| 1. |
- Imsland, Freyja, et al.
(författare)
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Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation underlying Dun camouflage colour in horses
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:2, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings. Here we show that pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes. Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs. We identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication. These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation.
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| 2. |
- Promerová, Marta, et al.
(författare)
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Worldwide frequency distribution of the 'Gait keeper' mutation in the DMRT3 gene
- 2014
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Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 45:2, s. 274-282
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Tidskriftsartikel (refereegranskat)abstract
- For centuries, domestic horses have represented an important means of transport and served as working and companion animals. Although their role in transportation is less important today, many horse breeds are still subject to intense selection based on their pattern of locomotion. A striking example of such a selected trait is the ability of a horse to perform additional gaits other than the common walk, trot and gallop. Those could be four-beat ambling gaits, which are particularly smooth and comfortable for the rider, or pace, used mainly in racing. Gaited horse breeds occur around the globe, suggesting that gaitedness is an old trait, selected for in many breeds. A recent study discovered that a nonsense mutation in DMRT3 has a major impact on gaitedness in horses and is present at a high frequency in gaited breeds and in horses bred for harness racing. Here, we report a study of the worldwide distribution of this mutation. We 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 32kb 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.
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| 3. |
- Wade, C. M., et al.
(författare)
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Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
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Tidskriftsartikel (refereegranskat)abstract
- We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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| 4. |
- Wright, Dominic, et al.
(författare)
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Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens
- 2009
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 5:6, s. e1000512-
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Tidskriftsartikel (refereegranskat)abstract
- Pea-comb is a dominant mutation in chickens that drastically reduces the size of the comb and wattles. It is an adaptive trait in cold climates as it reduces heat loss and makes the chicken less susceptible to frost lesions. Here we report that Pea-comb is caused by a massive amplification of a duplicated sequence located near evolutionary conserved non-coding sequences in intron 1 of the gene encoding the SOX5 transcription factor. This must be the causative mutation since all other polymorphisms associated with the Pea-comb allele were excluded by genetic analysis. SOX5 controls cell fate and differentiation and is essential for skeletal development, chondrocyte differentiation, and extracellular matrix production. Immunostaining in early embryos demonstrated that Pea-comb is associated with ectopic expression of SOX5 in mesenchymal cells located just beneath the surface ectoderm where the comb and wattles will subsequently develop. The results imply that the duplication expansion interferes with the regulation of SOX5 expression during the differentiation of cells crucial for the development of comb and wattles. The study provides novel insight into the nature of mutations that contribute to phenotypic evolution and is the first description of a spontaneous and fully viable mutation in this developmentally important gene.
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| 5. |
- Jäderkvist Fegraeus, Kim, et al.
(författare)
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The importance of the DMRT3 'Gait keeper' mutation on riding traits and gaits in Standardbred and Icelandic horses
- 2015
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Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 176, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that a single base-pair mutation, a change from cytosine (C) to adenine (A), in the DMRT3 gene affects both the ability to show ambling and lateral gaits in a wide range of horse breeds, as well as racing performance and trotting technique in Standardbred and Nordic trotters. The variant allele is present in gaited breeds but is absent, or found at a very low frequency, in breeds used for Western-European style riding and flat racing, like the Swedish Warmblood and Thoroughbreds as well as in draught horses. This indicates that the variant allele might have a negative effect on certain riding performance traits in horses. Therefore, one aim of this study was to investigate whether the DMRT3 variant affects canter in Standardbred trotters, and to test if heterozygous horses (CA) were better suited for Western-European style riding than homozygous horses (M). Riding traits were studied in 115 Standardbred horses, and a similar study was also performed with data from 55 Nordic trotters. The results showed that CA Standardbreds had significantly better balance in canter, both collected and extended canter, than M horses. The CA horses also got significantly higher scores for transitions in collected canter. For the rhythm we found no significant differences between the genotypes. In the Nordic trotters we were unable to establish any significant difference for canter ability. Another aim of this study was to investigate the effect of the variant allele on riding abilities and gaits in the Icelandic horse (n=446). Practically all horse breeds considered to be three-gaited have a CC genotype, in contrast Icelandic CC horses can show tolt We therefore tested whether the variant influenced how difficult it was to initiate tolt training for these horses. It was also investigated whether the variant affects which gaits Icelandic horses choose, both at liberty and during initial training. Icelandic CC horses were significantly more difficult to train to tolt compared to CA and AA horses. The M Icelandic horses showed the lateral gaits tolt and pace significantly more frequent, both at liberty and during initial training, than CA or CC horses. The majority of the Icelandic CC and CA horses chose trot at liberty and during initial training.
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| 6. |
- Sundström, Elisabeth, et al.
(författare)
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Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13, s. 365-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in STX17 to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the Grey mutation.Results: We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansions was indicated in five out of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher copy number in aggressive tumours was also found. Massively parallel resequencing of the similar to 350 kb Grey haplotype did not reveal any additional mutations perfectly associated with the phenotype, confirming the duplication as the true causative mutation. We identified three SNP alleles that were present in a subset of Grey haplotypes within the 350 kb region that shows complete linkage disequilibrium with the causative mutation. Thus, these three nucleotide substitutions must have occurred subsequent to the duplication, consistent with our interpretation that the Grey mutation arose more than 2,000 years before present.Conclusions: These results suggest that the mutation acts as a melanoma-driving regulatory element. The elucidation of the mechanistic features of the duplication will be of considerable interest for the characterization of these horse melanomas as well as for the field of human melanoma research.
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| 7. |
- Velie, Brandon, et al.
(författare)
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Frequencies of polymorphisms in myostatin vary in Icelandic horses according to the use of the horses
- 2015
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Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 46, s. 467-468
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Tidskriftsartikel (refereegranskat)abstract
- The recent association of the myostatin gene (MSTN) with best race distance has provided valuable insight into the influence of MSTN on racing performance. However, the importance of MSTN in horses is unlikely to be limited to racing performance. First described in mice, the effects of mutations in MSTN have long been associated with heavily muscled cattle. In cattle, some of the morphological variability between breeds can be attributed to MSTN and its effects on muscle fiber development. As such, it is highly probable that MSTN polymorphisms influence not only racing performance, but also the general use of a horse or breed. This variability would likely be reflected in the genotype frequencies of horses used for specific purposes, as certain genotypes would undoubtedly yield more desirable phenotypes. The aim of this study was to explore this idea by estimating the genotype frequencies of three SNPs in MSTN in the Icelandic horse breed, a breed traditionally used for both meat production and riding.
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| 8. |
- Andersson, Lisa, et al.
(författare)
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Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 642-646
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Tidskriftsartikel (refereegranskat)abstract
- Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). 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.
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| 9. |
- Boije, Henrik, et al.
(författare)
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Sonic Hedgehog-Signalling Patterns the Developing Chicken Comb as Revealed by Exploration of the Pea-comb Mutation
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e50890-
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis and mechanisms behind the morphological variation observed throughout the animal kingdom is stillrelatively unknown. In the present work we have focused on the establishment of the chicken comb-morphology byexploring the Pea-comb mutant. The wild-type single-comb is reduced in size and distorted in the Pea-comb mutant. Peacombis formed by a lateral expansion of the central comb anlage into three ridges and is caused by a mutation in SOX5,which induces ectopic expression of the SOX5 transcription factor in mesenchyme under the developing comb. Analysis ofdifferential gene expression identified decreased Sonic hedgehog (SHH) receptor expression in Pea-comb mesenchyme. Byexperimentally blocking SHH with cyclopamine, the wild-type single-comb was transformed into a Pea-comb-likephenotype. The results show that the patterning of the chicken comb is under the control of SHH and suggest that ectopicSOX5 expression in the Pea-comb change the response of mesenchyme to SHH signalling with altered combmorphogenesis as a result. A role for the mesenchyme during comb morphogenesis is further supported by the recentfinding that another comb-mutant (Rose-comb), is caused by ectopic expression of a transcription factor in combmesenchyme. The present study does not only give knowledge about how the chicken comb is formed, it also adds to ourunderstanding how mutations or genetic polymorphisms may contribute to inherited variations in the human face.
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| 10. |
- Francois, Liesbeth, et al.
(författare)
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Conformation Traits and Gaits in the Icelandic Horse are Associated with Genetic Variants in Myostatin (MSTN)
- 2016
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 107:5, s. 431-437
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Tidskriftsartikel (refereegranskat)abstract
- Many genes are known to have an influence on conformation and performance traits; however, the role of one gene, Myostatin (MSTN), has been highlighted in recent studies on horses. Myostatin acts as a repressor in the development and regulation of differentiation and proliferative growth of skeletal muscle. Several studies have examined the link between MSTN, conformation, and performance in racing breeds, but no studies have investigated the relationship in Icelandic horses. Icelandic horses, a highly unique breed, are known both for their robust and compact conformation as well as their additional gaits tolt and pace. Three SNPs (g.65868604G>T [PR8604], g.66493737C>T [PR3737], and g.66495826A>G [PR5826]) flanking or within equine MSTN were genotyped in 195 Icelandic horses. The SNPs and haplotypes were analyzed for association with official estimated breeding values (EBV) for conformation traits (n = 11) and gaits (n = 5). The EBV for neck, withers, and shoulders was significantly associated with both PR8604 and PR3737 (P < 0.05). PR8604 was also associated with EBV for total conformation (P = 0.05). These associations were all supported by the haplotype analysis. However, while SNP PR5826 showed a significant association with EBVs for leg stance and hooves (P < 0.05), haplotype analyses for these traits failed to fully support these associations. This study demonstrates the possible role of MSTN on both the form and function of horses from non-racing breeds. Further analysis of Icelandic horses as well as other non-racing breeds would be beneficial and likely help to completely understand the influence of MSTN on conformation and performance in horses.
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