Association between equine temperament and polymorphisms in dopamine D4 receptor gene.
Abstract: The variable number of tandem repeats (VNTR) polymorphism of the dopamine D4 receptor (DRD4) gene has been reported to be associated with the personality trait of novelty-seeking in humans. In the genus Equus, this region includes an 18-bp repeat unit and there are inter- and intraspecies differences in the number of repetitions. Because horses are unique among livestock species in that their temperament is considered important, we investigated the possible role of this region on equine temperament in thoroughbred horses. We simultaneously determined the sequences of this polymorphic region and administered a questionnaire survey to horse caretakers with questions about 20 different traits of their horses' temperament. Although there was no difference in the number of repeats among the 136 thoroughbred horses studied, two single nucleotide polymorphisms (SNPs), one of which might cause an amino acid change (A-G substitution), existed. By analyzing the association between these SNPs and temperament scores, a significant association was revealed between two temperament traits (Curiosity and Vigilance) and the A-G substitution. Horses without the A allele had significantly higher Curiosity and lower Vigilance scores than those with the A allele at the A-G substitution. In addition, similar associations between both temperament scores and each genotype of the A-G substitution were observed in two subgroups divided according to the time of their introduction to the farm. These results suggested that the SNP in the VNTR region of the equine DRD4 gene might be related to individual differences in equine temperament.
Publication Date: 2005-09-10 PubMed ID: 16151699DOI: 10.1007/s00335-005-0021-3Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examines whether there is a correlation between horse temperament and variations in the dopamine D4 receptor gene, focusing on thoroughbred horses specifically. Notably, the research indicates a connection between the A-G substitution within this gene and the behavioral traits of curiosity and vigilance.
About the Research
- The researchers are investigating the potential impact of a polymorphism of the dopamine D4 receptor (DRD4) gene on the temperament of horses, particularly thoroughbred ones. This gene in humans has been previously linked to the personality trait of novelty-seeking.
- In horses, the section of interest within the DRD4 gene contains an 18-bp repeat unit. Scientists have noted differences in the number of repetitions both between different horse species, and between individual horses of the same species.
Experiment Setup and Findings
- The study compiled the sequence data of the polymorphic region in question from 136 thoroughbred horses. Simultaneously, a survey was conducted among horse caretakers, asking about 20 different facets of their horses’ temperament.
- While the number of repeats found in this gene segment did not differ among the thoroughbreds, two distinct single nucleotide polymorphisms (SNPs) were observed. An SNP is a variation in a single nucleotide, the basic building block of DNA. One of the SNPs could potentially cause an amino acid change (an A-G substitution).
- Statistical analysis revealed a significant association between this A-G substitution and two specific temperament traits: Curiosity and Vigilance. Horses lacking the A allele had significantly higher Curiosity and lower Vigilance scores compared to those possessing the A allele.
- This pattern was consistently observed in two subgroups, separated based on the time they were introduced to the farm. This suggests that the observed relationships are not due to environmental influences but are related to the genetic difference.
- This evidence supports the hypothesis that the SNP in the DRD4 gene’s VNTR region may be associated with individual differences in horse temperament.
Cite This Article
APA
Momozawa Y, Takeuchi Y, Kusunose R, Kikusui T, Mori Y.
(2005).
Association between equine temperament and polymorphisms in dopamine D4 receptor gene.
Mamm Genome, 16(7), 538-544.
https://doi.org/10.1007/s00335-005-0021-3 Publication
Researcher Affiliations
- Laboratory of Veterinary Ethology, The University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-8657, Japan,
MeSH Terms
- Animals
- Base Sequence
- DNA Primers
- Horses / genetics
- Horses / physiology
- Minisatellite Repeats / genetics
- Molecular Sequence Data
- Mutation / genetics
- Polymorphism, Single Nucleotide
- Receptors, Dopamine D4 / genetics
- Sequence Analysis, DNA
- Surveys and Questionnaires
- Temperament / physiology
References
This article includes 27 references
- Livak KJ, Rogers J, Lichter JB. Variability of dopamine D4 receptor (DRD4) gene sequence within and among nonhuman primate species.. Proc Natl Acad Sci U S A 1995 Jan 17;92(2):427-31.
- Fishburn CS, Carmon S, Fuchs S. Molecular cloning and characterisation of the gene encoding the murine D4 dopamine receptor.. FEBS Lett 1995 Mar 20;361(2-3):215-9.
- Westberg L, Melke J, Landén M, Nilsson S, Baghaei F, Rosmond R, Jansson M, Holm G, Björntorp P, Eriksson E. Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women.. Mol Psychiatry 2003 Jan;8(1):118-22.
- Momozawa Y, Takeuchi Y, Tozaki T, Kikusui T, Hasegawa T, Raudsepp T, Chowdhary BP, Kusunose R, Mori Y. Sequence, detection of polymorphisms and radiation hybrid mapping of the equine catechol-o-methyltransferase gene.. Anim Genet 2005 Apr;36(2):190.
- Ito H, Nara H, Inoue-Murayama M, Shimada MK, Koshimura A, Ueda Y, Kitagawa H, Takeuchi Y, Mori Y, Murayama Y, Morita M, Iwasaki T, Ota K, Tanabe Y, Ito S. Allele frequency distribution of the canine dopamine receptor D4 gene exon III and I in 23 breeds.. J Vet Med Sci 2004 Jul;66(7):815-20.
- Mader DR, Price EO. Discrimination learning in horses: effects of breed, age and social dominance.. J Anim Sci 1980 May;50(5):962-5.
- Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine.. Nature 1991 Apr 18;350(6319):610-4.
- Visser EK, van Reenen CG, van der Werf JT, Schilder MB, Knaap JH, Barneveld A, Blokhuis HJ. Heart rate and heart rate variability during a novel object test and a handling test in young horses.. Physiol Behav 2002 Jun 1;76(2):289-96.
- Reif A, Lesch KP. Toward a molecular architecture of personality.. Behav Brain Res 2003 Feb 17;139(1-2):1-20.
- Comings DE, MacMurray JP. Molecular heterosis: a review.. Mol Genet Metab 2000 Sep-Oct;71(1-2):19-31.
- Liu IS, Seeman P, Sanyal S, Ulpian C, Rodgers-Johnson PE, Serjeant GR, Van Tol HH. Dopamine D4 receptor variant in Africans, D4valine194glycine, is insensitive to dopamine and clozapine: report of a homozygous individual.. Am J Med Genet 1996 Jan 22;61(3):277-82.
- Inoue-Murayama M, Matsuura N, Murayama Y, Tsubota T, Iwasaki T, Kitagawa H, Ito S. Sequence comparison of the dopamine receptor D4 exon III repetitive region in several species of the order Carnivora.. J Vet Med Sci 2002 Aug;64(8):747-9.
- Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character.. Arch Gen Psychiatry 1993 Dec;50(12):975-90.
- O'Malley KL, Harmon S, Tang L, Todd RD. The rat dopamine D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system.. New Biol 1992 Feb;4(2):137-46.
- Seeman P, Ulpian C, Chouinard G, Van Tol HH, Dwosh H, Lieberman JA, Siminovitch K, Liu IS, Waye J, Voruganti P. Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.. Am J Med Genet 1994 Dec 15;54(4):384-90.
- Nöthen MM, Cichon S, Hemmer S, Hebebrand J, Remschmidt H, Lehmkuhl G, Poustka F, Schmidt M, Catalano M, Fimmers R. Human dopamine D4 receptor gene: frequent occurrence of a null allele and observation of homozygosity.. Hum Mol Genet 1994 Dec;3(12):2207-12.
- Lusher JM, Chandler C, Ball D. Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues... Mol Psychiatry 2001 Sep;6(5):497-9.
- Cichon S, Nöthen MM, Catalano M, Di Bella D, Maier W, Lichtermann D, Minges J, Albus M, Borrmann M, Franzek E. Identification of two novel polymorphisms and a rare deletion variant in the human dopamine D4 receptor gene.. Psychiatr Genet 1995 Fall;5(3):97-103.
- Hausberger M, Bruderer C, Le Scolan N, Pierre JS. Interplay between environmental and genetic factors in temperament/personality traits in horses (Equus caballus).. J Comp Psychol 2004 Dec;118(4):434-46.
- Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH. Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking.. Nat Genet 1996 Jan;12(1):81-4.
- Paterson AD, Sunohara GA, Kennedy JL. Dopamine D4 receptor gene: novelty or nonsense?. Neuropsychopharmacology 1999 Jul;21(1):3-16.
- Catalano M, Nobile M, Novelli E, Nöthen MM, Smeraldi E. Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients.. Biol Psychiatry 1993 Oct 1;34(7):459-64.
- Bland JM, Altman DG. Multiple significance tests: the Bonferroni method.. BMJ 1995 Jan 21;310(6973):170.
- Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA. Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli.. J Neurosci 1999 Nov 1;19(21):9550-6.
- Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M, Belmaker RH. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking.. Nat Genet 1996 Jan;12(1):78-80.
- Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V. Multiple dopamine D4 receptor variants in the human population.. Nature 1992 Jul 9;358(6382):149-52.
- Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR, Kidd KK, Flodman P, Spence MA, Schuck S, Swanson JM, Zhang YP, Moyzis RK. Evidence of positive selection acting at the human dopamine receptor D4 gene locus.. Proc Natl Acad Sci U S A 2002 Jan 8;99(1):309-14.
Citations
This article has been cited 22 times.- Yokomori T, Ohnuma A, Tozaki T, Segawa T, Itou T. Identification of Personality-Related Candidate Genes in Thoroughbred Racehorses Using a Bioinformatics-Based Approach Involving Functionally Annotated Human Genes. Animals (Basel) 2023 Feb 20;13(4).
- Mai S, Wittor C, Merker S, Woog F. DRD4 allele frequencies in greylag geese vary between urban and rural sites. Ecol Evol 2023 Feb;13(2):e9811.
- Pan J, Purev C, Zhao H, Zhang Z, Wang F, Wendoule N, Qi G, Liu Y, Zhou H. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse. Open Life Sci 2022;17(1):1269-1281.
- Kim J, Jung H, Choi JY, Lee JW, Yoon M. Plasma concentration of dopamine varies depending on breed, sex, and the genotype of DRD4 in horses. J Anim Sci Technol 2022 Jul;64(4):792-799.
- Garza-Brenner E, Sifuentes-Rincón AM, Randel RD, Paredes-Sánchez FA, Parra-Bracamonte GM, Arellano Vera W, Rodríguez Almeida FA, Segura Cabrera A. Association of SNPs in dopamine and serotonin pathway genes and their interacting genes with temperament traits in Charolais cows. J Appl Genet 2017 Aug;58(3):363-371.
- Valente TS, Baldi F, Sant'Anna AC, Albuquerque LG, Paranhos da Costa MJ. Genome-Wide Association Study between Single Nucleotide Polymorphisms and Flight Speed in Nellore Cattle. PLoS One 2016;11(6):e0156956.
- Ninomiya S, Anjiki A, Nishide Y, Mori M, Deguchi Y, Satoh T. Polymorphisms of the Dopamine D4 Receptor Gene in Stabled Horses are Related to Differences in Behavioral Response to Frustration. Animals (Basel) 2013 Jul 26;3(3):663-9.
- Riyahi S, Sánchez-Delgado M, Calafell F, Monk D, Senar JC. Combined epigenetic and intraspecific variation of the DRD4 and SERT genes influence novelty seeking behavior in great tit Parus major. Epigenetics 2015;10(6):516-25.
- Komiyama T, Iwama H, Osada N, Nakamura Y, Kobayashi H, Tateno Y, Gojobori T. Dopamine receptor genes and evolutionary differentiation in the domestication of fighting cocks and long-crowing chickens. PLoS One 2014;9(7):e101778.
- Garamszegi LZ, Mueller JC, Markó G, Szász E, Zsebők S, Herczeg G, Eens M, Török J. The relationship between DRD4 polymorphisms and phenotypic correlations of behaviors in the collared flycatcher. Ecol Evol 2014 Apr;4(8):1466-79.
- Hori Y, Ozaki T, Yamada Y, Tozaki T, Kim HS, Takimoto A, Endo M, Manabe N, Inoue-Murayama M, Fujita K. Breed Differences in Dopamine Receptor D4 Gene (DRD4) in Horses. J Equine Sci 2013;24(3):31-6.
- 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.
- Kubinyi E, Vas J, Hejjas K, Ronai Z, Brúder I, Turcsán B, Sasvari-Szekely M, Miklósi A. Polymorphism in the tyrosine hydroxylase (TH) gene is associated with activity-impulsivity in German Shepherd Dogs. PLoS One 2012;7(1):e30271.
- Abe H, Ito S, Inoue-Murayama M. Polymorphisms in the extracellular region of dopamine receptor D4 within and among avian orders. J Mol Evol 2011 Mar;72(3):253-64.
- Bell AM, Aubin-Horth N. What can whole genome expression data tell us about the ecology and evolution of personality?. Philos Trans R Soc Lond B Biol Sci 2010 Dec 27;365(1560):4001-12.
- Kubikova L, Wada K, Jarvis ED. Dopamine receptors in a songbird brain. J Comp Neurol 2010 Mar 15;518(6):741-69.
- Kubikova L, Kostál L. Dopaminergic system in birdsong learning and maintenance. J Chem Neuroanat 2010 Mar;39(2):112-23.
- Fidler AE, van Oers K, Drent PJ, Kuhn S, Mueller JC, Kempenaers B. Drd4 gene polymorphisms are associated with personality variation in a passerine bird. Proc Biol Sci 2007 Jul 22;274(1619):1685-91.
- Sharma M, Singh A, Kumar V, Olla N, Arora R, Sharma R, Mohan NH, Ahlawat S. Advances in Equine Genomics: Decoding the Genetic Architecture of Morphology, Performance, Behavior, and Adaptation. Mol Biotechnol 2025 Dec 19;.
- Knox AL, Fenner K, Zsoldos RR, Wilson B, McGreevy P. Owner-Observed Behavioral Characteristics in Off-the-Track Thoroughbreds (OTTTBs) in Equestrian Second Careers. Animals (Basel) 2025 Jul 11;15(14).
- Sigurðardóttir H, Eriksson S, Niazi A, Rhodin M, Albertsdóttir E, Kristjansson T, Lindgren G. Genetic influence of a STAU2 frameshift mutation and RELN regulatory elements on performance in Icelandic horses. Sci Rep 2025 Apr 4;15(1):11641.
- Tomberg C, Petagna M, de Selliers de Moranville LA. Spontaneous eye blinks in horses (Equus caballus) are modulated by attention. Sci Rep 2024 Aug 20;14(1):19336.
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