Introduction
Inherited eye diseases (IEDs) cause pain and blindness in thousands of purebred and crossbred dogs every year. Funded by Dogs Trust, an interdisciplinary consortium comprised of veterinary ophthalmologists and canine geneticists from the Kennel Club Genetics Centre was established in 2019 specifically to research inherited eye diseases in dogs.
To date, over 86 eye disease mutations and 9 risk alleles believed to be associated with disease, located within 61 different genes, have been identified in hundreds of different dog breeds. Many of these ocular diseases are genetically heterogeneous, meaning that clinically similar diseases can be caused by different mutations. By identifying the causal mutations for specific diseases, DNA tests can be developed and made available to breeders and veterinary ophthalmologists, to prevent the spread of disease in future generations of dogs and to aide definitive diagnosis of patients.
The consortium to research inherited eye diseases in dogs – known as CRIEDD– aims to identify novel mutations responsible for inherited eye diseases in dogs and develop DNA screening tools for these mutations.
The Research Process
Step 1.
We have developed a multi-step laboratory work flow that we use to investigate both known and novel inherited eye diseases in all breeds of dog. DNA from multiple confirmed or suspected IED cases are screened simultaneously for all published mutations. By screening dogs of ALL breeds for ALL mutations the outcomes are three-fold:
- We are developing a better understanding of the frequency of specific mutations within different breeds
- We are identifying breeds that are segregating mutations previously found in other breeds
- We are identifying dogs that are clinically affected but that do not carry the mutation(s) associated with their specific breed
Step 2.
Cases that remain without a molecular diagnosis at the end of step 1 are investigated further, typically by whole genome sequencing. We compare the whole genome sequences of the IED cases with the sequences of unaffected dogs and use stringent filtering criteria to identify candidate variants, which are variants that could be associated or cause the IED under investigation.
Step 3.
Once candidate mutations have been identified we validate the mutation(s) by genotyping large cohorts of the relevant breed, comprising robust cases and controls to confirm the disease association. Once confirmed the ‘novel’ mutation will be added to the DNA screening panel in step 1.
Step 4.
We develop DNA tests for all novel mutations we identify. These DNA tests will be offered commercially by the Canine Genetic Testing service at the University of Cambridge once it officially opens for business in the Autumn of 2021 and all our findings are subject to appropriate peer-review.
Samples
We invite the submission of DNA from ANY dog of ANY breed that has been diagnosed with clinical signs of inherited eye disease. The DNA can be collected as buccal (cheek) swabs that can be taken by the dog’s veterinary ophthalmologist, veterinary nurse or owner. To help facilitate the research process we ask for detailed information about the dog and his/her diagnosis. We can provide DNA buccal swab kits free of charge.
For more information about the CRIEDD project and/or to request a free DNA collection kit please contact us.
Database
In addition to our research to identify novel IED mutations we have also developed a database that details all (currently 95) mutations known to cause inherited eye diseases (IED) in dogs; this database represents a much-needed resource for veterinary ophthalmologists attempting to keep abreast of developments in the field. The database is not currently available to the public (we hope it will be soon) but if you would like a copy of the database report please contact us.
Acknowledgements
We gratefully acknowledge Dogs Trust for funding this exciting project and all the veterinary ophthalmologists and dog owners who have submitted samples to this research.
