Novel Polymorphisms and Genetic Characteristics of the Shadow of Prion Protein Gene (SPRN) in Cats, Hosts of Feline Spongiform Encephalopathy

Abstract

Prion diseases are transmissible spongiform encephalopathies (TSEs) caused by pathogenic prion protein (PrPSc) originating from normal prion protein (PrPC) and have been reported in several types of livestock and pets. Recent studies have reported that the shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) interacts with prion protein (PrP) and accelerates prion diseases. In addition, genetic polymorphisms in the SPRN gene are related to susceptibility to prion diseases. However, genetic polymorphisms in the feline SPRN gene and structural characteristics of the Sho have not been investigated in cats, a major host of feline spongiform encephalopathy (FSE). We performed amplicon sequencing to identify feline SPRN polymorphisms in the 623 bp encompassing the open reading frame (ORF) and a small part of the 3′ untranslated region (UTR) of the SPRN gene. We analyzed the impact of feline SPRN polymorphisms on the secondary structure of SPRN mRNA using RNAsnp. In addition, to find feline-specific amino acids, we carried out multiple sequence alignments using ClustalW. Furthermore, we analyzed the N-terminal signal peptide and glycosylphosphatidylinositol (GPI)-anchor using SignalP and PredGPI, respectively. We identified three novel SNPs in the feline SPRN gene and did not find strong linkage disequilibrium (LD) among the three SNPs. We found four major haplotypes of the SPRN polymorphisms. Strong LD was not observed between PRNP and SPRN polymorphisms. In addition, we found alterations in the secondary structure and minimum free energy of the mRNA according to the haplotypes in the SPRN polymorphisms. Furthermore, we found four feline-specific amino acids in the feline Sho using multiple sequence alignments among several species. Lastly, the N-terminal signal sequence and cutting site of the Sho protein of cats showed similarity with those of other species. However, the feline Sho protein exhibited the shortest signal sequence and a unique amino acid in the omega-site of the GPI anchor. To the best of our knowledge, this is the first report on genetic polymorphisms of the feline SPRN gene.

First Report of Single Nucleotide Polymorphisms (SNPs) of the Leporine Shadow of Prion Protein Gene (SPRN) and Absence of Nonsynonymous SNPs in the Open Reading Frame (ORF) in Rabbits

“…Prior reports have shown that several prion-susceptible species, including cattle, sheep, cats, and goats, exhibit a high degree of nonsynonymous polymorphism in SPRN genes, leading to alterations in the amino acid sequence [ 1 , 4 , 5 , 14 , 17 , 22 , 23 , 25 ]. Of note, horses and dogs are prion-resistant species that only have one polymorphism in the SPRN gene [ 6 , 15 , 16 ].…”

“…Similarly, L-type atypical BSE-affected cattle showed an infrequent sequence variation within the coding sequence of the bovine SPRN gene [ 5 , 6 ] These studies demonstrate a strong relationship between genetic polymorphisms of the SPRN genes and the pathological mechanisms of prion diseases. To date, polymorphisms of the SPRN gene have been examined in prion disease-sensitive and -resistant species [ 1 , 6 , 13 , 14 , 15 , 16 , 17 ]. However, the genetic polymorphisms of the leporine SPRN gene have not been explored in depth.…”

Novel insertion/deletion polymorphisms and genetic features of the shadow of prion protein gene (SPRN) in dogs, a prion-resistant animal

“…In the present study, we found only one insertion/deletion polymorphism in the ORF of the canine SPRN gene. Previous studies have reported that prion-susceptible animals, including cattle, sheep, cats and goats, have highly polymorphic SPRN genes ( 11 , 12 , 21 – 26 ). In contrast, a prion-resistant animal, the horse, has one polymorphism of the SPRN gene ( 27 , 28 ).…”

Novel polymorphisms and genetic studies of the shadow of prion protein gene (SPRN) in pheasants

“…Genetic polymorphisms in prion-related genes contribute significantly to interindividual variation, so they have been investigated as useful biomarkers in medicine, as well as in the study of pathology, pharmacology, epidemiology, and clinical immunology ( 29 ). In addition, polymorphisms of the SPRN gene in prion disease-susceptible species play a crucial role in determining their susceptibility to prion diseases ( 12 , 30 , 31 ). The SPRN polymorphisms, which contribute to expression level or protein function, show strong associations with the pathogenesis of prion diseases in different species ( 32 , 33 ).…”