Vet Times The website for the veterinary profession https://www.vettimes.co.uk Advances in equine genetics Author : Charlotte Maile Categories : Equine, Vets Date : October 17, 2016 Coloured horse breeders may be particularly interested in coat colour genetic testing. In 2006, the Horse Genome Project completed the sequencing of the entire equine genome, which was subsequently published in Science 1. This was a huge collaborative project between scientists and marked a major step forward in both veterinary and comparative biology. Many people anticipated this sequencing could be the key to the future of horse breeding; however, it has transpired this is far from a precise science, as the Horse Genome Project web page states the study of the horse genome is more like studying the weather than inventing a sports car. Horse racing is a lucrative business, with an annual turnover in the region of 3.45 billion. It is unsurprising, then, money is no object when it comes to breeding the perfect racehorse. 1 / 5
Top-quality horses, such as Frankel, are reported to command stud fees of up to 125,000. Until relatively recently, pedigrees were the main dictators of breeding matches; however, equine genetic testing is now becoming increasingly popular among breeders, with people wanting the best guarantee of success from their investment. Several companies are now offering different genetic tests. Performing these tests is relatively straightforward for breeders and owners all that is required is a sample of mane or tail hair, enabling laboratories to extract DNA from the hair root, without the need for a vet visit. A major player in thoroughbred breeding genetics is the so-called speed gene, which was identified in 2010 2 and is now often taken into consideration. The speed gene is a polymorphism in the equine myostatin gene. Myostatin is an important negative regulator of muscle mass and a myostatin knockout mouse has marked hypermuscular phenotype, similar to the double muscled natural myostatin mutants seen in cows and bully whippets. Although this polymorphism does not result in a hypermuscular phenotype in horses, the different polymorphisms affect muscle fibre type 3, enabling breeders to characterise their horse as either a sprinter or stayer. Some breeding stallions now have their genotype for the myostatin gene on their stallion cards it makes financial sense for people to pick a suitable sire for their broodmare. Genetic testing Genetic testing is not only important in thoroughbred breeding (although a majority of breeding revenue comes from breeding racehorses). Several additional genetic tests may attract other types of breeder, including coat colour and projected height. The genetic locus, which enables geneticists to give an idea of projected height, was first identified in cattle as affecting stature, but subsequently, is now used in horses 4-6. The LCORL/NCAPG loci have two possible alleles: G or A base. Shorter horses have two A bases and taller horses have two G alleles, and heterozygote horses with one G and one A allele are somewhere in between. Personally, I am not sure how accurate this test is as I would also expect environmental factors, such as diet, to have a significant influence; however, I can understand the importance of this test where not succeeding a maximal height is important (for example, polo ponies or show ponies). Coat colours Coat colour genetics are particularly interesting and coat colour calculators exist, which provide a good idea of potential coat colours, based on the dam and sire s coat patterns. This might be 2 / 5
particularly important for people breeding coloured horses or unusual colours (such as palomino). Ann Bowling and Phillip Sponenberg, both veterinary geneticists in the US, are the main proponents of the development of coat colour genetics. Two main genes are involved in coat colour; the extension gene, which dictates if a horse s base colour is red (for example, red = chestnut coat colour and non-red = black coat colour with no additional genes acting) and the agouti gene, which dictates if the non-red colour is uniform (this is how a bay horse is created non-red extension gene, with the agouti gene restricting the black pigment to the extremities). Several other modifying genes exist, which are referred to as dilution genes, and can create additional colours, such as duns and dapple greys. Several diseases can now be detected via genetic testing not only for diagnosis purposes, but also to enable selective breeding to prevent these diseases in the progeny. An important disease that can be diagnosed by genotyping is type one polysaccharide storage myopathy (PSSM1), associated with a dominant missense mutation in the equine muscle glycogen synthase gene (GYS1) 7. In some breeds, namely continental draft breeds, the prevalence of this disease is as high as 64% 8 and, therefore, selection of breeding pairs dependent on genotype could prove fundamental in potentially eradicating the disease. However, as much as it may be desirable to eradicate the disease by selective breeding, it may be difficult to prioritise this outcome, especially if a breeding sire, for example, has several other more desirable traits, which means possessing the PSSM1 gene is less significant to a specific breeder. It has been suggested the high prevalence of the PSSM1 mutation in certain breeds is associated with positive selection for the GYS1 mutation 9 and, therefore, it may not be easy to breed out. Disease eradication Near eradication of disease by genetic testing of breeding animals is, however, a definite possibility and a marked reduction in cases of foal immunodeficiency syndrome was seen after genetic testing became available 10. The American Quarter Horse Association also supports the use of genetic testing to help eliminate hyperkalaemic periodic paralysis (HYPP), a potentially fatal muscle disease in the breed, after a genetic defect was identified in descendants of a sire called Impressive a successful and famous America quarter horse. Although he never suffered from HYPP, he did, however, pass the defective gene down to his progeny and has, subsequently, become just as famous for the negative connotations associated with being an Impressive descendant. Exciting time for equine genetics 3 / 5
In the future, breeding stallions and mares may be advertised by a genetic make-up card, enabling more specific breeding. I think it is a potentially more reliable way of breeding and may help to breed out certain diseases and undesirable traits. However, the potential of reducing the gene pool exists, which can be a huge disadvantage. Selective breeding before genetic testing has already resulted in limited genetic diversity within the thoroughbred population it has been shown 94% of paternal lineage is derived from a single founder stallion 11. Genetic testing may, however, have the opposite effect, by encouraging people to use what were previously considered less desirable stallions as they are shown to have similar or preferable genetic profiling and potentially lower stud fees. All in all, this is an exciting time for equine genetics we are potentially only a few years away from designer foals. References 1. Wade CM, Giulotto E, Sigurdsson S et al (2009). Genome sequence, comparative analysis, and population genetics of the domestic horse, Science 326(5,954): 865-867. 2. Hill EW, McGivney BA, Whiston R et al (2010). 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. 3. Petersen JL, Valberg SJ, Mickelson JR et al (2014). Haplotype diversity in the equine myostatin gene with focus on variants associated with race distance propensity and muscle fiber type proportions, Anim Genet 45(6): 827-835. 4. Eberlein A, Takasuga A, Setoguchi K et al (2009). Dissection of genetic factors modulating fetal growth in cattle indicates a substantial role of the non-smc condensin I complex, subunit G (NCAPG) gene, Genetics 183(3): 951-964. 5. Signer-Hasler H, Flury C, Haase B et al (2012). A genome-wide association study reveals loci influencing height and other conformation traits in horses, PLoS One 7(5): e37282. 6. Makvandi-Nejad S, Hoffman GE, Allen JJ et al (2012) Four loci explain 83 per cent of size variation in the horse, PLoS One 7(7): e39929. 7. McCue ME, Valberg SJ, Miller MB et al (2008). Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis, Genomics 91(5): 458-466. 8. McCue ME, Anderson SM, Valberg SJ et al (2010). Estimated prevalence of the type 1 polysaccharide storage myopathy mutation in selected North American and European breeds, Anim Genet 41 Suppl 2: 145-149. 9. McCoy AM, Schaefer R, Petersen JL et al (2014). Evidence of positive selection for a glycogen synthase (GYS1) mutation in domestic horse populations, J Hered 105(2): 163-172. 10. Carter SD, Fox-Clipsham LY, Christley R et al (2013). Foal immunodeficiency syndrome: carrier testing has markedly reduced disease incidence, Vet Rec 172(15): 398. 4 / 5
Powered by TCPDF (www.tcpdf.org) 11. Cunningham EP, Dooley JJ, Splan RK et al (2001). Microsatellite diversity, pedigree relatedness and the contributions of founder lineages to thoroughbred horses, Anim Genet 32(6): 360-364. 5 / 5