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.
Abstract: The wild progenitors of the domestic horse were subject to natural selection for speed and stamina for millennia. Uniquely, this process has been augmented in Thoroughbreds, which have undergone at least 3 centuries of intense artificial selection for athletic phenotypes. While the phenotypic adaptations to exercise are well described, only a small number of the underlying genetic variants contributing to these phenotypes have been reported. Objective: A panel of candidate performance-related genes was examined for DNA sequence variation in Thoroughbreds and the association with racecourse performance investigated. Methods: Eighteen candidate genes were chosen for their putative roles in exercise. Re-sequencing in Thoroughbred samples was successful for primer sets in 13 of these genes. SNPs identified in this study and from the EquCab2.0 SNP database were genotyped in 2 sets of Thoroughbred samples (n = 150 and 148) and a series of population-based case-control investigations were performed by separating the samples into discrete cohorts on the basis of retrospective racecourse performance. Results: Twenty novel SNPs were detected in 3 genes: ACTN3, CKM and COX4I2. Genotype frequency distributions for 3 SNPs in CKM and COX4I2 were significantly (P < 0.05) different between elite Thoroughbreds and racehorses that had never won a race. These associations were not validated when an additional (n = 130) independent set of samples was genotyped, but when analyses included all samples (n = 278) the significance of association at COX4I2 g.22684390C > T was confirmed (P < 0.02). Conclusions: While molecular genetic information has the potential to become a powerful tool to make improved decisions in horse industries, it is vital that rigour is applied to studies generating these data and that adequate and appropriate sample sets, particularly for independent replication, are used.
© 2010 EVJ Ltd.
Publication Date: 2011-05-27 PubMed ID: 21059062DOI: 10.1111/j.2042-3306.2010.00181.xGoogle Scholar: Lookup
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Summary
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The research examined the genetic variations in Thoroughbred racehorses, specifically targeting genes responsible for athletic performance. The study found that sequence changes in the CKM and COX4I2 genes are significantly associated with race-winning ability, although full confirmation of this association requires further sampling and analysis.
Objective and Methods
- The researchers intended to explore the sequence variation in various genes potentially linked with performance in racing horses. They analyzed the DNA sequences of 18 candidate genes known for their roles in exercise.
- Re-sequencing was successfully performed on Thoroughbred samples for 13 of these genes. Following this, the researchers identified Single Nucleotide Polymorphisms (SNPs), or genetic variations, in these genes.
- The detected SNPs were compared and genotyped in two separate sets of Thoroughbred samples. The researchers then performed a series of population-based case-control investigations by dividing the samples into discrete cohorts based on retrospective racing performance.
Results
- Twenty novel SNPs were found in three genes: ACTN3, CKM, and COX4I2. The CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) are particularly of interest as they relate to muscle function and cellular energy production respectively.
- The genotype frequency distributions for three SNPs – one in CKM and two in COX4I2 – were significantly different between elite Thoroughbreds that have won races, and those that haven’t.
- The associations were not validated when a third set of 130 independent samples was genotyped. However, when all samples (278 in total) were analyzed, the significance of the association with the COX4I2 SNP was confirmed.
Conclusions and Future Directions
- The researchers concluded that molecular genetic information could potentially enhance decision making in horse industries such as breeding and training. However, the importance of rigor, adequate sampling, and independent replication in studies generating such data was underscored.
- While the study provides initial evidence of a genetic link between certain sequence variations and racing performance in Thoroughbreds, more exhaustive research and larger sample sizes are needed for full validation.
Cite This Article
APA
Gu J, MacHugh DE, McGivney BA, Park SD, Katz LM, Hill EW.
(2011).
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(38), 569-575.
https://doi.org/10.1111/j.2042-3306.2010.00181.x Publication
Researcher Affiliations
- Animal Genomics Laboratory, UCD School of Agriculture, University Veterinary Hospital, Ireland.
MeSH Terms
- Animals
- Creatine Kinase, MM Form / genetics
- Creatine Kinase, MM Form / metabolism
- Electron Transport Complex IV / genetics
- Electron Transport Complex IV / metabolism
- Gene Expression Regulation / physiology
- Horses / genetics
- Horses / physiology
- Polymorphism, Single Nucleotide
- Running / physiology
Citations
This article has been cited 21 times.- Davie A, Beavers R, Hargitaiová K, Denham J. The Emerging Role of Hypoxic Training for the Equine Athlete.. Animals (Basel) 2023 Sep 3;13(17).
- Vincelette A. The Characteristics, Distribution, Function, and Origin of Alternative Lateral Horse Gaits.. Animals (Basel) 2023 Aug 8;13(16).
- Todd ET, Fromentier A, Sutcliffe R, Running Horse Collin Y, Perdereau A, Aury JM, Èche C, Bouchez O, Donnadieu C, Wincker P, Kalbfleisch T, Petersen JL, Orlando L. Imputed genomes of historical horses provide insights into modern breeding.. iScience 2023 Jul 21;26(7):107104.
- 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.
- Alfaro GF, Novak TE, Rodning SP, Moisá SJ. Preconditioning beef cattle for long-duration transportation stress with rumen-protected methionine supplementation: A nutrigenetics study.. PLoS One 2020;15(7):e0235481.
- Tozaki T, Ohnuma A, Kikuchi M, Ishige T, Kakoi H, Hirota KI, Kusano K, Nagata SI. Microfluidic Quantitative PCR Detection of 12 Transgenes from Horse Plasma for Gene Doping Control.. Genes (Basel) 2020 Apr 23;11(4).
- Srikanth K, Kim NY, Park W, Kim JM, Kim KD, Lee KT, Son JH, Chai HH, Choi JW, Jang GW, Kim H, Ryu YC, Nam JW, Park JE, Kim JM, Lim D. Comprehensive genome and transcriptome analyses reveal genetic relationship, selection signature, and transcriptome landscape of small-sized Korean native Jeju horse.. Sci Rep 2019 Nov 13;9(1):16672.
- 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.
- Kim DH, Lee HG, Sp N, Kang DY, Jang KJ, Lee HK, Cho BW, Yang YM. Validation of exercise-response genes in skeletal muscle cells of Thoroughbred racing horses.. Asian-Australas J Anim Sci 2021 Jan 1;34(1):134-142.
- 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.
- Jäderkvist Fegraeus K, Velie BD, Axelsson J, Ang R, Hamilton NA, Andersson L, Meadows JRS, Lindgren G. A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses.. Physiol Rep 2018 May;6(10):e13700.
- Do KT, Cho HW, Badrinath N, Park JW, Choi JY, Chung YH, Lee HK, Song KD, Cho BW. Molecular Characterization and Expression Analysis of Creatine Kinase Muscle (CK-M) Gene in Horse.. Asian-Australas J Anim Sci 2015 Dec;28(12):1680-5.
- Shin DH, Lee JW, Park JE, Choi IY, Oh HS, Kim HJ, Kim H. 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 2015 Jun;28(6):771-81.
- Jun J, Cho YS, Hu H, Kim HM, Jho S, Gadhvi P, Park KM, Lim J, Paek WK, Han K, Manica A, Edwards JS, Bhak J. Whole genome sequence and analysis of the Marwari horse breed and its genetic origin.. BMC Genomics 2014;15 Suppl 9(Suppl 9):S4.
- Schubert M, Jónsson H, Chang D, Der Sarkissian C, Ermini L, Ginolhac A, Albrechtsen A, Dupanloup I, Foucal A, Petersen B, Fumagalli M, Raghavan M, Seguin-Orlando A, Korneliussen TS, Velazquez AM, Stenderup J, Hoover CA, Rubin CJ, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, MacHugh DE, Kalbfleisch T, MacLeod JN, Rubin EM, Sicheritz-Ponten T, Andersson L, Hofreiter M, Marques-Bonet T, Gilbert MT, Nielsen R, Excoffier L, Willerslev E, Shapiro B, Orlando L. Prehistoric genomes reveal the genetic foundation and cost of horse domestication.. Proc Natl Acad Sci U S A 2014 Dec 30;111(52):E5661-9.
- Metzger J, Tonda R, Beltran S, Agueda L, Gut M, Distl O. Next generation sequencing gives an insight into the characteristics of highly selected breeds versus non-breed horses in the course of domestication.. BMC Genomics 2014 Jul 4;15(1):562.
- Finno CJ, Bannasch DL. Applied equine genetics.. Equine Vet J 2014 Sep;46(5):538-44.
- Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, 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, Penedo MC, Piercy RJ, Raekallio M, Rieder S, Røed KH, Swinburne J, Tozaki T, Vaudin M, Wade CM, McCue ME. Genome-wide analysis reveals selection for important traits in domestic horse breeds.. PLoS Genet 2013;9(1):e1003211.
- Doan R, Cohen ND, Sawyer J, Ghaffari N, Johnson CD, Dindot SV. Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare.. BMC Genomics 2012 Feb 17;13:78.
- Bower MA, McGivney BA, Campana MG, Gu J, Andersson LS, Barrett E, Davis CR, Mikko S, Stock F, Voronkova V, Bradley DG, Fahey AG, Lindgren G, MacHugh DE, Sulimova G, Hill EW. The genetic origin and history of speed in the Thoroughbred racehorse.. Nat Commun 2012 Jan 24;3:643.
- McGivney BA, McGettigan PA, Browne JA, Evans AC, Fonseca RG, Loftus BJ, Lohan A, MacHugh DE, Murphy BA, Katz LM, Hill EW. Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training.. BMC Genomics 2010 Jun 23;11:398.
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