X-Linked PRA XL-Test Code 108
For breeds: Samoyed and Siberian Husky
The OptiGen XL-PRA test is a DNA-based test that provides, for the first time, a method to unequivocally identify the X-Linked form of Progressive Retinal Atrophy (XL-PRA) in the Siberian Husky and the Samoyed. This will control the gene frequency in the breed so as to prevent producing puppies affected with the disease.
Normally, the vision receptors in the eyes undergo a continual process of replacement and renewal. But with PRA this process slows and, one day, stops. The night vision receptors are the first to fail, and then, a while later, day vision starts to degenerate.
XL-PRA is a "late-onset" form of PRA. It usually isn't until dogs are three to five years old that the first clinical signs of disease start to manifest. Indeed, deterioration can happen as early as five months of age--but no one notices it. Eventually, though, dog owners see that their pet's eyes have taken on a characteristic "shine." The pupils become increasingly dilated in the attempt to let in yet more light. Dogs develop "tunnel vision." It's like trying to look at the world through a narrow tube.
What's different about the XL form of PRA? First, remember that females have two X--or female--chromosomes. In genetic shorthand, that's XX. Males have one X and one Y, or XY. It's the Y that makes males male.
In XL-PRA, the defective gene for PRA is a recessive trait that is situated on the X chromosome. Females who inherit a defective gene on the X chromosome from one parent and a normal gene on the X from the other parent won't be affected. They will be carriers with partial retinal defects. These defects are so subtle that vision is not affected. Nonetheless, carriers silently pass the defective gene on to future generations.
With males it's a little different. A male pup with a carrier dam is going to get either a defective gene or a normal gene, depending on which copy of the X chromosome his carrier dam gives him. And if it's the defective gene, the dog will be affected. With X-linked diseases such as XL-PRA, there's no such thing as a male carrier. That's why male Huskies or Samoyeds are much likelier to be affected than females.
Reliable identification of female dogs that do not carry disease genes is the key to controlling diseases that are X-linked, that is, located on the X (sex) chromosome. The OptiGen XL-PRA test enables 100% accurate identification of these dogs. Called "genetically clear," "noncarriers" or, more formally, "homozygous normals," such females can pass only the normal gene on to all their pups-which means that none of their pups can ever be affected with XL-PRA. These "clear" females can be bred to any male dog, even to a XL-PRA-affected dog, which may be a desirable breeding prospect for other reasons.
Homozygous means both copies of the gene in your dog are the SAME - both normal or both mutant. A carrier has one normal and one mutant disease gene. Because the OptiGen XL-PRA test is a direct mutation-based gene test, it accurately and specifically identifies normal/clear dogs, carriers (heterozygous dogs) and affecteds. Possible test results are listed in the table below.
|Possible results for a Siberian Husky or Samoyed using the XL-PRA test|
|Test Result*||Genotype of Dog Tested||Significance for Breeding||Risk For Developing|
|N ||Normal||Normal females can be bred to any male. Normal males should be bred only to normal females.||Will never develop|
|C||Carrier||Carrier females should not be bred. Only females are carriers of XL-PRA.||Will never develop|
|A||Affected||Affected males should be bred only to normal females. Affected females should not be bred. They are rare since both copies must be mutant.||Has or will develop|
|*This is the result that will be reported by the OptiGen XL-PRA test.|
Other Conditions Mistaken for PRA
Not all vision loss in Huskies and Samoyeds is caused by XL-PRA. There are reports of acquired (not inherited) retinal changes that have been mistakenly diagnosed as PRA. Since the DNA test for XL-PRA is completely accurate and specific, it can be used to differentiate the inherited form of PRA from the acquired retinal abnormality. A dog clinically diagnosed with an acquired retinal abnormality that is similar to PRA will not test affected for XL-PRA.
The following table highlights all the desirable breedings that will not produce affected pups. These breedings include a female parent proven "normal" by the OptiGen XL-PRA test. All other breedings are at risk of producing XL-PRA-affected pups. It isn't necessary-or even desirable-to remove any male dog from the breeding population. But when choosing pups to retain as further potential breeding stock, it is important to select for dogs proven "normal" by the OptiGen XL-PRA test. Pups can be tested to distinguish carriers from normals as soon as they are old enough to have a small blood sample collected.
- To avoid producing XL-PRA, only Clear/Normal females should be bred.
- Neither Carrier nor Affected females should be used because affected progeny can result.
- Clear/Normal males bred to Clear/Normal females will produce all Clear/Normal pups.
- Affected males bred to Clear/Normal females will produce males that are all Clear/Normal and females that are all Carriers.
- It is not possible to have a Carrier male since males have only one X chromosome and that one X will have either a normal or a mutant copy, but not both.
|Expected results for breeding strategies using the OptiGen XL-PRA mutation test|
|XnXn = Normal||XnXa = Carrier||XaXa = Affected|
|XnY = Normal||All Males & Females|
|1/2 of Females - Normal|
1/2 of Females - Carrier
1/2 of Males - Normal
1/2 of Males - Affected
|All Females - Carrier|
All Males - Affected
|XaY = Affected||All Females - Carrier|
All Males - Normal
|1/2 of Females - Carrier|
1/2 of Females - Affected
1/2 of Males - Normal
1/2 of Males - Affected
|All Males & Females|
|Shaded boxes show the only recommended breeding pairs in order to avoid producing affected pups.|
Xn is an X chromosome with a normal PRA gene.
Xa is an X chromosome with a mutant (affected) PRA disease gene.
The OptiGen XL-PRA test has been extensively tested in Siberian Huskies and Samoyeds descended from different ancestors of the U.S. breeding population. The test is not currently applicable to other breeds of dogs.
How you can participate...
The XL-PRA 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. And, when you've completed one Form, a second Test Request Form for another dog or for a litter is easy and saves you time.
|This research couldn't have been done without the great support of the Siberian Husky Club of America, The Morris Animal Foundation, The Seeing Eye, The American Kennel Club Canine Health Foundation, The National Eye Institute of the National Institutes of Health, and The Foundation Fighting Blindness.|