Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.
Authors: Bellone Rebecca R, Holl Heather, Setaluri Vijayasaradhi, Devi Sulochana, Maddodi Nityanand, Archer Sheila, Sandmeyer Lynne, Ludwig Arne, Foerster Daniel, Pruvost Melanie, Reissmann Monika, Bortfeldt Ralf, Adelson David L, Lim Sim Lin, Nelson Janelle, Haase Bianca, Engensteiner Martina, Leeb Tosso, Forsyth George, Mienaltowski Michael J, Mahadevan Padmanabhan, Hofreiter Michael, Paijmans Johanna L A, Gonzalez-Fortes Gloria, Grahn Bruce, Brooks Samantha A
Journal: PloS one
Summary
# Editorial Summary The leopard complex coat pattern in horses—characterised by white spotting—has long been linked to congenital stationary night blindness (CSNB), a condition causing permanent loss of night vision in homozygous carriers. Bellone and colleagues identified the genetic mechanism behind both traits, pinpointing a 1378 base-pair retroviral insertion within the TRPM1 gene as the culprit; this insertion acts as a long terminal repeat that disrupts normal gene transcription through premature polyadenylation, effectively silencing the gene's function. Testing across 511 horses for the spotting pattern and 43 for CSNB confirmed a near-perfect association with the mutation, with statistical significance exceeding p<<0.0005, indicating this is almost certainly the causal variant. Ancient DNA samples spanning at least 17,000 years suggest the insertion has persisted in horse populations far longer than expected for such a deleterious mutation, raising intriguing questions about its evolutionary maintenance. For breeding programmes, these findings provide a reliable molecular test to identify carriers and homozygotes before purchase or breeding decisions, allowing informed management of both the cosmetic leopard pattern and the performance-limiting blindness phenotype in low-light conditions.
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Practical Takeaways
- •Horses with leopard complex spotting (particularly homozygotes) should be screened for congenital stationary night blindness as a clinically significant associated condition affecting vision in low light
- •Genetic testing for the TRPM1 LTR insertion can definitively identify carriers and homozygotes before clinical signs emerge, enabling informed breeding and management decisions
- •Understanding the genetic basis allows veterinarians to counsel owners on the expected phenotype and potential welfare implications of breeding LP-positive horses
Key Findings
- •A 1378 bp retroviral LTR insertion in TRPM1 intron 1 is completely associated with leopard complex spotting in 511 horses (χ²=1022.00, p<<0.0005)
- •The same TRPM1 insertion causes congenital stationary night blindness in homozygous horses (LP/LP genotype, χ²=43, p<<0.0005)
- •The LTR insertion disrupts TRPM1 transcription through premature poly-adenylation
- •Ancient DNA analysis shows this insertion has been maintained in horse populations for at least 17,000 years despite its deleterious effects