Dataset Information

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.

ABSTRACT: Prion diseases have a wide host range, but prion-infected cases have never been reported in horses. Genetic polymorphisms that can directly impact the structural stability of horse prion protein have not been investigated thus far. In addition, we noticed that previous studies focusing on horse-specific amino acids and secondary structure predictions of prion protein were performed for limited parts of the protein. In this study, we found genetic polymorphisms in the horse prion protein gene (PRNP) in 201 Thoroughbred horses. The identified polymorphism was assessed to determine whether this polymorphism impedes stability of protein using PolyPhen-2, PROVEAN and PANTHER. In addition, we evaluated horse-specific amino acids in horse and mouse prion proteins using same methods. We found only one single nucleotide polymorphism (SNP) in the horse prion protein, and three annotation tools predicted that the SNP is benign. In addition, horse-specific amino acids showed different effects on horse and mouse prion proteins, respectively. Abbreviations: PRNP: prion protein gene; SNP: single nucleotide polymorphism; CJD: Creutzfeldt-Jakob disease; CWD: chronic wasting disease; TME: transmissible mink encephalopathy; FSE: feline spongiform encephalopathy; MD: molecular dynamics; ER: endoplasmic reticulum; GPI: glycosylphosphatidylinositol; NMR: nuclear magnetic resonance; ORF: open reading frame; GWAS: genome-wide association study; NAPA: non-adaptive prion amplification; HMM: hidden Markov model; NCBI: National Center for Biotechnology Information.

SUBMITTER: Kim YC

PROVIDER: S-EPMC6277191 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.

Kim Yong-Chan YC Jeong Byung-Hoon BH

Prion 20180912 3-4

Prion diseases have a wide host range, but prion-infected cases have never been reported in horses. Genetic polymorphisms that can directly impact the structural stability of horse prion protein have not been investigated thus far. In addition, we noticed that previous studies focusing on horse-specific amino acids and secondary structure predictions of prion protein were performed for limited parts of the protein. In this study, we found genetic polymorphisms in the horse prion protein gene (PR ...[more]

PMID: 30165784

Similar Datasets

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: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.

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.

Dataset Information

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.

Publications

The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets