Progressive Retinal Atrophy (PRA4) in the Lhasa Apso
We are delighted to report that a mutation causing Progressive Retinal Atrophy (PRA4) in the Lhasa Apso has been identified at the Kennel Club Genetics Centre at the Animal Health Trust (AHT).
We are calling this form Progressive Retinal Atrophy, PRA4 to distinguish it from other genetic forms of PRA that occur in other breeds.
The DNA test for this mutation will be available from the 4th of September 2017.
Progressive Retinal Atrophy is seen in many different breeds. The causal mutations are often unique to a breed and some breeds have been found to have more than one. To date 29 mutations have been found to be associated with PRA.
This test is for a novel mutation identified here at the Animal Health Trust.
The PRA4 mutation has so far been found to be unique to the Lhasa Apso.
How common is the disease?
Between the official PRA4 DNA test launch date, 4th September 2017, and 29th January 2018, the AHT DNA testing facility has genetically tested 457 Lhasa Apso’s for the PRA4 mutation from 15 countries.
We can report that 354 of these dogs are from the UK population. The following figures relate to the UK cohort: 3 Lhasa Apso’s PRA4 affected, 61 carriers and 290 clear.
This gives a carrier frequency of approximately 17% in our UK DNA testing cohort. The frequency of the PRA4 allele is 0.09 which corresponds to the frequency of affected Lhasa Apso’s in this UK population as 0.009.
This means 1 in 111 PRA4 affected Lhasa Apso’s are expected and 1 in 6 carriers expected.
How is the disease inherited?
The disorder shows an autosomal recessive mode of inheritance, which means that two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease.
Individuals with one copy of the defective gene and one copy of the normal gene, called carriers, show no signs of disease but can pass the defective gene onto their offspring.
When two carriers are crossed, 25% (on average) of the offspring will be affected by the disease, 25% will be clear and the remaining 50% will themselves be carriers. Please note that these percentages refer to a statically significantly number of dogs, distribution will vary in individual litters.
Breeders using our DNA test will be sent results identifying their dog as belonging to one of three categories. In all cases the terms ‘normal’ and ‘mutation’ refer to the position in the DNA where this PRA mutation is located in the Lhasa Apso. It is not possible to learn anything about any other region of DNA from this test.
CLEAR: These dogs have two copies of the normal gene and will not develop PRA as a result of the PRA4 mutation we are testing for. Although we cannot exclude the possibility they might develop a similar condition due to other causes or the effect of other, unidentified mutations.
CARRIER: These dogs have one copy of the mutation and one normal copy of DNA. These dogs will not develop PRA themselves as a result of the PRA4 mutation, but they will pass the mutation on to approximately 50% of their offspring.
AFFECTED: These dogs have two copies of the PRA4 mutation and will almost certainly develop PRA during their lifetime.
We cannot exclude the possibility that carriers might develop a similar condition due to other mutations they might carry that are not detected by this test.
Our advice is to breed with carrier animals for the first few generations after the development of a DNA test. This ensures that desirable traits in the breed are also captured.
Carriers can still be bred to clear dogs. On average, 50% of such a litter will be clear and 50% carriers; there can be no affected dogs produced from such a mating.
Pups which will be used for breeding can themselves be DNA tested to determine whether they are clear or carriers of this PRA mutation.