The First Report of Genetic and Structural Diversities in the <i>SPRN</i> Gene in the Horse, an Animal Resistant to Prion Disease

• Main Authors: Sae-Young Won, Yong-Chan Kim, Seon-Kwan Kim, Byung-Hoon Jeong
• Format: Article
• Language: English
• Published: MDPI AG 2019-12-01
• Series: Genes
• Subjects: prion; shadow of prion protein gene (<i>sprn</i>); polymorphisms; horse; sho
• Online Access: https://www.mdpi.com/2073-4425/11/1/39

Prion diseases are fatal neurodegenerative diseases and are characterized by the accumulation of abnormal prion protein (PrP^Sc) in the brain. During the outbreak of the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, prion diseases in several species were reported; however, horse prion disease has not been reported thus far. In previous studies, the shadow of prion protein (Sho) has contributed to an acceleration of conversion from normal prion protein (PrP^C) to PrP^Sc, and the shadow of prion protein gene (<i>SPRN</i>) polymorphisms have been significantly associated with the susceptibility of prion diseases. We investigated the genotype, allele and haplotype frequencies of the <i>SPRN</i> gene using direct sequencing. In addition, we analyzed linkage disequilibrium (LD) and haplotypes among polymorphisms. We also investigated LD between <i>PRNP</i> and <i>SPRN</i> single nucleotide polymorphisms (SNPs). We compared the amino acid sequences of Sho protein between the horse and several prion disease-susceptible species using ClustalW2. To perform Sho protein modeling, we utilized SWISS-MODEL and Swiss-PdbViewer programs. We found a total of four polymorphisms in the equine <i>SPRN</i> gene; however, we did not observe an in/del polymorphism, which is correlated with the susceptibility of prion disease in prion disease-susceptible animals. The <i>SPRN</i> SNPs showed weak LD value with <i>PRNP</i> SNP. In addition, we found 12 horse-specific amino acids of Sho protein that can induce significantly distributional differences in the secondary structure and hydrogen bonds between the horse and several prion disease-susceptible species. To the best of our knowledge, this is the first report regarding the genetic and structural characteristics of the equine <i>SPRN</i> gene.