scholarly journals 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 ◽  
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.

scholarly journals The First Report of Polymorphisms and Genetic Features of the prion-like Protein Gene (PRND) in a Prion Disease-Resistant Animal, Dog

2019 ◽  
Vol 20 (6) ◽  
pp. 1404 ◽  
Author(s):  
Sae-Young Won ◽  
Yong-Chan Kim ◽  
Kiwon Kim ◽  
An-Dang Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Linkage Disequilibrium ◽  
Prion Disease ◽  
Genetic Linkage ◽  
Protein Gene ◽  
Prnp Gene ◽  
Nucleotide Polymorphisms ◽  
Direct Dna Sequencing ◽  
Disease Resistant ◽  
Genetic Features ◽  
Resistant Animal

Prion disease has displayed large infection host ranges among several species; however, dogs have not been reported to be infected and are considered prion disease-resistant animals. Case-controlled studies in several species, including humans and cattle, indicated a potent association of prion protein gene (PRNP) polymorphisms in the progression of prion disease. Thus, because of the proximal location and similar structure of the PRNP gene among the prion gene family, the prion-like protein gene (PRND) was noted as a novel candidate gene that contributes to prion disease susceptibility. Several case-controlled studies have confirmed the relationship of the PRND gene with prion disease vulnerability, and strong genetic linkage disequilibrium blocks were identified in prion-susceptible species between the PRNP and PRND genes. However, to date, polymorphisms of the dog PRND gene have not been reported, and the genetic linkage between the PRNP and PRND genes has not been examined thus far. Here, we first investigated dog PRND polymorphisms in 207 dog DNA samples using direct DNA sequencing. A total of four novel single nucleotide polymorphisms (SNPs), including one nonsynonymous SNP (c.149G>A, R50H), were identified in this study. We also found two major haplotypes among the four novel SNPs. In addition, we compared the genotype and allele frequencies of the c.149G>A (R50H) SNP and found significantly different distributions among eight dog breeds. Furthermore, we annotated the c.149G>A (R50H) SNP of the dog PRND gene using in silico tools, PolyPhen-2, PROVEAN, and PANTHER. Finally, we examined linkage disequilibrium between the PRNP and PRND genes in dogs. Interestingly, we did not find a strong genetic linkage between these two genes. To the best of our knowledge, this was the first genetic study of the PRND gene in a prion disease-resistant animal, a dog.

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

Animals ◽  
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.

scholarly journals Identification of single nucleotide polymorphisms in the prion protein gene in Santa Ines and Dorset sheep

2018 ◽  
Vol 38 (4) ◽  
pp. 624-628
Author(s):  
Caroline P. Andrade ◽  
José D. Barbosa Neto ◽  
David Driemeier
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Prion Protein ◽  
Protein Gene ◽  
Risk Group ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphisms ◽  
Moderate Risk ◽  
Single Nucleotide ◽  
Group 3 ◽  
Santa Inês

ABSTRACT: Scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats and results from accumulation of the abnormal isoform of a prion protein in the central nervous system. Resistance or susceptibility to the disease is dependent on several factors, including the strain of infecting agent, the degree of exposure, and the presence of single nucleotide polymorphisms (SNPs) in the prion protein gene. The most important polymorphisms are present in codons 136, 154, and 171. SNPs have also been identified in other codons, such as 118, 127, 141, 142, and 143. The objective of this study was to investigate the genotypic profile of Santa Ines (n=94) and Dorset (n=69) sheep and identify polymorphisms in the prion protein gene using real-time PCR techniques and sequencing. We analyzed SNPs in 10 different codons (127, 136, 138, 140, 141, 142, 143, 154, 171, and 172) in Santa Ines sheep. Classification of the flock into risk groups associated with scrapie revealed that approximately 68% of the Santa Ines herd was considered at moderate risk (group 3), and the most frequent haplotype was ARQ/ARQ (47.8%). For Dorset sheep, 42% of the herd was considered at moderate risk (group 3), 40% at low risk (group 2), and 12% at very low risk (group 1). These findings improve our understanding of the genotype breed and further highlight the importance of genotyping and identification of polymorphisms in Brazilian herds to assess their effects on potential infections upon exposure to the sheep prion.

Single nucleotide polymorphisms of the prion protein gene (PRNP) in Chinese pig breeds

2005 ◽  
Vol 12 (4) ◽  
pp. 324-326 ◽  
Author(s):  
Liping Meng ◽  
Deming Zhao ◽  
Hongxiang Liu ◽  
Jianmin Yang ◽  
Zhangyong Ning
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pig Breeds

scholarly journals 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

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yong-Chan Kim ◽  
Sae-Young Won ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Gene ◽  
Open Reading Frame ◽  
High Dose ◽  
Prion Protein Gene ◽  
Genetic Characteristics ◽  
Reading Frame ◽  
Disease Resistant ◽  
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.

Variation in the coding region of the prion protein gene in Slovak cattle

2012 ◽  
Vol 60 (2) ◽  
pp. 233-243
Author(s):  
Stanislav Hreško ◽  
Ľudmila Tkáčiková
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Prion Protein ◽  
Protein Gene ◽  
Silent Mutation ◽  
Genotype Distribution ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Single Nucleotide ◽  
Homozygous Genotype

This study was conducted to investigate the presence of single nucleotide polymorphisms (SNPs) in the coding region of the bovine prion protein (PrP) gene among healthy and bovine spongiform encephalopathy (BSE-) affected cattle in Slovakia. Denaturing gradient gel electrophoresis (DGGE) and single-strand conformation polymorphism (SSCP) followed by DNA sequencing were used to identify SNPs and variations in octapeptide repeats. Altogether three single nucleotide polymorphisms (g234a, c339t and c576t) and variations in the number of octapeptide repeat units (5 or 6) were found in the analysed part of the prion protein gene. All single nucleotide polymorphisms were silent, causing no amino acid changes. Significant differences (P < 0.05) in the genotype distribution of g234a polymorphism were observed when the homozygous genotype with a mutated allele (caa/caa) was compared to the heterozygous genotype -/cag among healthy and BSE-affected cattle. The homozygous genotype caa/caa was characteristic of the group of BSE-affected cattle. Additionally, the homozygous genotype caa/caa was significant for the group of Simmental crossbreeds among healthy cattle. The allele and genotype distribution of the other polymorphisms was not significantly different among groups of healthy and BSE-affected cattle. The possible influence of a silent mutation on expression of the gene is not clearly determined and needs further investigations.

Evaluation of proteinase K-resistant prion protein (PrPres) in Korean native black goats carrying a potential scrapie-susceptible haplotype of the prion protein gene (PRNP)

2021 ◽  
Author(s):  
Sae-Young Won ◽  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Linkage Disequilibrium ◽  
Prion Protein ◽  
Prion Disease ◽  
Protein Gene ◽  
Proteinase K ◽  
Broad Host Range ◽  
Strong Linkage Disequilibrium ◽  
Prion Protein Gene ◽  
Wasting Disease ◽  
Strong Linkage

AbstractPrion disease is a fatal neurodegenerative disease with a broad host range in humans and animals. It is caused by proteinase K-resistant prion protein (PrPres). In previous studies, a heterogeneous infection in Cervidae and Caprinae was reported. Chronic wasting disease (CWD) has been frequently reported as the only prion disease in Korea that occurs in livestock. Thus, there is a possibility of transmission of CWD to Korean native black goats. However, PrPres has not been investigated thus far in Korean native black goats. We found strong linkage disequilibrium between c.126G>A and c.414T>C (r2 = 1) and between c.718C>T and c.126G>A (r2 = 0.638). In addition, the haplotype GTGTAAAC (representing codons 42, 102, 127, 138, 143, 146, 218 and 240) showed the highest frequency with 45.1%. Among 41 Korean native black goats, 20 animals (48.78%) were homozygous for the susceptible haplotypes (histidine at codon 143, asparagine at codon 146 and arginine at codon 154). Interestingly, we did not detect PrPres bands in any of the tested animals, including the 20 animals carrying potential scrapie susceptible haplotypes.

scholarly journals Identification of single-nucleotide polymorphisms of the prion protein gene in sika deer (Cervus nippon laiouanus)

2007 ◽  
Vol 8 (3) ◽  
pp. 299 ◽  
Author(s):  
Hyun-Jeong Jeong ◽  
Joong-Bok Lee ◽  
Seung-Yong Park ◽  
Chang-Seon Song ◽  
Bo-Sook Kim ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Prion Protein ◽  
Sika Deer ◽  
Protein Gene ◽  
Cervus Nippon ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide
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