several non-synonymous SNPs of the SPRN gene have been reported in prion diseases-susceptible animals, the absence of non-synonymous SNP of the equine SPRN gene in the horses is noticeable. ABSTRACT: Prion disease is a fatal infectious disease caused by the accumulation of pathogenic prion protein (PrP(Sc)) in several mammals. However, to date, prion disease has not been reported in horses. The Sho protein encoded by the shadow of the prion protein gene (SPRN) plays an essential role in the pathomechanism of prion diseases. To date, the only genetic study of the equine SPRN gene has been reported in the inbred horse, Thoroughbred horse. We first discovered four SPRN single nucleotide polymorphisms (SNPs) in 141 Jeju and 88 Halla horses by direct DNA sequencing. In addition, we found that the genotype, allele and haplotype frequencies of these SNPs of Jeju horses were significantly different from those of Halla and Thoroughbred horses, this latter breed is also included in this study. Furthermore, we observed that the minimum free energy and mRNA secondary structure were significantly different according to haplotypes of equine SPRN polymorphisms by the RNAsnp program. Finally, we compared the SNPs in the coding sequence (CDS) of the SPRN gene between horses and prion disease-susceptible species. Notably, prion disease-susceptible animals had polymorphisms that cause amino acid changes in the open reading frame (ORF) of the SPRN gene, while these polymorphisms were not found in horses.