OMIA 001538-9796 : Racing distance in Equus caballus

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: no

Key variant known: no

Inheritance: Not surprisingly, this trait (Racing distance) is actually a quantitative trait, variation in which is determined by the combined effect of an unknown number of loci (the MSTN gene being one of these) plus an unknown number of non-genetic factors (Hill et al., 2019).

Molecular basis: Following a GWAS, Hill et al. (2010) reported "a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses."

Santagostino et al. (2015) reported a SINE insertion upstream of the MSTN gene that is in strong linkage disequilibrium with the g.66493737C>T SNP.

Rooney et al. (2018) reported that "In a large cohort of Thoroughbreds, we observed a complete concordance between the SNP and the SINE insertion. By means of in vitro assays in C2C12 myoblasts, we isolated the SNP variant from the SINE polymorphism and showed the latter is exclusively responsible for adversely affecting transcription initiation and gene expression thereby limiting myostatin protein production. Mapping the MSTN transcription start site in horse skeletal muscle likewise revealed anomalous transcription initiation in the presence of the SINE insertion. Our data provides mechanistic evidence that the SINE insertion uniquely accounts for the MSTN “speed gene” effect on race distance aptitude in the Thoroughbred horse." Consequently, the SNP has been removed from the OMIA table of likely causal variants below.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MSTN myostatin Equus caballus 18 NC_009161.3 (66610122..66605150) MSTN Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Racing distance MSTN insertion, gross (>20) 18 A "227 bp SINE insertion positioned upstream of exon 1" 2018 30379863

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Hill, E.W., McGivney, B.A., Rooney, M., Katz, L.M., Parnell, A., MacHugh, D.E. :
The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions. Equine Vet J :, 2019. Pubmed reference: 30604488. DOI: 10.1111/evj.13058.
2018 Farries, G., McGettigan, P.A., Gough, K.F., McGivney, B.A., MacHugh, D.E., Katz, L.M., Hill, E.W. :
Genetic contributions to precocity traits in racing Thoroughbreds. Anim Genet 49:193-204, 2018. Pubmed reference: 29230835. DOI: 10.1111/age.12622.
Padilha, F.G.F., El-Jaick, K.B., de Castro, L., Moreira, A.D.S., Ferreira, A.M.R. :
MSTN gene in Brazilian sport horses. J Equine Sci 29:21-24, 2018. Pubmed reference: 29593445. DOI: 10.1294/jes.29.21.
Rooney, M.F., Hill, E.W., Kelly, V.P., Porter, R.K. :
The "speed gene" effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion. PLoS One 13:e0205664, 2018. Pubmed reference: 30379863. DOI: 10.1371/journal.pone.0205664.
2017 Okuda, Y., Moe, H.H., Moe, K.K., Shimizu, Y., Nishioka, K., Shimogiri, T., Mannen, H., Kanemaki, M., Kunieda, T. :
Genotype distribution and allele frequencies of the genes associated with body composition and locomotion traits in Myanmar native horses. Anim Sci J 88:1198-1203, 2017. Pubmed reference: 27925399. DOI: 10.1111/asj.12756.
Rooney, M.F., Porter, R.K., Katz, L.M., Hill, E.W. :
Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse. PLoS One 12:e0186247, 2017. Pubmed reference: 29190290. DOI: 10.1371/journal.pone.0186247.
Serpa, P.B., Garbade, P., Natalini, C.C., Pires, A.R., Tisotti, T.M. :
High-resolution melting analysis for detection of a single-nucleotide polymorphism and the genotype of the myostatin gene in warmblood horses. Am J Vet Res 78:63-68, 2017. Pubmed reference: 28029290. DOI: 10.2460/ajvr.78.1.63.
Tozaki, T., Kikuchi, M., Kakoi, H., Hirota, K.I., Nagata, S.I. :
A genome-wide association study for body weight in Japanese Thoroughbred racehorses clarifies candidate regions on chromosomes 3, 9, 15, and 18. J Equine Sci 28:127-134, 2017. Pubmed reference: 29270069. DOI: 10.1294/jes.28.127.
2016 François, L., Jäderkvist Fegraeus, K., Eriksson, S., Andersson, L.S., Tesfayonas, Y.G., Viluma, A., Imsland, F., Buys, N., Mikko, S., Lindgren, G., Velie, B.D. :
Conformation Traits and Gaits in the Icelandic Horse are Associated with Genetic Variants in Myostatin (MSTN). J Hered 107:431-7, 2016. Pubmed reference: 27208149. DOI: 10.1093/jhered/esw031.
Negro Rama, S., Valera, M., Membrillo, A., Gómez, M.D., Solé, M., Menendez-Buxadera, A., Anaya, G., Molina, A. :
Quantitative analysis of short- and long-distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses. J Anim Breed Genet 133:347-56, 2016. Pubmed reference: 26991374. DOI: 10.1111/jbg.12208.
2015 Santagostino, M., Khoriauli, L., Gamba, R., Bonuglia, M., Klipstein, O., Piras, F.M., Vella, F., Russo, A., Badiale, C., Mazzagatti, A., Raimondi, E., Nergadze, S.G., Giulotto, E. :
Genome-wide evolutionary and functional analysis of the Equine Repetitive Element 1: an insertion in the myostatin promoter affects gene expression. BMC Genet 16:126, 2015. Pubmed reference: 26503543. DOI: 10.1186/s12863-015-0281-1.
Shin, D.H., Lee, J.W., Park, J.E., Choi, I.Y., Oh, H.S., Kim, H.J., 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 28:771-81, 2015. Pubmed reference: 25925054. DOI: 10.5713/ajas.14.0008.
van den Hoven, R., Gür, E., Schlamanig, M., Hofer, M., Onmaz, A.C., Steinborn, R. :
Putative regulation mechanism for the MSTN gene by a CpG island generated by the SINE marker Ins227bp. BMC Vet Res 11:138, 2015. Pubmed reference: 26100061. DOI: 10.1186/s12917-015-0428-3.
2014 Dall'Olio, S., Scotti, E., Fontanesi, L., Tassinari, M. :
Analysis of the 227 bp short interspersed nuclear element (SINE) insertion of the promoter of the myostatin (MSTN) gene in different horse breeds. Vet Ital 50:193-7, 2014. Pubmed reference: 25273961. DOI: 10.12834/VetIt.61.178.3.
Petersen, J.L., Valberg, S.J., Mickelson, J.R., McCue, M.E. :
Haplotype diversity in the equine myostatin gene with focus on variants associated with race distance propensity and muscle fiber type proportions. Anim Genet 45:827-35, 2014. Pubmed reference: 25160752. DOI: 10.1111/age.12205.
2013 Petersen, J.L., Mickelson, J.R., Rendahl, A.K., Valberg, S.J., Andersson, L.S., Axelsson, J., Bailey, E., Bannasch, D., Binns, M.M., Borges, A.S., Brama, P., da Câmara Machado, A., Capomaccio, S., Cappelli, K., Cothran, E.G., Distl, O., Fox-Clipsham, L., Graves, K.T., Guérin, G., Haase, B., Hasegawa, T., Hemmann, K., Hill, E.W., Leeb, T., Lindgren, G., Lohi, H., Lopes, M.S., McGivney, B.A., Mikko, S., Orr, N., Penedo, M.C., Piercy, R.J., Raekallio, M., Rieder, S., Røed, K.H., Swinburne, J., Tozaki, T., Vaudin, M., Wade, C.M., McCue, M.E. :
Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLoS Genet 9:e1003211, 2013. Pubmed reference: 23349635. DOI: 10.1371/journal.pgen.1003211.
2012 Bower, M.A., McGivney, B.A., Campana, M.G., Gu, J., Andersson, L.S., Barrett, E., Davis, C.R., Mikko, S., Stock, F., Voronkova, V., Bradley, D.G., Fahey, A.G., Lindgren, G., MacHugh, D.E., Sulimova, G., Hill, E.W. :
The genetic origin and history of speed in the Thoroughbred racehorse. Nat Commun 3:643, 2012. Pubmed reference: 22273681. DOI: 10.1038/ncomms1644.
Hill, E.W., Fonseca, R.G., McGivney, B.A., Gu, J., MacHugh, D.E., Katz, L.M. :
MSTN genotype (g.66493737C/T) association with speed indices in Thoroughbred racehorses. J Appl Physiol 112:86-90, 2012. Pubmed reference: 22016373. DOI: 10.1152/japplphysiol.00793.2011.
Hill, E.W., Ryan, D.P., MacHugh, D.E. :
Horses for courses: a DNA-based test for race distance aptitude in thoroughbred racehorses. Recent Pat DNA Gene Seq 6:203-8, 2012. Pubmed reference: 22845060.
McGivney, B.A., Browne, J.A., Fonseca, R.G., Katz, L.M., Machugh, D.E., Whiston, R., Hill, E.W. :
MSTN genotypes in Thoroughbred horses influence skeletal muscle gene expression and racetrack performance. Anim Genet 43:810-2, 2012. Pubmed reference: 22497477. DOI: 10.1111/j.1365-2052.2012.02329.x.
Tozaki, T., Hill, E.W., 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 43:42-52, 2012. Pubmed reference: 22221024. DOI: 10.1111/j.1365-2052.2011.02201.x.
2010 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 Suppl 2:154-8, 2010. Pubmed reference: 21070290. DOI: 10.1111/j.1365-2052.2010.02126.x.
Hill, E.W., Gu, J., Eivers, S.S., Fonseca, R.G., McGivney, B.A., Govindarajan, P., Orr, N., Katz, L.M., MacHugh, D.E., MacHugh, D. :
A sequence polymorphism in MSTN predicts sprinting ability and racing stamina in thoroughbred horses. PLoS One 5:e8645, 2010. Pubmed reference: 20098749. DOI: 10.1371/journal.pone.0008645.
Hill, E.W., McGivney, B.A., Gu, J., Whiston, R., Machugh, D.E. :
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 11:552, 2010. Pubmed reference: 20932346. DOI: 10.1186/1471-2164-11-552.
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 41 Suppl 2:28-35, 2010. Pubmed reference: 21070273. DOI: 10.1111/j.1365-2052.2010.02095.x.
2009 Gu, J., Orr, N., Park, S.D., Katz, L.M., Sulimova, G., MacHugh, D.E., Hill, E.W. :
A genome scan for positive selection in thoroughbred horses. PLoS One 4:e5767, 2009. Pubmed reference: 19503617. DOI: 10.1371/journal.pone.0005767.

Edit History


  • Created by Frank Nicholas on 01 Dec 2010
  • Changed by Frank Nicholas on 29 Sep 2015
  • Changed by Frank Nicholas on 05 Feb 2019
  • Changed by Frank Nicholas on 11 Feb 2019