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HLA2024; 103(2); e15387; doi: 10.1111/tan.15387

Diversity of major histocompatibility complex (MHC) and natural killer cell receptor (NKR) genes and their interactions in domestic horses.

Abstract: The immunogenome is the part of the genome that underlies immune mechanisms and evolves under various selective pressures. Two complex regions of the immunogenome, major histocompatibility complex (MHC) and natural killer cell receptor (NKR) genes, play an important role in the response to selective pressures of pathogens. Their importance is expressed by their genetic polymorphism at the molecular level, and their diversity associated with different types of diseases at the population level. Findings of associations between specific combinations of MHC/NKR haplotypes with different diseases in model species suggest that these gene complexes did not evolve independently. No such associations have been described in horses so far. The aim of the study was to detect associations between MHC and NKR gene/microsatellite haplotypes in three horse breed groups (Camargue, African, and Romanian) by statistical methods; chi-square test, Fisher's exact test, Pearson's goodness-of-fit test and logistic regression. Associations were detected for both MHC/NKR genes and microsatellites; the most significant associations were found between the most variable KLRA3 gene and the EQCA-1 or EQCA-2 genes. This finding supports the assumption that the KLRA3 is an important receptor for MHC I and that interactions of these molecules play important roles in the horse immunity and reproduction. Despite some limitations of the study such as low numbers of horses or lack of knowledge of the selected genes functions, the results were consistent across different statistical methods and remained significant even after overconservative Bonferroni corrections. We therefore consider them biologically plausible.
© 2024 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.
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Publication Date: 2024-02-15 PubMed ID: 38358031DOI: 10.1111/tan.15387Google 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.

Overview

  • This study investigates the genetic diversity and interaction of major histocompatibility complex (MHC) and natural killer cell receptor (NKR) genes in domestic horses, aiming to understand how these gene families might co-evolve and influence immunity and reproduction.

Background and Significance

  • The immunogenome encompasses the parts of the genome responsible for immune functions, evolving under pressures from pathogens and environment.
  • Two critical regions in the immunogenome are the MHC and NKR genes, both highly polymorphic and important in pathogen response.
  • Genetic polymorphism in these regions indicates strong selective forces and has been linked to disease susceptibility or resistance in various species.
  • Studies in model organisms have suggested co-evolution or interaction between MHC and NKR gene complexes, influencing immune function, but such associations remain unexplored in horses until now.

Aims of the Study

  • To detect statistical associations between MHC and NKR gene haplotypes in horses.
  • To analyze these associations across three distinct horse breed groups: Camargue, African, and Romanian horses.
  • To examine both gene-based and microsatellite markers to identify patterns of linkage or interaction.

Methodology

  • Sample groups: Three horse populations representing different breeds were selected.
  • Genotyping: Both MHC and NKR gene haplotypes as well as microsatellite markers were typed.
  • Statistical analysis: Multiple statistical tests were employed to validate associations:
    • Chi-square test
    • Fisher’s exact test
    • Pearson’s goodness-of-fit test
    • Logistic regression analysis
  • Correction for multiple testing was applied using the Bonferroni method to control false positives.

Main Findings

  • Significant associations were identified between MHC and NKR gene haplotypes, particularly involving the KLRA3 gene.
  • KLRA3, known for its high variability, showed strong associations with the MHC class I genes EQCA-1 and EQCA-2.
  • This suggests KLRA3 functions as a key receptor interacting with MHC I molecules in horses, analogous to findings in other species.
  • These molecular interactions likely influence immune response mechanisms as well as reproductive processes.
  • The statistical significance persisted across different tests and remained robust after stringent corrections, supporting biological relevance.

Limitations and Considerations

  • Study sample size was relatively small, which can limit the generalizability of the results.
  • Functional roles of some selected genes, including detailed mechanisms of KLRA3, are not fully characterized in horses.
  • Despite these, consistent results from multiple analytic approaches strengthen confidence in findings.

Implications and Future Directions

  • Demonstrates the potential co-evolution and interaction between MHC and NKR genes in horses, a novel finding in this species.
  • Suggests that immune and reproductive fitness in horses may be influenced by specific MHC-NKR gene combinations.
  • Provides a foundation for further functional studies on KLRA3 and other NKR genes in relation to equine immunity and disease resistance.
  • Encourages broader population-level studies with larger cohorts and additional horse breeds.
  • Could inform breeding strategies aimed at enhancing disease resistance and reproductive success through genetic markers.

Cite This Article

APA
Bubenikova J, Plasil M, Futas J, Stejskalova K, Klumplerova M, Oppelt J, Suchentrunk F, Burger PA, Horin P. (2024). Diversity of major histocompatibility complex (MHC) and natural killer cell receptor (NKR) genes and their interactions in domestic horses. HLA, 103(2), e15387. https://doi.org/10.1111/tan.15387

Publication

HLA
ISSN: 2059-2310
NlmUniqueID: 101675570
Country: England
Language: English
Volume: 103
Issue: 2
Pages: e15387

Researcher Affiliations

Bubenikova, Jana
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
Plasil, Martin
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
Futas, Jan
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
Stejskalova, Karla
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czechia.
Klumplerova, Marie
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
Oppelt, Jan
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
Suchentrunk, Franz
  • Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria.
Burger, Pamela A
  • Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Vienna, Austria.
Horin, Petr
  • Research Group Animal Immunogenomics, CEITEC VETUNI, University of Veterinary Sciences Brno, Brno, Czechia.
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czechia.

MeSH Terms

  • Animals
  • Horses / genetics
  • Humans
  • Receptors, Natural Killer Cell / genetics
  • Alleles
  • Major Histocompatibility Complex / genetics
  • Polymorphism, Genetic
  • Breeding

Grant Funding

  • DSP_2022_4 / VETUNI Brno
  • Ceitec/Horin/ITA/2020 / VETUNI Brno

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Citations

This article has been cited 1 times.
  1. Vychodilova L, Plasil M, Futas J, Kopecka A, Molinkova D, Wijacki T, Jahn P, Knoll A, Horin P. Genetic susceptibility to sarcoid in Arabian horses: associations with MHC class II and compound MHC class I/KLRA genotypes. Vet Res Commun 2025 May 1;49(3):184.
    doi: 10.1007/s11259-025-10748-2pubmed: 40310488google scholar: lookup
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