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BMC genomics2014; 15; 259; doi: 10.1186/1471-2164-15-259

Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds.

Abstract: Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown pathogenesis that significantly affects performance in Thoroughbreds. A genetic contribution to the pathogenesis of RLN is suggested by the higher prevalence of the condition in offspring of RLN-affected than unaffected stallions. To better understand RLN pathogenesis and its genetic basis, we performed a genome-wide association (GWAS) of 282 RLN-affected and 268 control Thoroughbreds. Results: We found a significant association of RLN with the LCORL/NCAPG locus on ECA3 previously shown to affect body size in horses. Using height at the withers of 505 of these horses, we confirmed the strong association of this locus with body size, and demonstrated a significant phenotypic and genetic correlation between height and RLN grade in this cohort. Secondary genetic associations for RLN on ECA18 and X did not correlate with withers height in our cohort, but did contain candidate genes likely influencing muscle physiology and growth: myostatin (MSTN) and integral membrane protein 2A (ITM2A). Conclusions: This linkage between body size and RLN suggests that selective breeding to reduce RLN prevalence would likely reduce adult size in this population. However, our results do not preclude the possibility of modifier loci that attenuate RLN risk without reducing size or performance, or that the RLN risk allele is distinct but tightly linked to the body size locus on ECA3. This study is both the largest body size GWAS and the largest RLN GWAS within Thoroughbred horses to date, and suggests that improved understanding of the relationship between genetics, equine growth rate, and RLN prevalence may significantly advance our understanding and management of this disease.
Publication Date: 2014-04-03 PubMed ID: 24707981PubMed Central: PMC4051171DOI: 10.1186/1471-2164-15-259Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores the genetic causes of equine recurrent laryngeal neuropathy (RLN), a disease affecting Thoroughbred horses, demonstrating that there is a strong correlation between the genetic factors influencing horse body size and the development of RLN. It suggests that any selective breeding to minimize RLN disease prevalence would need to account for potential reductions in adult body size.

Research Context and Methodology

  • The pathogenesis of equine recurrent laryngeal neuropathy (RLN), a common disease affecting the respiratory function of Thoroughbred horses, remains unknown. However, this study was anchored on the notion that a genetic factor is possibly involved. This hypothesis stems from observations of higher disease prevalence in offspring of RLN-affected stallions compared to those unaffected.
  • To investigate the genetic basis of RLN, a genome-wide association (GWAS) study was conducted on a cohort of 282 RLN-affected and 268 unaffected Thoroughbreds.

Results and Findings

  • The research found a significant association between RLN and the LCORL/NCAPG locus on ECA3, a genetic segment previously shown to affect body size in horses. The association between body size and this genetic locus was confirmed using height measurements of 505 horses from the study group.
  • Crucially, the researchers observed a significant correlation between horse height (indicating body size) and the grade of RLN, indicating a potential shared genetic basis.
  • Two other genetic associations for RLN were identified on the ECA18 and X chromosomes, which didn’t have any correlation with body size but were found to contain genes, MSTN and ITM2A, that influence muscle physiology and growth.
  • The research concludes that selective breeding to minimize RLN prevalence in Thoroughbreds could potentially reduce adult body size in the population. However, this doesn’t negate the possibility of other genes potentially having an attenuating effect on RLN risk without affecting body size or performance.

Significance and Implications of the Study

  • This study holds significance as the largest genome-wide association study exploring body size and RLN disease within Thoroughbred horses until now. It thus represents an emphasis on understanding the relationship between genetics, equine growth rate, and RLN prevalence.
  • The findings highlight the complexities of selective breeding in animals, showing that tempering with one genetic trait may directly or indirectly influence another.
  • Fundamentally, the research suggests a path for managing RLN disease through a genetic understanding, with potential implications for similar genetic diseases in other animal species.

Cite This Article

APA
Boyko AR, Brooks SA, Behan-Braman A, Castelhano M, Corey E, Oliveira KC, Swinburne JE, Todhunter RJ, Zhang Z, Ainsworth DM, Robinson NE. (2014). Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds. BMC Genomics, 15, 259. https://doi.org/10.1186/1471-2164-15-259

Publication

ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 15
Pages: 259

Researcher Affiliations

Boyko, Adam R
    Brooks, Samantha A
      Behan-Braman, Ashley
        Castelhano, Marta
          Corey, Elizabeth
            Oliveira, Kyle C
              Swinburne, June E
                Todhunter, Rory J
                  Zhang, Zhiwu
                    Ainsworth, Dorothy M
                      Robinson, Norman Edward
                      • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA. robinson@cvm.msu.edu.

                      MeSH Terms

                      • Alleles
                      • Animals
                      • Body Size / genetics
                      • Case-Control Studies
                      • Chromosome Mapping
                      • Female
                      • Gene Frequency
                      • Genetic Markers
                      • Genome-Wide Association Study
                      • Genotype
                      • Haplotypes
                      • Horse Diseases / genetics
                      • Horses
                      • Linkage Disequilibrium
                      • Male
                      • Phenotype
                      • Quantitative Trait Loci
                      • Quantitative Trait, Heritable

                      References

                      This article includes 35 references
                      1. Stick JA, Peloso JG, Morehead JP, Lloyd J, Eberhart S, Padungtod P, Derksen FJ. Endoscopic assessment of airway function as a predictor of racing performance in Thoroughbred yearlings: 427 cases (1997-2000). J Am Vet Med Assoc 2001;15(7):962–967.
                        doi: 10.2460/javma.2001.219.962pubmed: 11601794google scholar: lookup
                      2. Duncan ID, Griffiths IR, Madrid RE. A light and electron microscopic study of the neuropathy of equine idiopathic laryngeal hemiplegia. Neuropathol Appl Neurobiol 1978;15(6):483–501.
                      3. López-Plana C, Sautet JY, Pons J, Navarro G. Morphometric study of the recurrent laryngeal nerve in young ‘normal’ horses. Res Vet Sci 1993;15(3):333–337.
                        doi: 10.1016/0034-5288(93)90103-Mpubmed: 8284497google scholar: lookup
                      4. Hahn CN, Matiasek K, Dixon PM, Molony V, Rodenacker K, Mayhew IG. Histological and ultrastructural evidence that recurrent laryngeal neuropathy is a bilateral mononeuropathy limited to recurrent laryngeal nerves. Equine Vet J 2008;15(7):666–672.
                        doi: 10.2746/042516408X335711pubmed: 19165936google scholar: lookup
                      5. Hackett RP, Ducharme NG, Fubini SL, Erb HN. The reliability of endoscopic examination in assessment of arytenoid cartilage movement in horses: part I: subjective and objective laryngeal evaluation. Vet Surg 1991;15(3):174–179.
                      6. Collins N, Milne E, Hahn C, Dixon P. Correlation of the Havemeyer endoscopic laryngeal grading system with histopathological changes in equine Cricoarytenoideus dorsalis muscles. Ir Vet J 2009;15(5):334–338.
                        doi: 10.1186/2046-0481-62-5-334pmc: PMC3113812pubmed: 21851734google scholar: lookup
                      7. Dixon PM, McGorum BC, Railton DI, Hawe C, Tremaine WH, Pickles K, McCann J. Clinical and endoscopic evidence of progression in 152 cases of equine recurrent laryngeal neuropathy (RLN). Equine Vet J 2002;15(1):29–34.
                        pubmed: 11817549
                      8. Morris EA, Seeherman HJ. Evaluation of upper respiratory tract function during strenuous exercise in racehorses. J Am Vet Med Assoc 1990;15(3):431–438.
                        pubmed: 2298672
                      9. Sweeney CR, Maxson AD, Soma LR. Endoscopic findings in the upper respiratory tract of 678 Thoroughbred racehorses. J Am Vet Med Assoc 1991;15(6):1037–1038.
                        pubmed: 2032910
                      10. Goulden BE, Anderson LJ, Cahill JI. Roaring in Clydesdales. N Z Vet J 1985;15(5):73–76.
                        doi: 10.1080/00480169.1985.35170pubmed: 16031164google scholar: lookup
                      11. Brakenhoff JE, Holcombe SJ, Hauptman JG, Smith HK, Nickels FA, Caron JP. The prevalence of laryngeal disease in a large population of competition draft horses. Vet Surg 2006;15(6):579–583.
                      12. Dixon PM, Hahn CN, Barakzai SZ. Recurrent laryngeal neuropathy (RLN) research: where are we and to where are we heading?. Equine Vet J 2009;15(4):324–327.
                        doi: 10.2746/042516409X423082pubmed: 19562891google scholar: lookup
                      13. Bower MA, Campana MG, Whitten M, Edwards CJ, Jones H, Barrett E, Cassidy R, Nisbet RE, Hill EW, Howe CJ, Binns M. The cosmopolitan maternal heritage of the Thoroughbred racehorse breed shows a significant contribution from British and Irish native mares. Biol Let 2011;15(2):316–320.
                        doi: 10.1098/rsbl.2010.0800pmc: PMC3061175pubmed: 20926431google scholar: lookup
                      14. Petersen JL, Mickelson JR, Cothran EG, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, Distl O, Felicetti M, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MCT, Piercy RJ, Raekallio M. Genetic diversity in the modern horse illustrated from genome-wide SNP data. PloS One 2013;15(1):e54997.
                      15. Poncet PA, Montavon S, Gaillard C, Barrelet F, Straub R, Gerber H. A preliminary report on the possible genetic basis of laryngeal hemiplegia. Equine Vet J 1989;15(2):137–138.
                      16. Ohnesorge B, Deegen E, Miesner K, Geldermann H. Laryngeal hemiplegia in Warmblood horses–a study of stallions, mares and their offspring. Zentralbl Veterinarmed A 1993;15(2):134–154.
                        pubmed: 8480462
                      17. 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 2011;15(9–10):613–620.
                        pubmed: 21698472
                      18. Castelhano MG, Acland GM, Ciccone PA, Corey EE, Mezey JG, Schimenti JC, Todhunter RJ. Development and use of DNA archives at veterinary teaching hospitals to investigate the genetic basis of disease in dogs. J Am Vet Med Assoc 2009;15(1):75–80.
                        doi: 10.2460/javma.234.1.75pmc: PMC2754738pubmed: 19119968google scholar: lookup
                      19. Patterson N, Price AL, Reich D. Population structure and eigenanalysis. PLoS Genetics 2006;15(12):e190.
                      20. Zhou X, Stephens M. Genome-wide efficient mixed-model analysis for association studies. Nat Genet 2012;15(7):821–824.
                        doi: 10.1038/ng.2310pmc: PMC3386377pubmed: 22706312google scholar: lookup
                      21. Delaneau O, Zagury JF, Marchini J. Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 2013;15(1):5–6.
                        doi: 10.1038/nchembio.1414pubmed: 23269371google scholar: lookup
                      22. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;15(2):263–265.
                        doi: 10.1093/bioinformatics/bth457pubmed: 15297300google scholar: lookup
                      23. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;15(3):559–575.
                        doi: 10.1086/519795pmc: PMC1950838pubmed: 17701901google scholar: lookup
                      24. R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2012.
                      25. Signer-Hasler H, Flury C, Haase B, Burger D, Simianer H, Leeb T, Rieder S. A genome-wide association study reveals loci influencing height and other conformation traits in horses. PloS One 2012;15(5):e37282.
                      26. Makvandi-Nejad S, Hoffman GE, Allen JJ, Chu E, Gu E, Chandler AM, Loredo AI, Bellone RR, Mezey JG, Brooks SA, Sutter NB. Four loci explain 83% of size variation in the horse. PLoS One 2012;15(7):e39929.
                      27. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2011;15(1):76–82.
                        doi: 10.1016/j.ajhg.2010.11.011pmc: PMC3014363pubmed: 21167468google scholar: lookup
                      28. Rhee HS, Steel CM, Derksen FJ, Robinson NE, Hoh JF. Immunohistochemical analysis of laryngeal muscles in normal horses and horses with subclinical recurrent laryngeal neuropathy. J Histochem Cytochem 2009;15(8):787–800.
                        doi: 10.1369/jhc.2009.953844pmc: PMC2713078pubmed: 19398607google scholar: lookup
                      29. Harrison GD, Duncan ID, Clayton MK. Determination of the early age of onset of equine recurrent laryngeal neuropathy: 1: muscle pathology. Acta Neuropathol 1992;15(3):307–315.
                        pubmed: 1384268
                      30. Tetens J, Widmann P, Kuhn C, Thaller G. A genome-wide association study indicates LCORL/NCAPG as a candidate locus for withers height in German warmblood horses. Anim Genet 2013;15(4):467–471.
                        doi: 10.1111/age.12031pubmed: 23418885google scholar: lookup
                      31. Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara M, Capomaccio S, Cappelli K, Cothran EG, Distl O, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N. Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLoS Genetics 2013;15(1):e1003211.
                      32. Sovio U, Bennett AJ, Millwood IY, Molitor J, O’Reilly PF, Timpson NJ, Kaakinen M, Laitinen J, Haukka J, Pillas D, Tzoulaki I, Molitor J, Hoggart C, Coin LJ, Whittaker J, Pouta A, Hartikainen AL, Freimer NB, Widen E, Peltonen L, Elliott P, McCarthy MI, Jarvelin MR. Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. PLoS Genetics 2009;15(3):e1000409.
                      33. Soranzo N, Rivadeneira F, Chinappen-Horsley U, Malkina I, Richards JB, Hammond N, Stolk L, Nica A, Inouye M, Hofman A, Stephens J, Wheeler E, Arp P, Gwilliam R, Jhamai PM, Potter S, Chaney A, Ghori MJ, Ravindrarajah R, Ermakov S, Estrada K, Pols HA, Williams FM, McArdle WL, van Meurs JB, Loos RJ, Dermitzakis ET, Ahmadi KR, Hart DJ, Ouwenhand WH. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size. PLoS Genetics 2009;15(4):e1000445.
                      34. Bongiorni S, Mancini G, Chillemi G, Pariset L, Valentini A. Identification of a short region on chromosome 6 affecting direct calving ease in Piedmontese cattle breed. PloS One 2012;15(12):e50137.
                      35. Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010;15(2):166–176.
                        doi: 10.1056/NEJMra0905980pubmed: 20647212google scholar: lookup