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Home / Equine Research Bank / Vet Med Sci / Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity ...
Veterinary medicine and science2025; 11(2); e70230; doi: 10.1002/vms3.70230

Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds.

Abstract: Toll-like receptors (TLRs) play important roles in innate immunity and developmental processes. Due to their nature as molecular pattern recognition receptors, their genetic diversity may reflect the effects of various pathogen pressures. Here, the extent of variability in the TLR1-6-10 gene cluster in three geographically and historically distinct breeds of horses was analysed. A genetically diverse group of representatives of 14 other horse breeds provided additional information on the variability of this gene cluster in the domestic horse. Altogether, 25 SNPs were identified in the TLR6-1-10 gene cluster across the 4 equine breed groups studied, of which 7 were synonymous and 18 non-synonymous. Twenty-eight inferred SNPs and 22 in silico translated amino acid haplotypes were identified. A predominant major haplotype present in all breed groups along with several group-specific haplotypes were identified. Strong linkage disequilibrium was detected for several SNPs, as well as effects of pervasive, site-specific selection. The existence of a major haplotype suggests it may confer a selective advantage across breeds. Less frequent breed-specific haplotypes may represent variability required or beneficial for responses to local pathogen pressures. Purifying site-specific selection was detected in the TIR domain and its vicinity in TLR6, whereas AA sites under diversifying selection were located in LRR domains and/or their surroundings in TLR1. Population structure models based on immune-related TLR6-1-10 markers did not distinguish between breed groups, whereas in models based on neutral microsatellite markers, breed groups clustered separately. This supports the assumption that the diversity of the TLR6-1-10 cluster is of adaptive value. The TLR6-1-10 alleles and haplotypes identified represent potential candidate markers for disease association studies.
© 2025 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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Publication Date: 2025-02-07 PubMed ID: 39918481DOI: 10.1002/vms3.70230Google 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 research investigates genetic diversity in a cluster of genes related to immune response across different breeds of horses. The findings highlight a common gene variation across all studied breeds and several breed-specific variations, suggesting their pivotal role in adapting to local pathogen pressures.

Investigating Genetic Diversity

  • The study analyses the genetic diversity in a specific group of genes, called the Toll-like receptor (TLR) 1-6-10 cluster, across varying horse breeds. TLRs play a critical role in innate immunity, the body’s first line of defense against pathogens, and developmental processes.
  • The researchers focused on three geographically and historically distinct breeds of horses, as well as a genetically diverse group from 14 other breeds.
  • The study identified 25 single nucleotide polymorphisms (SNPs), or gene variations, in the TLR 1-6-10 cluster across the four groups of horse breeds analysed. Among these, seven causes no change in the resulting protein (synonymous), while 18 cause changes (non-synonymous).
  • The researchers found 28 inferred SNPs and 22 translated amino acid haplotypes, which are unique combinations of alleles for different genes present on one chromosome.

Major and Breed-Specific Haplotypes

  • Analysis suggested a major haplotype common across all studied breed groups and several group-specific haplotypes.
  • These breed-specific haplotypes may represent genetic variations favourable for responding to local pathogen pressures.
  • The existence of a predominant major haplotype suggests that it provides a selective advantage across horse breeds.

Implications of Linkage Disequilibrium and Site-Specific Selection

  • The study also noticed strong linkage disequilibrium for several SNPs, referring to a situation where some combinations of alleles occur more frequently than would be expected under a state of random association.
  • Effects of pervasive, site-specific selection were observed, suggesting that certain genetic variants are selected over time because they confer advantageous traits for survival.
  • A purifying site-specific selection, which favours the survival of one specific allele, was detected in the TIR domain in TLR6.
  • In contrast, certain areas in TLR1 were found under the influence of diversifying or positive selection, a mechanism that encourages genetic diversity within a population.

Potential Candidate Markers for Disease Association Studies

  • The alleles and haplotypes found in the TLR 1-6-10 cluster may serve as potential markers for investigating how genetics are associated with susceptibility or resistance to diseases in horses.
  • The results support the concept that genetic diversity in the TLR 1-6-10 cluster is crucial for adaptive immunity, highlighting its importance in understanding disease resistance and susceptibility across horse breeds.

Cite This Article

APA
Stejskalova K, Vychodilova L, Janova E, Oppelt J, Horin P. (2025). Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds. Vet Med Sci, 11(2), e70230. https://doi.org/10.1002/vms3.70230

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 11
Issue: 2
Pages: e70230

Researcher Affiliations

Stejskalova, Karla
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czech Republic.
Vychodilova, Leona
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czech Republic.
Janova, Eva
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czech Republic.
  • CEITEC VETUNI, RG Animal Immunogenomics, University of Veterinary Sciences Brno, Brno, Czech Republic.
Oppelt, Jan
  • CEITEC VETUNI, RG Animal Immunogenomics, University of Veterinary Sciences Brno, Brno, Czech Republic.
Horin, Petr
  • Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Brno, Czech Republic.
  • CEITEC VETUNI, RG Animal Immunogenomics, University of Veterinary Sciences Brno, Brno, Czech Republic.

MeSH Terms

  • Animals
  • Horses / genetics
  • Immunity, Innate / genetics
  • Haplotypes
  • Genetic Variation
  • Polymorphism, Single Nucleotide
  • Toll-Like Receptors / genetics
  • Toll-Like Receptor 6 / genetics
  • Multigene Family
  • Linkage Disequilibrium

Grant Funding

  • 2021ITA12 / VETUNI

References

This article includes 52 references
  1. Areal H, Abrantes J, Esteves PJ. Signatures of Positive Selection in Toll‐Like Receptor (TLR) Genes in Mammals. BMC Evolutionary Biology 2011;11:368.
    doi: 10.1186/1471-2148-11-368google scholar: lookup
  2. Bagheri M, Zahmatkesh A. Evolution and Species‐Specific Conservation of Toll‐Like Receptors in Terrestrial Vertebrates. International Reviews of Immunology 2018;37(5):217-228.
    doi: 10.1080/08830185.2018.1506780google scholar: lookup
  3. Bayerova Z, Janova E, Matiasovic J, Orlando L, Horin P. Positive Selection in the SLC11A1 Gene in the Family Equidae. Immunogenetics 2016;68(5):353-364.
    doi: 10.1007/s00251-016-0905-2google scholar: lookup
  4. Behzadi P, García-Perdomo HA, Karpiński TM. Toll‐Like Receptors: General Molecular and Structural Biology. Journal of Immunology Research 2021;2021:9914854.
    doi: 10.1155/2021/9914854google scholar: lookup
  5. Bergman I-M, Edman K, Ekdahl KN, Rosengren KJ, Edfors I. Extensive Polymorphism in the Porcine Toll‐Like Receptor 10 Gene. International Journal of Immunogenetics 2012;39(1):68-76.
    doi: 10.1111/j.1744-313x.2011.01057.xgoogle scholar: lookup
  6. Bergman I-M, Rosengren JK, Edman K, Edfors I. European Wild Boars and Domestic Pigs Display Different Polymorphic Patterns in the Toll‐Like Receptor (TLR) 1, TLR2, and TLR6 Genes. Immunogenetics 2010;62(1):49-58.
    doi: 10.1007/s00251-009-0409-4google scholar: lookup
  7. Bielefeldt-Ohmann H, Bosco-Lauth A, Hartwig A-E. Characterization of Non‐Lethal West Nile Virus (WNV) Infection in Horses: Subclinical Pathology and Innate Immune Response. Microbial Pathogenesis 2017;103:71-79.
    doi: 10.1016/j.micpath.2016.12.018google scholar: lookup
  8. Bjørnstad G, Røed KH. Breed Demarcation and Potential for Breed Allocation of Horses Assessed by Microsatellite Markers. Animal Genetics 2001;32(2):59-65.
    doi: 10.1046/j.1365-2052.2001.00705.xgoogle scholar: lookup
  9. Brennan JJ, Gilmore TD. Evolutionary Origins of Toll‐Like Receptor Signaling. Molecular Biology and Evolution 2018;35(7):1576-1587.
    doi: 10.1093/molbev/msy050google scholar: lookup
  10. Bryant CE, Monie TP. Mice, Men and the Relatives: Cross‐Species Studies Underpin Innate Immunity. Open Biology 2012;2(4):120015.
    doi: 10.1098/rsob.120015google scholar: lookup
  11. Cieslak M, Pruvost M, Benecke N. Origin and History of Mitochondrial DNA Lineages in Domestic Horses. PLoS One 2010;5(12):e15311.
    doi: 10.1371/journal.pone.0015311google scholar: lookup
  12. Dannemann M, Andrés AM, Kelso J. Introgression of Neandertal‐ and Denisovan‐Like Haplotypes Contributes to Adaptive Variation in Human Toll‐Like Receptors. American Journal of Human Genetics 2016;98(1):22-33.
    doi: 10.1016/j.ajhg.2015.11.015google scholar: lookup
  13. Darfour-Oduro KA, Megens H-J, Roca AL, Groenen MAM, Schook LB. Adaptive Evolution of Toll‐Like Receptors (TLRs) in the Family Suidae. PLoS One 2015;10(4):e0124069.
    doi: 10.1371/journal.pone.0124069google scholar: lookup
  14. Futas J, Horin P. Natural Killer Cell Receptor Genes in the Family Equidae: Not Only Ly49. PloS One 2013;8(5):e64736.
    doi: 10.1371/journal.pone.0064736google scholar: lookup
  15. Gasteiger G, D'Osualdo A, Schubert DA, Weber A, Bruscia EM, Hartl D. Cellular Innate Immunity: An Old Game With New Players. Journal of Innate Immunity 2017;9(2):111-125.
    doi: 10.1159/000453397google scholar: lookup
  16. Głażewska I. Speculations on the Origin of the Arabian Horse Breed. Livestock Science 2010;129(1):49-55.
    doi: 10.1016/j.livsci.2009.12.009google scholar: lookup
  17. Horín P, Cothran EG, Trtková K. Polymorphism of Old Kladruber Horses, a Surviving but Endangered Baroque Breed. European Journal of Immunogenetics 1998;25(5):357-363.
    doi: 10.1046/j.1365-2370.1998.00117.xgoogle scholar: lookup
  18. Imler J-L, Zheng L. Biology of Toll Receptors: Lessons From Insects and Mammals. Journal of Leukocyte Biology 2004;75(1):18-26.
    doi: 10.1189/jlb.0403160google scholar: lookup
  19. Ishengoma E, Agaba M. Evolution of Toll‐Like Receptors in the Context of Terrestrial Ungulates and Cetaceans Diversification. BMC Evolutionary Biology 2017;17(1):54.
    doi: 10.1186/s12862-017-0901-7google scholar: lookup
  20. Janova E, Futas J, Klumplerova M. Genetic Diversity and Conservation in a Small Endangered Horse Population. Journal of Applied Genetics 2013;54(3):285-292.
    doi: 10.1007/s13353-013-0151-3google scholar: lookup
  21. Johnson CM, Lyle EA, Omueti KO. Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects Against Leprosy. Journal of Immunology 2007;178(12):7520-7524.
    doi: 10.4049/jimmunol.178.12.7520google scholar: lookup
  22. Kawai T, Akira S. Toll‐Like Receptors and Their Crosstalk With Other Innate Receptors in Infection and Immunity. Immunity 2011;34(5):637-650.
    doi: 10.1016/j.immuni.2011.05.006google scholar: lookup
  23. Klumplerova M, Splichalova P, Oppelt J. Genetic Diversity, Evolution and Selection in the Major Histocompatibility Complex DRB and DQB Loci in the Family Equidae. BMC Genomics 2020;21:677.
    doi: 10.1186/s12864-020-07089-6google scholar: lookup
  24. Kopelman NM, Mayzel J, Jakobsson M, Rosenberg NA, Mayrose I. CLUMPAK: A Program for Identifying Clustering Modes and Packaging Population Structure Inferences Across K. Molecular Ecology Resources 2015;15(5):1179-1191.
    doi: 10.1111/1755-0998.12387google scholar: lookup
  25. Kruithof EKO, Satta N, Liu JW, Dunoyer-Geindre S, Fish RJ. Gene Conversion Limits Divergence of Mammalian TLR1 and TLR6. BMC Evolutionary Biology 2007;7:148.
    doi: 10.1186/1471-2148-7-148google scholar: lookup
  26. Kumar V. Toll‐Like Receptors in Adaptive Immunity. Toll-like Receptors in Health and Disease: Handbook of Experimental Pharmacology 2022:95-131.
    doi: 10.1007/164_2021_543google scholar: lookup
  27. Lazarus R, Raby BA, Lange C. TOLL‐Like Receptor 10 Genetic Variation Is Associated With Asthma in Two Independent Samples. American Journal of Respiratory and Critical Care Medicine 2004;170(6):594-600.
    doi: 10.1164/rccm.200404-491ocgoogle scholar: lookup
  28. Lee S, Cho G. Parentage Testing of Thoroughbred Horse in Korea Using Microsatellite DNA Typing. Journal of Veterinary Science 2006;7(1):63-67.
    doi: 10.4142/jvs.2006.7.1.63google scholar: lookup
  29. Lindsay SA, Wasserman SA. Conventional and Non‐Conventional Drosophila Toll Signaling. Developmental and Comparative Immunology 2014;42(1):16-24.
    doi: 10.1016/j.dci.2013.04.011google scholar: lookup
  30. Liu G, Zhang H, Zhao C, Zhang H. Evolutionary History of the Toll‐Like Receptor Gene Family Across Vertebrates. Genome Biology and Evolution 2020;12(1):3615-3634.
    doi: 10.1093/gbe/evz266google scholar: lookup
  31. Ma X, Yuhua L, Gowen BB, Graviss EA, Clark AG, Musser JM. Full‐Exon Resequencing Reveals Toll‐Like Receptor Variants Contribute to Human Susceptibility to Tuberculosis Disease. PLoS One 2007;2(12):e1318.
    doi: 10.1371/journal.pone.0001318google scholar: lookup
  32. Meyer CG, Reiling N, Ehmen C. TLR1 Variant H305L Associated With Protection From Pulmonary Tuberculosis. PLoS One 2016;11(5):e0156046.
    doi: 10.1371/journal.pone.0156046google scholar: lookup
  33. Mukherjee S, Huda S, Sinha Babu SP. Toll‐Like Receptor Polymorphism in Host Immune Response to Infectious Diseases: A Review. Scandinavian Journal of Immunology 2019;90(1):e12771.
    doi: 10.1111/sji.12771google scholar: lookup
  34. Opsal MA, Våge DI, Hayes B, Berget I, Lien S. Genomic Organization and Transcript Profiling of the Bovine Toll‐Like Receptor Gene Cluster TLR6‐TLR1‐TLR10. Gene 2006;384:45-50.
    doi: 10.1016/j.gene.2006.06.027google scholar: lookup
  35. Parker HG, Kim LV, Sutter NB. Genetic Structure of the Purebred Domestic Dog. Science 2004;304(5674):1160-1164.
    doi: 10.1126/science.1097406google scholar: lookup
  36. Peakall R, Smouse PE. GenAlEx 6.5: Genetic Analysis in Excel. Population Genetic Software for Teaching and Research—An Update. Bioinformatics 2012;28(19):2537-2539.
    doi: 10.1093/bioinformatics/bts460google scholar: lookup
  37. Pérez-González J, Carranza J, Anaya G. Comparative Analysis of Microsatellite and SNP Markers for Genetic Management of Red Deer. Animals 2023;13(21):3374.
    doi: 10.3390/ani13213374google scholar: lookup
  38. Pritchard JK, Stephens M, Donnelly P. Inference of Population Structure Using Multilocus Genotype Data. Genetics 2000;155(2):945-959.
    doi: 10.1093/genetics/155.2.945google scholar: lookup
  39. Rahal O, Aissaoui C, Ata N. Genetic Characterization of Four Algerian Cattle Breeds Using Microsatellite Markers. Animal Biotechnology 2021;32(6):699-707.
    doi: 10.1080/10495398.2020.1746321google scholar: lookup
  40. Roach JC, Glusman G, Rowen L. The Evolution of Vertebrate Toll‐Like Receptors. Proceedings of the National Academy of Sciences of the United States of America 2005;102(27):9577-9582.
    doi: 10.1073/pnas.0502272102google scholar: lookup
  41. Rodrigues CR, Balachandran Y, Aulakh GK, Singh B. TLR10: An Intriguing Toll‐Like Receptor With Many Unanswered Questions. Journal of Innate Immunity 2024;16(1):96-104.
    doi: 10.1159/000535523google scholar: lookup
  42. Schierup MH, Vekemans X, Charlesworth D. The Effect of Subdivision on Variation at Multi‐Allelic Loci Under Balancing Selection. Genetical Research 2000;76(1):51-62.
    doi: 10.1017/s0016672300004535google scholar: lookup
  43. Seabury CM, Cargill EJ, Womack JE. Sequence Variability and Protein Domain Architectures for Bovine Toll‐Like Receptors 1, 5, and 10. Genomics 2007;90(4):502-515.
    doi: 10.1016/j.ygeno.2007.07.001google scholar: lookup
  44. Stejskalova K, Cvanova M, Oppelt J. Genetic Susceptibility to West Nile Virus Infection in Camargue Horses. Research in Veterinary Science 2019;124:284-292.
    doi: 10.1016/j.rvsc.2019.04.004google scholar: lookup
  45. Stejskalova K, Janova E, Horecky C. Associations Between the Presence of Specific Antibodies to the West Nile Virus Infection and Candidate Genes in Romanian Horses From the Danube Delta. Molecular Biology Reports 2019;46(4):4453-4461.
    doi: 10.1007/s11033-019-04900-wgoogle scholar: lookup
  46. Stejskalova K, Janova E, Splichalova P. Twelve Toll‐Like Receptor (TLR) Genes in the Family Equidae—Comparative Genomics, Selection and Evolution. Veterinary Research Communications 2023;48:725-741.
    doi: 10.1007/s11259-023-10245-4google scholar: lookup
  47. Stevens VL, Hsing AW, Talbot JT. Genetic Variation in the Toll‐Like Receptor Gene Cluster (TLR10‐TLR1‐TLR6) and Prostate Cancer Risk. International Journal of Cancer 2008;123(11):2644-2650.
    doi: 10.1002/ijc.23826google scholar: lookup
  48. Uddin MJ, Suen WW, Bosco-Lauth A. Kinetics of the West Nile Virus Induced Transcripts of Selected Cytokines and Toll‐Like Receptors in Equine Peripheral Blood Mononuclear Cells. Veterinary Research 2016;47:61.
    doi: 10.1186/s13567-016-0347-8google scholar: lookup
  49. Veltkamp M, van Moorsel CHM, Rijkers GT, Ruven HJT, Grutters JC. Genetic Variation in the Toll‐Like Receptor Gene Cluster (TLR10‐TLR1‐TLR6) Influences Disease Course in Sarcoidosis. Tissue Antigens 2012;79(1):25-32.
    doi: 10.1111/j.1399-0039.2011.01808.xgoogle scholar: lookup
  50. Vijay K. Toll‐Like Receptors in Immunity and Inflammatory Diseases: Past, Present, and Future. International Immunopharmacology 2018;59:391-412.
    doi: 10.1016/j.intimp.2018.03.002google scholar: lookup
  51. Vychodilova L, Matiasovic J, Bobrova O. Immunogenomic Analysis of Insect Bite Hypersensitivity in a Model Horse Population. Veterinary Immunology and Immunopathology 2013;152(3):260-268.
    doi: 10.1016/j.vetimm.2012.12.013google scholar: lookup
  52. Weaver S, Shank SD, Spielman SJ, Li M, Muse SV, Kosakovsky Pond SL. Datamonkey 2.0: A Modern Web Application for Characterizing Selective and Other Evolutionary Processes. Molecular Biology and Evolution 2018;35(3):773-777.
    doi: 10.1093/molbev/msx335google scholar: lookup

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