Whole-genome sequencing identifies missense mutation in GRM6 as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse.
Authors: Hack Yael L, Crabtree Elizabeth E, Avila Felipe, Sutton Roger B, Grahn Robert, Oh Annie, Gilger Brian, Bellone Rebecca R
Journal: Equine veterinary journal
Summary
# Editorial Summary: GRM6 Mutation Identified as Novel Cause of Night Blindness in Tennessee Walking Horses Congenital stationary night blindness (CSNB) in horses has been attributed exclusively to a TRPM1 insertion, but a Tennessee Walking Horse with clinical CSNB lacked this known variant, prompting researchers to search for an alternative genetic cause. Whole-genome sequencing of the affected horse and comparison against 29 horses from seven other breeds identified a missense mutation in the GRM6 gene (c.533C>T, p.Thr178Met)—a SNP not found in 273 control horses from three additional breeds. Protein modelling analysis predicted that this mutation impairs glutamate binding to the metabotropic glutamate receptor 6, disrupting the critical signalling pathway between retinal rod cells and ON-bipolar cells that enables low-light vision. With an estimated allele frequency of 10% in Tennessee Walking Horses, the authors propose this variant may account for additional undiagnosed cases within the breed. For practitioners, this finding expands our understanding of CSNB genetics beyond the TRPM1 locus and suggests that GRM6 screening should be considered in night-blind Tennessee Walking Horses lacking the known insertion, whilst also highlighting the value of genomic testing in identifying breed-specific disease variants for future breeding programmes and early diagnosis.
Read the full abstract on PubMed
Practical Takeaways
- •Tennessee Walking Horse breeders should be aware that CSNB can result from a GRM6 mutation independent of the known TRPM1 variant; genetic screening recommendations should be updated accordingly
- •Affected horses show impaired vision in low light conditions; owners and handlers should provide appropriate lighting accommodations and account for safety limitations during night work
- •With a 10% allele frequency in the breed, a significant carrier population likely exists; consider genetic testing and counseling for breeding programs to reduce disease incidence
Key Findings
- •A missense mutation in GRM6 (c.533C>T p.Thr178Met) was identified as the likely genetic cause of CSNB in a Tennessee Walking Horse lacking the previously known TRPM1 insertion variant
- •The GRM6 variant is predicted to impair glutamate binding and signal transmission from retinal rod cells to ON-bipolar cells, explaining night blindness phenotype
- •The variant has an estimated allele frequency of 10% in Tennessee Walking Horses, suggesting additional affected horses likely exist in the breed
- •The mutation was not detected in 273 horses from three other breeds, indicating breed-specific prevalence