Abstract
Bovine spongiform encephalopathy (BSE) is a fatal infectious neurodegenerative disease caused by the accumulation of pathogenic prion protein (PrPSc) in the central nervous system (CNS), particularly in the brain. In a recent study, the shadow of prion protein (Sho), encoded by the shadow of prion protein (SPRN) gene, accelerates the progression of prion diseases, and a 12-bp insertion/deletion polymorphism in the coding region of the SPRN gene is associated with susceptibility to atypical BSE-affected Polish cattle. To date, the genetic study of the SPRN gene in Korean cattle has not been performed. In this study, we investigated the genotype and allele frequencies of SPRN polymorphisms in 235 Hanwoo and 212 Holstein cattle and analyzed the linkage disequilibrium (LD) and haplotypes of SPRN polymorphisms. In addition, we compared the distribution of the 12-bp insertion/deletion polymorphism between atypical BSE-diagnosed Polish cattle and Korean cattle to evaluate the susceptibility of atypical BSE. Furthermore, we estimated a deleterious effect of polymorphisms on the Sho protein using PROVEAN. We found a total of seven polymorphisms, including one novel single nucleotide polymorphism (SNP), c.231G>A. We also found significantly different distributions of genotype, allele and haplotype frequencies of seven polymorphisms between Hanwoo and Korean Holstein cattle. In addition, all polymorphisms showed strong LDs among the seven polymorphisms. Interestingly, Hanwoo cattle showed more potential susceptible distribution in the genotype and allele frequencies of the 12-bp insertion/deletion polymorphisms of the SPRN gene than Holstein cattle. Finally, using PROVEAN, we found one novel deleterious nonsynonymous SNP to Sho protein, c.110G>C (G37A). To the best of our knowledge, this is the first study of the SPRN gene in Korean cattle.
Highlights
Transmissible spongiform encephalopathies (TSEs) are infectious neurodegenerative diseases in humans and animals that are associated with the accumulation of abnormal prion protein (PrPSc) originating from the structural conversion of normal prion proteins (PrPC) in brain tissue[1,2]
The amplicon composed of 628 bp including open reading frame (ORF) (432 bp) was confirmed by agarose gel electrophoresis (Supplementary Figs. 1, 2) and was homologous with the shadow of prion protein gene (SPRN) gene of Bos taurus that is registered in GenBank (Gene ID: 616266)
We found a total of seven polymorphisms, including 3 nonsynonymous single nucleotide polymorphism (SNP) [c.110G>C (G37A), c.125C>T (A42V) and c.128G>A (R43K)], three synonymous SNPs [c.231G>A (A77A), c.288A>G (E96E) and c.360G>A (G120G)] and 1 insertion/deletion polymorphism [c.199_210delGCCGCGGCGGGG(67_70delAAAG)] in the coding region (Fig. 1A)
Summary
Transmissible spongiform encephalopathies (TSEs) are infectious neurodegenerative diseases in humans and animals that are associated with the accumulation of abnormal prion protein (PrPSc) originating from the structural conversion of normal prion proteins (PrPC) in brain tissue[1,2]. BSE was first discovered in the UK in 1985, and consumption of BSE-infected meat is a major cause of variant CJD in humans[17,18,19] In cattle, several single nucleotide polymorphisms (SNPs) have been reported in the open reading frame (ORF) of the prion protein gene (PRNP), these SNPs showed no significant correlations with BSE susceptibility. Previous studies have reported that polymorphisms of the shadow of prion protein gene (SPRN) were associated with susceptibility to CJD, scrapie and BSE. A 12-bp insertion/deletion polymorphism causing a deletion of 4 amino acids (67_70delAAAG) in the repetitive alanine-rich sequence of the SPRN gene was found in only one case of L-type atypical BSE in Polish cattle[28]. The association of prion diseases with polymorphisms in the SPRN gene has apparently existed, genetic studies of the SPRN gene in Korean cattle, including Hanwoo and Holstein cattle, have not been performed far. We evaluated a deleterious effect of polymorphisms causing protein sequence changes in the shadow of prion protein (Sho) using PROVEAN (https://provean.jcvi.org/seq_submit.php)[29,30]
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