The First Report of Genetic and Structural Diversities in the SPRN Gene in the Horse, an Animal Resistant to Prion Disease.
Abstract: Prion diseases are fatal neurodegenerative diseases and are characterized by the accumulation of abnormal prion protein (PrP) in the brain. During the outbreak of the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, prion diseases in several species were reported; however, horse prion disease has not been reported thus far. In previous studies, the shadow of prion protein (Sho) has contributed to an acceleration of conversion from normal prion protein (PrP) to PrP, and the shadow of prion protein gene () polymorphisms have been significantly associated with the susceptibility of prion diseases. We investigated the genotype, allele and haplotype frequencies of the gene using direct sequencing. In addition, we analyzed linkage disequilibrium (LD) and haplotypes among polymorphisms. We also investigated LD between and single nucleotide polymorphisms (SNPs). We compared the amino acid sequences of Sho protein between the horse and several prion disease-susceptible species using ClustalW2. To perform Sho protein modeling, we utilized SWISS-MODEL and Swiss-PdbViewer programs. We found a total of four polymorphisms in the equine gene; however, we did not observe an in/del polymorphism, which is correlated with the susceptibility of prion disease in prion disease-susceptible animals. The SNPs showed weak LD value with SNP. In addition, we found 12 horse-specific amino acids of Sho protein that can induce significantly distributional differences in the secondary structure and hydrogen bonds between the horse and several prion disease-susceptible species. To the best of our knowledge, this is the first report regarding the genetic and structural characteristics of the equine gene.
Publication Date: 2019-12-28 PubMed ID: 31905681PubMed Central: PMC7016944DOI: 10.3390/genes11010039Google Scholar: Lookup
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Summary
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The research article deals with the study of genetic and structural diversities in the SPRN gene in horses, who are known to resist prion diseases. The researchers investigate how polymorphisms in this gene could play a role in this prion disease resistance.
Investigation of the SPRN Gene
- The objective of the research was to understand the susceptibility of horses to prion diseases, which are fatal neurodegenerative ailments, characterized by accumulation of abnormal prion protein (PrP) in the brain.
- The study focused on the shadow of prion protein (Sho), which in past research had significantly correlated with the susceptibility of prion diseases. Polymorphisms (genetic variations) in the SPRN gene, which encodes this protein, were the main subject of the study.
- The researchers carried out direct sequencing of the SPRN gene to find out the genotype, allele, and haplotype frequencies.
Analyzing Linkage and Polymorphisms
- A detailed analysis was conducted regarding linkage disequilibrium (LD), which pertains to the non-random association genotypic arrangements across genes or DNA sequences, and haplotypes among polymorphisms.
- The study also investigated LD between SPRN and PRNP single nucleotide polymorphisms (SNPs). SNPs are variations at a single position in a DNA sequence, and the PRNP gene codes for the prion protein.
- The findings included a total of four polymorphisms in the equine SPRN gene. Nonetheless, the researchers noted an absence of an in/del polymorphism, which is generally correlated with prion disease susceptibility in animals known to contract this kind of disease.
Comparison and Modeling of Sho Protein
- The amino acid sequences of the Sho protein in horses and several other prion disease-susceptible species were compared using ClustalW2, a bioinformatic tool for multiple sequence alignment.
- For modeling the Sho protein, programs like SWISS-MODEL and Swiss-PdbViewer were used.
- The research observed 12 horse-specific amino acids of the Sho protein. These could significantly induce differences in the secondary structure and hydrogen bonds between the horse and several prion disease-susceptible species.
- These differences in the biochemical properties of the Sho protein could potentially contribute to the resistance horses show towards prion diseases.
Significance of Findings
- The research marks the first detailed report on the genetic and structural characteristics of the equine SPRN gene, signifying a crucial step in understanding the resistance mechanisms towards prion diseases in horses.
Cite This Article
APA
Won SY, Kim YC, Kim SK, Jeong BH.
(2019).
The First Report of Genetic and Structural Diversities in the SPRN Gene in the Horse, an Animal Resistant to Prion Disease.
Genes (Basel), 11(1), 39.
https://doi.org/10.3390/genes11010039 Publication
Researcher Affiliations
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
- Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
- Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
MeSH Terms
- Animals
- Disease Resistance
- Haplotypes
- Horses
- Hydrogen Bonding
- Linkage Disequilibrium
- Models, Molecular
- Nerve Tissue Proteins / chemistry
- Nerve Tissue Proteins / genetics
- Polymorphism, Single Nucleotide
- Prion Proteins / genetics
- Protein Structure, Secondary
- Sequence Analysis, DNA
- Sequence Analysis, Protein
- Species Specificity
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 25 references
- Prusiner SB. Prions.. Proc Natl Acad Sci U S A 1998 Nov 10;95(23):13363-83.
- Prusiner SB. The prion diseases.. Brain Pathol 1998 Jul;8(3):499-513.
- Collee JG, Bradley R. BSE: a decade on--Part 2.. Lancet 1997 Mar 8;349(9053):715-21.
- Collee JG, Bradley R. BSE: a decade on--Part I.. Lancet 1997 Mar 1;349(9052):636-41.
- Aguilar-Calvo P, García C, Espinosa JC, Andreoletti O, Torres JM. Prion and prion-like diseases in animals.. Virus Res 2015 Sep 2;207:82-93.
- Fernández-Borges N, Eraña H, Castilla J. Behind the potential evolution towards prion resistant species.. Prion 2018 Mar 4;12(2):83-87.
- Sanchez-Garcia J, Fernandez-Funez P. D159 and S167 are protective residues in the prion protein from dog and horse, two prion-resistant animals.. Neurobiol Dis 2018 Nov;119:1-12.
- Pérez DR, Damberger FF, Wüthrich K. Horse prion protein NMR structure and comparisons with related variants of the mouse prion protein.. J Mol Biol 2010 Jul 9;400(2):121-8.
- Zhang J. The structural stability of wild-type horse prion protein.. J Biomol Struct Dyn 2011 Oct;29(2):369-77.
- Sigurdson CJ, Joshi-Barr S, Bett C, Winson O, Manco G, Schwarz P, Rülicke T, Nilsson KP, Margalith I, Raeber A, Peretz D, Hornemann S, Wüthrich K, Aguzzi A. Spongiform encephalopathy in transgenic mice expressing a point mutation in the β2-α2 loop of the prion protein.. J Neurosci 2011 Sep 28;31(39):13840-7.
- Won SY, Kim YC, Kim K, Kim AD, Jeong BH. The First Report of Polymorphisms and Genetic Features of the prion-like Protein Gene (PRND) in a Prion Disease-Resistant Animal, Dog.. Int J Mol Sci 2019 Mar 20;20(6).
- Jeong MJ, Jeong BH. No polymorphisms in the coding region of the prion-like protein gene in Thoroughbred racehorses.. Acta Vet Hung 2019 Jun;67(2):174-182.
- Kim YC, Jeong BH. The first report of polymorphisms and genetic characteristics of the prion protein gene (PRNP) in horses.. Prion 2018;12(3-4):245-252.
- Daude N, Westaway D. Biological properties of the PrP-like Shadoo protein.. Front Biosci (Landmark Ed) 2011 Jan 1;16(4):1505-16.
- Ciric D, Richard CA, Moudjou M, Chapuis J, Sibille P, Daude N, Westaway D, Adrover M, Béringue V, Martin D, Rezaei H. Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.. J Virol 2015 Jun;89(12):6287-93.
- Gurgul A, Polak MP, Larska M, Słota E. PRNP and SPRN genes polymorphism in atypical bovine spongiform encephalopathy cases diagnosed in Polish cattle.. J Appl Genet 2012 Aug;53(3):337-42.
- Peletto S, Bertolini S, Maniaci MG, Colussi S, Modesto P, Biolatti C, Bertuzzi S, Caramelli M, Maurella C, Acutis PL. Association of an indel polymorphism in the 3'UTR of the caprine SPRN gene with scrapie positivity in the central nervous system.. J Gen Virol 2012 Jul;93(Pt 7):1620-1623.
- Beck JA, Campbell TA, Adamson G, Poulter M, Uphill JB, Molou E, Collinge J, Mead S. Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease.. J Med Genet 2008 Dec;45(12):813-7.
- Bian J, Khaychuk V, Angers RC, Fernández-Borges N, Vidal E, Meyerett-Reid C, Kim S, Calvi CL, Bartz JC, Hoover EA, Agrimi U, Richt JA, Castilla J, Telling GC. Prion replication without host adaptation during interspecies transmissions.. Proc Natl Acad Sci U S A 2017 Jan 31;114(5):1141-1146.
- Jeong MJ, Kim YC, Jeong BH. Prion-like protein gene (PRND) polymorphisms associated with scrapie susceptibility in Korean native black goats.. PLoS One 2018;13(10):e0206209.
- Mesquita P, Garcia V, Marques MR, Santos Silva F, Oliveira Sousa MC, Carolino I, Pimenta J, Fontes CM, Horta AE, Prates JA, Pereira RM. The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep.. Anim Genet 2016 Feb;47(1):128-32.
- Kim SK, Kim YC, Won SY, Jeong BH. Potential scrapie-associated polymorphisms of the prion protein gene (PRNP) in Korean native black goats.. Sci Rep 2019 Oct 25;9(1):15293.
- Kim YC, Kim SK, Jeong BH. Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats.. Sci Rep 2019 Oct 24;9(1):15261.
- Kim YC, Jeong MJ, Jeong BH. Strong association of regulatory single nucleotide polymorphisms (SNPs) of the IFITM3 gene with influenza H1N1 2009 pandemic virus infection.. Cell Mol Immunol 2020 Jun;17(6):662-664.
- Wilson IA, Haft DH, Getzoff ED, Tainer JA, Lerner RA, Brenner S. Identical short peptide sequences in unrelated proteins can have different conformations: a testing ground for theories of immune recognition.. Proc Natl Acad Sci U S A 1985 Aug;82(16):5255-9.
Citations
This article has been cited 5 times.- Kim YC, Kim HH, Kim AD, Jeong BH. Novel insertion/deletion polymorphisms and genetic features of the shadow of prion protein gene (SPRN) in dogs, a prion-resistant animal.. Front Vet Sci 2022;9:942289.
- Kim YC, Kim HH, Jeong BH. The First Report of Polymorphisms and Genetic Characteristics of the Shadow of Prion Protein (SPRN) in Prion Disease-Resistant Animal, Chickens.. Front Vet Sci 2022;9:904305.
- Won SY, Kim YC, Do K, Jeong BH. The First Report of Genetic Polymorphisms of the Equine SPRN Gene in Outbred Horses, Jeju and Halla Horses.. Animals (Basel) 2021 Sep 1;11(9).
- 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).
- Won SY, Kim YC, Jeong BH. First Report of the Potential Bovine Spongiform Encephalopathy (BSE)-Related Somatic Mutation E211K of the Prion Protein Gene (PRNP) in Cattle.. Int J Mol Sci 2020 Jun 15;21(12).
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