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Home / Equine Research Bank / Genes (Basel) / Absence of Strong Genetic Linkage Disequilibrium between Sin...
Genes2020; 11(5); 518; doi: 10.3390/genes11050518

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.

Abstract: Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrP). 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 () have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between and prion-like protein gene () 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 gene and measured the LD values between the and SNPs and the impact of a nonsynonymous SNP found in the horse gene. To identify SNPs in the gene, we performed direct sequencing of the gene. In addition, to assess whether the weak LD value between the and SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the and SNPs using D' and 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 and 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.
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Publication Date: 2020-05-07 PubMed ID: 32392732PubMed Central: PMC7290373DOI: 10.3390/genes11050518Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 research investigates the relationship between certain gene variations in horses, a species known to resist prion disease, and the absence of this fatal neurodegenerative disorder. The study suggests that a weak genetic linkage between the prion protein gene and the prion-like protein gene could be a characteristic of animals resistant to the disease.

Prion Disease and Horses

  • The study focuses on prion disease, a fatal condition affecting the brain. Prion disease is caused by detrimental mutations of the prion protein gene. Significantly, it has not been reported in horses despite other animal species suceptibility during outbreaks of transmissible spongiform encephalopathies (TSEs).
  • The study sought to explore potential reasons why horses are resistant to prion diseases, considering genetic factors in this investigation.

Single Nucleotide Polymorphisms (SNP) and Genetic Linkage

  • The research predominantly focuses on Single Nucleotide Polymorphisms (SNPs), which are variations within DNA sequences. Previous research has shown a strong correlation between SNPs in both the prion protein gene (PRNP) and the prion-like protein gene (PRND) in species susceptible to prion disease.
  • Conversely, weak genetic ties (or linkage disequilibrium, LD) have been found in dogs, a species that is also resistant to prion disease. This suggests a potential correlation between weak LD and resilience to prion diseases.

Research Approach and Findings

  • The research team investigated SNPs in the PRNP gene in horses and measured the LD values between the PRNP and PRND SNPs.
  • The study found two new SNPs (c.331G > A (A111T) and c.411G > C) within the PRNP gene, with varying genotype and allele frequencies among horse breeds. In total, three haplotypes (GG, AG, and GC), combinations of alleles or genetic markers on a chromosome, were discovered.
  • A non-synonymous SNP (A111T) was identified in the Doppel protein (a protein similar to the PrP), however, it was predicted to be benign, implying it doesn’t have a harmful effect.
  • Crucially, a weak LD value was found between the PRNP and PRND SNPs in horses, consistent with findings in dogs and further suggesting a correlation between weak LD and resistance to prion diseases.

Conclusions

  • The presence of a weak LD between the PRNP and PRND genes in horses, a known prion disease-resistant species, supports the theory that weak LD could be a feature in prion disease-resistant animals.
  • This discovery broadens our understanding of genetic factors influencing prion disease resistance, potentially aiding future research and treatment approaches for this neurodegenerative disease across species.

Cite This Article

APA
Won SY, Kim YC, Do K, Jeong BH. (2020). 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 (Basel), 11(5), 518. https://doi.org/10.3390/genes11050518

Publication

Genes
ISSN: 2073-4425
NlmUniqueID: 101551097
Country: Switzerland
Language: English
Volume: 11
Issue: 5
PII: 518

Researcher Affiliations

Won, Sae-Young
  • Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
  • Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
Kim, Yong-Chan
  • Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
  • Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
Do, Kyoungtag
  • Lab of Equine Science, Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju 63243, Korea.
Jeong, Byung-Hoon
  • Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
  • Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.

MeSH Terms

  • Alleles
  • Animals
  • Chromosome Mapping
  • Disease Resistance / genetics
  • GPI-Linked Proteins / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes / genetics
  • Horse Diseases / genetics
  • Horses / classification
  • Horses / genetics
  • Linkage Disequilibrium
  • Mammals / genetics
  • Polymorphism, Single Nucleotide
  • Prion Diseases / genetics
  • Prion Diseases / veterinary
  • Prions / genetics
  • Species Specificity

Conflict of Interest Statement

The authors declare no conflict of interest, financial or otherwise.

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Citations

This article has been cited 3 times.
  1. Yang M, Zhang HX, Geng GJ, Wang FJ, Liu CW, Liu JL. Artificial Selection Drives SNPs of Olfactory Receptor Genes into Different Working Traits in Labrador Retrievers.. Genet Res (Camb) 2022;2022:8319396.
    doi: 10.1155/2022/8319396pubmed: 35185392google scholar: lookup
  2. 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).
    doi: 10.3390/ani11092574pubmed: 34573540google scholar: lookup
  3. 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).
    doi: 10.3390/genes12010013pubmed: 33374431google scholar: lookup
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