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Type B PRA in Miniature Schnauzers                  Code 212

Test Pricing

Background

Progressive Retinal Atrophies (PRAs) form a large group of inherited diseases that are a major cause of blindness among multiple dog breeds. PRA-affected dogs typically show a similar sequence of clinical abnormalities in the course of the disease: night blindness followed by progressive loss of day vision and eventual blindness under all light conditions. Routine eye exams reveal the progressive thinning due to degeneration or “atrophy” of the retina, hence the name given to the disease.

Although they share the same name of “PRA”, there are several known -- and also many more unknown/uncharacterized-- genetic abnormalities (mutations) that cause PRA in dogs. For many years, OptiGen has provided a DNA test, “Type A PRA”, that is able to detect one form of this disease. Through OptiGen’s Free DNA Testing/PRA Research program, in which we have tested dozens of pedigreed miniature schnauzers that have been diagnosed by veterinary ophthalmologists as having PRA, we have determined that the Type A form of PRA is very rare in the breed. None of these PRA cases (in recent years) have been due to the Type A PRA mutation. These new cases formed the basis of our research aimed at identifying other genes and mutations responsible for PRA in the breed.

New Genetic Test for PRA: Type B PRA Risk Variant

In collaboration with Drs. Doreen Becker and Gus Aguirre at the University of Pennsylvania, OptiGen’s R&D scientists, have discovered a new genetic variant that explains a large portion of PRA cases in the Miniature Schnauzer. Based on that discovery, OptiGen now offers a genetic test called Type B PRA test for Miniature Schnauzers. This DNA test is able to identify dogs that carry zero, one or two copies of the Type B PRA risk variant. The results of this test are intended to assist breeders when selecting the breeding pairs in order to prevent matings that would result in Type B PRA-affected puppies.

Test results for Type B PRA are reported as:

·       Homozygous wild type/Clear: the dog carries NO copies of the risk variant; will not develop Type B PRA

·       Heterozygous/Carrier: the dog carries ONE copy of the risk variant; will not develop Type B PRA

·       Homozygous Risk Variant: the dog carries TWO copies of the risk variant; at high risk of developing Type B PRA

The Type B PRA test results are reported as Risk Variants because, although dogs carrying two copies of the variant are very likely to develop PRA, a subset (14%) of the research sample set that were homozygous for the variant did not develop PRA by 7 years of age. It is not clear at this time whether the variant represents a causal mutation –and that other factors influence the “penetrance” of the mutation—i.e. its ability to cause disease-- or if the variant is a genetic marker that resides near the causal mutation. OptiGen and the University of Pennsylvania scientists will continue research aimed at better understanding this question.

Dogs that are Homozygous Risk Variant for Type B PRA have a high risk of developing Type B PRA. Within the research sample set, these dogs had an 86% chance of developing PRA, based on the initial research group of 108 genotyped dogs.

Type B PRA is inherited as an autosomal recessive disease and in order to prevent producing offspring that will develop this form of PRA, at least one parent should be DNA tested prior to breeding and shown to be Homozygous wild type/Clear for the Type B PRA risk variant..

Other forms of PRA in the breed:

The newly developed Type B PRA DNA test does not explain all cases of the disease in the breed, and it is concluded that there is at least one more form of PRA (in addition to Types A and B) present in the breed. In other words, if a dog has been tested Homozygous wild type/Clear or Heterozygous/Carrier for the Type B PRA risk variant, it can still develop (another form of) PRA, as well as transmit that other disease-causing genetic variant to offspring. Of the 76 PRA- clinically diagnosed Miniature Schnauzers in the research sample set, 42 (55%) of the cases were shown to be homozygous for the Type B risk variant. The remaining 45% of cases were either heterozygous (11%) or Clear (34%) of the Type B Risk Variant. In several of these cases, genome analysis by Genome Wide Association Studies (GWAS) indicated that the disease mapped to a different genomic region than Type B PRA thus confirming the presence of another PRA disease locus.

Recommendations for Breeding:

Even though the dogs that do not carry any copies for Type B genetic variant can still develop another form of PRA, the Type B PRA test provides a useful tool for breeders to prevent matings that result in puppies with homozygous variant genotypes. Only matings that do not result such genotypes (yellow boxes in chart below) are recommended. In matings that produce the disease variant, ~86% of the dogs that are homozygous for the variant will develop PRA.

Expected results for breeding strategies using the
Type B PRA Test

Parent 1
Genotype
Parent 2 Genotype

Homozygous
Wild Type/Clear

Heterozygous/
Carrier
Homozygous
Variant
Homozygous
Wild Type/Clear
All = Normal/Clear1/2 = Clear
1/2 = Carrier
All = Carrier
Heterozygous/
Carrier
1/2 = Clear
1/2 = Carrier
1/4 = Clear
1/2 = Carrier
1/4 = Variant
1/2 = Carrier
1/2 = Variant
Homozygous
Variant
All = Carrier
1/2 = Carrier
1/2 = Variant
All = Variant


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Tel: 607 257 0301 · Fax: 607 257 0353 · email: genetest@optigen.com or optigen@clarityconnect.com
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