Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement1. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles2. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
Introduction The BLUP methodology has been applied to the genetic evaluation of Swedish standard‐bred trotters for well over a decade. Initially a BLUP sire model was applied for evaluating breeding values of stallions on the basis of the racing performance of their offspring (Árnason et al. 1989). In 1992 an animal model (AM‐) BLUP was introduced and official publication of index values were offered as an aid for effective selection of stallions and brood mares (Árnason 1992; Árnason and S vendsen 1991). The implementation of the BLUP animal model index has apparently caused profound enhancement in the selection intensity for both stallions and mares (Árnason 1997). The AM‐BLUP evaluation has involved the following traits, which were all based on accumulated racing results as 3‐ to 5‐year‐olds: Number of races (starts); % of races ranked first to third at the finish (i.e. placed first to third); earnings per race; total earnings; best racing time per km; and racing (or start) status, which is denoted as one if the horse did race at least once as a 3‐ to 5‐year‐old and zero otherwise. The two traits: number of races and racing status were initially treated as single traits, in the AM‐BLUP analyses, uncorrelated with the other racing performance traits. Those other traits are direct measures of racing performance for horses that have actually competed on the race track. They are highly intercorrelated and have been treated as a multivariate complex in the analyses. The computational load of general multivariate analyses has been considerably reduced by transformation of the records into uncorrelated canonical variates (e.g. Árnason 1982). In Sweden, about 40% of standard‐bred trotters do not enter a race course and their racing performance variables have previously been treated as missing. Early analysis on the population of standard‐bred trotters in Sweden did not show any correlation between racing status of brood mares and the racing performance of their offspring (M. B endroth, unpublished results). That gave justification for assuming that racing status had mainly environmental causes, and to be practically genetically uncorrelated with performance. The exclusion of nonracers (nonstarters) was therefore not expected to bias genetic evaluations for the performance traits. The expansion of the population during the 1980s and the early 1990s, and increase in the level of prize money, has probably invalidated the implication of these results and partly changed the racing status into a preselection criterion for racing performance. K lemetsdal (1992) has clearly illustrated that such a culling process can result in substantial bias in estimated breeding values. In 1995 a new enhanced procedure replaced the older version used for routine genetic evaluation of Swedish standard‐bred trotters, with the aim of eliminating, or at least reducing, the selection bias and increasing the accuracy in the genetic evaluations. The main objective of this paper was to describe the enhanced procedure for genetic evaluati...
A nonsense mutation in DMRT3 ('Gait keeper' mutation) has a predominant effect on gaiting ability in horses, being permissive for the ability to perform lateral gaits and having a favourable effect on speed capacity in trot. The DMRT3 mutant allele (A) has been found in high frequency in gaited breeds and breeds bred for harness racing, while other horse breeds were homozygous for the wild-type allele (C). The aim of this study was to evaluate further the effect of the DMRT3 nonsense mutation on the gait quality and speed capacity in the multigaited Icelandic horse and demonstrate how the frequencies of the A- and C- alleles have changed in the Icelandic horse population in recent decades. It was confirmed that homozygosity for the DMRT3 nonsense mutation relates to the ability to pace. It further had a favourable effect on scores in breeding field tests for the lateral gait tölt, demonstrated by better beat quality, speed capacity and suppleness. Horses with the CA genotype had on the other hand significantly higher scores for walk, trot, canter and gallop, and they performed better beat and suspension in trot and gallop. These results indicate that the AA genotype reinforces the coordination of ipsilateral legs, with the subsequent negative effect on the synchronized movement of diagonal legs compared with the CA genotype. The frequency of the A-allele has increased in recent decades with a corresponding decrease in the frequency of the C-allele. The estimated frequency of the A-allele in the Icelandic horse population in 2012 was 0.94. Selective breeding for lateral gaits in the Icelandic horse population has apparently altered the frequency of DMRT3 genotypes with a predicted loss of the C-allele in relatively few years. The results have practical implications for breeding and training of Icelandic horses and other gaited horse breeds.
Genetic evaluation of Icelandic horses is currently based on results from breeding field tests where riding ability and conformation of the horses are evaluated over the course of 1-2 days. Only a small part of registered horses attend these field tests, and it can be assumed that these are not a random sample of the population. In this study, the trait test status was introduced, describing whether a horse was assessed in a breeding field test. This trait was analysed to find out whether it has a genetic variation and how it correlates genetically to other traits in the breeding goal. Breeding field test data included 39,443 mares born in Iceland in 1990-2001, of which 7431 were assessed in the period 1994-2007. The trait was defined in relation to age, gender and stud of horses. Variance and covariance components were estimated using the Markov Chain Monte Carlo method by applying the Gibbs sampler procedure in the DMU program. Three multivariate analyses were performed where the test status trait was analysed with breeding field test traits. Animal models and sire models were applied. Based on estimated heritabilities (0.51-0.67) and genetic correlations (0.00-0.87), the test status trait showed significant genetic variation and was strongly correlated to some traits. The test status trait reflects preselection in the breeding field test traits and should be included in the genetic evaluation to enhance the procedure, reduce selection bias and increase accuracy of the estimation.
In a previous study it was shown that a nonsense mutation in the DMRT3 gene alters the pattern of locomotion in horses and that this mutation has a strong positive impact on trotting performance of Standardbreds. One aim of this study was to test if racing performance and trotting technique in the Nordic (Coldblood) trotters are also influenced by the DMRT3 genotype. Another aim was to further investigate the effect of the mutation on performance in Standardbreds, by using a within-family analysis and genotype-phenotype correlations in a larger horse material than in the previous study. We genotyped 427 Nordic trotters and 621 Standardbreds for the DMRT3 nonsense mutation and a SNP in strong linkage disequilibrium with it. In Nordic trotters, we show that horses homozygous for the DMRT3 mutation (A) had significantly higher EBV for trotting performance traits than heterozygous (CA) or homozygous wild-type (CC) horses (P = 0.001). Furthermore, AA homozygotes had a higher proportion of victories and top 3 placings than horses heterozygous or homozygous wild-type, when analyzing performance data for the period 3 to 6 yr of age (P = 0.06 and P = 0.05, respectively). Another finding in the Nordic trotters was that the DMRT3 mutation influenced trotting technique (P = 2.1 × 10(-8)). Standardbred horses homozygous AA had significantly higher EBV for all traits than horses with at least 1 wild-type allele (CA and CC; P = 1.6 × 10(-16)). In a within-family analysis of Standardbreds, we found significant differences in several traits (e.g., earnings, P = 0.002; number of entered races, P = 0.004; and fraction of offspring that entered races, P = 0.002) among paternal half-sibs with genotype AA or CA sired by a CA stallion. For most traits, we found significant differences at young ages. For Nordic trotters, most of the results were significant at 3 yr of age but not for the older ages, and for the Standardbreds most of the results for the ages 3 to 5 were significant. For Nordic trotters, the proportion of victories and placings were the only traits that were significant for other ages than 3 yr.
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