Abstract
Prion diseases are fatal neurodegenerative diseases and are characterized by the accumulation of abnormal prion protein (PrPSc) 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 (PrPC) to PrPSc, and the shadow of prion protein gene (SPRN) polymorphisms have been significantly associated with the susceptibility of prion diseases. We investigated the genotype, allele and haplotype frequencies of the SPRN gene using direct sequencing. In addition, we analyzed linkage disequilibrium (LD) and haplotypes among polymorphisms. We also investigated LD between PRNP and SPRN 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 SPRN 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 SPRN SNPs showed weak LD value with PRNP 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 SPRN gene.
Highlights
Prion diseases are fatal neurodegenerative diseases that cause death due to brain accumulation of abnormal prion protein (PrPSc ), which is characterized by proteinase K resistance [1,2].Bovine spongiform encephalopathy (BSE) in cattle was first reported in the United Kingdom in 1986 and spread throughout the cattle industry in the United Kingdom through contaminated feedstuff [3,4]
This result indicates that the protective effect of horse specific amino acid, 167S, is elusive and suggests there is another factor related to the resistance of prion disease in horse beside the properties of the PrP sequence encoded in the prion protein gene (PRNP)
We investigated polymorphisms of the PRNP gene and PRND gene in the horse, which is known to be a prion disease-resistant animal
Summary
Prion diseases are fatal neurodegenerative diseases that cause death due to brain accumulation of abnormal prion protein (PrPSc ), which is characterized by proteinase K resistance [1,2].Bovine spongiform encephalopathy (BSE) in cattle was first reported in the United Kingdom in 1986 and spread throughout the cattle industry in the United Kingdom through contaminated feedstuff [3,4]. Previous studies have reported that the stability of prion protein (PrP) and species-specific amino acids of PrP are related to prion disease susceptibility. Spontaneous PrP aggregation was observed in the transgenic mouse model expressing mouse PrP with a horse-specific amino acid substitution of D167S [10] This result indicates that the protective effect of horse specific amino acid, 167S, is elusive and suggests there is another factor related to the resistance of prion disease in horse beside the properties of the PrP sequence encoded in the prion protein gene (PRNP). We investigated polymorphisms of the PRNP gene and PRND gene in the horse, which is known to be a prion disease-resistant animal. The PRNP and PRND genes have been studied in prion disease-resistant species, a member of the prion gene family called the shadow of prion protein gene (SPRN) has not been reported far in horses
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