The Canine Genetics team is currently involved in several projects that aim to identify genetic variants that contribute to the risk of developing Hereditary Cataract (HC) in several breeds. Using this information, we will develop DNA-based tools that breeders can use to try and lower the incidence of HC in their breeds.
Findings from our initial studies in the Golden Retriever, American Cocker Spaniel, Large Munsterlander and German Pinscher suggest that HC might be a complex disease in these breeds, possibly involving several genes that might act independently or together with the environment to influence the development of HC. Some of these susceptibility loci may be shared across breeds, like the HSF4 insertion mutation, but it is likely that there will be some that are specific to only one or two breeds.
To tease apart the genetics underlying HC for each of the breeds above, and to add to the data that we already have, we will need to collect at least 48 dogs affected by HC and 48 older dogs that are clear of cataracts (see below) for each individual breed.
Hereditary Cataract in the Labrador Retriever
Labrador Retriever Health Day -
We welcomed more than 30 Labradors over eight years old to the AHT in October for a free eye test to support the below project. The day was a huge success, and helped us gather valuable DNA samples for our research. We enjoyed hosting the day and meeting people passionate about the breed and the health of their dogs.
Our researchers are trying to investigate the genetics of hereditary cataract, a potentially blinding disease in this popular breed, and the research desperately needs DNA from more Labradors over the age of eight - with a clear eye test. Without enough controls, we can't progress this study.
For this study we need up to 180 Labrador Retrievers affected by hereditary cataract, and an equal number of dogs over the age of eight which have had a clear eye test. For us to start the first stage of the research, a genome scan, we need 120 of each.
So far we have almost enough affected dogs for the initial stage, but we only have 50 unaffected dogs. We need DNA samples from at least 70 additional dogs over the age of eight with a recent clear eye certificate.
Could you and your dog help?
Please contact: firstname.lastname@example.org, Tel: 01638 751000 x1251
We will send you a cheek swab collection kit free of charge. All you need to do is follow the simple instructions for collecting DNA samples and return the cheek swab kit to us, along with a copy of your dog’s eye certificate.
More about the project:
We are trying to improve our understanding of the genetic causes of HC in the Labrador Retriever through a new research project. We aim to conduct a GWAS (Genome Wide Association Study), or DNA scan, using DNA from 120 dogs affected by HC (cases) and 120 dogs over the age of eight with a recent clear eye examination (controls).
If our GWAS identifies any regions of the genome which are associated with HC, we will then aim to find any changes in the DNA code (variants) in that region which could contribute to the risk of developing the disease.
Should we find any candidate causal variants we would then want to use an additional 60 cases and 60 controls to help characterise them. A case is a Labrador of any age that has been diagnosed with a HC and has an eye certificate to confirm the diagnosis. A control is a Labrador over the age of eight with a current clear eye certificate.
HC in Northern breeds
Our investigation in Northern breeds (Siberian Husky, Samoyed, Alaskan Malamute and Icelandic Sheepdog) has identified a variant in a gene that is strongly associated with HC (posterior polar subcapsular cataracts in both eyes) in three of these breeds and shows a consistent but not statistically significant association in another breed. This variant is very common in all four breeds and we therefore think that it is a susceptibility variant; possessing two copies of it confers an increased risk of developing HC, but as there are older dogs that have two copies that do not have cataracts, there is obviously something else (genetic or environmental) that is required for dogs to go on to develop HC. Therefore it would be inappropriate to develop a DNA test for this variant alone.
We are currently investigating the possibility of additional genetic variants that might be present that will explain these findings, but it may be that we will need to design a new study to try to investigate further what we have observed.
HC in the Australian Shepherd
For the Australian Shepherd, we are investigating the possibility that there may be further gene(s), in addition to the HSF4 deletion mutation, that affect risk of HC in this breed. We have used genome-wide association study (whole genome scanning) to search for genomic regions involved in HC in addition to the characterised HSF4 mutation. These methods screen the genome for regions that are consistently shared among affected dogs but are different in unaffected dogs.
We genotyped 24 HC cases and 72 controls (controls were dogs over the age of eight years with a current clear eye examination). All dogs were free of the HSF4 mutation. We used a high density canine scanning array that assesses around 174,000 unique points in the genome and received good quality data for 94 individuals. Our analyses of these data have indicated a region of the genome that shows strong association with HC.
We are currently conducting follow-up investigations and have resequenced the associated region, which spans several million nucleotides of DNA. Our analysis of this sequence will hopefully uncover the causative mutation underlying this association.
In collaboration with the Australian Shepherd Health & Genetics Institute in the USA, we are currently running a survey for owners of Australian Shepherds that have been tested for the hereditary cataract HSF4 mutation.
We are hoping that this survey will tell us a bit more about how many dogs who have the HSF4 mutation go on to develop cataracts, at what age they do so, what type of cataracts they develop, and whether there is a difference between dogs with only one copy and those with two.
This survey is open to any purebred Australian Shepherd which has had an HSF4 (hereditary cataract) DNA test, no matter what the results of the test. To complete the survey, please click here.
The survey should only take around 10 minutes to complete and, importantly, will help us to plan future research into cataracts in the Australian Shepherd. Many thanks for your time and help with our research.
HC in the Irish Red and White Setter
We have recently conducted a genome scan for HC in the Irish Red and White Setter using a high-density canine scanning array to assess around 174,000 markers spanning the DNA. For this analysis, we used 16 cases (dogs with posterior polar subcapsular cataract in both eyes) and 20 controls (dogs with clear eyes aged 6 years or older). Unfortunately, we did not find any evidence for an associated region in this breed. As we assessed only a small number of cases and controls, it is difficult at present to exclude a particular mode of inheritance for HC, although our data from other breeds suggests that HC might be a complex condition with perhaps several genes involved. To tease apart the genetics of this condition we will therefore need additional samples. Please see below for more information on submitting samples.
Congenital hereditary cataracts (CHC) and HC in the Miniature Schnauzer
We used a genome scanning approach to search for regions of the DNA involved in CHC. We genotyped 16 CHC cases and 16 controls (controls were either unaffected full siblings identified at litter screen or, where we had pedigree information, were a parent of the affected dog). We used a high density canine scanning array that assesses around 174,000 unique points in the genome and received good quality data for all 32 individuals genotyped. Unfortunately we were unable to identify any regions of the DNA that show strong association with CHC. We are therefore returning to sample collection, and as such we are still in great need of samples from dogs with CHC and their unaffected littermates or parents.
We will investigate HC in any other breeds that are thought to have an inherited susceptibility to cataracts and for which we can collect sufficient DNA samples.
If you would like additional information regarding our HC research please contact Sally Ricketts at email@example.com.
Q. Which dogs can contribute to the AHT’s Hereditary Cataract research?
A. There are two types of dog that are useful to our research:
i) Dogs of any breed that have been diagnosed as AFFECTED with any bilateral cataract.
ii) Dogs of any breed over the age of 6 years that have had a current eye examination by a veterinary ophthalmologist and are CLEAR of cataracts.
NB for Australian Shepherds the age cut-off for CLEAR dogs is eight years. We are currently providing a free DNA test to all Australian Shepherds affected by any bilateral cataract and to any clear of cataract that are over eight years old.