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Physiological reports2018; 6(10); e13700; doi: 10.14814/phy2.13700

A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses.

Abstract: The Swedish-Norwegian Coldblooded trotter and the heavier North-Swedish draught horse both descend from the North-Swedish horse, but the Coldblooded trotters have been selected for racing performance while the North-Swedish draught horse is mainly used for agricultural and forestry work. By comparing the genomes of Coldblooded trotters, North-Swedish draught horses and Standardbreds for a large number of single-nucleotide polymorphisms (SNPs), the aim of the study was to identify genetic regions that may be under selection for racing performance. We hypothesized that the selection for racing performance, in combination with unauthorized crossbreeding of Coldblooded trotters and Standardbreds, has created regions in the genome where the Coldblooded trotters and Standardbreds are similar, but differ from the North-Swedish draught horse. A fixation index (Fst) analysis was performed and sliding window Delta Fst values were calculated across the three breeds. Five windows, where the average Fst between Coldblooded trotters and Standardbreds was low and the average Fst between Coldblooded trotters and North-Swedish draught horses was high, were selected for further investigation. Associations between the most highly ranked SNPs and harness racing performance were analyzed in 400 raced Coldblooded trotters with race records. One SNP showed a significant association with racing performance, with the CC genotype appearing to be negatively associated. The SNP identified was genotyped in 1915 horses of 18 different breeds. The frequency of the TT genotype was high in breeds typically used for racing and show jumping while the frequency of the CC genotype was high in most pony breeds and draught horses. The closest gene in this region was the Endothelin3 gene (EDN3), a gene mainly involved in melanocyte and enteric neuron development. Both functional genetic and physiological studies are needed to fully understand the possible impacts of the gene on racing performance.
© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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Publication Date: 2018-05-31 PubMed ID: 29845762PubMed Central: PMC5974718DOI: 10.14814/phy2.13700Google Scholar: Lookup
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  • Journal Article
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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 factors influencing racing performance and coat color variation in horses, focusing specifically on the Endothelin3 gene (EDN3).

Understanding the Study

The principal objective of this research study was to pinpoint genetic variances that have been acquired through selective breeding for harness racing performance. In this context, the research studied three breeds of horses:

  • The Swedish-Norwegian Coldblooded trotter – a breed selected for racing performance
  • The North-Swedish draught horse – primarily used for agricultural/forestry work and considered close to the ancestral gene pool
  • The Standardbreds – used for harness racing, like the Coldblooded trotters

The researchers scanned the genomes of these horse breeds to identify single-nucleotide polymorphisms (SNPs) – variations at a single position in a DNA sequence among individuals. They anticipated that genetic selection towards racing aptitude, coupled with unauthorized crossbreeding between Coldblooded trotters and Standardbreds, might have resulted in specific gene regions in which these two breeds are similar, differing from the North-Swedish draught horse.

Methods and Analysis

At the core of their approach was the fixation index (Fst) analysis. This method calculates the difference between genetic diversity within a species and genetic diversity across different species. The study generated ‘sliding window Delta Fst values’ to identify areas of the genome where variation was most significant across breeds. They eventually selected five windows, characterized by both low Fst values between Coldblooded trotters and Standardbreds (indicating shared genes likely due to racing selection or crossbreeding) and high Fst values between Coldblooded trotters and North-Swedish draught horses (indicating genetic difference).

Findings of the Study

A subsequent analysis linked one of the top-ranked SNPs with racing performance in a tested group of 400 raced Coldblooded trotters. The CC genotype of this SNP was found to have a negative association with racing performance. When this SNP was observed in a larger group of 1915 horses from 18 breeds, they found that high-performance breeds (used for racing and show jumping) typically had the TT genotype, while lower-performance breeds (ponies and draught horses) frequently had the CC genotype.

Interestingly, the gene proximate to this performance-related SNP was the EDN3, mainly involved in melanocyte (cells responsible for pigmentation) and enteric neuron (neurons governing gut function) development, suggesting it may influence both performance and coat color. However, the exact influence of the EDN3 gene on racing performance remains to be clarified through in-depth functional genetic and physiological studies.

Cite This Article

APA
Jäderkvist Fegraeus K, Velie BD, Axelsson J, Ang R, Hamilton NA, Andersson L, Meadows JRS, Lindgren G. (2018). A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses. Physiol Rep, 6(10), e13700. https://doi.org/10.14814/phy2.13700

Publication

Physiological reports
ISSN: 2051-817X
NlmUniqueID: 101607800
Country: United States
Language: English
Volume: 6
Issue: 10
Pages: e13700

Researcher Affiliations

Jäderkvist Fegraeus, Kim
  • Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Velie, Brandon D
  • Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Axelsson, Jeanette
  • Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ang, Rachel
  • Faculty of Science, University of Sydney, Sydney, Australia.
Hamilton, Natasha A
  • Faculty of Science, University of Sydney, Sydney, Australia.
Andersson, Leif
  • Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
Meadows, Jennifer R S
  • Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Lindgren, Gabriella
  • Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Animals
  • Endothelin-3 / genetics
  • Female
  • Gene Frequency
  • Haplotypes
  • Horses / genetics
  • Male
  • Norway
  • Polymorphism, Single Nucleotide
  • Regulatory Sequences, Nucleic Acid
  • Running
  • Selective Breeding
  • Sweden

References

This article includes 41 references
  1. Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.. Nature 488:642–646.
    pmc: PMC3523687pubmed: 22932389
  2. Árnason T. The importance of different traits in genetic improvement of trotters.. Proceedings of World Congress on Genetics Applied to Livestock Production University of Guelph, Guelph, Canada. August 7‐12, 17: 462‐469.
  3. Árnason T. Trends and asymptotic limits for racing speed in Standardbred trotters.. Livest. Prod. Sci. 72:135–145.
  4. Árnason T, Bendroth M, Philipsson J, Henriksson K, Darenius A. Genetic evaluations of Swedish trotters.. State of breeding evaluation in trotters. Proceedings of the European Federation of Animal Science symposium of the Commission on horse production Pp. 106–129, 1 July 1989, Helsinki, Finland. European Federation of Animal Science publication no. 42. Pudoc, Wageningen, The Netherlands.
  5. Baynash AG, Hosoda K, Giaid A, Richardsson JA, Emoto N, Hammer RE. Interaction of endothelin‐3 with endothelin‐B receptor is essential for development of epidermal melanocytes and enteric neurons.. Cell 79:1277–1285.
    pubmed: 8001160
  6. Benamou AE, Art T, Marlin DJ, Roberts CA, Lekeux P. Variations in systemic and pulmonary endothelin‐1 in horses with recurrent airway obstruction (heaves).. Pulm. Pharmacol. Ther. 11:231–235.
    pubmed: 9918762
  7. Binns MM, Boehler DA, Lambert DH. Identification of the Myostatin locus (MSTN) as having a major effect on optimum racing distance in the Thoroughbred horse in the USA.. Anim. Genet. 41:154–158.
    pubmed: 21070290
  8. Bohlin O, Rönningen K. Inbreeding and relationship within the North‐Swedish horse.. Acta Agric. Scand. 25:121–125.
  9. Brown AHD. The estimation of Wright′s fixation index from genotypic frequencies.. Genetica 41:399–406.
    pubmed: 5488990
  10. Edery P, Attié T, Amiel J, Pelet A, Eng C, Hofstra RMW. Mutation of the endothelin‐3 gene in the Waardenburg disease (shah‐Waardenburg syndrome).. Nat. Genet. 12:442–444.
    pubmed: 8630502
  11. Evans DL. Physiology of equine performance and associated tests of function.. Equine Vet. J. 39:373–383.
    pubmed: 17722733
  12. Gu J, Orr N, Park SD, Katz LM, Sulimova G, MacHugh DE. A genome scan for positive selection in Thoroughbred horses.. PLoS ONE 4:e5767.
    doi: 10.1371/journal.pone.0005767pmc: PMC2685479pubmed: 19503617google scholar: lookup
  13. Gu J, MacHugh DE, McGivney BA, Park SDE, Katz LM, Hill EW. Association of sequence variants in CKM (creatine kinase muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses.. Equine Vet. J. 42:569–575.
    pubmed: 21059062
  14. Hill EW, Gu J, Eivers SS, Fonseca RG, McGivney BA, Govindarajan P. A Sequence Polymorphism in MSTN Predicts Sprinting Ability and Racing Stamina in Thoroughbred Horses.. PLoS ONE 5:e8645.
    doi: 10.1371/journal.pone.0008645pmc: PMC2808334pubmed: 20098749google scholar: lookup
  15. Hill EW, Gu J, McGivney BA, MacHugh DE. Targets of selection in the Thoroughbred genome contain exercise‐relevant gene SNPs associated with elite racecourse performance.. Anim. Genet. 41:56–63.
    pubmed: 21070277
  16. Hofstra RMW, Osinga J, Tan‐Sindhunata G, Wu Y, Kamsteeg EJ, Stulp RP. A homozygous mutation in the endothelin‐3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah‐Waardenburg syndrome).. Nat. Genet. 12:445–447.
    pubmed: 8630503
  17. Hosoda K, Hammer RE, Richardsson JA, Baynash AG, Cheung JC, Giaid A. Targeted and natural (piebald‐lethal) mutations of Endothelin‐B receptor gene produce megacolon associated with spotted coat color in mice.. Cell 79:1267–1276.
    pubmed: 8001159
  18. Inoue A, Yanagisawa M, Kimula S, Kasuya Y, Miyauchi T, Goto K. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.. Proc. Natl Acad. Sci. USA 86:2863–2867.
    pmc: PMC287019pubmed: 2649896
  19. International Consortium for Blood Pressure Genome‐Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.. Nature 478:103–109.
    pmc: PMC3340926pubmed: 21909115
  20. Jäderkvist Fegraeus K, Lawrence C, Petäjistö K, Johansson MK, Wiklund M, Olsson C. Lack of significant associations with early career performance suggest no link between the DMRT3 “Gait Keeper” mutation and precocity in Coldblooded trotters.. PLoS ONE 12: e0177351.
    doi: 10.1371/journal.pone.0177351pmc: PMC5425215pubmed: 28489879google scholar: lookup
  21. Jäderkvist K, Andersson LS, Johansson AM, Árnason T, Mikko S, Eriksson S. The DMRT3 ‘Gait keeper’ mutation affects performance of Nordic and Standardbred trotters.. J. Anim. Sci. 92:4279–4286.
    pubmed: 25085403
  22. Kusafuka T, Wang Y, Puri P. Mutation analysis of the RET, the Endothelin‐B receptor and the Endothelin‐3 genes in sporadic cases of Hirschsprung′s disease.. J. Pediatr. Surg. 32:501–504.
    pubmed: 9094028
  23. Lee HO, Levorse JM, Shin MK. The endothelin receptor‐B is required for the migration of neural crest‐derived melanocyte and enteric neuron precursors.. Dev. Biol. 259:162–175.
    pubmed: 12812796
  24. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A. Genome‐wide association study of blood pressure and hypertension.. Nat. Genet. 41:677–687.
    pmc: PMC2998712pubmed: 19430479
  25. McKeever KH, Antas LA, Kearns CF. Endothelin response during and after exercise in horses.. Vet. J. 164:38–46.
    pubmed: 12359483
  26. Metallinos DL, Bowling AT, Rine J. A missense mutation in the endothelin‐B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung Disease.. Mamm. Genome 9:426–431.
    pubmed: 9585428
  27. Puffenberger EG, Hosoda K, Washington SS, Nakao K, deWit D, Yanagisawa M. A missense mutation of the endothelin‐B receptor gene in multigenic Hirschprung′s disease.. Cell 79:1257–1266.
    pubmed: 8001158
  28. Purcell S, Neale B, Todd‐Brown K, Thomas L, Ferreira MAR, Bender D. PLINK: a toolset for whole‐genome association and population‐based linkage analysis.. Am. J. Hum. Genet. 81:559–575.
    pmc: PMC1950838pubmed: 17701901
  29. R Development Core Team. R: a language and environment for statistical computing.. R Foundation for Statistical Computing, Vienna, Austria Available at http://www.r-project.org/(accessed 01 February 2018).
  30. Santschi EM, Purdy AK, Valberg SJ, Vrotsos PD, Kaese H, Mickelson JR. Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.. Mamm. Genome 9:306–309.
    pubmed: 9530628
  31. Schröder W, Klostermann A, Distl O. Candidate genes for physical performance in the horse.. Vet. J. 190:39–48.
    pubmed: 21115378
  32. Sinnwell JP, Schaid DJ. Haplo. stats: statistical analysis of haplotypes with traits and covariates when linkage phase is ambiguous. R package version 1.7.7.. Available at http://www.mayo.edu/research/labs/statistical-genetics-genetic-epidemiology/software (accessed 01 February 2018).
  33. Sponenberg DP. Mealy: definition and classification. Equine color genetics Pp. 32–35, 3rd ed. Wiley‐Blackwell, Hobeken, NJ.
  34. Stanchina L, Baral V, Robert F, Pingault V, Lemort N, Pachnis V. Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development.. Dev. Biol. 295:232–249.
    pubmed: 16650841
  35. Thiruvenkadan AK, Kandasamy N, Panneerselvam S. Inheritance of racing performance of trotter horses: an overview.. Livest Sci. 124:163–181.
  36. Thomas KC, Hamilton NA, North KN, Houweling PJ. Sequence analysis of the equine ACTN3 gene in Australian horse breeds.. Gene 538:88–93.
    pubmed: 24440781
  37. nValutan. 9999. Available at https://www.valuta.se (accessed 04 June 2016).
  38. Velie BD, Shrestha M, François L, Schurink A, Tesfayonas YG, Stinckens A. Using an inbred horse breed in a high density genome‐wide scan for genetic risk factors of insect bite hypersensitivity (IBH).. PLoS ONE 11:e0152966.
    doi: 10.1371/journal.pone.0152966pmc: PMC4829256pubmed: 27070818google scholar: lookup
  39. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 326:865–867.
    pmc: PMC3785132pubmed: 19892987
  40. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y. A novel potent vasoconstrictor peptide produced by vascular endothelial cells.. Nature 332:411–415.
    pubmed: 2451132
  41. Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D. A dinucleotide mutation in the endothelin‐B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease (HSCR).. Hum. Mol. Genet. 7:1047–1052.
    pubmed: 9580670

Citations

This article has been cited 11 times.
  1. Ding W, Gong W, Bou T, Shi L, Lin Y, Shi X, Li Z, Wu H, Dugarjaviin M, Bai D. Whole-Genome Resequencing Analysis of Athletic Traits in Grassland-Thoroughbred. Animals (Basel) 2025 Aug 7;15(15).
    doi: 10.3390/ani15152323pubmed: 40805113google scholar: lookup
  2. Sigurðardóttir H, Ablondi M, Kristjansson T, Lindgren G, Eriksson S. Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies. BMC Genomics 2024 Aug 8;25(1):772.
    doi: 10.1186/s12864-024-10682-8pubmed: 39118059google scholar: lookup
  3. Fegraeus K, Rosengren MK, Naboulsi R, Orlando L, Åbrink M, Jouni A, Velie BD, Raine A, Egner B, Mattsson CM, Lång K, Zhigulev A, Björck HM, Franco-Cereceda A, Eriksson P, Andersson G, Sahlén P, Meadows JRS, Lindgren G. An endothelial regulatory module links blood pressure regulation with elite athletic performance. PLoS Genet 2024 Jun;20(6):e1011285.
    doi: 10.1371/journal.pgen.1011285pubmed: 38885195google scholar: lookup
  4. Perdomo-González DI, García de Paredes RLA, Valera M, Bartolomé E, Gómez MD. Morpho-Functional Traits in Pura Raza Menorquina Horses: Genetic Parameters and Relationship with Coat Color Variables. Animals (Basel) 2022 Sep 7;12(18).
    doi: 10.3390/ani12182319pubmed: 36139184google scholar: lookup
  5. Ricard A, Duluard A. Genomic analysis of gaits and racing performance of the French trotter. J Anim Breed Genet 2021 Mar;138(2):204-222.
    doi: 10.1111/jbg.12526pubmed: 33249655google scholar: lookup
  6. Silva ILS, Junqueira GSB, Oliveira CAA, Costa RB, DE Camargo GMF. Inconsistencies in horse coat color registration: A case study. J Equine Sci 2020 Oct;31(3):57-60.
    doi: 10.1294/jes.31.57pubmed: 33061785google scholar: lookup
  7. Li D, Sun G, Zhang M, Cao Y, Zhang C, Fu Y, Li F, Li G, Jiang R, Han R, Li Z, Wang Y, Tian Y, Liu X, Li W, Kang X. Breeding history and candidate genes responsible for black skin of Xichuan black-bone chicken. BMC Genomics 2020 Jul 23;21(1):511.
    doi: 10.1186/s12864-020-06900-8pubmed: 32703156google scholar: lookup
  8. Pu Y, Zhang Y, Zhang T, Han J, Ma Y, Liu X. Identification of Novel lncRNAs Differentially Expressed in Placentas of Chinese Ningqiang Pony and Yili Horse Breeds. Animals (Basel) 2020 Jan 11;10(1).
    doi: 10.3390/ani10010119pubmed: 31940795google scholar: lookup
  9. Grilz-Seger G, Neuditschko M, Ricard A, Velie B, Lindgren G, Mesarič M, Cotman M, Horna M, Dobretsberger M, Brem G, Druml T. Genome-Wide Homozygosity Patterns and Evidence for Selection in a Set of European and Near Eastern Horse Breeds. Genes (Basel) 2019 Jun 28;10(7).
    doi: 10.3390/genes10070491pubmed: 31261764google scholar: lookup
  10. Velie BD, Solé M, Fegraeus KJ, Rosengren MK, Røed KH, Ihler CF, Strand E, Lindgren G. Genomic measures of inbreeding in the Norwegian-Swedish Coldblooded Trotter and their associations with known QTL for reproduction and health traits. Genet Sel Evol 2019 May 27;51(1):22.
    doi: 10.1186/s12711-019-0465-7pubmed: 31132983google scholar: lookup
  11. Velie BD, Lillie M, Fegraeus KJ, Rosengren MK, Solé M, Wiklund M, Ihler CF, Strand E, Lindgren G. Exploring the genetics of trotting racing ability in horses using a unique Nordic horse model. BMC Genomics 2019 Feb 4;20(1):104.
    doi: 10.1186/s12864-019-5484-9pubmed: 30717660google scholar: lookup
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