Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kim DJ

PROVIDER: S-EPMC7311962 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Kim Dong-Ju DJ Kim Yong-Chan YC Kim An-Dang AD Jeong Byung-Hoon BH

International journal of molecular sciences 20200610 11

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 di ...[more]

PMID: 32532135

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Project description:Prion diseases, a protein misfolded disorder (PMD) caused by misfolded prion protein (PrPSc), present in a wide variety of hosts, ranging from ungulates to humans. To date, prion infections have not been reported in horses, which are well-known as prion disease-resistant animals. Several studies have attempted to identify distinctive features in the prion protein of horses compared to prion disease-susceptible animals, without the study on polymorphisms of the horse prion protein gene (PRNP). Since single nucleotide polymorphisms (SNPs) of PRNP in prion disease-susceptible animals are major susceptibility factors, the investigation of SNPs in the horse PRNP gene is important; however, only one study investigated a single horse breed, Thoroughbred. Thus, we investigated genetic polymorphisms and potential characteristics of the PRNP gene in 2 additional horse breeds. To this end, we performed amplicon sequencing of the horse PRNP gene and investigated SNPs in Jeju and Halla horses. We compared genotype, allele and haplotype frequencies among three horse breeds, namely, Thoroughbred, Jeju and Halla horses. In addition, we evaluated the potential influence of the identified nonsynonymous SNPs on the prion protein using PolyPhen-2, PROVEAN, and PANTHER. Furthermore, we measured the aggregation propensity of prion proteins using AMYCO and analyzed linkage disequilibrium (LD) between PRNP and prion-like protein gene (PRND) SNPs. A total of 4 SNPs were found, including two nonsynonymous SNPs (c.301 T > A, c.525 C > A) and three novel SNPs (c.-3A > G, c.301 T > A and c.570 G > A). There were significant differences in genotype, allele and haplotype frequencies among the three horse breeds. The nonsynonymous SNP, c.301 T > A (W101R), was predicted to be benign, deleterious, and possibly damaging by PolyPhen-2, PROVEAN and PANTHER, respectively. In addition, the amyloid propensity of horse prion protein according to 4 haplotypes of nonsynonymous SNPs was predicted to be benign by AMYCO. Finally, we identified weak LD between PRNP and PRND SNPs.

Project description:Transmissible spongiform encephalopathies (TSEs) also known as prion diseases, are fatal neurodegenerative diseases. Prion diseases are caused by abnormal prion protein (PrPSc) derived from normal prion protein (PrPC), which is encoded by the prion protein gene (PRNP). Prion diseases have been reported in several mammals. Notably, chickens, one species of bird, have not been reported to develop prion diseases and showed resistance to bovine spongiform encephalopathy (BSE) infection. However, genetic polymorphisms of the PRNP gene and protein structure of the prion protein (PrP) related to vulnerability to prion diseases have not been investigated in pheasants, another species of bird. We performed amplicon sequencing of the pheasant PRNP gene to identify genetic polymorphisms in 148 pheasants. We analyzed the genotype, allele and haplotype frequencies of the pheasant PRNP polymorphisms. In addition, we evaluated the effect of genetic polymorphisms of the pheasant PRNP gene on pheasant PrP by the AMYCO, PROVEAN, PolyPhen-2 and PANTHER softwares. Furthermore, we compared the amino acid sequences of tandem repeat domains and secondary and tertiary structures of prion proteins (PrPs) among several animals. Finally, we investigated the impact of non-synonymous single nucleotide polymorphisms (SNPs) on hydrogen bonds and tertiary structures of pheasant PrP by Swiss PDB viewer software. We identified 34 novel genetic polymorphisms of the pheasant PRNP gene including 8 non-synonymous SNPs and 6 insertion/deletion polymorphisms. Among the non-synonymous SNPs, the L23F, G33C and R177Q SNPs showed that they could have a deleterious effect on pheasant PrP. In addition, the R177Q SNP was predicted to show an increase in amyloid propensity and a reduction in hydrogen bonds of pheasant PrP. Among the insertion/deletion polymorphisms, c.163_180delAACCCGGGGTATCCCCAC showed that it could have a detrimental effect on pheasant PrP. Furthermore, secondary and tertiary structures of pheasant PrP were predicted to have structures similar to those of chicken PrP. To the best of our knowledge, this is the first study on genetic polymorphisms of the pheasant PRNP gene.

Project description:Prion diseases are irreversible neurodegenerative disorders caused by the aggregated form of prion protein (PrPSc) derived from the normal form of prion protein (PrPC). Previous studies have reported that shadow of prion protein (Sho) interacts with prion protein (PrP) and accelerates the conversion of PrPC to PrPSc. In addition, genetic polymorphisms of the shadow of the prion protein gene (SPRN) are related to the vulnerability of prion diseases in various hosts. However, to date, polymorphisms and genetic features of the SPRN gene have not been investigated in chickens, which are prion disease-resistant animals. We investigated genetic polymorphisms of the SPRN gene in 2 breeds of chickens, i.e., Dekalb White and Ross, using amplicon sequencing. We analyzed genotype, allele and haplotype frequencies and linkage disequilibrium (LD) among the genetic polymorphisms. In addition, we compared the amino acid sequences of Sho among several prion-related species to identify the unique genetic features of chicken Sho using ClustalW. Furthermore, we evaluated the N-terminal signal peptide and glycosylphosphatidylinositol (GPI)-anchor using SignalP and PredGPI, respectively. Finally, we compared the number of SPRN polymorphisms between prion disease-resistant and prion disease-susceptible animals. We identified 7 novel single nucleotide polymorphisms (SNPs), including 1 synonymous SNP in the open reading frame (ORF) of the chicken SPRN gene. We also found significantly different genotypes, allele frequencies and haplotypes between the 2 chicken breeds. In addition, we found that the interaction regions between Sho and PrP and the NXT glycosylation motif were conserved among all species. Notably, sequence similarity was extremely low in the N-terminal and C-terminal regions between mammals and chickens. Furthermore, we found that chicken Sho was the longest N-terminal signal peptide, and the amino acids of the cutting site of chicken are different from those of mammals. Last, unlike other species investigated, omega-site and signal sequences of the GPI-anchor were not found in chickens. To the best of our knowledge, this is the first report of genetic polymorphisms of the SPRN gene in chickens.

Dataset Information

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

Publications

Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene (<i>PRNP</i>) in Dogs-A Resistant Animal of Prion Disease.

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