Racing Australia monitors developments in Thoroughbred breeding trends to ensure that breeders are kept informed of important findings.
This paper describes the discovery of two very rare, but fatal, genetic disorders in Thoroughbred horses in other parts of the world.
This report was compiled by the Australian Stud Book and Equine Genetics Research Centre and supported by the Racing Australia Research & Development Fund.
You can also find a downloadable Fact Sheet and a link to a short presentation below.
Genetic disorders in horses
Recently, two fatal recessive genetic disorders have been identified in Thoroughbred horses in other parts of the world. In this document, we provide the background information and tools you might need to ensure you do not encounter an affected foal. To understand the impact of these disorders, you do not need to be an expert in genetics.
What is DNA & genes?
DNA is a molecule found in most cells of living things. Genes are sections of DNA that tell the body how to make proteins. Genes occur in matching pairs, with one of each pair inherited from each parent. Consequently, most cells carry two copies of most genes.
What is DNA variation?
Whilst most DNA is identical across horses, it is normal that there is also some variation in its sequence. A lot of this variation has no observable effect. Other variants contribute to differences between individuals that we can see, like coat colour, size and speed.
However, some DNA variation can be harmful and cause illness. Genetic disorders can occur when something goes wrong with the DNA sequence in a gene.
What are ‘recessive’ genetic disorders?
Some variants only cause illness if both copies of the gene are affected. In these cases, there is no noticeable effect if a horse has only one copy of the harmful variant. There is only an impact if the foal inherits the harmful variant from both its parents, meaning it has two copies. Because the illness appears only sporadically when two carriers of the harmful variant are mated, these disorders are considered hidden or ‘recessive’ genetic disorders.
By the time we become aware of these variants, they are often already carried by a significant number of horses. Once they are established in the population, these variants are often called mutations.
The next section describes the two recessive genetic disorders that have been documented in Thoroughbreds in the US and UK.
Fragile Foal Syndrome 1 (FFS1)
FFS1 prevents the normal formation of collagen. Affected foals have hyperextensible (lax and stretchy) leg joints and very fragile skin which tears easily. The condition is obvious at birth and newborn foals are immediately euthanised as it is untreatable. FFS1 is also suspected to cause early embryonic loss so it may manifest as poor fertility. More research needs to be done to confirm this.
The DNA mutation causing FFS1 was originally identified in 2013. Foals need to inherit a copy of the mutation from both of their parents to be affected by the disorder. Horses with only one copy of the mutation are not affected.
This disorder was originally called “Warmblood Fragile Foal Syndrome” because it occurred most frequently in Warmbloods. Between 11 and 18 percent of Warmbloods are carriers. However, it is now known that many breeds carry the mutation (Reiter et al. 2021). The latest studies have shown that the FFS1 mutation is found at lower frequencies (17/716; 2.4% and 25/1789; 1.8%) in American Thoroughbreds (Bellone et al. 2019; Elcombe et al 2022).
The EGRC tested anonymous samples from 550 Thoroughbreds for the FFS1 mutation, finding 7 carriers. The Australian carrier frequency of 1.3% is considerably lower than that observed in US Thoroughbreds.
A case of an affected Thoroughbred foal born in the UK has recently been documented (Grillos et al. 2021) so it has since been proposed the disorder should be re-named Fragile Foal Syndrome Type 1.
Equine Familial Isolated Hypoparathyroidism (EFIH)
EFIH prevents the foal from using calcium properly. This causes low calcium in the blood, resulting in painful muscle contractions, seizures, and eventually death. Foals with this disorder are born without parathyroid glands, which is why their bodies can’t process calcium.
The disorder has been fatal in all documented cases so far (n = 9). The symptoms of EFIH are unspecific, so it is possible that foals have been born with EFIH in Australia, but the cause was not recognised.
The mutation causing EFIH was identified in 2020 and affected foals must inherit a copy of the mutated gene from each parent (Rivas et al. 2020).
Unlike FFS1, EFIH has only been identified in Thoroughbreds. The mutation was first published in 2020, where it was found in 3/82 randomly selected Thoroughbreds (3.7% carrier frequency). A larger study found that 28/1789 (1.6%) Thoroughbreds were carriers (Elcombe et al 2022).
Testing of 880 anonymous Thoroughbreds by the EGRC found that 12 carried the mutation (1.4% carrier frequency).
The FFS1 and EFIH DNA mutations are present in the Australian Thoroughbred population. However, both mutations are found at very low frequencies.
There is no observable effect of these variants on horses that carry one copy and there is nothing wrong with horses that carry these DNA mutations.
The EGRC DOES NOT SUPPORT the prohibition of carriers from breeding. These horses only have a problem with one copy of one gene. If they have made it to the breeding population, they clearly have more than 20,000 other perfectly good genes so they should not be prevented from mating because of these DNA variants with hidden effects.
The only danger is if two carriers are mated, there is a one in four chance of the resultant foal being affected by the disorder. Based on the published frequencies, we would expect to see one foal affected by either FFS1 or EFIH born every two years. Therefore, these disorders are very rare.
What to do if you are concerned your horse is a carrier
Contact the EGRC (email@example.com) if you suspect you have an affected foal. The EGRC will provide free DNA testing for the foal and any available parents in these cases. All enquiries and DNA test results will be kept confidential. You do not need to provide the names of the parents of the foal.
A foal with suspected FFS1 will likely require immediate euthanasia. The EGRC can arrange with the attending veterinarian what sample would be the most suitable to take from the foal to confirm diagnosis. Blood is the best sample (ideally in an EDTA (purple) vacutainer; although LithHep (green) also works), but we can work with what you are able to obtain at the time.
DNA testing can also confirm a definitive diagnosis of EFIH, allowing for informed decision making.
The EGRC offers routine DNA testing for these disorders. DNA testing costs $48 (incl GST) for one disorder and $65 (incl GST) for both. Tests for Thoroughbreds can be ordered by emailing the EGRC (firstname.lastname@example.org).
For the 2023 breeding season, the EGRC is offering free testing of mares that have proven difficult to get in foal, lost foals for an undiagnosed reason, or have had foals that may have been affected by either FFS1 or EFIH. Contact the EGRC if you have a mare that fits any of these criteria and you would like to have them tested. This testing is sponsored by the Racing Australia Research and Development Fund.
Please contact the EGRC if you have any other concerns about these disorders.
Reiter et al. (2021). Distribution of WFFS1 mutation (PLOD) in different breeds from Europe and US. Genes 11:1518 doi.org/10.3390/genes11121518.
Bellone et al. (2019). Warmblood fragile foal syndrome type 1 mutation (PLOD1 .2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed. Equine Veterinary Journal 52:411-414. DOI: 10.1111/evj.13182
Elcombe et al. (2023). Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US Thoroughbred population (1988–2019). Equine Veterinary Journal 55:666–671. DOI: 10.1111/evj.13883. Not available without subscription.
Grillos et al. (2021). First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1c2032GA. Equine Veterinary Journal 54:1086-1093. DOI: 10.1111/evj.13547. Not available without subscription.
Rivas et al. (2020). A nonsense variant in Rap Guanine nucleotide Exchange Factor 5 (RAPGEF5) is associated with equine familial isolated hypoparathyroidism in Thoroughbred foals. PLoS Genetics. 16:e1009028. doi.org/10.1371/journal.pgen.1009028