Genetic defect associated with painful eye condition identified

An interdisciplinary team of scientists and clinicians, led by Dr. Rebecca Bellone at the University of California Davis Veterinary Genetics Laboratory, has identified a genetic variant associated with distichiasis in Friesian horses. 

Distichiasis, is a condition affecting the eye in which aberrant hairs grow from abnormal positions along the eyelid. These hairs rub on the cornea, causing irritation and pain. Severe cases may progress to corneal ulceration, leading to vision impairment and even loss 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% 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 family trees 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 was strongly associated with distichiasis. 

 

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 this study. 

 

Additionally, the results of this test can be used clinically. "Those horses that test homozygous for this variant should be evaluated for abnormal lashes to potentially provide clinical intervention prior to the development of irreversible corneal damage," said Dr. Hanneke, co-author of the study and equine surgeon with a focus in ophthalmology.

 

For more details, see:

 

Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses. 

Hisey, E.A., Hermans, H., Lounsberry, Z.T. et al. 

BMC Genomics 21, 848 (2020). 

https://doi.org/10.1186/s12864-020-07265-8

 

https://vgl.ucdavis.edu/news/vgl-led-team-identifies-genetic-variant-distichiasis-friesians