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Aimee Llewellyn-Zaidi

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    104
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About Aimee Llewellyn-Zaidi

  • Rank
    Stellar Member

Contact Methods

  • Skype
    aimee llewellyn-zaidi

Profile Information

  • Region
    North America
  • Location
    Oregon
  • Country
    USA
  • Current Affiliation
    IPFD
  • Position / Title
    Project Director Harmonization Inititative
  • Interests
    Dog Health
    Genetics
  • Academic Credentials
    Bachelors degree
  • Expertise/Proficiencies
    Dog Health/Veterinary Medicine
    Education
    Research
    Writing/Communication
  • Specific Breed(s) of Interest
    Pembroke Welsh Corgi
  • Breed Club Rep; Board Member or Breeding/ Health Committee member
    No
  • Attended an International Dog Health Workshop
    No
  • Theme attended at 3rd IDHW in Paris
    IPFD Harmonization of Genetic Testing for Dogs

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  1. 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,
  2. I do not know how parentage and heritable disease testing relate in terms of privacy concerns or crossovers between the 2 - if a dog tests positive for a deleterious genetic mutation (registration of litters denied) & that dog has relatives in a parentage db - can those relatives be subjected to further testing? Ann has sent through some good questions, which I think I can address: Genetic profile-based "kennel clubs" or any registration-type body are going to happen. This process would mean that your dog is registered based on their genetic profile, and any other relatives (and health tests) would be linked to them genetically creating a gene-based pedigree. Both genetic profiles and parentage have standardisation behind them, primarily through ISAG, which is international. There are challenges, potentially, when you are moving from using the 2004 to the 2006 parentage panel, but the technology is now in place that this can be overcome robustly - and of course, it only impacts the dogs that have been tested under 2004, which should be very few now. As we move forward, these tests will almost certainly be done under a SNP-chip (i.e. panel) system in any case, which can screen for 2004, 2006, any subsequent panels, as well as the profiles. Regarding privacy... It is possible, and fairly easy, to "reverse detect" any anomalies that may be occurring in your line or breeding, if you have access to an ancestry.com style database. It can become apparent that you might not have the dog, or breed, you think you do, if the 1st cousins or siblings start showing different DNA test results that should be possible if the parentage/etc. is correct. If, for example, I had a stud dog that was a carrier for X disease, I might not want that to become known. If I'm smart, I'll only use him on clear bitches, so that none of the puppies have problems, but it wouldn't be long before a puppy is tested as carrier, and the whole world knows my champion working dog is a carrier (i.e. Facebook), or maybe affected, etc. etc. I know this happens already, but this would start happening en masse, and as the owner of the stud dog, I have not agreed to this "medical" information being in the public domain. There is also a whole hot-bed of possibilities for suing if you have mis-represented or mis-sold a dog, very often in innocence if there was a split litter or an accidental mating where you guessed the stud. With Tom's paper on hereditarily clear, this is where of course you're talking about issues that could be 3+ generations back - either a testing error or parentage error, and if you're a careful breeder, could take a long time before discovered... usually when a litter is born with affected pups that shouldn't be possible. By then, you could have a lot of carriers out in the world that you are assuming quite reasonably are clear. Aimée Llewellyn-Zaidi
  3. Dear Aimee, Do you know if the JADD in NSDTR is simple mendelian or complex? UC Davies genetics lab is offering a test. Do you know if it is a reliable test? Do you think the test should be mandatory for NSDTR used for breeding given its early age of onset and serious impact on an affected dog's health and welfare? I would be very grateful for your comments. Kind Regards, Anon UK NSDTR Breeder Dear NSDTR Breeder, It is my understanding that the JADD (Juvenile Addison's Disease) genetic test that is available is a simple inheritance (autosomal recessive) and based on the published discovery research, it seems likely at this time that this test for the NSDTR has a 75% penetrance. According to the researchers, this means that the dog that is tested as genetically affected for JADD has a 75% risk of going on to develop the clinical signs of the disease. This is sometimes referred to autosomal-recessive, with incomplete penetrance. They don't know why 25% of genetically affected dogs don't get the disease, and they don't know for sure that this mutation is the only one associated with developing the disease. We don't yet know how "common" this disease or the risk is. This makes it difficult to know how important it is as a disease to test for. It may be worth you contacting the UK NSDTR Breed Club, as they appear to be aware of the disease, but also seem to only have noted 1 reported case in the UK. (you can find links to their club website, including health pages below) It is very possible for a disease to be more or less common in different countries. As for UC Davis, I believe they worked closely with the research team (who is also based at UC Davis) to develop the test, so while it isn't to say that other test providers aren't also doing a good job, it is a general good idea to have the test performed by the team who discovered it, or who worked closely/collaborated, as they should be familiar with any technical challenges. They are also, I believe still working with breeders in furthering research for this disease, so they may be hoping to have a better idea of prevalence in the future, and perhaps addressing that unknown 25% aspect. (see reference below) As for it being a mandatory test for breeding, I guess you mean the Kennel Club registered dogs? It is hard to know. I believe the test can have value, and that the researchers are providing most of the information needed to help with breeding decisions, but it is not as black and white as a classic autosomal recessive disease, with 100% penetrance. In an ideal world, a club might organize (or researchers might somehow support/collaborate) to test dogs randomly across the population, and get some idea of how common the mutation is. This would help them determine how to prioritize testing for this disease. If pushed, I'd probably personally test for JADD, based on the potential welfare impact, and for contributing to further research. But, not at the expense of not doing hip scoring, or tests for the more common eye conditions. I hope that helps! Take-away Points: New genetic mutations are being discovered all the time. It is important to consider why you are considering genetic testing, and to prioritize what is important for your dog’s welfare, and consider what is best for the breed/population as a whole. When a test isn’t a straightforward “simple” inheritance, it may mean that you don’t have the full-picture of the disease and its inheritance. It can still be beneficial to test – you’ll get some information about your dog, you might want to incorporate it into breeding plans, and you’ll probably be contributing to the research – especially if you are engaging with the original test developers/researchers. But, these tests will not provide any yes or no answers. If the inheritance is complex, or the test is still essentially in a research phase, you shouldn’t necessarily prioritize a new test over the conditions and concerns that are established in your breed. If you have limited resources, focusing on established DNA tests for common diseases in your breed, any clinical screening such as hips/elbows/eyes/hearts/etc., and breeding for soundness and behavior should be your first priorities. References/Further reading and resources: TWO NEW DNA BASED TESTS AVAILABLE FOR THE NSDTR Written by Danika Bannasch DVM PhD; Professor Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis Published Spring 2012 Issue-Quacker. http://nsdtrc-usa.org/pdf_files/2012/Quakers-JADD-CP1-0512.pdf UK-Based Breed Club, with Health resources: www.toller-club.co.uk
  4. This report is to be viewed as a dynamic document summarizing the pre-thru-post 4th IDHW meeting activities around the Genetic Testing theme. Please note that additions and changes may occur. We will be welcoming comments and suggestions from participants in the workshop and working groups as we move forward. Please contact Aimee at aimee.llewellyn-zaidi@ipfdogs.com.
  5. Jane - I really appreciate your passion and obvious commitment to canine health. Personally, I think we start by doing everything we can to build collaborations between all the stakeholders in canine health, and to do all we can to support and encourage those who are already motivated to make positive changes. Leading by good example, and working together is a very powerful start. Every country has different laws, resources, and challenges to improve dog health, but we are trying to start by sharing the experiences of many different groups from around the world in the hopes that we can all learn from each other, and adapt tools and resources that have found to work. Unfortunately, there doesn't seem to be a one-size-fits-all approach, but we can share our successes (and failures) to help others with similar challenges. I would encourage you to look out for information after the upcoming 4th International Dog Health Workshop to see what projects are being undertaken, and information on progress since the last meeting.
  6. 2019 Lewis TW, Mellersh CS. Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. Plos One, https://doi.org/10.1371/journal.pone.0209864 DNA Testing - General Subject: DNA Testing Type: Research Journal/Source: peer-reviewed research publication Authors/Researchers: University, Kennel Club (IPFD Partners); HGTD Participants Recommended For: Veterinarians, Owners/Breeders This study is one of the very few to investigate the impact of DNA testing on changing a dog population's disease risk. The research looked at determining changes in frequency of disease causing mutations (how common a mutant gene is in a population) as a result of breeding-pair selection based on DNA test results. The results indicated that there has been an overall decline in disease causing mutations in the 8 diseases in 8 breeds investigated. While the paper recognises that there can be variations in how quickly a disease is reduced or eliminated (such as breed population size), it concluded that where dog breeders appear to incorporate DNA test results as part of breeding plans, there is success in decreasing the frequency of mutation. The study looked at: prcd-PRA in Labrador Retriever and Cocker Spaniel, HC in Staffordshire Bull Terriers, EIC in Labrador Retriever, PLL in Mini-Bull Terrier, EF and DE/CC in Cavalier King Charles Spaniel, PRA rcd-4 in Gordon, and Irish Setter, and spinocerebellar ataxia in Parson Russell Terrier. Within the UK at least, this represents a spectrum of large and small breeds, and generally "known" diseases within the breeds. 2019 Lewis TW, Mellersh CS. Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. Plos One, https://doi.org/10.1371/journal.pone.0209864 See also: Nearly 20 Years of DNA Testing – What Can We Learn? : IPFD CEO's blog post with discussion of wider implications of the study's approach and findings; based on Ian Seath's commentary (Dog-ED: Social Enterprise) with a breeder/health council perspective on the article above. IPFD Harmonization of Genetic Testing (HGTD) and search on the mentioned diseases for more information on the the condition, phenes, tests and more.
  7. Here we offer information for Genetic Testing Providers (GTPs) that wish to participate in the Harmonization of Genetic Testing for Dogs (HGTD).
  8. Thank you so much for your positive feedback Janean! We really want to help the whole dog community to access useful information, and it is really helpful to us to know when it's been a benefit!
  9. This introduction to genetic testing can tell you more about the different types of testing that are available, and guidance on what resources can help you find, choose, and use, the right tests for your dog.
  10. Choosing a genetic test provider can be daunting. This short article helps you to consider what is important to you, and your dogs, in finding the right test provider for you.
  11. I am very pleased to be joining the IPFD as project manager of the Harmonization of Genetic Testing of Dogs.  With the aim of Improving standardization of, and access to, robust genetic testing to support health improvements and ensure a sustainable future for healthy dogs.”

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