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Asian-Australasian journal of animal sciences2015; 28(6); 771-781; doi: 10.5713/ajas.14.0008

Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds.

Abstract: Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.
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Publication Date: 2015-05-01 PubMed ID: 25925054PubMed Central: PMC4412973DOI: 10.5713/ajas.14.0008Google 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 study aimed to identify genetic variants that are associated with the racing performance of 1,156 thoroughbred horses by conducting a two-stage genome-wide association study. The researchers found 28 significant single-nucleotide polymorphisms (SNPs) related to 17 genes which are different from those discovered in the previous research.

Methodology

The researchers conducted a two-stage genome-wide association study to investigate the genetic variants that could be associated with the performance of racehorses.

  • The first stage of the association study involved evaluating a large number of markers (approximately 54,000 SNPs) in a smaller sample size of horses (240 horses).
  • In the second stage, a relatively smaller number of markers (170 SNPs) with large effects, as identified in the first stage, were evaluated against a larger sample size (1,156 horses).

Validating MSTN

The known SNPs related to myostatin (MSTN), a gene highly related with horse racing performance, were validated. Significant associations were found in the second stage, but none in the first stage.

Findings

The study ultimately identified 28 significant SNPs associated with 17 genes that might impact the racing performance of thoroughbred horses:

  • Six of these genes were found to have a function related to myogenesis, the process of muscle cell formation and growth.
  • Five of these genes were involved in the maintenance of muscle, crucial for the strenuous activity of racing.

These genes, previously unreported for their genetic association with racing performance, supplement recent genome-wide association studies of horse racing performance that identified other SNPs and genes as significant variants.

Implications

The results of this thoroughbred-specific study contribute to our understanding of the complex genetic traits that determine horse racing performance. Recognizing the polygenic nature of racing performance in thoroughbreds, the research expands our knowledge of the variety of genes that could influence speed and stamina in these animals. This could potentially inform future breeding and training strategies.

Cite This Article

APA
Shin DH, Lee JW, Park JE, Choi IY, Oh HS, Kim HJ, Kim H. (2015). Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds. Asian-Australas J Anim Sci, 28(6), 771-781. https://doi.org/10.5713/ajas.14.0008

Publication

Asian-Australasian journal of animal sciences
ISSN: 1011-2367
NlmUniqueID: 9884245
Country: Korea (South)
Language: English
Volume: 28
Issue: 6
Pages: 771-781

Researcher Affiliations

Shin, Dong-Hyun
  • Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea.
Lee, Jin Woo
  • Horse Industry Research Center, Korea Racing Authority (KRA), Gwacheon 427-711, Korea .
Park, Jong-Eun
  • Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea.
Choi, Ik-Young
  • Genome Analysis Center, National Instrumentation and Environmental Management (NICEM), Seoul National University, Seoul 151-921, Korea .
Oh, Hee-Seok
  • Department of Statistics, Seoul National University, Seoul 151-747, Korea .
Kim, Hyeon Jeong
  • C&K Genomics, Seoul 151-742, Korea .
Kim, Heebal
  • Department of Agricultural Biotechnology, Animal Biotechnology Major, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea ; C&K Genomics, Seoul 151-742, Korea .

References

This article includes 37 references
  1. Bach AS, Enjalbert S, Comunale F, Bodin S, Vitale N, Charrasse S, Gauthier-Rouvière C. ADP-ribosylation factor 6 regulates mammalian myoblast fusion through phospholipase D1 and phosphatidylinositol 4,5-bisphosphate signaling pathways.. Mol Biol Cell 2010 Jul 15;21(14):2412-24.
    pmc: PMC2903670pubmed: 20505075doi: 10.1091/mbc.e09-12-1063google scholar: lookup
  2. 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 2010 Dec;41 Suppl 2:154-8.
    pubmed: 21070290doi: 10.1111/j.1365-2052.2010.02126.xgoogle scholar: lookup
  3. Bosio Y, Berto G, Camera P, Bianchi F, Ambrogio C, Claus P, Di Cunto F. PPP4R2 regulates neuronal cell differentiation and survival, functionally cooperating with SMN.. Eur J Cell Biol 2012 Aug;91(8):662-74.
    pubmed: 22559936doi: 10.1016/j.ejcb.2012.03.002google scholar: lookup
  4. Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: the 2006-2007 update.. Med Sci Sports Exerc 2009 Jan;41(1):35-73.
    pubmed: 19123262doi: 10.1249/mss.0b013e3181844179google scholar: lookup
  5. Gaffney B, Cunningham EP. Estimation of genetic trend in racing performance of thoroughbred horses.. Nature 1988 Apr 21;332(6166):722-4.
    pubmed: 3357536doi: 10.1038/332722a0google scholar: lookup
  6. Goldstein JL, Brown MS. Regulation of the mevalonate pathway.. Nature 1990 Feb 1;343(6257):425-30.
    pubmed: 1967820doi: 10.1038/343425a0google scholar: lookup
  7. Grozdanov PN, Roy S, Kittur N, Meier UT. SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs.. RNA 2009 Jun;15(6):1188-97.
    pmc: PMC2685518pubmed: 19383767doi: 10.1261/rna.1532109google scholar: lookup
  8. Gu J, MacHugh DE, McGivney BA, Park SD, 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 Suppl 2010 Nov;(38):569-75.
    pubmed: 21059062doi: 10.1111/j.2042-3306.2010.00181.xgoogle scholar: lookup
  9. Gu J, Orr N, Park SD, Katz LM, Sulimova G, MacHugh DE, Hill EW. A genome scan for positive selection in thoroughbred horses.. PLoS One 2009 Jun 2;4(6):e5767.
    pmc: PMC2685479pubmed: 19503617doi: 10.1371/journal.pone.0005767google scholar: lookup
  10. Hill EW, Bradley DG, Al-Barody M, Ertugrul O, Splan RK, Zakharov I, Cunningham EP. History and integrity of thoroughbred dam lines revealed in equine mtDNA variation.. Anim Genet 2002 Aug;33(4):287-94.
    pubmed: 12139508doi: 10.1046/j.1365-2052.2002.00870.xgoogle scholar: lookup
  11. Hill EW, Eivers SS, McGivney BA, Fonseca RG, Gu J, Smith NA, Browne JA, MacHugh DE, Katz LM. Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred horse skeletal muscle.. Equine Vet J Suppl 2010 Nov;(38):576-81.
    pubmed: 21059063doi: 10.1111/j.2042-3306.2010.00206.xgoogle scholar: lookup
  12. 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 2010 Dec;41 Suppl 2:56-63.
    pubmed: 21070277doi: 10.1111/j.1365-2052.2010.02104.xgoogle scholar: lookup
  13. Hill EW, Gu J, Eivers SS, Fonseca RG, McGivney BA, Govindarajan P, Orr N, Katz LM, MacHugh DE. A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses.. PLoS One 2010 Jan 20;5(1):e8645.
    pmc: PMC2808334pubmed: 20098749doi: 10.1371/journal.pone.0008645google scholar: lookup
  14. Hill EW, McGivney BA, Gu J, Whiston R, Machugh DE. A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses.. BMC Genomics 2010 Oct 11;11:552.
    pmc: PMC3091701pubmed: 20932346doi: 10.1186/1471-2164-11-552google scholar: lookup
  15. Jelinsky SA, Archambault J, Li L, Seeherman H. Tendon-selective genes identified from rat and human musculoskeletal tissues.. J Orthop Res 2010 Mar;28(3):289-97.
    pubmed: 19780194doi: 10.1002/jor.20999google scholar: lookup
  16. Jorgensen TJ, Ruczinski I, Kessing B, Smith MW, Shugart YY, Alberg AJ. Hypothesis-driven candidate gene association studies: practical design and analytical considerations.. Am J Epidemiol 2009 Oct 15;170(8):986-93.
    pmc: PMC2765367pubmed: 19762372doi: 10.1093/aje/kwp242google scholar: lookup
  17. Kim J, Löwe T, Hoppe T. Protein quality control gets muscle into shape.. Trends Cell Biol 2008 Jun;18(6):264-72.
    pubmed: 18495480doi: 10.1016/j.tcb.2008.03.007google scholar: lookup
  18. Kimball SR, Vary TC, Jefferson LS. Regulation of protein synthesis by insulin.. Annu Rev Physiol 1994;56:321-48.
    pubmed: 8010743doi: 10.1146/annurev.ph.56.030194.001541google scholar: lookup
  19. Ko JA, Kimura Y, Matsuura K, Yamamoto H, Gondo T, Inui M. PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes.. J Cell Sci 2006 Dec 15;119(Pt 24):5106-13.
    pubmed: 17118964doi: 10.1242/jcs.03290google scholar: lookup
  20. Liscurn L. Cholesterol biosynthesis. New Comprehensive Biochemistry 2002;36:409–431.
  21. Moritsu Y, Funakoshi H, Ichikawa S. Genetic evaluation of sires and environmental factors influencing best racing times of Thoroughbred horses in Japan. J Equine Sci 1994;5:53–58.
  22. Moschella MC, Watras J, Jayaraman T, Marks AR. Inositol 1,4,5-trisphosphate receptor in skeletal muscle: differential expression in myofibres.. J Muscle Res Cell Motil 1995 Aug;16(4):390-400.
    pubmed: 7499479doi: 10.1007/bf00114504google scholar: lookup
  23. Mota MD, Abrahão AR, Oliveira HN. Genetic and environmental parameters for racing time at different distances in Brazilian Thoroughbreds.. J Anim Breed Genet 2005 Dec;122(6):393-9.
    pubmed: 16274423doi: 10.1111/j.1439-0388.2005.00551.xgoogle scholar: lookup
  24. Myers AJ, Gibbs JR, Webster JA, Rohrer K, Zhao A, Marlowe L, Kaleem M, Leung D, Bryden L, Nath P, Zismann VL, Joshipura K, Huentelman MJ, Hu-Lince D, Coon KD, Craig DW, Pearson JV, Holmans P, Heward CB, Reiman EM, Stephan D, Hardy J. A survey of genetic human cortical gene expression.. Nat Genet 2007 Dec;39(12):1494-9.
    pubmed: 17982457doi: 10.1038/ng.2007.16google scholar: lookup
  25. O'Connor MS, Carlson ME, Conboy IM. Differentiation rather than aging of muscle stem cells abolishes their telomerase activity.. Biotechnol Prog 2009 Jul-Aug;25(4):1130-7.
    pmc: PMC2746102pubmed: 19455648doi: 10.1002/btpr.223google scholar: lookup
  26. Oki H, Sasaki Y, Willham RL. Genetics of racing performance in the Japanese Thoroughbred horse:: II. Environmental variation of racing time on turf and dirt tracks and the influence of sex, age, and weight carried on racing time.. J Anim Breed Genet 1994 Jan 12;111(1-6):128-37.
    pubmed: 21395760doi: 10.1111/j.1439-0388.1994.tb00446.xgoogle scholar: lookup
  27. Ooms LM, Horan KA, Rahman P, Seaton G, Gurung R, Kethesparan DS, Mitchell CA. The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease.. Biochem J 2009 Apr 1;419(1):29-49.
    pubmed: 19272022doi: 10.1042/bj20081673google scholar: lookup
  28. Park J-E, Lee J-R, Oh S, Lee JW, Oh H-S, Kim H. Principal components analysis applied to genetic evaluation of racing performance of Thoroughbred race horses in Korea. Livest Sci 2011;135:293–299.
  29. 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 Sep;81(3):559-75.
    pmc: PMC1950838pubmed: 17701901doi: 10.1086/519795google scholar: lookup
  30. Richards JB, Waterworth D, O'Rahilly S, Hivert MF, Loos RJ, Perry JR, Tanaka T, Timpson NJ, Semple RK, Soranzo N, Song K, Rocha N, Grundberg E, Dupuis J, Florez JC, Langenberg C, Prokopenko I, Saxena R, Sladek R, Aulchenko Y, Evans D, Waeber G, Erdmann J, Burnett MS, Sattar N, Devaney J, Willenborg C, Hingorani A, Witteman JC, Vollenweider P, Glaser B, Hengstenberg C, Ferrucci L, Melzer D, Stark K, Deanfield J, Winogradow J, Grassl M, Hall AS, Egan JM, Thompson JR, Ricketts SL, König IR, Reinhard W, Grundy S, Wichmann HE, Barter P, Mahley R, Kesaniemi YA, Rader DJ, Reilly MP, Epstein SE, Stewart AF, Van Duijn CM, Schunkert H, Burling K, Deloukas P, Pastinen T, Samani NJ, McPherson R, Davey Smith G, Frayling TM, Wareham NJ, Meigs JB, Mooser V, Spector TD. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.. PLoS Genet 2009 Dec;5(12):e1000768.
    pmc: PMC2781107pubmed: 20011104doi: 10.1371/journal.pgen.1000768google scholar: lookup
  31. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies.. Nat Genet 2006 Feb;38(2):209-13.
    pubmed: 16415888doi: 10.1038/ng1706google scholar: lookup
  32. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Optimal designs for two-stage genome-wide association studies.. Genet Epidemiol 2007 Nov;31(7):776-88.
    pubmed: 17549752doi: 10.1002/gepi.20240google scholar: lookup
  33. Szustakowski JD, Lee JH, Marrese CA, Kosinski PA, Nirmala NR, Kemp DM. Identification of novel pathway regulation during myogenic differentiation.. Genomics 2006 Jan;87(1):129-38.
    pubmed: 16300922doi: 10.1016/j.ygeno.2005.08.009google scholar: lookup
  34. Thomas D, Xie R, Gebregziabher M. Two-Stage sampling designs for gene association studies.. Genet Epidemiol 2004 Dec;27(4):401-14.
    pubmed: 15543639doi: 10.1002/gepi.20047google scholar: lookup
  35. Tozaki T, Hill EW, Hirota K, Kakoi H, Gawahara H, Miyake T, Sugita S, Hasegawa T, Ishida N, Nakano Y, Kurosawa M. A cohort study of racing performance in Japanese Thoroughbred racehorses using genome information on ECA18.. Anim Genet 2012 Feb;43(1):42-52.
    pubmed: 22221024doi: 10.1111/j.1365-2052.2011.02201.xgoogle scholar: lookup
  36. Tozaki T, Miyake T, Kakoi H, Gawahara H, Sugita S, Hasegawa T, Ishida N, Hirota K, Nakano Y. A genome-wide association study for racing performances in Thoroughbreds clarifies a candidate region near the MSTN gene.. Anim Genet 2010 Dec;41 Suppl 2:28-35.
    pubmed: 21070273doi: 10.1111/j.1365-2052.2010.02095.xgoogle scholar: lookup
  37. Velleman SG, Shin J, Li X, Song Y. Review: The skeletal muscle extracellular matrix: Possible roles in the regulation of muscle development and growth. Can J Anim Sci 2012;92:1–10.

Citations

This article has been cited 7 times.
  1. Tozaki T, Ohnuma A, Kikuchi M, Ishige T, Kakoi H, Hirota KI, Kusano K, Nagata SI. Rare and common variant discovery by whole-genome sequencing of 101 Thoroughbred racehorses. Sci Rep 2021 Aug 6;11(1):16057.
    doi: 10.1038/s41598-021-95669-1pubmed: 34362995google scholar: lookup
  2. Littiere TO, Castro GHF, Rodriguez MDPR, Bonafé CM, Magalhães AFB, Faleiros RR, Vieira JIG, Santos CG, Verardo LL. Identification and Functional Annotation of Genes Related to Horses' Performance: From GWAS to Post-GWAS. Animals (Basel) 2020 Jul 10;10(7).
    doi: 10.3390/ani10071173pubmed: 32664293google scholar: lookup
  3. Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Anim Genet 2019 Dec;50(6):569-597.
    doi: 10.1111/age.12857pubmed: 31568563google scholar: lookup
  4. Nolte W, Thaller G, Kuehn C. Selection signatures in four German warmblood horse breeds: Tracing breeding history in the modern sport horse. PLoS One 2019;14(4):e0215913.
    doi: 10.1371/journal.pone.0215913pubmed: 31022261google scholar: lookup
  5. Pereira GL, Malheiros JM, Ospina AMT, Chardulo LAL, Curi RA. Exome sequencing in genomic regions related to racing performance of Quarter Horses. J Appl Genet 2019 Feb;60(1):79-86.
    doi: 10.1007/s13353-019-00483-1pubmed: 30666567google scholar: lookup
  6. Velie BD, Fegraeus KJ, Solé M, Rosengren MK, Røed KH, Ihler CF, Strand E, Lindgren G. A genome-wide association study for harness racing success in the Norwegian-Swedish coldblooded trotter reveals genes for learning and energy metabolism. BMC Genet 2018 Aug 29;19(1):80.
    doi: 10.1186/s12863-018-0670-3pubmed: 30157760google scholar: lookup
  7. Ramadan S, Miyake T, Yamaura J, Inoue-Murayama M. LDHA gene is associated with pigeon survivability during racing competitions. PLoS One 2018;13(5):e0195121.
    doi: 10.1371/journal.pone.0195121pubmed: 29775483google scholar: lookup
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