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Home / Equine Research Bank / HLA / Complex variation in the KLRA (LY49) immunity-related genomi...
HLA2020; 96(3); 257-267; doi: 10.1111/tan.13939

Complex variation in the KLRA (LY49) immunity-related genomic region in horses.

Abstract: Natural killer (NK) cells play important roles in innate and adaptive immunity, as well as in the reproduction of placental mammals. Ly49 (KLRA) molecules represent a lectin-like type of NK cell receptor encoded within a complex genomic region, the NK cell complex. In rodents and horses, an expansion of the genes encoding Ly49 receptors leading to the formation of a gene family was observed. High sequence similarities and frequent high polymorphism of multiple family members represent an obstacle both for their individual identification and for annotation in the reference genomes of their respective species. Here, we focused on resolving complex variation of the KLRA gene family observed in domestic and Przewalski's horses. The KLRA (LY49) genomic region contains six genes (KLRA2-KLRA7) and one putative pseudogene, KLRA1. Two types of polymorphism were observed in the horses analyzed. Copy number variation between haplotypes was documented for the gene KLRA7 by polymerase chain reaction. As expected, the major source of variation of all KLRA genes, including KLRA7, is because of single nucleotide polymorphisms, many of them being nonsynonymous substitutions. Extensive allelic variability of the expanded KLRA (LY49) genes was observed. For four out of the six functional KLRA, high numbers of novel allelic amino acid sequence variants were identified in the genes studied, suggesting that this variation might be of functional importance, especially in the context of high polymorphism of their presumed ligands encoded by major histocompatibility complex class I genes. In fact, polymorphic amino acid sites were mostly found in the ligand-binding C-type lectin-like domain of the putative receptor molecule.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Publication Date: 2020-07-02 PubMed ID: 32421927DOI: 10.1111/tan.13939Google 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.

This research explores the complex variation in a particular gene region (KLRA or LY49) associated with natural killer (NK) cell function in horses. The findings reveal notable polymorphism in these genes, potentially contributing to the diversity of adaptive immune responses in these animals.

Introduction

  • Natural Killer (NK) cells are a critical part of both innate and adaptive immune responses and also play a role in the reproduction of placental mammals.
  • This study focuses on a specific set of NK cell receptors known as Ly49 or KLRA molecules, encoded within a complex genomic region called the NK cell complex.
  • In certain animals like rodents and horses, there is a gene family expansion of the genes encoding these Ly49 receptors. However, studying this gene family is challenging due to high sequence similarities and frequent polymorphism.

Focus of the Study

  • The researchers concentrated on the complex variation of the KLRA gene family in domestic and Przewalski’s horses, focusing particularly on six genes (KLRA2-KLRA7) and one potential pseudogene, KLRA1.
  • Two main types of polymorphisms were observed: Copy number variation (changes in the number of copies of particular genes) detected in KLRA7 and single nucleotide polymorphisms (changes in the DNA sequence at particular spots) appearing in all KLRA genes.

Results of the Study

  • Extensive allelic variation was detected in the expanded KLRA (LY49) genes. Greater numbers of novel allelic amino acid sequence variants were identified in four out of the six functional KLRA genes.
  • The researchers suggest that this wide-ranging variation might influence the NK cell function, especially given the high polymorphism of their anticipated ligands, encoded by major histocompatibility complex class I genes.
  • Polymorphic amino acid sites were mostly found in the ligand-binding C-type lectin-like domain, which is part of the presumed receptor molecule.

Conclusions

  • The research unravels an intricate pattern of genetic variation in part of the horse’s immune system, with potential implications for the diversity and flexibility of their immune responses.
  • This study can serve as a basis for further investigation into the functional importance of these variations and their impact on NK cell activity and disease resistance in horses.

Cite This Article

APA
Futas J, Oppelt J, Janova E, Musilova P, Horin P. (2020). Complex variation in the KLRA (LY49) immunity-related genomic region in horses. HLA, 96(3), 257-267. https://doi.org/10.1111/tan.13939

Publication

HLA
ISSN: 2059-2310
NlmUniqueID: 101675570
Country: England
Language: English
Volume: 96
Issue: 3
Pages: 257-267

Researcher Affiliations

Futas, Jan
  • RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic.
Oppelt, Jan
  • RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.
Janova, Eva
  • RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic.
Musilova, Petra
  • RG Cytogenomics, Central European Institute of Technology (CEITEC)-Veterinary Research Institute, Brno, Czech Republic.
Horin, Petr
  • RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic.

MeSH Terms

  • Alleles
  • Animals
  • DNA Copy Number Variations
  • Female
  • Genomics
  • Horses
  • Killer Cells, Natural
  • Placenta
  • Pregnancy
  • Receptors, NK Cell Lectin-Like

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Citations

This article has been cited 4 times.
  1. Jaworska J, de Mestre AM, Wiśniewska J, Wagner B, Nowicki A, Kowalczyk-Zięba I, Wocławek-Potocka I. Populations of NK Cells and Regulatory T Cells in the Endometrium of Cycling Mares-A Preliminary Study. Animals (Basel) 2022 Nov 30;12(23).
    doi: 10.3390/ani12233373pubmed: 36496894google scholar: lookup
  2. Dornburg A, Mallik R, Wang Z, Bernal MA, Thompson B, Bruford EA, Nebert DW, Vasiliou V, Yohe LR, Yoder JA, Townsend JP. Placing human gene families into their evolutionary context. Hum Genomics 2022 Nov 11;16(1):56.
    doi: 10.1186/s40246-022-00429-5pubmed: 36369063google scholar: lookup
  3. Antczak DF, Allen WRT. Placentation in Equids. Adv Anat Embryol Cell Biol 2021;234:91-128.
    doi: 10.1007/978-3-030-77360-1_6pubmed: 34694479google scholar: lookup
  4. 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.
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