CEA?

[Journey]

Curious after reading many of the articles on CEA...has the causative mutation for Coloboma's ever been found?

[Mark Billadeau]

I think you’ll find there are many genes causally associated with ocular colobomas, among those genes is NHEJ1.

This review of human genetic variants of ocular colobomas lists >40 loci causally associated with ocular colobomas.

https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31831

 

This article has a description of the processes involved in the development of eyes in the embryo and why there can be many genes that cause ocular colobomas 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302742/

[Journey]

Thanks for the info Mark. WRT CEA, is it not the Colobomas that cause the blindness? 

[Mark Billadeau]

This site has a summary of the defects that are associated with NGEJ1 (which causes incomplete eye development).  Among these defects is coloboma.

https://www.ashgi.org/home-page/genetics-info/eyes/collie-eye-anomaly
 

Coloboma and retinal detachment are listed as causes of blindness.

[Journey]

Right. The DNA test is for CH though, not Colobomas, which is what causes blindness. So what type of DNA test is this then? Isn't it a marker test?

[Mark Billadeau]

The test is for the deletion of the NHEJ1 gene (not a marker test).  Are you certain that this mutation only causes CH?  Or are you basing your argument on the association of this mutation with CH in certain breeds when the use of this test is described?  I think you'll find genetics is more complex than the simple association you are describing.

 

This has a good overview

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies (nih.gov)

 

and this one describes CEA as complex

The genetics of eye disorders in the dog | Canine Medicine and Genetics | Full Text (biomedcentral.com)

Quote

Another complex congenital defect of the retina is collie eye anomaly (CEA), although retinal involvement is secondary to the primary ocular defects associated with this disorder. The primary phenotypic element of the disorder is regional hypoplasia of the choroid, the highly vascular layer underlying the retina. Associated retinal lesions, known as colobomas are often detectable ophthalmoscopically, as are tortuous retinal vessels and multiple retinal folds in a minority of cases [91]. CEA, which segregates in several herding breeds with Collie ancestry, was mapped to a large region of CFA37 that included over 40 genes [92]; subsequently the fact that the disorder segregates in multiple, closely related breeds was used to reduce the size of the critical disease-associated region and pinpoint the causal mutation to a 7.8 kb intronic deletion in the NHEJ1 gene, which spans a highly conserved binding domain to which several developmentally important genes bind [91]. The precise mechanism by which the deletion causes CEA has not however been established to date.

 

[Mark Billadeau]

I have provided links to publications which indicate the mutation assessed by the genetic test is associated with CEA in certain breeds which is described as a set of retina disorders including CH and colobomas.  Please provide a link or links to published studies which argue this mutation is only associated with CH in these same breeds.  I’ll read those studies and then get back to this topic.