Molecular mechanism
Collie Eye Anomaly (CEA), now more broadly referred to as Choroidal Hypoplasia (CH), is an inherited developmental disorder of the eye characterised primarily by underdevelopment of the choroid, with severity ranging from no detectable visual impairment to complete blindness. Affected dogs may also develop colobomas, retinal folds and, in more severe cases, retinal detachment and intraocular haemorrhage, which can result in permanent vision loss (Lowe et al., 2003; Fredholm et al., 2016).
Collie Eye Anomaly is inherited as an autosomal recessive condition with variable clinical expression. Parker et al., (2007) identified a 7.8 kb deletion (37.28,697,542–28,705,340del) associated with CEA within the NHEJ1 gene on canine chromosome 37 (CFA37), which is widely used as the genetic marker for CEA screening. Although subsequent studies have suggested that this deletion may be linked to, rather than be the causative variant in, some breed populations, it remains strongly associated with the disease and is widely used for genetic testing (Fredholm et al., 2016; Brown et al., 2018; Clark et al., 2023).
References
References
Clark, J.A., Anderson, H., Donner, J., Pearce-Kelling, S., Ekenstedt, K.J. : Global frequency analyses of canine progressive rod-cone degeneration-progressive retinal atrophy and Collie eye anomaly using commercial genetic testing data. Genes (Basel) 14:2093, 2023. Pubmed reference: 38003037. DOI: 10.3390/genes14112093.
Brown, E.A., Thomasy, S.M., Murphy, C.J., Bannasch, D.L. : Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye anomaly mutation). Vet Ophthalmol 21:144-150, 2018. Pubmed reference: 28702949. DOI: 10.1111/vop.12488.
Fredholm, M., Larsen, R.C., Jönsson, M., Söderlund, M.A., Hardon, T., Proschowsky, H.F. : Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs. Anim Genet 47:250-2, 2016. Pubmed reference: 26732749. DOI: 10.1111/age.12405.
Parker, H.G., Kukekova, A.V., Akey, D.T., Goldstein, O., Kirkness, E.F., Baysac, K.C., Mosher, D.S., Aguirre, G.D., Acland, G.M., Ostrander, E.A. : Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res 17:1562-71, 2007. Pubmed reference: 17916641. DOI: 10.1101/gr.6772807.
Lowe, JK., Kukekova, AV., Kirkness, EF., Langlois, MC., Aguirre, GD., Acland, GM., Ostrander, EA. : Linkage mapping of the primary disease locus for collie eye anomaly. Genomics 82:86-95, 2003. Pubmed reference: 12809679.
