Identification of a Potential Candidate Mutation for the Genetic Inheritance of Progressive Retinal Degeneration in the Curly Coated Retriever.
Retinal degeneration resulting in blindness has been observed in the Australian and USA Curly Coated Retriever (CCR) breed and is also likely to be present in lines from other countries. A number of Australian and USA CCR breeders, including Helen Jones and Kevin Chamberlain, have observed this condition in their pedigrees and have been determined to better understand the genetics behind this condition. Examination of limited numbers of individuals from these pedigrees suggests that retinal degeneration in the CCR may follow basic Mendelian inheritance as a single locus, recessive trait. Helen and Kevin contacted Genetic Technologies (GTG) to assist them in understanding the genetics behind the retinal degeneration (ophthalmic classification of these dogs was Progressive Retinal Atrophy) observed in the CCR.
GTG provides genetic testing services for inherited diseases in purebred dogs and has a number of different tests for specific types of retinal degeneration. In most cases, the specific types of retinal degeneration are limited to only a single breed or closely related breeds. In some instances, especially with recessive traits, the mutations that are responsible for the different types of diseases can be quite “ancient” and may have existed prior to the formation of the breed in which it is observed today. In these cases, it is not uncommon to observe a mutation that is known to cause disease in one breed, in low frequency within other, apparently diverse breeds. Usually, these mutations are present at such low frequencies that the probability of observing an affected dog is effectively zero (this can change through further bottleneck events such as breeding closely related animals). Further, penetrance1 of the mutated gene may be different between the breeds, due to their interaction with different breed specific genetic content (ie other genes etc).
As a first pass, GTG decided to test CCR samples that were either i) clinically affected, ii) produced clinically affected offspring or iii) whose sire or dam were clinically affected, with our panel of tests for published mutations shown to cause retinal degeneration in other canine breeds. Interestingly, we observed that the CCR animals we tested were all either heterozygous or homozygous for the mutation responsible for Cone-Rode Dystrophy in Miniature Longhaired Dachshunds . This mutation is a 44 base pair insertion in exon 2 of the RPGRIP1 gene. Segregation analysis across a small number of pedigrees revealed that retinal degeneration affected CCR’s are homozygous for the CORD1 mutation. All other CCR’s tested from the three groups above were heterozygous and have not developed any clinical symptoms at the time of testing.
It is important to note that the results from this study are only preliminary and the penetrance of the CORD1 mutation has not been studied in outbred CCR lines. It is possible, as reported by Myadera et al 2009  and Busse et al 2011 , that other modifying genes may change the penetrance of the CORD1 mutation, whereby homozygous animals will show no clinical symptoms of this disease. Likewise, it is also possible that other undiscovered mutations may also exist in the CCR and may produce retinal degeneration in CORD1 genetically “Clear” and “Carrier” animals. As such the presence (or absence) of the CORD1 mutation in an individual does not provide conclusive proof of the development (non-development) of Retinal Degeneration. These factors should be taken into account when ordering such a test.
That being said, this test provides CCR breeders with the ability to test their animals and undergo breeding strategies to prevent producing animals that are homozygote for the CORD1 mutation and also to decrease the frequency of the mutation in the breeding population.
Dr Craig McLure
Senior R&D Scientist
Genetic Technologies Limited
1. Penetrance – The proportion of individuals carrying a particular variation of a gene (allele or genotype) that also express an associated trait.
1. Mellersh CS, Boursnell ME, Pettitt L, Ryder EJ, Holmes NG, Grafham D, Forman OP, Sampson J, Barnett KC, Blanton S, et al: Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 2006, 88:293-301.
2. Miyadera K, Kato K, Aguirre-Hernandez J, Tokuriki T, Morimoto K, Busse C, Barnett K, Holmes N, Ogawa H, Sasaki N, et al: Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Mol Vis 2009, 15:2287-2305.
3. Busse C, Barnett KC, Mellersh CS, Adams VJ: Ophthalmic and cone derived electrodiagnostic findings in outbred Miniature Long-haired Dachshunds homozygous for a RPGRIP1 mutation. Vet Ophthalmol 2011, 14:146-152.