Principal Investigator: Eleanor Raffan MRCVS, Institute of Metabolic Science, University of Cambridge, CB2 0QQ. Tel: 01223 336792. Email: er311@cam.ac.uk This is an introductory guide to the GOdogs project. The success of the project depends entirely on recruitment by vets and nurses in practices around the country getting involved in sample recruitment, and that recruitment is done in as standardised way as possible so that we can reasonably compare dogs from different practices. This handout covers: Why it s worth studying the genetics of obesity How we can make the study work by carefully selecting the right dogs The practicalities of condition scoring, saliva sampling and paperwork. I ve also prepared a video which you can view on the GOdogs website (http://www.godogs.org.uk/can-yourpractice-help) or on YouTube (http://www.youtube.com/watch?v=fcpgvi8uefm). It lasts just 20 minutes and might be an easier and more entertaining way of taking on board this information than reading the next couple of pages! Why study canine obesity? About 1/3 of UK dogs are overweight that s over 2.5 million dogs! Being overweight is associated with: Orthopaedic disease. e.g. arthritis Cancer Respiratory disease. e.g. laryngeal paralysis Shorter lifespan Endocrine disease e.g. Diabetes Lower quality of life Why study obesity genetics? We know causes dogs to become overweight: too much food and not enough exercise. That s true, but if it were that straightforward, why do we see high rates of obesity in some breeds of dogs and not in others? Where strong breed predispositions like that exist, genetics are implicated. There s more evidence that genes are important from humans in us, between 40-70% of our tendency to gain weight is due to our genes. In humans, the genes which have been shown to have the biggest influence on body weight are all to do with how an ancient part of the brain (the hypothalamus) processes and responds to signals from the gut, fat tissue and elsewhere. However, there is a lot to learn and we hope studying dogs will teach us some fascinating biology.
It s not just for geeks! Clinical Relevance Identification of the genetic causes of obesity in retriever breeds is likely to have a real clinical benefits: To help motivate retriever owners to manage their dogs diet and exercise such that they stay slim, despite being genetically predisposed to having a large appetite. To remove some of the stigma of having lost the battle and being the owner of an obese retriever, and to provide the stimulus that although a dog may be genetically predisposed to being greedy, it can lose weight given the correct management. Possibly, the research will identify a target for drug therapy. But this is not a main motivation; a healthy lifestyle is still the best option for weight control in dogs. We are not likely to find a single genetic marker which can be tested for and even if we did, that kind of selective breeding can cause more trouble than it solves. How will the study work? We will perform a genome-wide mapping study for obesity genes in Labradors and Golden Retrievers. Gene mapping relies on us knowing the entire genome sequence of dogs, and the position of hundreds of thousands of markers along it. By comparing patterns of markers in obese dogs with lean dogs, we can identify regions of the genome likely to harbour the causative genes. The plan is to study Labrador and Golden Retrievers; both breeds originated from a single breed back in the 1800s, the St Johns water dog. Those were fishermen s dogs used to retrieve nets in the icy waters of Newfoundland; in that context, it might have made sense to maintain a good fat layer under the skin and eat whenever food was available. We hypothesise that their genetic tendency to gain weight was passed on to their modern descendents who live much cushier lives, and may therefore be a common root of the obesity problem in both Labradors and Golden Retrievers. Careful case selection is extremely important The big potential barrier to the success of this project comes from that mapping study design: it will only work if all the dogs in the lean group are genetically predisposed to be lean, and all the dogs in the obese group are genetically predisposed to being obese. We know that in our patients there is far more than genes which influence body weight particularly our dogs owners. So I m hoping to find a particular subset of dogs for the initial study and that s where this project is so reliant on your knowledge and expertise as vets and nurses who really know your clients and their dogs, because I hope you can help me find them!
Practicalities of Recruitment and Sampling Which dogs do we want? Obese, greedy dogs: Body condition score (BCS) 7-9/9 o see below re condition scoring No medical reason for obesity o e.g. hypothyroidism, treatment with corticosteroids/anti-epileptics o false obesity such as pot bellies from Cushing s disease Lean, non-greedy dogs: BCS 4-5/5, older than 5 years. But not every lean dog: ideally only the rare subset of retrievers who just aren t as food motivated as other Labradors and Golden Retrievers. These are the dogs which are likely to have a lean genetic background. o They do exist! If possible, I would like to avoid dogs with a greedy genotype but which are kept thin because: o Their owners are very careful at managing their diet or exercise o They have a obvious or subclinical disease which means they don t over-eat or don t use their food properly. Deciding whether lean dogs are suitable can be tricky please be inclusive and if you are in doubt, take the sample and let me know your concerns on the sampling form. I ll give some examples below: Some owners say they don t make much effort to control their Labrador s weight, but then admit they do weigh it s food and never give titbits. Obviously, lots of exercise can keep even the greediest dog slim, but there are also working dogs which have genuinely small appetites; it s great when owners can compare the non-greedy dogs to others they ve owned in the past. Finally, identifying health reasons why a dog might not tend to display greedy tendencies despite an underlying greedy genotype usually requires specific questions: has the dog lost weight recently? Does the dog get regular gut upsets? Does it have any food intolerances? There are a significant number of dogs out there whose owners describe them as having sensitive stomachs, and who probably have a low grade inflammatory bowel disease or pancreatitis; it s usually under control with a good diet and doesn t need veterinary attention, but it might well be a reason to exclude them from the genetically lean group. If you are approached by a keen owner with a dog which probably doesn t fit into those categories (wrong condition score or wrong appetite), it s probably best not to turn them away, simply because that might put them off telling their friends and relations about the study. We will be able to use those samples in future for validation work and follow up studies.
Condition Scoring The condition scoring chart that comes in the packs is well validated, but it only works if people really pay attention to the descriptors and follow them closely. To do that properly, please remember to palpate the dog as well as look at it. In general, I ve found people are rather too kind when condition scoring Labradors we are so used to seeing them overweight that we forget that to be classed as lean (BCS4-5/9) their ribs should be easily palpated and possibly seen, and they should have neat waists from above and the sides. Obese dogs are easier, but again, please pay attention to the chart. Saliva Sampling Sampling kits come with full instructions on each pack and extras in the packs. Tips for using the kits: Dogs seem to mind less if you let their cheeks go and hold their muzzle closed around the swabs Wear gloves I don t want your DNA! Remember: no food for 30mins or water for 10 mins before sampling Once you ve got the sample, it s fine at room temperature for a year, so just store it upright until posting. If you think you will get a few samples, keep them until you can send a batch. If not, just post them with their accompanying paperwork one at a time.
Paperwork Kits sent to practices are very user-friendly and have all the instructions, condition score charts, inclusion criteria, kits, post and packaging materials and so forth included. There are 3 bits of paperwork to go with each sample, 2 for the owner and one for the vet or nurse doing the sampling. Consent form (make sure it is informed consent) Dog information survey - for owner to complete Sampling Checklist and Vet Professional s Opinion form, for nurses or vets to complete o This is straightforward. It reminds you to label the sample, print out the case history (if owner agrees) and check the other paperwork is collected together. o It also asks you to record the dog s weight and condition score, to say why you think (from discussing with the owner) the dog is either lean or obese, and reminds you to ask specific questions about the dog s health that might be relevant to it s weight. If in doubt, take the sample but let me know! A Plea! Thank you for your patience getting to this point of the instruction. It only remains for me to say that I am enormously grateful for the help of people like you in helping with sample recruitment without it the project would be a non-starter. In my experience so far, people often have a lot of good ideas about suitable dogs when they first think about the project that lovely lean dog which came in for a vaccine last month, or the one that used to come to obesity clinics before the owners gave up but translating that into actual samples is the difficult bit. So can I make a plea to you? If you can think of those dogs, please consider approaching their owners now to invite them to participate. Most owners are either flattered to have been noticed as having a lean dog or relieved to be given an excuse for their dog being fat either way, they usually respond well and are keen to help and it would be great if these samples could arrive over the next few weeks rather than waiting for them for months and months. I will send posters and leaflets with the practice packs and would encourage you to spread them far and wide, and if you have practice Facebook pages or Twitter feeds, perhaps you can send out links to the GOdogs website (www.godogs.org.uk) and promote the fact that you are involved in the research. If you have any questions, please feel free to get in touch by email, phone or via the website. I think there is real clinical and scientific value in the GOdogs project, and I hope you will find it rewarding to be part of it. Principal Investigator: Eleanor Raffan MRCVS, Institute of Metabolic Science, University of Cambridge, CB2 0QQ. Tel: 01223 336792. Email: er311@cam.ac.uk