Canine Disease Research at the Broad
History of our research:
Our journey started back in 2005 when we completed the dog genome with the help of a purebred boxer named Tasha. After the completion of the dog genome we developed tools and strategies for disease gene mapping and made these available to researchers across the worlds. Now we perform disease gene mapping with the purpose of helping both dogs and their human companions to a healthier life.
Initially we focused on finding genes for simple traits with clear characteristics to be able to prove that our methodology worked. Some of these include coat color in the boxer, the presence of the ridge in the Rhodesian ridgeback, and hairlessness in Chinese crested dogs. We then moved to diseases where one, or a few, genes could be expected to underlie the disease. We discovered mutations resulting in arrhythmic right ventricular cardiomyopathy in boxers, Amyotrophic Lateral Sclerosis in the Pembroke Welsh corgi and several other breeds, brittle bone (osteoimperfecta) and day blindness in dachshunds, and a neurodegenerative disorder called neuronal ceroid-lipofuscinosis (NCL) in Tibetan terriers. The most complicated of these was Familial Shar-Pei Fever (FSF), a periodic fever disease linked with chronic inflammation and kidney failure and caused by mutation present in many copies in some dogs and located some distance from the hyaluronic acid synthetase 2 gene. For many of these disorders, these discoveries have led to the identification of mutations in the same genes in people.
For a real challenge we then set out to find the genetic mutations for complex diseases such as cancer, epilepsy and inflammatory disorders. Our proof of principle study included finding five risk loci for a systemic lupus erythematosus (SLE)- like disease in Nova Scotia duck tolling retrievers. These genes point to a pathway involved in activating T cells in the immune system. This pathway is now being investigated in human patients with SLE.
A complete list of our publications can be found here.
We are current working on more than 20 diseases.
Why is it easy to find disease genes in dogs?
Domesticated dogs split from their wolf ancestors approximately 30,000 years ago, while most breeds were created only a few hundred years ago. In the process of breeding dogs for certain desired traits, over successive generations, many genetic mutations have inadvertently come along for the ride with undesirable side effects. This includes a genetic predisposition to many common diseases ranging from epilepsy, cancer, diabetes, and hip problems as well as more breed-specific conditions.
We use dogs to study diseases because the disease genes are much easier to find. To find disease genes for complex diseases in humans, thousands of people and millions of genomic markers (SNPs) are needed. In dogs 20K markers and a few hundred dogs will suffice to find genes for complex diseases like cancer.
With you and your dogs help in donating blood samples – for cancers both a blood and a tumor sample is helpful – we are hoping to continue to identify these risk factors in many more diseases which will help us to understand the overall health risks for your dog and humans alike.
To donate a blood sample from your dog please click here for instructions and our consent form.
For information on the dog genome or dog SNP arrays, please click here.