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  1. Vets – what can HGTD do for you? Genetic testing is part of our dog's lives Just as genetic testing has become normalized in the human world, thanks to popular direct to consumer products like 23 and Me, or Ancestry.com, so it has in the veterinary world. While perhaps once the preserve of specialist dog breeders, it is increasingly common for vets in practice to have questions from clients about DNA testing. While covering the basics of testing and inheritance is part of many veterinary educations, it is unreasonable to expect anyone to have knowledge of the 300+ different genetic tests available to 400+ recognized dog breeds, and their crosses – let alone which of the 2,500+ breed x test combinations might be the most relevant for your client. This is where Harmonization of Genetic Testing for Dogs (HGTD) can help. How HGTD can support veterinarians and their clients HGTD provides a searchable, comprehensive list of genetic tests available internationally. With a quick breed search, you can instantly find transparent information on breed and type-specific tests for advising clients on options for pre-breeding genetic tests, gene-based diagnostic/risk testing, parentage/maternity/paternity. There are even breed relevancy ratings (BRR) for most tests – indicating the research underpinning the relevance of a specific test for a breed. At a glance, for each test you can find clinical information, links to original research papers (most open access) and additional education sources for both veterinary health professionals and clients. HGTD information works in conjunction with wider breed-specific health testing and information from the International Partnership for Dogs (IPFD), via www.dogwellnet.com. Examples include: - breed-specific health strategies from international kennel and breed clubs - clinical health testing (e.g. eyes, hip, elbow, heart schemes around the world) - veterinary collaborations – IPFD is a World Small Animal Association (WSAVA) Educational partner and FECAVA is a Collaborating Partner of IPFD Find yourself with a client wanting to know about inherited eye diseases in the Cesky terrier? All the DNA tests available for the Otterhound? Whether there is a genetic test for mustaches in Schipperkes? Which companies offer genetic testing for dogs in Belgium? HGTD has a search option for all! Start a search of the Harmonization (HGTD) database here! How does HGTD fit into wider health concerns? Genetic testing is just one tool to improving canine health and welfare. There are a number of additional resources from IPFD on dogwellnet.com providing breed and type specific health data, and how genetic testing fits into the Big Picture of health and welfare. Check out: Globally Relevant Integrated Health Profiles e.g. 'Get a GRIHP!' This series of articles focuses on the Big Picture of health and welfare within breeds including international resources for veterinarians, owners, caretakers, breeders and others who want to understand the key issues for individual dogs and breed populations monthly IPFD feature articles in the WSAVA Bulletin. breed-specific health reports Can HGTD do more? HGTD is built on a principle of working collaboratively to meet the needs of our canine community. If you're a veterinary scientist, or canine health professional and have a question about genetic testing, or an idea of how HGTD could improve to further improve access to, and understanding of genetic testing, please let us know. Photos: La Miko (main image) and Alana Sousa (inset image) from Pexels.
  2. HGTD This Week, 7 Aug 2020: Canine Crime Scene Investigators When we think about genetic testing, we often focus on how it can be a tool to improve health and welfare - generally centered around breeding for health or finding more about the health or potential health risks for an individual dog. Knowing about health risks that are especially relevant to specific breeds or dog types makes testing even more powerful in helping reduce risks of disease or undesirable traits (see Breed Relevancy Ratings). Most commonly, genetic screening and diagnostic testing focuses on: disease tests, breed estimation tests, diagnostics, parentage/paternity, inbreeding estimations, etc. (search for genetic tests and providers, here). This week, I received a very interesting question from a DogWellNet.com user, who wanted to know if genetic testing could help them with a dog attack incident. Their dog had been bitten, and they wanted to know if genetic testing could be used to identify the attacking dog, using saliva from the collar. The short answer is… probably not, but maybe not for the reasons you think. In principle, it should be possible to extract DNA from saliva from a surface like a dog collar. The challenge is that, even with a genetic profile: You won’t know if the profile is from the attacking dog, or some other dog your pet has met at a dog park, on a walk, at the vet’s… Without a profile of a known dog to compare it to, you won’t be able to identify the dog (and therefore owner) This is because dogs are generally not required to be registered with a genetic fingerprint. So, unless you know the dog and the dog's owners, it is impossible to confirm identification using DNA alone - much like the challenges in human criminal DNA identification. This brings us around to thinking about some of the more forensic things genetic testing can, and cannot do: Can do: Act as a permanent identification for an individual dog (genetic profiling) Determine parentage, when relatives’ profiles are known for comparison Comment on the risks of specific genetic mutations for specific diseases (disease/phene screening testing) Aid in the diagnosis of specific risks/diseases (only with diagnostic testing as opposed to screening testing) Cannot do: Identify a specific dog, without that dog’s genetic information/owner being on an accessible registration list “Prove” that a dog is responsible for an action, without other evidence Be used to make “permanent” decisions (e.g. euthanasia) on its own, without other veterinary health information, and welfare considerations While there are plenty of incredibly useful things genetic testing can do, beyond genetic screening tests, it is really important to consider why you are testing and how you are going to use any test results. As with any tool, genetic testing has its limitations. Want to go further? Check out this blog - Confidentiality and Genetic Testing: more benefits and risks - by IPFD CEO Dr. Brenda Bonnett, looking a other parallels and challenges with the human situation. Relevant to the discussion above - confidentiality and availability of identifying information is an important issue to consider. Or explore the whole new world of 'poop forensics' : Dog Poop DNA Tracking Introduces Spy Tech to Our Backyards. (IPFD disclaims any responsibility for the information presented there!) Photos: pixabay (cover photo): G. Fring (image) via Pexels
  3. The continued review of breed-specific tests for assigning relevancy ratings, and ongoing discussions with genetic experts has led to a refinement of the breed relevancy ratings (please see: BRR) . To better accommodate the spectrum of genetic test validation, we’ve added a new orange BRR. The orange BRR indicates where all current available evidence has been reviewed, but the relevancy is inconclusive. It could be that a mutation is detectable in a specific breed, but that there is no evidence that this correlates with clinical development of the disease/phene. It could also be that there is evidence that testing for the mutation does not correlate with the clinical development of the disease. One example is the wire-fox terrier and degenerative myelopathy. Despite research indicating a 94% mutation frequency (Zeng et. al, 2014) - meaning that practically every dog the researchers tested for SOD 1 mutation for degenerative myelopathy had 2 copies of the mutation - the development of the clinical signs of DM for the breed hasn't yet been reported. In practical terms, this means that while you may still wish to test for the mutation in your breed, or it may be included on any testing panels, there isn’t currently a good reason to prioritize test results in any breeding or other health decisions. Unnecessarily excluding a dog from breeding based on irrelevant or inconclusive test results can be, on balance, very damaging to the genetic diversity of the breed. Thinking back to DM and the wire-fox terrier, this would mean that if breeding decisions were made on DM test results alone, you'd be excluding the vast majority of the dog population where the test does not for this breed seem to predict clinical disease. For any orange BRR, it would be worth looking at the test’s breed-specific information in more detail (search for test information HERE) to help put any potential test results into perspective. Wherever possible, the phenes database includes comments directly from the researchers and original test developers. As always, talk to your genetic test provider and/or veterinary scientist if you are concerned about genetic test results. And, if you missed it the first time around, you may want to check out the previous blog including updated breed relevancy ratings, and breed-specific publications, HERE. References: Zeng R., Coates J.R., Johnson G.C., Hansen L., Awano T., Kolicheski A., Ivansson E., Perloski M., Lindblad-Toh K., O'Brien D.P., Guo J., Katz M.L., Johnson G.S. (2014) Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med 28: 515-521 Photo thanks to: Engin Akyurt, via Pexels
  4. A recent article provided by the Golden Retriever Club of America, Golden Retriever Health and Genetics Highlight: Neuronal Ceroid Lipofuscinosis in Golden Retrievers, by Ann Hubbs and Ron Rubrecht,, discussed the challenges faced in Fall 2018, by a breeder who had unsuspectingly bred a litter of puppies from two carriers of neuronal ceroid lipofuscinosis (NCL 5) – a devastating neurological disease considered rare in the breed. While a DNA test existed, most Golden Retriever owners wouldn’t be aware of the condition, let alone testing options. The breeder did the absolute right thing when realizing there was a problem, by working swiftly to genetically test their dogs, contacting owners, and working with the Breed Club to make other breeders aware of the risks of NCL 5. The situation for this breeder could arise for various conditions in many breeds. Inherited diseases that are generally rare in a breed are unlikely to be considered in selection by breeders. It could be that a genetic test isn’t available, or that it is not a priority for testing compared to more common inherited risks, or, increasingly, it might be a well-known condition in a breed in one country, but less known internationally. This is understandable, especially considering that the risks of an inherited disease in the breed as a whole, is not necessarily reflective of the risks for the breeding population. (Fig 1.) The dogs who are left intact and used in breeding, particularly by Show/Field breeders, is only a tiny percentage of the dogs making up the whole breed. It is easy to imagine how a few popular dogs who happen to be genetic carriers [See 'carrier' defined in glossary for AR inheritance] for a rare disease like NCL 5, could shift the risks of inheritance within a few generations without anyone realizing that there is a problem at all. For NCL 5 in the Golden Retrievers, fortunately, there is a genetic test available that can identify those dogs who are clear, carrier, or genetically affected for the condition. This will be especially valuable for those specific breeding lines within which the disease has occurred or is suspected. However, it is important to put into perspective how concerning NCL 5 is for the breed, relative to other important factors, in order to be sure that breeding decisions are made sensibly across all the considerations when making breeding plans. Currently, within a US population tested by Embark, only <1% of the dogs tested are carriers of the NCL 5 mutation. This is known as carrier frequency. At this level of carrier frequency, breeders can develop breeding plans that include clear and carrier tested dogs, to efficiently breed away from the mutation risk, without causing a genetic bottleneck or producing genetically affected puppies. It is important for a disease like NCL, which is still likely to be clinically rare in the breed, to breed away steadily to balance any other inherited risks, as well as allowing selection for positive characteristics. Avoiding a knee-jerk reaction will help to ensure that future generations have a greater variety of breeding lines to choose from. IPFD is continuing to develop plans for the Health Strategies Database for Dogs that aims to catalog all conditions that are being addressed by those designing breed-specific health programs around the world, especially kennel and breed clubs. See “Get a GRIHP on Breed Health” - Breed Health Strategies Presentation given by Brenda Bonnett at the 4th International Dog Health Workshop. What’s a GRIHP? Globally Relevant Integrated Health Profile... https://dogwellnet.com/files/file/422-4th-idhw-breed-specific-health-strategies-dogwellnet-resources-brenda-bonnett/ Additional information HGTD has a number of resources to help breeders and owners make informed decisions on genetic testing. You can search for genetic test providers, breed-specific diseases, and more information on tests/diseases HERE. Recently, HGTD has launched relevancy ratings for many of the tests that the participating genetic test providers are offering. Using data and information from researchers, test providers, kennel and breed clubs, and veterinary scientists, relevancy ratings are a way of indicating all of the currently known research material on a specific test for a specific breed. Additional information University of Missouri - Golden NCL: http://www.caninegeneticdiseases.net/GoldenNCL/ The Orthopedic Foundation for Animals records the NCL5 test results for Goldens - search at https://www.ofa.org/diseases/breed-statistics. Also see further information on Neuronal Ceroid Lipofuscinosis at OFA: https://www.ofa.org/diseases/dna-tested-diseases/neuronal-ceroid-lipofuscinosis. Research The NCL 5 mutation origin paper: Melville, SA., Wilson, CL., Chiang, CS., Studdert, VP., Lingaas, F., Wilton, AN. : A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics 86:287-94, 2005. Pubmed reference: 16033706. DOI: 10.1016/j.ygeno.2005.06.005. 2019 Villani, N.A., Bullock, G., Michaels, J.R., Yamato, O., O'Brien, D.P., Mhlanga-Mutangadura, T., Johnson, G.S., Katz, M.L. : A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Mol Genet Metab 127:107-115, 2019. Pubmed reference: 31101435. DOI: 10.1016/j.ymgme.2019.04.003. 2017 Katz, M.L., Rustad, E., Robinson, G.O., Whiting, R.E.H., Student, J.T., Coates, J.R., Narfstrom, K. : Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis :, 2017. Pubmed reference: 28860089. DOI: 10.1016/j.nbd.2017.08.017. 2016 Kolicheski, A., Johnson, G.S., O'Brien, D.P., Mhlanga-Mutangadura, T., Gilliam, D., Guo, J., Anderson-Sieg, T.D., Schnabel, R.D., Taylor, J.F., Lebowitz, A., Swanson, B., Hicks, D., Niman, Z.E., Wininger, F.A., Carpentier, M.C., Katz, M.L. : Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. J Vet Intern Med :, 2016. Pubmed reference: 27203721. DOI: 10.1111/jvim.13971. Mizukami, K., Yabuki, A., Kohyama, M., Kushida, K., Rahman, M.M., Uddin, M.M., Sawa, M., Yamato, O. : Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling. Vet J 214:21-3, 2016. Pubmed reference: 27387721. DOI: 10.1016/j.tvjl.2016.05.004. 2015 Gilliam, D., Kolicheski, A., Johnson, G.S., Mhlanga-Mutangadura, T., Taylor, J.F., Schnabel, R.D., Katz, M.L. : Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab 115:101-9, 2015. Pubmed reference: 25934231. DOI: 10.1016/j.ymgme.2015.04.001. 2013 Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. : Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009. 2012 Mizukami, K., Kawamichi, T., Koie, H., Tamura, S., Matsunaga, S., Imamoto, S., Saito, M., Hasegawa, D., Matsuki, N., Tamahara, S., Sato, S., Yabuki, A., Chang, H.S., Yamato, O. : Neuronal ceroid lipofuscinosis in Border Collie dogs in Japan: clinical and molecular epidemiological study (2000-2011). ScientificWorldJournal 2012:383174, 2012. Pubmed reference: 22919312. DOI: 10.1100/2012/383174. 2011 Mizukami, K., Chang, H.S., Yabuki, A., Kawamichi, T., Kawahara, N., Hayashi, D., Hossain, M.A., Rahman, M.M., Uddin, M.M., Yamato, O. : Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan. J Vet Diagn Invest 23:1131-9,
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    Oculoskeletal dysplasia • Canine genetics research at the Animal Health Trust • Basic genetics • Finding disease mutations • Genetics of OSD – Part 1 – Identifying the causal mutation • Genetics of OSD – Part 2 – Implications for the breed • Summary and Breeding Advice • Acknowledgements • OSD3 DNA Test Breeds information/impacts... - the drd1 mutation in the gene COL9A3 in the Labrador retriever - the drd2 mutation in the gene COL9A2 in the Samoyed - autosomal recessive mode of inheritance of the complete phenotype • Clinical findings in the Labrador retriever & in the Samoyed (Carrig et al. 1988 & Goldstein et al. 2010) - disproportionate dwarfism - corneal opacities, cataracts, persistent hyaloid artery remnants, vitreal dysplasia, alterations in optic nerve head colour + size, retinal dysplasia retinal detachment • Recently observed in 7 Northern Inuit Dogs (NID)
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