Canine Collie Eye Anomaly (CEA) underlying genetic causes and future medical/therapeutic implications

Collie eye anomaly (CEA) is a recessive genetic disorder that brings about serious ocular effects, including retinal abnormalities and even blindness. This disease affects many dog breeds, the most common being collies. The causation of CEA is the deletion of 7,799 bp located in the intronic, part of the NHEJ1 (non-homologous end-joining factor 1) gene on chromosome 37. The mechanism of action of how the genotype is correlated to the phenotypic expression is still unknown in canines. PCR is currently used to diagnose CEA. Newer studies have shown that select high CEA frequency breeds express the disease’s phenotype without the NHEJ1 mutation. This suggests the existence of multiple genotypes responsible for CEA yet to be discovered. Observing analogous NHEJ1 gene mutations within humans with similar ocular defects can contribute to a better understanding of the mechanism of action in canines. Human medicine studies have identified that the intronic segment of NHEJ1 gene that is deleted in genetic ocular defects is also an enhancer for another gene necessary for normal eye development, the Indian Hedgehog gene (IHH). I theorize that this mechanism of action is conserved between species explaining how the deletion of the NHEJ1 gene segment can cause CEA. It is also further theorized that dogs with CEA phenotypic expression lacking the NHEJ1 mutation could possess mutations to other enhancers to the IHH gene or direct mutations within the IHH gene itself. Further research is needed and could lead to future preventive genetic testing or gene therapies for CEA for dogs.