Analyze Diet
Equine veterinary journal2019; 52(2); 174-180; doi: 10.1111/evj.13171

Exploring the genetics underpinning dynamic laryngeal collapse associated with poll flexion in Norwegian-Swedish Coldblooded Trotter racehorses.

Abstract: Dynamic laryngeal collapse (DLC) associated with poll flexion is the most common disorder of the upper respiratory tract (URT) in the Norwegian-Swedish Coldblooded Trotter (NSCT). The disorder, which has also been diagnosed in other breeds of trotters and gaited horses, appears to be related to anatomic phenotypes and only occurs during poll flexion when the horse is exercised 'on the bit'. Objective: Identify genomic regions associated with DLC in the NSCT by combining a rigorous phenotyping protocol with genomic data from a high-density equine genotyping array. Methods: Prospective case/control study. Methods: High-speed treadmill endoscopy was used to phenotype horses (n = 61) for DLC, distinguishing between cases and controls. Genome-wide association (GWA) analysis of DLC status was then performed using a principal component approach (PCA) with haplotype analyses subsequently performed for regions containing single-nucleotide polymorphisms (SNPs) above the suggestive genome-wide significance (GWS) threshold (P<1.0 × 10 ). Results: One region containing 10 SNPs (Equus caballus chromosome [ECA] 7: 89,601,935-94,647,192) was above the suggestive GWS threshold. Two inferred haplotypes in this region demonstrated significant differences (P<0.001) between cases and controls, with the most frequent haplotype resulting in a significantly increased risk of DLC. Conclusions: Small sample size as a result of stringent phenotyping protocols. Conclusions: The current study highlights a candidate genomic region on ECA7 as potentially important with regard to the manifestation of DLC. Further exploration of this region and the genes included within it will bring veterinarians and researchers closer to fully understanding the biological mechanisms underlying DLC in horses.
Publication Date: 2019-09-23 PubMed ID: 31461557DOI: 10.1111/evj.13171Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

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 aims to identify and understand the genetic regions linked to a common upper respiratory tract disorder known as Dynamic Laryngeal Collapse (DLC) in Norwegian-Swedish Coldblooded Trotter racehorses. The team used high-speed treadmill endoscopy and genome-wide association analyses, concluding that a specific genomic region might be significant in causing DLC.

Research Objective

  • The primary objective of this research was to identify the genomic regions that could be associated with Dynamic Laryngeal Collapse (DLC), a common upper respiratory tract disorder among Norwegian-Swedish Coldblooded Trotter (NSCT) racehorses. This was achieved by combining rigorous phenotyping protocols with genetic data from high-density equine genotyping arrays.

Methods of the Study

  • A high-speed treadmill endoscopy was used to phenotype horses (n = 61) for DLC to differentiate between cases and controls.
  • A genome-wide association (GWA) analysis of DLC status was carried out using a principal component approach (PCA).
  • This was followed by haplotype analyses for regions containing single-nucleotide polymorphisms (SNPs) that were above the suggestive genome-wide significance (GWS) threshold.

Results of the Study

  • An area on Equus caballus chromosome 7 (ECA7), containing ten SNPs, exceeded the suggestive GWS threshold.
  • Two inferred haplotypes in this particular region indicated significant differences between infected and non-infected horses, with the most frequent haplotype significantly increasing the risk of DLC.

Conclusions of the Study

  • The authors acknowledged the constraints of the study, with the small sample size being a direct result of the largely strict phenotyping protocols.
  • Nevertheless, the research shed essential insights into our understanding of the genomic regions impacting DLC manifestation.
  • The identified candidate genomic region on ECA7 is crucial and needs further investigation along with the genes included within it. Such exploration will enhance our understanding of the biological mechanisms underlying DLC in horses.

Cite This Article

APA
Velie BD, Smith PM, Fjordbakk CT, Solé M, Jäderkvist Fegraeus K, Rosengren MK, Røed KH, Ihler CF, Lindgren G, Strand E. (2019). Exploring the genetics underpinning dynamic laryngeal collapse associated with poll flexion in Norwegian-Swedish Coldblooded Trotter racehorses. Equine Vet J, 52(2), 174-180. https://doi.org/10.1111/evj.13171

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 2
Pages: 174-180

Researcher Affiliations

Velie, B D
  • Faculty of Science, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Smith, P M
  • Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.
Fjordbakk, C T
  • Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.
Solé, M
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Jäderkvist Fegraeus, K
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Rosengren, M K
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Røed, K H
  • Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo, Norway.
Ihler, C F
  • Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.
Lindgren, G
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Livestock Genetics, Department of Biosystems, KU Leuven, Leuven, Belgium.
Strand, E
  • Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences, Oslo, Norway.

MeSH Terms

  • Animals
  • Genome-Wide Association Study / veterinary
  • Horse Diseases
  • Horses
  • Larynx
  • Norway
  • Prospective Studies
  • Sweden

Grant Funding

  • H-15-47-075 / Swedish-Norwegian Foundation for Equine Research

References

This article includes 31 references
  1. Strand E, Hanche-Olsen S, Gronvold AMR, Mellum CN. Dynamic bilateral arytenoid and vocal fold collapse associated with head flexion in 5 Norwegian Coldblooded Trotter racehorses. Equine Vet. Educ. 16, 242-250.
  2. Strand E, Fjordbakk CT, Sundberg K, Spangen L, Lunde H, Hanche-Olsen S. Relative prevalence of upper respiratory tract obstructive disorders in two breeds of harness racehorses (185 cases: 1998-2006). Equine Vet. J. 44, 518-523.
  3. Hanche-Olsen S, Rannem L, Strand E. Bilateral dynamic laryngeal collapse associated with collection in “high poll flexion” in a gaited Icelandic horse. Pferdeheilkunde 26, 810-813.
  4. McCarrel TM, Woodie JB. Update on laryngeal disorders and treatment. Vet. Clin. N. Am.: Equine Pract. 31, 13-26.
  5. Strand E, Fjordbakk CT, Holcombe SJ, Risberg A, Chalmers HJ. Effect of poll flexion and dynamic laryngeal collapse on tracheal pressure in Norwegian Coldblooded Trotter racehorses. Equine Vet. J. 41, 59-64.
  6. Strand E, Skjerve E. Complex dynamic upper airway collapse: associations between abnormalities in 99 harness racehorses with one or more dynamic disorders. Equine Vet. J. 44, 524-528.
  7. Fjordbakk CT, Chalmers HJ, Holcombe SJ, Strand E. Results of upper airway radiography and ultrasonography predict dynamic laryngeal collapse in affected horses. Equine Vet. J. 45, 705-710.
  8. Fjordbakk CT, Strand E, Hanche-Olsen S. Surgical and conservative management of bilateral dynamic laryngeal collapse associated with poll flexion in harness race horses. Vet. Surg. 37, 501-507.
  9. Development Core Team R. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.
  10. Everitt BS, Hothorn T. A Handbook of Statistical Analyses Using R. Chapman & Hall/CRC, Boca Raton, Florida.
  11. Barret JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263-265.
  12. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA. Score tests for association of traits with haplotypes when linkage phase is ambiguous. Am. J. Hum. Genet. 70, 425-434.
  13. Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ. Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum. Hered. 55, 56-65.
  14. Thomas PD, Campbell MJ, Kejariwal A, Mi HY, Karlak B, Daverman R, Diemer K, Muruganujan A, Narechania A. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129-2141.
  15. Mi H, Poudel S, Muruganujan A, Casagrande JT, Thomas PD. PANTHER version 10: expanded protein families and functions, and analysis tools. Nucleic Acids Res. 44, D336-342.
  16. Panagiotou OA, Ioannidis JPA. What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations. Int. J. Epidemiol. 41, 273-286.
  17. Brooks SA, Stick J, Braman A, Palermo K, Robinson NE, Ainsworth DM. Identification of loci affecting sexually dimorphic patterns for height and recurrent laryngeal neuropathy risk in American Belgian Draft horses. Physiol. Genomics 50, 1051-1058.
  18. Boyko AR, Brooks SA, Behan-Braman A, Castelhano M, Corey E, Oliveira KC, Swinburne JE, Todhunter RJ, Zhang Z, Ainsworth DM, Robinson NE. Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds. BMC Genomics 15, 259.
  19. Dupuis MC, Zhang Z, Druet T, Denoix JM, Charlier C, Lekeux P, Georges M. Results of a haplotype-based GWAS for recurrent laryngeal neuropathy in the horse. Mamm. Genome 22, 613-620.
  20. Fjordbakk CT, Revold T, Goodwin D, Piercy RJ. Histopathological assessment of intrinsic laryngeal musculature in horses with dynamic laryngeal collapse. Equine Vet. J. 47, 603-608.
  21. Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren G, Andersson L, Kullander K. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature 488, 642-646.
  22. Promerová M, Andersson LS, Juras R, Penedo MC, Reissmann M, Tozaki T, Bellone R, Dunner S, Horin P, Imsland F, Mikko S, Modry D, Roed KH, Schwochow D, Vega-Pla JL, Mehrabani-Yeganeh H, Yousefi-Mashouf N, Cothran GE, Lindgren G, Andersson L. Worldwide frequency distribution of the “Gait keeper” mutation in the DMRT3 gene. Anim. Genet. 45, 274-282.
  23. Jäderkvist Fegraeus K, Hirschberg I, Árnason T, Andersson L, Velie BD, Andersson LS, Lindgren G. To pace or not to pace: a pilot study of four- and five-gaited Icelandic horses homozygous for the DMRT3 ‘Gait Keeper’ mutation. Anim. Genet. 48, 694-697.
  24. Jäderkvist Fegraeus K, Johansson L, Mäenpää M, Mykkänen A, Andersson LS, Velie BD, Andersson L, Árnason T, Lindgren G. Different DMRT3 genotypes are best adapted for harness racing and riding in Finnhorses. J. Hered. 106, 734-740.
  25. Jäderkvist Fegraeus K, Lawrence C, Petäjistö K, Johansson MK, Wiklund M, Olsson M, Andersson L, Andersson LS, Røed KH, Ihler CF, Strand E, Lindgren G, Velie BD. Lack of significant associations with early career performance suggest no link between the DMRT3 “Gait Keeper” mutation and precocity in Coldblooded trotters. PLoS One 10, e0177351.
  26. Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Girón CG, Gil L, Gordon L, Haggerty L, Haskell E, Hourlier T, Izuogu OG, Janacek SH, Juettemann T, To JK, Laird MR, Lavidas I, Liu Z, Loveland JE, Maurel T, McLaren W, Moore B, Mudge J, Murphy DN, Newman V, Nuhn M, Ogeh D, Ong CK, Parker A, Patricio M, Riat HS, Schullenburg H, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Zadissa A, Frankish A, Hunt SE, Kostadima M, Langridge N, Martin FJ, Muffato M, Perry E, Ruffler M, Staines DM, Trevanion SJ, Aken BL, Cunningham F, Yates A, Flicek P. Ensembl 2018. Nucleic Acids Res. 46, 754-761.
  27. Zhang X, Zara J, Siu RK, Ting K, Soo C. The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration. J. Dent. Res. 89, 865-878.
  28. Desai J, Shannon ME, Johnson MD, Ruff DW, Hughes LA, Kerley MK, Carpenter DA, Johnson DK, Rinchik EM, Culiat CT. Nell1-deficient mice have reduced expression of extracellular matrix proteins causing cranial and vertebral defects. Hum. Mol. Genet. 15, 1329-1341.
  29. Charlesworth G, Plagnol V, Holmström KM, Bras J, Sheerin UM, Preza E, Rubio-Agusti I, Ryten M, Schneider SA, Stamelou M, Trabzuni D, Abramov AY, Bhatia KP, Wood NW. Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogensis. Am. J. Hum. Genet. 91, 1041-1050.
  30. Jin L, Liu Y, Sun F, Collins MT, Blackwell K, Woo AS, Reichenberger EJ, Hu Y. Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia. Sci. Rep. 7, 40935.
  31. Papadopoulos C, Laforet P, Nectoux J, Stojkovic T, Wahbi K, Carlier RY, Carlier PG, Leonard-Louis S, Leturcq F, Romero N, Eymard B, Behin A. Hyperckemia and myalgia are common presentations of anoctamin-5-related myopathy in French patients. Muscle Nerve 56, 1096-1100.

Citations

This article has been cited 2 times.
  1. Tilley P, Simões J, Sales Luis JP. Effects of a 15° Variation in Poll Flexion during Riding on the Respiratory Systems and Behaviour of High-Level Dressage and Show-Jumping Horses. Animals (Basel) 2023 May 22;13(10).
    doi: 10.3390/ani13101714pubmed: 37238147google scholar: lookup
  2. Finno CJ. Science-in-brief: Genomic and transcriptomic approaches to the investigation of equine diseases. Equine Vet J 2022 Mar;54(2):444-448.
    doi: 10.1111/evj.13549pubmed: 35133024google scholar: lookup