Using genetic tests for breeding

Alexia Ross, looks at the value of testing for life-threatening genetic variants when breeding horses

Breeding a foal from a mare that has done a good job is always tempting whether it is a regular objective or a once in a lifetime experience. Either way one needs the best chance of a successful result, a healthy foal and a worthwhile horse for the future.

Equine genetic testing has come a long way over the last 30 years. Most breeds have a percentage of carriers of more than one genetic lethal but tests for these mean that there is one less thing to worry about when the foal arrives. Equine genome profiling is building momentum and performance assessment from a genetic profile is on the horizon.

DNA marker assays replaced blood typing in the 1990’s as a parentage check for horse breed registers. It was more effective, using analysis of a panel of microsatellite markers that worked across breeds. The knowledge moved on rapidly from here to pinning down markers for genetically inherited diseases. These tests work on the basis of exclusion with genetic markers identified to show the presence of a lethal variant in the genetic makeup of a horse; this identification of markers predates by many years the first mapping of the whole horse genome which did not happen until 2009. There is a dizzying array of tests available which include colour, height and speed predictions as well as deleterious genes. Most of the genetic diseases and some other tests are breed specific.

DNA tests require a sample that can be provided by pulled mane hair. The hair has to be pulled not cut as the DNA is found in the bulb around the hair root.  Samples are easily taken by horse owners and can be sent direct to a testing laboratory with results usually returned within 1 to 2 weeks.  Once the results are back, they just need to be assessed for their impact on breeding decisions.

Disease inheritance

The key fact about genetically lethal diseases is that they tend to be recessive traits, although a few non-lethal traits are dominant.  Lethal genes that are dominant pass directly from a parent so would not survive, which explains why this is the case. This means that it is perfectly possible to breed from a horse that carries a lethal gene as long as it is not bred to an individual that carries the same lethal factor.  Recessives are not expressed when present in combination with a dominant gene in a pair. The phenotype is what you see while the genotype is all the genes present, expressed or not. This is explained easily using the example of colour.

The colour chestnut is recessive while the colour bay is dominant. If you breed a chestnut with only chestnut ancestors to a bay with only bay ancestors, the foal will appear bay but it will have inherited one copy of the chestnut gene from the other parent. Two such bay parents bred together have a one in four chance of passing on the bay gene from both parents, a two in four chance of a foal that looks bay but also carries one chestnut gene and, a one in four chance of the foal popping out chestnut, having inherited the chestnut gene from both parents. That is exactly how lethal genes work. The diagram shows how it is safe to breed a carrier to a horse that is clear of the gene variant they carry but, a carrier to carrier mating stands a one in four chance of producing an affected foal. Carriers are not affected by the gene they carry so modern testing means that their worthwhile talents can be passed on without risk.

Lethal diseases

In the UK Warmbloods are strongly represented in sporthorse breeding but mares with native blood, Thoroughbred and foreign breeds also feature depending on the discipline. It is important to know the main breeds present to understand which lethal genes to test for. Many studs will advertise if their stallion is tested clear of relevant genetic diseases but can be less transparent if the horse is a carrier. It is also possible a stallion has not been tested at all as not all breed societies require this. A carrier or untested stallion should only be used if the mare is tested clear of all possible lethal variants.  On the other hand, a stallion who tests clear of all possible lethal traits is safe to use on an untested mare.  For the one-time breeder, this is often the best option.

For rare breeds, where options are limited, by far the best strategy is to test both mares and stallions so that the greatest variety of lines can be maintained safely. Genetic conservation is another subject but has benefitted greatly from the availability of genetic testing.

Testing centres usually have search filters online allowing you to look at the tests applicable for the breed of horse, with some breeds having panel or bundle testing of groups of tests that apply. Cross-bred or part-bred horses would need to be tested for all the relevant breeds in their ancestry.

Warmbloods and Thoroughbreds

Warmblood Fragile Foal Syndrome type 1(WFFS) is a defect that results in abnormally fragile skin and mucous membranes. Affected horses exhibit open lesions, hyperextensible joints, hematomas whilst premature birth is common.  There is no cure and euthanasia shortly after birth is the only option. This variant has also been found in Thoroughbreds at a low frequency so testing is recommended for the breed.

Equine Familial Isolated Hypoparathyroidism (EFIH) is an inherited form of hypocalcemia or low calcium in the blood. It has been identified in Thoroughbred foals, impairing limb movement, weakening bones and can lead to seizures, intestinal problems, heart issues and ataxia.

Breed specifics

The rare Fell and Dales pony breeds can carry a Foal Immunodeficiency Syndrome (FIS or Fell Pony syndrome).  Affected foals have a severely compromised immune system.  They lack the ability to produce their own antibodies and there is no effective treatment resulting in death or euthanasia by 4 years of age.

Connemara ponies

Connemara Hoof Wall Separation Disease (HWSD) causes separation and cracking of the hoof wall. This results in weight being taken on the soul of the foot causing inflammation, and laminitis which can be extremely painful. Even with careful management, laminitis will develop and quality of life is affected meaning that euthanasia is necessary.

Friesians can suffer from Hydrocephaslus and Dwarfism. Foals with the former are aborted, stillborn or born with severe neurological issues for which euthanasia is the only option. Dwarfism results in reduced bone length of limbs and ribs leading to shortened stature and limbs relative to body size. There is no treatment but foals do grow, albeit more slowly, and are able to function while some are even ridden.

Arabians

Severe Combined Immunodeficiency (SCID) results in a seemingly healthy foal that has a severely weakened immune system. They are highly susceptible to infections and die or have to be euthanized within the first 6 months, frequently much sooner than that.

Lavender Foal Syndrome (LFS) gets its name from the characteristic dilute coat colour often described as lavender or silver. Foals have neurological impairments resulting in seizures and hyperextension of limbs which also makes the process of foaling quite unsafe for the mare. Affected foals die or are euthanized shortly after birth.

Cerebellar Abiotrophy (CA) has a more variable effect. The death of neurons in the brain causes ataxia like symptoms.  Some horses may be capable of life as pasture pets but will always be prone to accident and injury.

Occipitoatlantoaxial Malformation (OAAM) is a malformation of the first two vertebrae of the neck. This is a variable condition probably due to a group of malformations with a genetic test for one at the moment. Abnormal head and neck carriage or neck twisting is the most obvious sign and foals are usually euthanized.

Other issues

Polysaccharide Storage Myopathy type 1 (PSSM1) is a dominant genetic hereditary condition that passes directly from parent to foal. There are several forms of PSSM. It causes tying-up of muscles resulting in muscle damage and the inability to move. At least 20 breeds have been identified with type 1 PSSM with approximately half of the Belgian Draft being affected and approximately 8% of Quarter Horses and related breeds. Management of PSSM is possible (see Briony Witherow on Feeding the horse with polysaccharide storage myopathy link) but this is not a helpful condition for horse or rider.

PSSM is not the only cause of tying-up but it is a worthwhile test for almost any breed if you want to end up with a healthy, active horse up to any job.

There are many other tests available breeding for particular outcomes such as colour.  Not all equine genetic tests are for lethal conditions although these are the most important. Horse DNA does not change from foal to veteran so one set of testing will keep you informed for any breeding decisions you wish to make. Investigation of the whole equine genome is progressing rapidly with researchers keen to find markers for performance and temperament; speed versus long distance tests are already available to the racehorse industry.  In the meantime, a few tests will help to support the arrival of a healthy and useful foal.

Detailed information on the full range of genetic tests and their symptoms can be found at the website of research pioneers UC Davis, Callifornia, USA  https://vgl.ucdavis.edu/