Gene responsible for painful eye condition in Friesian horses identified

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Distichiasis in a Friesian horse.
Distichiasis in a Friesian horse. A shows normal eyelashes developing from the outer surface of the lid. B shows aberrant eyelashes growing from the Meibomian gland orifices of the inferior eyelid margin. Note the eyelashes growing such that they are in direct contact with the cornea. Hisey, Hermans, et al 10.1186/s12864-020-07265-8

Researchers have identified a genetic variant associated with distichiasis in Friesian horses, and have developed a genetic test for it.

The research, led by Dr Rebecca Bellone at the University of California Davis Veterinary Genetics Laboratory, found the genetic variant linked to equine distichiasis, an ocular disease characterized by eyelashes that grow from abnormal positions along the edge of the eyelid and often lead to irritation and damage to the cornea (the clear outer “windshield of the eye”).

In typical mammalian eyelids, glands called Meibomian glands line the edge of the eyelid and secrete oils that help prevent evaporation of the eye’s protective tear film. Distichiasis occurs when aberrant eyelashes emerge from the orifice of the Meibomian glands, which puts the misplaced eyelashes in a position where they may come in contact with the cornea and cause irritation to the surface of the eye. In some individuals, the disease may be mild enough to go unnoticed, but in other horses, these abnormal lashes can cause chronic irritation, ocular pain, and corneal ulcers. Damage to the eye from corneal ulceration may cause vision loss or necessitate removal of the eye.

The condition can be treated, by removing the offending hairs, for example with thermocautery. However, the condition has been reported to recur in up to 50% of cases.

Friesians are by far the most likely breed to be affected. They are known for being relatively highly inbred and prone to a range of genetic diseases. This knowledge prompted the research team to investigate the genetic basis of the condition.

For a start, researchers traced the pedigrees of affected horses which provided evidence of an autosomal recessive mode of inheritance. Then they conducted a Genome-Wide Association Study comparing samples from 14 affected and 38 normal animals. This narrowed down the search to a section of the ECA13 chromosome.

Investigating the ECA13 further with Whole Genome Sequencing, they identified a large chromosome deletion between two genes that were strongly associated with distichiasis.

"Given the strong association and the frequency of the variant in the population of Friesian horses we evaluated, testing for this variant can be used to avoid crosses that can produce animals homozygous for the variant."
Image by AlkeMade

Eighteen out of 19 affected Friesian horses were homozygous for (had two copies of) the distichiasis associated variant. This pointed to a recessive mode of inheritance.

However, seven out of 75 horses with no evidence of distichiasis were also homozygous for the variant. This led the research team to suggest that distichiasis in Friesians appears to be a trait with incomplete penetrance. (That is, the condition may be expressed in only some individuals that have two copies of the variant, while some homozygous individuals may never show signs of the condition.)

To see if the variant occurs in other breeds, they tested samples from 955 horses of 54 different breeds and identified the deletion in only 11 non-Friesians, all of which only had one copy of the variant.

“Given the strong association and the frequency of the variant in the population of Friesian horses we evaluated, testing for this variant can be used to avoid crosses that can produce animals homozygous for the variant,” said Erin Hisey, the UC Davis veterinary student who was the first author on the study, which has been published in the journal BMC Genomics.

The work was supported by the UC Davis Provost Undergraduate Research Fellowship, the Morris Animal Foundation, and the UC Davis Center for Equine Health.

The test for distichiasis is the third available for Friesian horses, the other two being dwarfism and hydrocephalus.

Hisey, E.A., Hermans, H., Lounsberry, Z.T., Avila, F., Grahn, R.A., Knickelbein, K.E., Duward-Akhurst, S.A., McCue, M.E., Kalbfleisch, T., Lassaline, M.E., Back, W., & Bellone, R.R. (2020). Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses. BMC Genomics 21, 848 (2020). https://doi.org/10.1186/s12864-020-07265-8

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