First report of a strong association between genetic polymorphisms of the prion protein gene (
            <i>PRNP</i>
            ) and susceptibility to chronic wasting disease in sika deer (
            <i>Cervus nippon</i>
            )

Roh, In-Soon; Kim, Yongchan; Won, Sae-Young; Jeong, Min-Ju; Park, Kyung-Je; Park, Hoo-Chang; Lee, Yu-Ran; Kang, Hae‐Eun; Sohn, Hyun‐Joo; Jeong, Byung‐Hoon

doi:10.1111/tbed.14543

Cited by 9 publications

(8 citation statements)

References 33 publications

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“…A small number of SNP have been reported in dogs and horses, which are prion-resistant animals [ 25 – 27 ]. In contrast, sheep, goats, cattle, deer, and humans, which are prion-susceptible animals, show high genetic diversity for the PRNP gene [ 8 , 28 – 31 ]. This phenomenon may provide clues to explain the high genetic diversity of the elk PRNP gene.…”

Section: Discussionmentioning

confidence: 99%

“…The differences in genotype and allele distributions of the PRNP gene between CWD-negative and CWD-positive elk were analyzed using the χ 2 test and Fisher exact test. The Hardy-Weinberg equilibrium (HWE), haplotype analyses and LD tests were conducted by Haploview version 4.2 (Broad Institute, Cambridge, MA, USA) as previously described [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…Notably, although certain individuals have been infected with CWD, certain individuals have shown resistance to CWD on the farms where CWD occurred [ 7 ]. As the cause of this phenomenon, several studies have suggested that genetic polymorphisms of the PRNP gene play a pivotal role in susceptibility/resistance to CWD [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP)

Lee

Kim

Won

et al. 2023

Vet Res

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Prion diseases are fatal and malignant infectious encephalopathies induced by the pathogenic form of prion protein (PrPSc) originating from benign prion protein (PrPC). A previous study reported that the M132L single nucleotide polymorphism (SNP) of the prion protein gene (PRNP) is associated with susceptibility to chronic wasting disease (CWD) in elk. However, a recent meta-analysis integrated previous studies that did not find an association between the M132L SNP and susceptibility to CWD. Thus, there is controversy about the effect of M132L SNP on susceptibility to CWD. In the present study, we investigated novel risk factors for CWD in elk. We investigated genetic polymorphisms of the PRNP gene by amplicon sequencing and compared genotype, allele, and haplotype frequencies between CWD-positive and CWD-negative elk. In addition, we performed a linkage disequilibrium (LD) analysis by the Haploview version 4.2 program. Furthermore, we evaluated the 3D structure and electrostatic potential of elk prion protein (PrP) according to the S100G SNP using AlphaFold and the Swiss-PdbViewer 4.1 program. Finally, we analyzed the free energy change of elk PrP according to the S100G SNP using I-mutant 3.0 and CUPSAT. We identified 23 novel SNP of the elk PRNP gene in 248 elk. We found a strong association between PRNP SNP and susceptibility to CWD in elk. Among those SNP, S100G is the only non-synonymous SNP. We identified that S100G is predicted to change the electrostatic potential and free energy of elk PrP. To the best of our knowledge, this was the first report of a novel risk factor, the S100G SNP, for CWD.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP)

Lee

Kim

Won

et al. 2023

Vet Res

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“…In addition, when a substitution to incorporate a specific amino acid from chicken PrP occurred in the PrP sequence of domestic ducks, the amyloid propensity was observed to decrease, compared with that of wildtype duck (33). Furthermore, polymorphisms of the PRNP gene have been identified in many animals (10,31,32,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). However, no studies on PRNP polymorphisms in domestic ducks have yet been reported.…”

Section: Introductionmentioning

confidence: 99%

The first report of polymorphisms of the prion protein gene (PRNP) in Pekin ducks (Anas platyrhynchos domestica)

Jeong,

Wang,

Zou

et al. 2023

Front. Vet. Sci.

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BackgroundPrion diseases have been extensively reported in various mammalian species and are caused by a pathogenic prion protein (PrPSc), which is a misfolded version of cellular prion protein (PrPC). Notably, no cases of prion disease have been reported in birds. Single nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) that encodes PrP have been associated with susceptibility to prion diseases in several species. However, no studies on PRNP polymorphisms in domestic ducks have been reported thus far.MethodTo investigate PRNP polymorphisms in domestic ducks, we isolated genomic DNA from 214 Pekin duck samples and sequenced the coding region of the Pekin duck PRNP gene. We analyzed genotype, allele, and haplotype distributions and linkage disequilibrium (LD) among the SNPs of the Pekin duck PRNP gene. In addition, we evaluated the effects of the one non-synonymous SNP on the function and structure of PrP using the PROVEAN, PANTHER, SNPs & GO, SODA, and AMYCO in silico prediction programs.ResultsWe found five novel SNPs, c.441 T > C, c.495 T > C, c.582A > G, c.710C > T(P237L), and c.729C > T, in the ORF region of the PRNP gene in 214 Pekin duck samples. We observed strong LD between c.441 T > C and c.582A > G (0.479), and interestingly, the link between c.495 T > C and c.729C > T was in perfect LD, with an r2 value of 1.0. In addition, we identified the five major haplotype frequencies: TTACC, CTGCC, CTACC, CCGCT, and CTATC. Furthermore, we found that the non-synonymous SNP, c.710C > T (P237L), had no detrimental effects on the function or structure of Pekin duck PrP. However, the non-synonymous SNP had deleterious effects on the aggregation propensity and solubility of Pekin duck PrP compared with wildtype Pekin duck PrP.ConclusionTo the best of our knowledge, this study is the first report on the genetic characteristics of PRNP SNPs in Pekin ducks.

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“…However, the possibility of prion infection in raccoon dogs has not been investigated thus far. In addition, although polymorphisms of the PRNP gene have been reported in various hosts, PRNP polymorphisms have not been investigated in raccoon dogs ( 13 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

First report of structural characteristics and polymorphisms of the prion protein gene in raccoon dogs: The possibility of prion disease-resistance

Kim

Oem

et al. 2022

Front. Vet. Sci.

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Prion diseases are fatal degenerative encephalopathies caused by misfolded prion protein (PrPSc) converted from normal prion protein (PrPC). Previous studies have reported that genetic polymorphisms of the prion protein gene (PRNP) play a critical role in susceptibility to prion diseases. In addition, prion disease-resistant animals showed unique structural features of prion protein (PrP) related to species-specific amino acids. However, investigations of genetic polymorphisms of the PRNP gene and structural characteristics of PrP have not been performed in raccoon dogs thus far. We investigated genetic polymorphisms of PRNP in 87 raccoon dogs using amplicon sequencing and analyzed the genotype, allele, haplotype frequencies, and linkage disequilibrium (LD) using Haploview version 4.2. In addition, we performed phylogenetic analysis and multiple sequence alignment (MSA) using MEGA X version 10.1.8 and Clustal X version 2.1, respectively. We estimated the impact of raccoon dog and Canidae family-specific amino acids using PolyPhen-2, PROVEAN, and AMYCO. Furthermore, we analyzed the effect of raccoon dog and Canidae family-specific amino acids using the AlphaFold2 and Swiss-PdbViewer programs. We found 4 novel single nucleotide polymorphisms (SNPs) of the raccoon dog PRNP gene. In addition, the raccoon dog PrP showed 99.61% identity and the closest genetic distance to dog PrP. Among the substitutions of Canidae-specific amino acids with interspecific amino acids, D163N showed increased amyloidogenic propensity, and R181H showed alterations of hydrogen bonds. Furthermore, electrostatic potentials were changed according to the substitutions of D163N and R181H. By comparing PrP between raccoon dogs and raccoons, R168K and K224R were found to be related to changes in hydrogen bonds, and K224R altered the electrostatic potential of raccoon dog PrP. In the present study, we first reported 4 novel synonymous SNPs of the raccoon dog PRNP gene. We also identified that the PrP of raccoon dog has high homology (99.61%) with PrP of dog, which is a prion-resistant animal. In addition, raccoon dog PrP-specific amino acids are related to low amyloid propensity and inherent characteristics of 3D structure of raccoon dog PrP compared to the PrP of prion-susceptible species.

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First report of a strong association between genetic polymorphisms of the prion protein gene ( PRNP ) and susceptibility to chronic wasting disease in sika deer ( Cervus nippon )

Abstract: In-Soon Roh and Yong-Chan Kim have contributed equally to this work.

Cited by 9 publications

References 33 publications

Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP)

Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP)

The first report of polymorphisms of the prion protein gene (PRNP) in Pekin ducks (Anas platyrhynchos domestica)

First report of structural characteristics and polymorphisms of the prion protein gene in raccoon dogs: The possibility of prion disease-resistance

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