Identification of the novel polymorphisms and potential genetic features of the prion protein gene (PRNP) in horses, a prion disease-resistant animal.
Abstract: Prion diseases, a protein misfolded disorder (PMD) caused by misfolded prion protein (PrP), 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.
Publication Date: 2020-06-02 PubMed ID: 32488112PubMed Central: PMC7265282DOI: 10.1038/s41598-020-65731-5Google Scholar: Lookup
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- Journal Article
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Summary
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The research article explores the distinctive genetic characteristics of the prion protein gene (PRNP) in horses, animals known for their resistance to prion diseases. The focus is on the identification of novel polymorphisms in the PRNP gene in two additional breeds of horses, by comparing genotype, allele and haplotype frequencies, and evaluating the potential influence of identified nonsynonymous SNPs.
Research Methodology
- The study employed amplicon sequencing which is a type of targeted gene sequencing, to investigate the PRNP gene in Jeju and Halla horses.
- The genotype, allele and haplotype frequencies were compared among three different breeds of horses: Thoroughbred, Jeju and Halla horses.
- To assess the potential influence that the identified nonsynonymous single nucleotide polymorphisms (SNPs) have on the prion protein, the study used PolyPhen-2, PROVEAN, and PANTHER – tools for the prediction of the impact of an amino acid substitution on the structure and function of a protein.
- The aggregation propensity of prion proteins, which is the tendency of misfolded proteins to accumulate, was measured using the AMYCO tool. This is crucial in understanding diseases caused by protein misfolding.
- Linkage disequilibrium (LD), which is the non-random association of alleles at different loci, was analyzed between PRNP and prion-like protein gene (PRND) SNPs.
Research Findings
- A total of four single nucleotide polymorphisms (SNPs) were identified, including two nonsynonymous SNPs (c.301 T > A, c.525 C > A) and three new SNPs (c.-3A > G, c.301 T > A and c.570 G > A).
- There were noticeable differences in the genotype, allele and haplotype frequencies amongst the three horse breeds studied.
- The nonsynonymous SNP, c.301 T > A (W101R), was predicted to have varying effects on the prion protein, with it being classified as benign, harmful and possibly damaging by PolyPhen-2, PROVEAN and PANTHER, respectively.
- The propensity for prion protein molecules to aggregate, based on four haplotypes of nonsynonymous SNPs, was predicted to be benign by AMYCO, meaning it would not cause disease.
- The study identified weak linkage disequilibrium (LD) between PRNP and PRND SNPs. This indicates that there is a weak non-random association between these two sets of alleles at different loci.
In summary, the research provides important insights into why horses are resistant to prion diseases, which could aid in the development of future treatments for such diseases in susceptible species.
Cite This Article
APA
Kim YC, Won SY, Do K, Jeong BH.
(2020).
Identification of the novel polymorphisms and potential genetic features of the prion protein gene (PRNP) in horses, a prion disease-resistant animal.
Sci Rep, 10(1), 8926.
https://doi.org/10.1038/s41598-020-65731-5 Publication
Researcher Affiliations
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, 54531, Republic of Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk, 54896, Republic of Korea.
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, 54531, Republic of Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk, 54896, Republic of Korea.
- Lab of Equine Science, Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju, 63243, Republic of Korea.
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, 54531, Republic of Korea. bhjeong@jbnu.ac.kr.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk, 54896, Republic of Korea. bhjeong@jbnu.ac.kr.
MeSH Terms
- Animals
- Gene Frequency
- Genes / genetics
- Horses / genetics
- Linkage Disequilibrium / genetics
- Polymorphism, Single Nucleotide / genetics
- Prion Diseases / genetics
- Prion Diseases / veterinary
- Prion Proteins / genetics
- Prions / genetics
Conflict of Interest Statement
The authors declare no competing interests.
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Citations
This article has been cited 6 times.- Lee YR, Kim YC, Won SY, Jeong MJ, Park KJ, Park HC, Roh IS, Kang HE, Sohn HJ, Jeong BH. Identification of a novel risk factor for chronic wasting disease (CWD) in elk: S100G single nucleotide polymorphism (SNP) of the prion protein gene (PRNP).. Vet Res 2023 Jun 16;54(1):48.
- Jo WS, Kim YC, Oem JK, Jeong BH. First report of structural characteristics and polymorphisms of the prion protein gene in raccoon dogs: The possibility of prion disease-resistance.. Front Vet Sci 2022;9:989352.
- Kim KH, Kim YC, Jeong BH. Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene in Pheasants.. Front Vet Sci 2022;9:935476.
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- Jeong MJ, Kim YC, Jeong BH. The First Report of the Prion Protein Gene (PRNP) Sequence in Pekin Ducks (Anas platyrhynchos domestica): The Potential Prion Disease Susceptibility in Ducks.. Genes (Basel) 2021 Jan 28;12(2).
- Kim HH, Kim YC, Kim K, Kim AD, Jeong BH. Novel Polymorphisms and Genetic Features of the Prion Protein Gene (PRNP) in Cats, Hosts of Feline Spongiform Encephalopathy.. Genes (Basel) 2020 Dec 24;12(1).
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