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.

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.

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.

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

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.

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.

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). 

• 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

·      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.

-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

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.

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

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.

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

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