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Home / Equine Research Bank / Vet Res / Novel polymorphisms in the prion protein gene (PRNP) and sta...
Veterinary research2023; 54(1); 94; doi: 10.1186/s13567-023-01211-8

Novel polymorphisms in the prion protein gene (PRNP) and stability of the resultant prion protein in different horse breeds.

Abstract: Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrP) into an abnormal and misfolded isoform known as PrP. Most prion diseases and their susceptibility and pathogenesis are mainly modulated by the PRNP gene that codes for PrP. Mutations and polymorphisms in the PRNP gene can alter PrP amino acid sequence, leading to a change in transmission efficiency depending on the place where it occurs. Horses are animals that are considered to be highly resistant to prions. Several studies have attempted to identify polymorphisms in the PRNP gene that explain the reason for this high resistance. In this study, we have analysed 207 horses from 20 different breeds, discovering 3 novel PRNP polymorphisms. By using computer programmes such as PolyPhen-2, PROVEAN, PANTHER, Meta-SNP and PredictSNP, we have predicted the possible impact that these new polymorphisms would have on the horse prion protein. In addition, we measured the propensity for amyloid aggregation using AMYCO and analysed the lack of hydrogen bridges that these changes would entail together with their electrostatic potentials using Swiss-PdbViewer software, showing that an increased amyloid propensity could be due to changes at the level of electrostatic potentials.
© 2023. L’Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE).
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Publication Date: 2023-10-17 PubMed ID: 37848924PubMed Central: PMC10583458DOI: 10.1186/s13567-023-01211-8Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how gene differences, or polymorphisms, in the prion protein gene (PRNP) in various horse breeds could affect the stability of the prion protein. The researchers analysed hundreds of horses and found 3 new PRNP polymorphisms. Through computational tools, they predicted the impact of these new polymorphisms on the horse prion protein and found a possible increase in amyloid propensity due to changes in electrostatic potentials.

Understanding Prion Diseases and Role of the PRNP Gene

  • Prion diseases are fatal neurodegenerative disorders caused by the transformation of the cellular prion protein (PrP) into an abnormal and misfolded form.
  • This alteration of PrP is primarily regulated by the PRNP gene, which encodes for PrP.
  • Any mutation, or variation, in the PRNP gene can therefore change the PrP’s amino acid sequence. This change can affect the transmission efficiency of prion diseases depending on where the mutation occurs.

Horse Resistance to Prion Diseases

  • Horses are typically resistant to prion diseases, and this has prompted researchers to look into the possibility that variations in the PRNP gene may be responsible for this resistance.
  • For the purpose of this study, the researchers analysed 207 horses from 20 different breeds to identify polymorphisms in the PRNP gene.

Findings and Analysis of PRNP Polymorphisms

  • The researchers discovered 3 novel PRNP polymorphisms. To understand their possible impact on the horse prion protein, they used computational modeling tools such as PolyPhen-2, PROVEAN, PANTHER, Meta-SNP, and PredictSNP.
  • They also used a software called AMYCO to measure the propensity of these changes to lead to amyloid aggregation (formation of harmful protein clumps).
  • Analysis of the lack of hydrogen bridges and changes in electrostatic potentials resulting from these variations was performed using the Swiss-PdbViewer software.
  • The prediction from the analyses indicated that the new polymorphisms could potentially increase the likelihood of amyloid aggregation due to changes in the electrostatic potentials of the prion proteins.

Cite This Article

APA
Sola D, Artigas R, Mediano DR, Zaragoza P, Badiola JJ, Martín-Burriel I, Acín C. (2023). Novel polymorphisms in the prion protein gene (PRNP) and stability of the resultant prion protein in different horse breeds. Vet Res, 54(1), 94. https://doi.org/10.1186/s13567-023-01211-8

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 54
Issue: 1
Pages: 94
PII: 94

Researcher Affiliations

Sola, Diego
  • Centro de Encefalopatías Y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragón, 50013, Zaragoza, Spain. diegosola95@unizar.es.
Artigas, Rody
  • Facultad de Veterinaria, Unidad Académica de Genética Y Mejora Animal, Universidad de La República, Ruta 8 Km18, 13000, Montevideo, Uruguay.
Mediano, Diego R
  • Laboratory of Biochemical Genetics (LAGENBIO), Faculty of Veterinary, Institute for Health Research Aragon (IIS Aragón), AgriFood Institute of Aragon (IA2), University of Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain.
Zaragoza, Pilar
  • Laboratory of Biochemical Genetics (LAGENBIO), Faculty of Veterinary, Institute for Health Research Aragon (IIS Aragón), AgriFood Institute of Aragon (IA2), University of Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain.
  • Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, 28029, Madrid, Spain.
Badiola, Juan José
  • Centro de Encefalopatías Y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragón, 50013, Zaragoza, Spain.
Martín-Burriel, Inmaculada
  • Centro de Encefalopatías Y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragón, 50013, Zaragoza, Spain.
  • Laboratory of Biochemical Genetics (LAGENBIO), Faculty of Veterinary, Institute for Health Research Aragon (IIS Aragón), AgriFood Institute of Aragon (IA2), University of Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain.
  • Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, 28029, Madrid, Spain.
Acín, Cristina
  • Centro de Encefalopatías Y Enfermedades Transmisibles Emergentes, Universidad de Zaragoza, IA2, IIS Aragón, 50013, Zaragoza, Spain.

MeSH Terms

  • Animals
  • Amino Acid Sequence
  • Horse Diseases / genetics
  • Horses / genetics
  • Polymorphism, Genetic
  • Prion Diseases / genetics
  • Prion Diseases / veterinary
  • Prion Proteins / genetics
  • Prion Proteins / metabolism
  • Prions / genetics

Grant Funding

  • A19-20R / Government of Aragu00f3n

Conflict of Interest Statement

The authors declare that they have no competing interests.

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