OMIA:001715-9796 : Gaitedness, DMRT3-related in Equus caballus (horse)

In other species: ass (donkey) , Przewalski's horse , mule

Categories: Normal phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614754 (gene)

Mendelian trait/disorder: yes

Disease-related: no

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: All horses have three naturally occurring gaits, namely (in order of increasing speed) walk (four-beat, lateral), trot (two-beat, diagonal) and gallop (four-beat). Some breeds of horse exhibit more than one form of a particular gait, particularly at intermediate speeds. The alternate forms of intermediate-speed gait are classified as pace (a two-beat gait) or ambling (a four-beat gait), which can be regular (including the Tölt gait of Icelandic horses), lateral or diagonal. Some breeds are four-gaited (e.g. walk, tölt, trot and gallop) and others are five-gaited (e.g. walk, tölt, trot, gallop and pace). "Gaitedness" is the ability to exhibit alternate forms of gait. Gaited breeds included Icelandic horses, Kentucky mountain saddle horse, Missouri fox trotter, Paso fino, Peruvian paso, and Rocky mountain horse, Tennessee walking horse. Non-gaited breeds include Arabian horse, Gotland pony, North-Swedish draft horse, Przewalski’s horse, Shetland pony, Swedish ardennes, Swedish warmblood, and Thoroughbred. (Information taken from Andersson et al., 2012)
Renamed from 'Gaitedness' to 'Gaitedness, DMRT3-related' [10/06/2024]

Inheritance: Sigurðardóttir et al. (2023) provided convincing evidence of the multifactorial nature of gaitedness. However, this entry focuses on variation in gaitedness due to DMRT3 variants and is therefore listed as single locus related in horses.

Markers: Noting that the DMRT3 likely causal variant "is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing", McCoy et al. (2019) realised that "This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations." A GWAS enabled these authors to eventually identify seven SNPs located on six chromosomes (1, 6, 17, 23, 25, 30) that jointly "predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters)". This is a classic illustration of the multifactorial nature of this trait.

Molecular basis: From a genome scan of 70 Icelandic horses (40 that can pace and 30 that can't pace), Andersson et al. (2012) identified a 684kb region of chromosome ECA23 showing a very strong association with ability to pace. Resequencing within this region eventually identified the causative mutation as a nonsense mutation (Ser301STOP) in DMRT3 (previously listed as LOC100147177 in NCBI), which encodes a transcription factor with a DM domain. Detailed analysis of wild-type and DMRT3-null mice revealed that Dmrt3 has "a pivotal role for configuring the spinal circuits controlling stride in vertebrates". In horses, "The [DMRT3] mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance". In Icelandic horses, "homozygosity for the DMRT3 nonsense mutation is required for the ability to pace in this breed".

Prevalence: Promerová et al. (2014) "genotyped 4396 horses representing 141 horse breeds for the DMRT3 stop mutation. More than half (2749) of these horses also were genotyped for a SNP situated 32 kb upstream of the DMRT3 nonsense mutation because these two SNPs are in very strong linkage disequilibrium. We show that the DMRT3 mutation is present in 68 of the 141 genotyped horse breeds at a frequency ranging from 1% to 100%. We also show that the mutation is not limited to a geographical area, but is found worldwide. The breeds with a high frequency of the stop mutation (>50%) are either classified as gaited or bred for harness racing."

Breeds: American Trotter (Horse) (VBO_0000899), Bhotia Pony, India (Horse) (VBO_0010442), French Trotter (Horse) (VBO_0000968), Icelandic Horse (Horse) (VBO_0000991), Kentucky Mountain Saddle, United States of America (Horse) (VBO_0016871), Missouri Fox Trotting Horse (Horse) (VBO_0017148), Morgan (Horse) (VBO_0001022), Paso Fino (Horse) (VBO_0001040), Peruvian Paso (Horse) (VBO_0001042), Quarter Horse (Horse) (VBO_0001057), Rocky Mountain Horse (Horse) (VBO_0017168), Scandinavian Coldblood Trotter (Horse) (VBO_0017173), Spiti Pony, India (Horse) (VBO_0011561), Tennessee Walking Horse (Horse) (VBO_0001081), Thoroughbred (Horse) (VBO_0001083), Zaniskari Pony (Horse) (VBO_0017198).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DMRT3 doublesex and mab-3 related transcription factor 3 Equus caballus 23 NC_009166.3 (22378399..22392510) DMRT3 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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
321 American Trotter (Horse) Bhotia Pony, India (Horse) French Trotter (Horse) Icelandic Horse (Horse) Kentucky Mountain Saddle, United States of America (Horse) Missouri Fox Trotting Horse (Horse) Morgan (Horse) Paso Fino (Horse) Peruvian Paso (Horse) Quarter Horse (Horse) Rocky Mountain Horse (Horse) Scandinavian Coldblood Trotter (Horse) Spiti Pony, India (Horse) Tennessee Walking Horse (Horse) Thoroughbred (Horse) Zaniskari Pony (Horse) Gaitedness DMRT3 nonsense (stop-gain) Naturally occurring variant EquCab3.0 23 NC_009166.3:g.22391254C>A NM_001317265.1:c.902C>A NP_001304194.1:p.(S301*) rs1150690013 2012 22932389 Breed information updated based on PMID:38600096 and PMID:37149793

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001715-9796: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2024 Durward-Akhurst, S.A., Marlowe, J.L., Schaefer, R.J., Springer, K., Grantham, B., Carey, W.K., Bellone, R.R., Mickelson, J.R., McCue, M.E. :
Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 14:8396, 2024. Pubmed reference: 38600096. DOI: 10.1038/s41598-024-57872-8.
2023 Amano, T., Yokawa, H., Masuda, Y., Tozaki, T., Kawai, M., Shirai, K. :
Genome-wide search reveals the uniqueness of DNA regions associated with coat color and innate immunity in Hokkaido Native Horse. Anim Sci J 94:e13884, 2023. Pubmed reference: 37983921. DOI: 10.1111/asj.13884.
Han, H., Randhawa, I.A.S., MacHugh, D.E., McGivney, B.A., Katz, L.M., Dugarjaviin, M., Hill, E.W. :
Selection signatures for local and regional adaptation in Chinese Mongolian horse breeds reveal candidate genes for hoof health. BMC Genomics 24:35, 2023. Pubmed reference: 36658473. DOI: 10.1186/s12864-023-09116-8.
Herman, M., Caceres, A.M., Albuquerque, A.L.H., Leite, R.O., Araújo, C.E.T., Delfiol, D.J.Z., Curi, R.A., Borges, A.S., Oliveira-Filho, J.P. :
DMRT3 allele frequencies in batida- and picada-gaited donkeys and mules in Brazil. Animals (Basel) 13:3829, 2023. Pubmed reference: 38136866. DOI: 10.3390/ani13243829.
Saito, I., Nakamura, K., Tozaki, T., Hano, K., Takasu, M. :
Genetic characterization of Japanese native horse breeds by genotyping variants that are associated with phenotypic traits. J Equine Sci 34:115-120, 2023. Pubmed reference: 38274555. DOI: 10.1294/jes.34.115.
Sigurðardóttir, H., Boije, H., Albertsdóttir, E., Kristjansson, T., Rhodin, M., Lindgren, G., Eriksson, S. :
The genetics of gaits in Icelandic horses goes beyond DMRT3, with RELN and STAU2 identified as two new candidate genes. Genet Sel Evol 55:89, 2023. Pubmed reference: 38082412. DOI: 10.1186/s12711-023-00863-6.
Sonali, Bhardwaj, A,, Unnati, Nayan, V., Legha, R.A., Bhattacharya, T.K., Pal, Y., Giri, S.K. :
Identification and characterization of single nucleotide polymorphisms in DMRT3 gene in Indian horse (Equus caballus) and donkey (Equus asinus) populations. Anim Biotechnol 34:4910-4920, 2023. Pubmed reference: 37149793. DOI: 10.1080/10495398.2023.2206866.
Vincelette, A. :
The characteristics, distribution, function, and origin of alternative lateral horse gaits. Animals (Basel) 13:2557, 2023. Pubmed reference: 37627349. DOI: 10.3390/ani13162557.
2021 Patterson Rosa, L., Staiger, E.A., Martin, K., Vierra, M., Foster, G., Lundquist, E., Brooks, S.A., Lafayette, C. :
Stock-type equine disciplines Hunter, Reining and Roping are associated with the A allele at the DMRT3 locus for gait phenotypes in the horse. Anim Genet 52:773-4, 2021. Pubmed reference: 34250625. DOI: 10.1111/age.13110.
Ricard, A., Duluard, A. :
Genomic analysis of gaits and racing performance of the French trotter. J Anim Breed Genet 138:204-222, 2021. Pubmed reference: 33249655. DOI: 10.1111/jbg.12526.
Rosengren, M.K., Sigurðardóttir, H., Eriksson, S., Naboulsi, R., Jouni, A., Novoa-Bravo, M., Albertsdóttir, E., Kristjánsson, Þ., Rhodin, M., Viklund, Å., Velie, B.D., Negro, J.J., Solé, M., Lindgren, G. :
A QTL for conformation of back and croup influences lateral gait quality in Icelandic horses. BMC Genomics 22:267, 2021. Pubmed reference: 33853519. DOI: 10.1186/s12864-021-07454-z.
2020 Nguyen, T.B., Paul, R.C., Okuda, Y., LE, T.N.A., Pham, P.T.K., Kaissar, K.J., Kazhmurat, A., Bibigul, S., Bakhtin, M., Kazymbet, P., Maratbek, S.Z., Meldebekov, A., Nishibori, M., Ibi, T., Tsuji, T., Kunieda, T. :
Genetic characterization of Kushum horses in Kazakhstan based on haplotypes of mtDNA and Y chromosome, and genes associated with important traits of the horses. J Equine Sci 31:35-43, 2020. Pubmed reference: 33061782. DOI: 10.1294/jes.31.35.
2019 McCoy, A.M., Beeson, S.K., Rubin, C.J., Andersson, L., Caputo, P., Lykkjen, S., Moore, A., Piercy, R.J., Mickelson, J.R., McCue, M.E. :
Identification and validation of genetic variants predictive of gait in standardbred horses. PLoS Genet 15:e1008146, 2019. Pubmed reference: 31136578. DOI: 10.1371/journal.pgen.1008146.
2018 Novoa-Bravo, M., Jäderkvist Fegraeus, K., Rhodin, M., Strand, E., García, L.F., Lindgren, G. :
Selection on the Colombian paso horse's gaits has produced kinematic differences partly explained by the DMRT3 gene. PLoS One 13:e0202584, 2018. Pubmed reference: 30118522. DOI: 10.1371/journal.pone.0202584.
2017 Jäderkvist Fegraeus, K., Lawrence, C., Petäjistö, K., Johansson, M.K., Wiklund, M., Olsson, C., Andersson, L., Andersson, L.S., Røed, K.H., Ihler, C.F., Strand, E., Lindgren, G., Velie, B.D. :
Lack of significant associations with early career performance suggest no link between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters. PLoS One 12:e0177351, 2017. Pubmed reference: 28489879. DOI: 10.1371/journal.pone.0177351.
Jäderkvist Fegraeus, K., Hirschberg, I., Árnason, T., Andersson, L., Velie, B.D., Andersson, L.S., 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, 2017. Pubmed reference: 29023800. DOI: 10.1111/age.12610.
Staiger, E.A., Almén, M.S., Promerová, M., Brooks, S., Cothran, E.G., Imsland, F., Jäderkvist Fegraeus, K., Lindgren, G., Mehrabani Yeganeh, H., Mikko, S., Vega-Pla, J.L., Tozaki, T., Rubin, C.J., Andersson, L. :
The evolutionary history of the DMRT3 'Gait keeper' haplotype. Anim Genet 48:551-559, 2017. Pubmed reference: 28741731. DOI: 10.1111/age.12580.
2016 Leroy, G., Besbes, B., Boettcher, P., Hoffmann, I., Capitan, A., Baumung, R. :
Rare phenotypes in domestic animals: unique resources for multiple applications. Anim Genet 47:141-53, 2016. Pubmed reference: 26662214. DOI: 10.1111/age.12393.
Regatieri, I.C., Eberth, J.E., Sarver, F., Lear, T.L., Bailey, E. :
Comparison of DMRT3 genotypes among American Saddlebred horses with reference to gait. Anim Genet 47:603-5, 2016. Pubmed reference: 27295976. DOI: 10.1111/age.12458.
Wutke, S., Andersson, L., Benecke, N., Sandoval-Castellanos, E., Gonzalez, J., Hallsson, J.H., Lõugas, L., Magnell, O., Morales-Muniz, A., Orlando, L., Pálsdóttir, A.H., Reissmann, M., Muñoz-Rodríguez, M.B., Ruttkay, M., Trinks, A., Hofreiter, M., Ludwig, A. :
The origin of ambling horses. Curr Biol 26:R697-9, 2016. Pubmed reference: 27505236. DOI: 10.1016/j.cub.2016.07.001.
2015 Han, H., Zeng, L., Dang, R., Lan, X., Chen, H., Lei, C. :
The DMRT3 gene mutation in Chinese horse breeds. Anim Genet 46:341-2, 2015. Pubmed reference: 25917306. DOI: 10.1111/age.12292.
Jäderkvist Fegraeus, K., Johansson, L., Mäenpää, M., Mykkänen, A., Andersson, L.S., Velie, B.D., Andersson, L., Árnason, T., Lindgren, G. :
Different DMRT3 Genotypes Are Best Adapted for Harness Racing and Riding in Finnhorses. J Hered 106:734-40, 2015. Pubmed reference: 26285915. DOI: 10.1093/jhered/esv062.
Patterson, L., Staiger, E.A., Brooks, S.A. :
DMRT3 is associated with gait type in Mangalarga Marchador horses, but does not control gait ability. Anim Genet 46:213-5, 2015. Pubmed reference: 25690906. DOI: 10.1111/age.12273.
2014 Jäderkvist, K., Andersson, L.S., Johansson, A.M., Árnason, T., Mikko, S., Eriksson, S., Andersson, L., Lindgren, G. :
The DMRT3 'Gait keeper' mutation affects performance of Nordic and Standardbred trotters. J Anim Sci 92:4279-86, 2014. Pubmed reference: 25085403. DOI: 10.2527/jas.2014-7803.
Promerová, M., Andersson, L.S., Juras, R., Penedo, M.C., Reissmann, M., Tozaki, T., Bellone, R., Dunner, S., Hořín, P., Imsland, F., Imsland, P., Mikko, S., Modrý, D., Roed, K.H., Schwochow, D., Vega-Pla, J.L., Mehrabani-Yeganeh, H., Yousefi-Mashouf, N., G Cothran, E., Lindgren, G., Andersson, L. :
Worldwide frequency distribution of the 'Gait keeper' mutation in the DMRT3 gene. Anim Genet 45:274-82, 2014. Pubmed reference: 24444049. DOI: 10.1111/age.12120.
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 Andersson, L.S., Larhammar, M., Memic, F., Wootz, H., Schwochow, D., Rubin, C.J., Patra, K., Arnason, T., Wellbring, L., Hjälm, G., Imsland, F., Petersen, J.L., McCue, M.E., Mickelson, J.R., 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 488:642-6, 2012. Pubmed reference: 22932389. DOI: 10.1038/nature11399.
1987 Cothran, E.G., MacCluer, J.W., Weitkamp, L.R., Bailey, E. :
Genetic differentiation associated with gait within American standardbred horses. Anim Genet 18:285-96, 1987. Pubmed reference: 3481678. DOI: 10.1111/j.1365-2052.1987.tb00772.x.
1907 Bateson, W. :
Trotting and pacing: dominant and recessive? Science 26:908, 1907.

Edit History


  • Created by Frank Nicholas on 30 Aug 2012
  • Changed by Frank Nicholas on 30 Aug 2012
  • Changed by Frank Nicholas on 31 Aug 2012
  • Changed by Frank Nicholas on 01 Feb 2014
  • Changed by Frank Nicholas on 21 Aug 2018
  • Changed by Frank Nicholas on 30 May 2019
  • Changed by Imke Tammen2 on 14 Aug 2021
  • Changed by Imke Tammen2 on 14 Nov 2023
  • Changed by Frank Nicholas on 15 Dec 2023
  • Changed by Imke Tammen2 on 03 Jun 2024
  • Changed by Imke Tammen2 on 04 Jun 2024
  • Changed by Imke Tammen2 on 05 Jun 2024
  • Changed by Imke Tammen2 on 07 Jun 2024
  • Changed by Imke Tammen2 on 10 Jun 2024