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The mutation for gaited horses is a result of a substitution that causes an early stop codon in the DMRT3 gene. A lot of early Icelandic horses have the ambling allele. It is believed the Norse settlers liked this comfortable movement of the horses so they selected for it.

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Condition / Trait: Polysaccharide Storage Myopathy type 1 (PSSM1)

Breed/Population: Seen in several including; Quarter Horse, Warmbloods, and Draft horses.

Mutation Type: missense (single-nucleotide substitution)

Genomic Change: GYS1 c.926G>A → p.Arg309His

Effect on Protein: amino-acid change in glycogen synthase; gain-of-function → excess glycogen

Phenotype in Horses: exertional rhabdomyolysis (“tying up”), muscle pain/weakness, stiffness; variable severity

Key Source (citation):

McCue, M.E., Valberg, S.J., Mickelson, J.R. and Geyer, C.B., 2008. Polysaccharide storage myopathy in quarter horse–related breeds is associated with a mutation in the glycogen synthase 1 (GYS1) gene. PLoS Genetics, 4(3), e1000143.

https://doi.org

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Glycogen branching enzyme (GBE1) mutation affects quarter horses. It is caused by a substitution mutation at base 102 where C substitutes to A. Signs of the mutation are stillbirths, seizures, respiratory or cardiac failure, intermittent hypoglycaemia.

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Glycogen Branching Enzyme Deficiency (GBED)

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Glycogen Branching Enzyme Deficiency (GBED)

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breeds affected: Quarter horses (8.3%)

GBED is an autosomal recessive disease, clinical signs include; stillborn or aborted foals, if the foal survivies they may appear weak and hypothermic at birth and may progress to sudden death following hypoglycemic seizures, cardiac arrest or respiratory failure. Affected foals may have flexural limb deformities. All affected foals studied to date have died or been euthanized by 18 weeks of age due to the severity of muscle weakness. This is due to a C to A point mutation - results in a stop codon in gene encoding glycogen branching enzyme. As a result, cardiac and skeletal muscle, liver and the brain cannot store or mobilise glycogen to maintain normal glucose levels. there is no known treatment or cure

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Whole genome sequence was completed o 16 modern sport horses and 35 non-sport horses. 49 shared mutated genes in modern sport horses were found relating to musculoskeletal development and limb development, which have been targeted by selective pressures in sport horses. Sport breeds were Dutch warmblood, Hanoverians, Holsteins, Oldenburgs and trakehners. LCORL and NCAPG as height indicators and MYO5C as muscular function in German warmbloods specifically.

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Breed it affects: Mostly American Paint Horses, but also can affect American Quarter Horses

Type of mutation and change to the gene: A misense mutation to the endothelin-B receptor gene (EDNRB) which causes a non-functioning EDNRB protein. This results in a lack of Melanocytes and Enteric Nerve Cells.

Impact to horse: Foals born with LWOS typically die at birth or in the days after as the syndrome is fast-progressing. The lack of melanocytes causes pink skin and therefore a completely white coat. The mutation also causes the colon to be non-functioning due to the lack of the Enteric Nerve Cells, which are ganglia in the intestines. This means that foals born with LWOS die of colic due to intense gastrointestinal blockages.

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Overbreeding, controlling breeding and reducing the size of breeding stock, limits the power of negative selection against deleterious mutations. Inbreeding depression is a big contributor to mutations in domesticates and Przewalski horses. There is a significant correlation between inbreeding and mutation load this corroborates the role of inbreeding effecting fitness. In the last few centuries there has been ~4% raise in mutation load within protein coding regions.

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HYPP is caused by a heterozygous mutation in the SCN4A (sodium channel) gene

There is wide phenotypic variability of the disorder, and it can appear with varying symptoms and extremities

HYPP results from a mutation in the muscle’s sodium channel. The channel becomes leaky, which causes the muscle to be more sensitive. As a result, the muscles contract involuntarily with blood potassium changes.

It is a Dominant gene, only one version of the gene needs to be defective for the horse to suffer from muscle tremors, paralysis, weakness, myotonia or collapse.

Primarily affects quarter horses, but can also affect other breeds like paints and appaloosas

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Misense mutation causing dilution of black coat colour causing silver dapple coat colour (PMEL17)

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Misense mutation causing dilution of black coat colour causing silver dapple coat colour (PMEL17)

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Breeds it affects: Icelandic, Arabians, American miniatures, Rocky Mountain horses, Ardennes, Morgan horses, American paint, quarter horses, American saddlebred, Shetland pony, Norwegian nordland, Welsh ponies and Swedish WB.

Change to gene: misense mutation in exon 11 changing the second amino acid in the cytoplasmic region for arginine to cytisine.

Interesting fact: majority of Icelandic horses with silver coat colour have stripped hooves in theirs first years of life.

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-Type of mutation- Nonsense mutation in mares

-Incontinentia pigmenti (IP)- Condition caused my mutation

-Causes skin disorder, areas of alopecia with occasional wooly hair regrowth

-affected horses can also have streaks of darker and lighter coat coloration from birth

-Only occurs in mares, males die during development in utero

-heterozygous nonsense variant in the X-chromosomal IKBKG gene

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Affects Friesian horses

The impact that it has to the horse is that it often results in stillbirth of the foals that are affected. It can also result in dystocia in dams.

Change to gene/amino acid sequence:

A single basepair substitution, where Cytosine (C) is changed to Thymine (T) in the B3GALNT2 gene. This introduces a stop codon in the amino acid sequence and results in a nonfunctional protein.

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·      It’s an inherited autosomal dominate disorder that affects the sodium channels in the horse’s nervous system. This causes the horse to undergo temporary periods of muscle weakness or paralysis.

·      It affects quarter horses, American paint horses, appaloosas and quarter horse cross bred.

·      It’s a missense mutation

·      What change to gene/amino acid sequence= phenylalanine/leucine substitution

·      Impact to horse= in episodes, sweating and muscle twitching can occur. In more extreme cases, horses may sway, stagger or dog-sit.

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A study was led on white-spotted Thoroughbred horses. These horses have a gene (KIT), which is responsable for the amount of white coat a horse has (ranging from white spots to fully white). In some cases, it has been observed that a deletion occured, and a new mutated allele variant is created. Horses that posess this allele have a completely white phenotype.

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Autosomal dominant trait affecting quaterhorses (around 4%)

signs can be asymptomatic or range to daily involuntary muscle twitching and weakness

foals homozygous for HYPP show signs of disease early in life

signs in foals can include respiratory issues/distress

due to a miss-sense mutation (C to G substitution) leading to a phenylalanine/leucine substitution

in 1996 the American Quarter Horse Association recognised HYPP as a genetic defect and mandatory testing was instituted

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Quarter horses, warmbloods and draft breeds, average age 5

10 single base-pair substitution mutation in a gene on chromosome 10.

Main impact is unregulated glycogen synthesis which can result in ‘tying up’, muscle pain/stiffness, and slower metabolism.

Can be controlled by dietary changes (including an increase in fibre and reducing the starch and sugar intake).

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Severe Combined Immunodeficiency (SCID), Issy

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Severe Combined Immunodeficiency (SCID), Issy

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Affects Arabian horses (Australia, Canada, UK & US).

8.4% of Arabian foals born in the US are gene carriers.

Caused by a five-base-pair deletion at codon 9480, and a 967 amino acid deletion. Along with a deletion of the entire P13 Kinase domain.

Foals with the gene are typically normal at birth and the onset depends on passive transfer and environmental factors, but is typically 6-10 weeks post-partum. Clinical signs include:

Diarrhoea

Meningitis

Respiratory disease

Secondary bacterial infections

Lesions such as necrosis, pericarditis and pleuritis

Foals typically succumb to this mutation around 5 months of age. Supportive care may prolong the course of the disease, and research has been carried out on affected foals e.g bone marrow transplantation and hyperimmunised plasma with anti-adenovirus antibodies but none of which have succeeded to result in survival. Euthanasia is recommended for affected foals. Genetic testing when breeding Arabian horses can also be crucial.

This mutation is autosomal recessive, and therefore the foal must inherit two copies of the faulty gene via both parents.

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Breeds affected: non breed specific, case studies included Lippizanner, Trakehner cross, Shagya-Arabian, Icelandic horse (Brodesser et al 2025).

This mutation is coat-colour specific.

Mutation type: nonsense mutation, caused by a duplication of the Syntaxin 17 gene (a gene that is linked to both the grey coat colour phenotype and also to a high susceptibility to melanomas)

Impact to horse: horses will often develop tumours on the dock of the tail, as well as around the head and lesions. Metastasis may appear at organ sites if the tumours are malignant.

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Caused by a mis-sense mutation

Results in a single amino acid change from Isoleucine to Lysine

Foals are born with hair lacking pigment, sensory organ abnormalities and deficiency in neuronal innervation of the intestinal tract. Therefore, Colic symptoms appear due to intestinal obstruction leading to the progression of intestinal rupture and toxicity resulting in death

Usually in the American Paint Horse breed, but it also occurs in other breeds including the Quarter Horse, Pinto Horse, and American Miniature Horse

No treatment but it can be prevented by genetic testing of parents

With American Paint horses, the white spotting Overo allele is associated with a defective transmembrane protein that prevents melanocyte migration, leaving large, pigmented areas along with white areas of no pigmentation

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Breed it affects = Autosomal dominant trait which effects Quarter Horses, American Paint horses, Appaloosas and Quarter horse crossbred animals worldwide. Genetic disease has been associated with a Quarter horse sire named ‘Impressive’.

Type of Mutation and what change to sequence = HYPP is due to a missense mutation (C to G substitution) which results in a phenylalanine/leucine substitution.

Impact to horse = Symptoms range from asymptomatic to daily muscle fasciculations and weakness resulting in recumbency.

Episodes of weakness or paralysis appear similar between N/H and H/H horses, although the H/H will have more frequent episodes and tend to show more severe signs of upper airway obstruction during an episode.

-In both, clinical episodes start with a period of brief hypotonia  (twitching or delayed relaxation of muscles) with some horses showing prolapse of the third eyelid.

-Sweating and muscle fasiculations

-Muscle tremors

-Muscle cramping

-Severe attacks – swaying, staggering, dog sitting

Other info ....

Foals that are homozygous usually show symptoms within the first few days of life, and clinical signs in these foals include respiratory stridor and periodic obstruction of the upper respiratory tract. Foals also may present for dysphagia or respiratory distress, and endoscopic findings include pharyngeal collapse and edema, largyngopalatal dislocation and laryngeal paralysis. Affected homozygous horses also exhibit dysphonia (high-pitched whinny) even between episodes. Foals that are heterozygous N/H are less severely affected and typically do not demonstrate clinical signs of disease until they are weaned. By the time training is initiated, typically by 2–3 years of age, most N/H horses have shown intermittent clinical signs with no apparent abnormalities between episodes.

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This describes malformations in the C1 and C2 area characterised by an ‘anterior developmental shift’.

This mutation (genetic deletion) tended to cause progressive ataxia (loss of control of motor functions) or, at worst, death at birth. The deletion is located between two homeobox genes (HOXD4/HOXD3) which encode for the formation of the occiput, atlas and axis, and the cervical C/1/2/3 vertebrae.

Fun fact: these clinical findings were actually originally found in a 3-year-old Poitou donkey.

Finno, C.J. (2025). Occipitoatlantoaxial malformations in equids. Equine Veterinary Education. doi:https://doi.org/10.1111/eve.14160.

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Breed it affects = Friesian horses

Type of Mutation = nonsense mutations

What change to gene/amino acid sequence = shortens the protein, impairing DNA-binding which in turn prevents it from acting as a transcription factor

Impact to horse = misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye.

Anything else interesting? = Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesised to be a simply inherited Mendelian trait.