Absence of single nucleotide polymorphisms (SNPs) in the open reading frame (ORF) of the prion protein gene (PRNP) in a large sampling of various chicken breeds

Abstract Background Prion diseases are zoonotic diseases with a broad infection spectrum among mammalian hosts and are caused by the misfolded prion protein (PrPSc) derived from the normal prion protein (PrPC), which encodes the prion protein gene (PRNP). Currently, although several prion disease-resistant animals have been reported, a high dose of prion agent inoculation triggers prion disease infection in these disease-resistant animals. However, in chickens, natural prion disease-infected cases have not been reported, and experimental challenges with prion agents have failed to cause infection. Unlike other prion disease-resistant animals, chickens have shown perfect resistance to prion disease thus far. Thus, investigation of the chicken PRNP gene could improve for understanding the mechanism of perfect prion-disease resistance. Here, we investigated the genetic characteristics of the open reading frame (ORF) of the chicken PRNP gene in a large sampling of various chicken breeds. Results We found only tandem repeat deletion polymorphisms of the chicken PRNP ORF in the 4 chicken breeds including 106 Dekalb White, 100 Ross, 98 Ogolgye and 100 Korean native chickens. In addition, the distribution of chicken insertion/deletion polymorphisms was significantly different among the 4 chicken breeds. Finally, we found significant differences in the number of PRNP SNPs between prion disease-susceptible species and prion disease-resistant species. Notably, chickens lack SNPs in the ORF of the prion protein. Conclusion In this study, we found that the absence of SNPs in the chicken PRNP ORF is a notable feature of animals with perfect resistant to prion disease.

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Identification of the novel polymorphisms and potential genetic features of the prion protein gene (PRNP) in horses, a prion disease-resistant animal

Scientific Reports ◽

10.1038/s41598-020-65731-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Yong-Chan Kim ◽

Sae-Young Won ◽

Kyoungtag Do ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Prion Disease ◽

Protein Gene ◽

Prion Protein Gene ◽

The Novel ◽

Disease Resistant ◽

Genetic Features ◽

Resistant Animal

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Absence of Strong Genetic Linkage Disequilibrium between Single Nucleotide Polymorphisms (SNPs) in the Prion Protein Gene (PRNP) and the Prion-Like Protein Gene (PRND) in the Horse, a Prion-Resistant Species

Genes ◽

10.3390/genes11050518 ◽

2020 ◽

Vol 11 (5) ◽

pp. 518

Author(s):

Sae-Young Won ◽

Yong-Chan Kim ◽

Kyoungtag Do ◽

Byung-Hoon Jeong

Keyword(s):

Linkage Disequilibrium ◽

Prion Protein ◽

Prion Disease ◽

Protein Gene ◽

Prion Protein Gene ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Resistant Species ◽

Disease Resistant ◽

The Impact

Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrPSc). However, prion disease has not been reported in horses during outbreaks of transmissible spongiform encephalopathies (TSEs) in various animals in the UK. In previous studies, single nucleotide polymorphisms (SNPs) in the prion protein gene (PRNP) have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between PRNP and prion-like protein gene (PRND) SNPs has been identified in prion disease-susceptible species. On the other hand, weak LD values have been reported in dogs, a prion disease-resistant species. In this study, we investigated SNPs in the PRND gene and measured the LD values between the PRNP and PRND SNPs and the impact of a nonsynonymous SNP found in the horse PRND gene. To identify SNPs in the PRND gene, we performed direct sequencing of the PRND gene. In addition, to assess whether the weak LD value between the PRNP and PRND SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the PRNP and PRND SNPs using D’ and r2 values. Furthermore, we evaluated the impact of a nonsynonymous SNP in the Doppel protein with PolyPhen-2, PROVEAN, and PANTHER. We observed two novel SNPs, c.331G > A (A111T) and c.411G > C. The genotype and allele frequencies of the c.331G > A (A111T) and c.411G > C SNPs were significantly different between Jeju, Halla, and Thoroughbred horses. In addition, we found a total of three haplotypes: GG, AG, and GC. The GG haplotype was the most frequently observed in Jeju and Halla horses. Furthermore, the impact of A111T on the Doppel protein was predicted to be benign by PolyPhen-2, PROVEAN, and PANTHER. Interestingly, a weak LD value between the PRNP and PRND SNPs was found in the horse, a prion disease-resistant animal. To the best of our knowledge, these results suggest that a weak LD value could be one feature of prion disease-resistant animals.

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The First Report of the Prion Protein Gene (PRNP) Sequence in Pekin Ducks (Anas platyrhynchos domestica): The Potential Prion Disease Susceptibility in Ducks

Genes ◽

10.3390/genes12020193 ◽

2021 ◽

Vol 12 (2) ◽

pp. 193

Author(s):

Min-Ju Jeong ◽

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Dna Sequence ◽

Prion Disease ◽

Protein Gene ◽

Prnp Gene ◽

Pekin Duck ◽

Prion Protein Gene ◽

First Report ◽

Aggregation Propensity ◽

Pekin Ducks

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.

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Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene ? N. Engl. J. Med. 326, 444–449

Trends in Genetics ◽

10.1016/0168-9525(92)90073-d ◽

1992 ◽

Vol 8 (1) ◽

pp. 123

Keyword(s):

Prion Protein ◽

Prion Disease ◽

Protein Gene ◽

Fatal Familial Insomnia ◽

Prion Protein Gene

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Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene (PRNP) in Dogs—A Resistant Animal of Prion Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21114160 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4160 ◽

Cited By ~ 1

Author(s):

Dong-Ju Kim ◽

Yong-Chan Kim ◽

An-Dang Kim ◽

Byung-Hoon Jeong

Keyword(s):

Hydrogen Bonds ◽

Prion Protein ◽

Protein Gene ◽

Direct Sequencing ◽

Transmissible Spongiform Encephalopathies ◽

Prion Protein Gene ◽

Genetic Characteristics ◽

Aggregation Propensity ◽

Wide Range ◽

The Impact

Transmissible spongiform encephalopathies (TSEs) have been reported in a wide range of species. However, TSE infection in natural cases has never been reported in dogs. Previous studies have reported that polymorphisms of the prion protein gene (PRNP) have a direct impact on the susceptibility of TSE. However, studies on polymorphisms of the canine PRNP gene are very rare in dogs. We examined the genotype, allele, and haplotype frequencies of canine PRNP in 204 dogs using direct sequencing and analyzed linkage disequilibrium (LD) using Haploview version 4.2. In addition, to evaluate the impact of nonsynonymous polymorphisms on the function of prion protein (PrP), we carried out in silico analysis using PolyPhen-2, PROVEAN, and PANTHER. Furthermore, we analyzed the structure of PrP and hydrogen bonds according to alleles of nonsynonymous single nucleotide polymorphisms (SNPs) using the Swiss-Pdb Viewer program. Finally, we predicted the impact of the polymorphisms on the aggregation propensity of dog PrP using AMYCO. We identified a total of eight polymorphisms, including five novel SNPs and one insertion/deletion polymorphism, and found strong LDs and six major haplotypes among eight polymorphisms. In addition, we identified significantly different distribution of haplotypes among eight dog breeds, however, the kinds of identified polymorphisms were different among each dog breed. We predicted that p.64_71del HGGGWGQP, Asp182Gly, and Asp182Glu polymorphisms can impact the function and/or structure of dog PrP. Furthermore, the number of hydrogen bonds of dog PrP with the Glu182 and Gly182 alleles were predicted to be less than those with the Asp182 allele. Finally, Asp163Glu and Asp182Gly showed more aggregation propensity than wild-type dog PrP. These results suggest that nonsynonymous SNPs, Asp182Glu and Asp182Gly, can influence the stability of dog PrP and confer the possibility of TSE infection in dogs.

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First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle

International Journal of Molecular Sciences ◽

10.3390/ijms21124246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4246 ◽

Cited By ~ 2

Author(s):

Sae-Young Won ◽

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Prion Protein ◽

Somatic Mutation ◽

Prion Disease ◽

In Silico ◽

Somatic Mutations ◽

Protein Gene ◽

Prnp Gene ◽

Spongiform Encephalopathy ◽

Prion Protein Gene

Bovine spongiform encephalopathy (BSE) is a prion disease characterized by spongiform degeneration and astrocytosis in the brain. Unlike classical BSE, which is caused by prion-disease-contaminated meat and bone meal, the cause of atypical BSE has not been determined. Since previous studies have reported that the somatic mutation in the human prion protein gene (PRNP) has been linked to human prion disease, the somatic mutation of the PRNP gene was presumed to be one cause of prion disease. However, to the best of our knowledge, the somatic mutation of this gene in cattle has not been investigated to date. We investigated somatic mutations in a total of 58 samples, including peripheral blood; brain tissue including the medulla oblongata, cerebellum, cortex, and thalamus; and skin tissue in 20 individuals from each breed using pyrosequencing. In addition, we estimated the deleterious effect of the K211 somatic mutation on bovine prion protein by in silico evaluation tools, including PolyPhen-2 and PANTHER. We found a high rate of K211 somatic mutations of the bovine PRNP gene in the medulla oblongata of three Holsteins (10% ± 4.4%, 28% ± 2%, and 19.55% ± 3.1%). In addition, in silico programs showed that the K211 somatic mutation was damaging. To the best of our knowledge, this study is the first to investigate K211 somatic mutations of the bovine PRNP gene that are associated with potential BSE progression.

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

Animals ◽

10.3390/ani11092574 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2574

Author(s):

Sae-Young Won ◽

Yong-Chan Kim ◽

Kyoungtag Do ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Prion Disease ◽

Protein Gene ◽

Prion Diseases ◽

Minimum Free Energy ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Reading Frame ◽

Direct Dna Sequencing ◽

Thoroughbred Horses

Prion disease is a fatal infectious disease caused by the accumulation of pathogenic prion protein (PrPSc) 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.

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