Collie Eye Anomaly / Choroidal Hypoplasia (CEA) Test
|Collie - Rough & Smooth||66.7%||8.75%||1.88%|
The frequency of the CEA/CH gene mutation in U.S. Rough and Smooth Collies appears to be extremely high. In general, the frequency of affecteds in Rough and Smooth Collies is well over 50%, and in some populations has been observed to be as high as 85-90% of dogs examined. Of the remaining, most are carriers. The frequency of the CEA/CH gene mutation in European Shetland Sheepdogs appears to be significantly higher than in the U.S.
The OptiGen genetic test for CEA/CH provides a powerful management tool for the breeder. This genetic test can distinguish all three genetic states – normal, carrier and affected. With this information, the breeder can plan matings that avoid producing any affected dogs by always selecting one parent that is normal. The other parent can be normal, carrier or even affected, and no affected dogs will result. (See table at the end.) This breeding recommendation is a big step forward, especially for breeds and countries where frequency of CEA/CH is much lower. Earlier advice cautioned against breeding affected dogs, their parents, their offspring or their siblings (unless eye exams before 3 months of age demonstrate the sib is unaffected).
Understandably, genetic testing will be a difficult tool to use for some breeders of “standard” collies (i.e., Rough, Smooth, Show, Standard) where the disease is very common. In some circumstances, genetically normal – homozygous normal – collies could be difficult to find and it may not be practical for the breeder to plan matings that include one normal dog. And, it may not be reasonable to expect complete avoidance of CEA/CH in one generation. All the same, genetic testing is a sure-fire tool to move toward elimination of the disease. To start, breeding a carrier to a carrier will produce an average of 25% normals, 50% carriers and 25% affecteds. With genetic testing at each subsequent generation, and with a goal of breeding normal by carrier or normal by affected, the frequency of disease will drop and frequency of normals will increase without loss of other desirable traits valued in collies.
Breeders should pay attention to protecting the genetic diversity of breeds that have very high frequencies of an inherited disease. In the case of CEA/CH, the genetic test can be viewed as an adjunct to traditional strategies for avoiding severe cases of CEA. Over the last 30 years, many animals have been examined and those with only mild CEA (no colobomas or detachments) have been selected for breeding. The result is the percentage of collies affected with choroidal hypoplasia remains high, but the severe grades of the disease (colobomas and retinal detachments) have decreased due to this conscientious breeding.
Even though the ideal recommendation is to breed genetically normals, preservation of other desirable physical traits might override the ideal in the short-term. Reduction or even elimination of the CEA/CH mutant gene can be viewed as a longer-term goal. You should consult with your breed club for further breeding recommendations.
You might ask: if the mild form and the severe form of CEA/CH disease are caused by the exact same genetic mutation, why do some dogs have only mild disease while others have severe disease? Is the severity due to diet, activity, or other insults like infections or trauma? So far, there are no clues that non-genetic factors are responsible. Instead, there are probably other independently acting “modifier” genes that influence CEA/CH gene expression. If that is so, eventually these modifier genes will be detected, although the chore will be difficult. Possibly, by choosing mildly affected dogs and avoiding severely affecteds in a breeding program, breeders have concentrated positive influencing independent modifier genes in their line. The CEA/CH gene frequency may not have changed, but the disease may be partially suppressed as long as the modifying genes are carried along. This is a risky approach, since the identity of those influencing genes – indeed even their number and action – is a complete unknown.
You might also ask: is it true that early choroidal hypoplasia can “go normal,” that is, reverse to a normal appearance? There are occasional reports of puppies, found to be affected as early as 5 weeks of age, that appear to “go normal” when re-examined some months later. The abnormal features seem to disappear or lessen due to pigment changes and masking of the thin choroid areas. (However, if a dog had a coloboma, this will remain – it is a permanent lesion.) The majority of dogs that “go normal” are homozygous for the CEA/CH mutation, especially if they “go normal” slowly or incompletely. A small minority, however, are heterozygous carriers that tend to “go normal” at a very young age. Regardless, the genetic status of such dogs was and remains constant during their lifetime, so these dogs can pass the mutant disease gene to their offspring. Testing will help you identify the genetic status of dogs that have an ambiguous clinical diagnosis.
The CEA/CH genetic test provides the life-long genetic status of a dog for this disease. In conjunction with genetic testing, an eye exam by a veterinary ophthalmologist is recommended before 8-9 weeks of age, with annual eye exams thereafter. The eye exam will give you information about mild versus severe CEA/CH disease among affected dogs. Annual eye exams are always recommended for all dogs of all breeds. Clinical exams detect a wide variety of eye problems, both genetic and non-genetic.
|Expected Results of Breeding Strategies for Inherited Recessive Diseases|
|Parent 1 |
|Parent 2 Genotype|
|Normal||All = Normal||1/2 = Normal |
1/2 = Carriers
|All = Carriers|
|Carrier||1/2 = Normal|
1/2 = Carriers
|1/4 = Normal |
1/2 = Carriers
1/4 = Affected
|1/2 = Carriers|
1/2 = Affected
|Affected||All = Carriers||1/2 = Carriers|
1/2 = Affected
|All = Affected|
|The table shows the desirable breedings (gray-shaded boxes) which have at least one parent that is Normal by the OptiGen CEA/CH test. All other breedings are at risk of producing pups affected with CEA/CH.|
Limits to All Genetic Testing
There are basic limits for any and all DNA genetic tests. Whether a test is mutation-based or marker-based, it identifies only the specific mutation being tested or the association between a specific marker set and the disease. For example, a mutation test detects one specific mutation in one specific gene. If there are several different mutations or several different genes that can cause the same condition, one must discover and then test for each mutation and each gene. Likewise, a marker test uses one marker or set of markers to define a specific condition. If the condition is associated with several different marker combinations, one must discover and then test for each marker combination. It can be difficult or even impossible to know how many mutations or how many marker sets exist in all the members of a specific breed. As more and more dogs are tested, previously unknown variations may come to light.
In the case of CEA/CH, the OptiGen genetic test for the listed breeds is a mutation-based test.
Acland, G., Aguirre, G., Personal Communications.
A.C.V.O. Genetics Committee, “Ocular Disorders Presumed to be Inherited in Purebred Dogs.” 1999 Edition.
Riis, R., “Inherited Eye Anomalies of Australian Shepherds, Collies, and Shetland Sheepdogs.” In: Small Animal Ophthalmology Secrets, Chapter 38, Hanley & Belfus, Inc., 2002.
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 2003 Jul;82(1):86-95.
How you can participate
The CEA/CH test is done on a small sample of blood obtained by your veterinarian. This allows the lowest risk of contamination of the sample and added assurance of a match of the sample with the identified dog.
Read and print the instructions on the Ship Sample page. Then fill out the Test Request Form. On-line submission of the Test Request Form lets you be sure accurate information and correct spellings are put in the database. When you've completed one Form, a second Test Request Form for another dog or for a litter is easy and saves you time.
Special recognition is due to the ABCA - American Border Collie Association for financial support of the research and to other concerned groups and individuals in the community for their participation in the development of this test. The research leading to this discovery was undertaken by scientists at the James A. Baker Institute for Animal Health at Cornell University's College of Veterinary Medicine in Ithaca, New York, and at The Fred Hutchinson Center for Cancer Research in Seattle, Washington. The patented technology underlying this test is under exclusive license to OptiGen from Cornell Research Foundation, Inc.