Hypomyelination in Weimaraner Dogs:
Researchers from the University of Wisconsin Madison lead by Dr. Ian Duncan in collaboration with researchers from Dr. Patels Laboratory at The University of Southern California and Dr. Bannaschs Laboratory here at University of California Davis have identified the genetic basis for hypomyelination in the Weimaraner. The manuscript detailing this discovery is in press in the journal GLIA. This condition leads to tremors during puppyhood. The disease is inherited as a simple autosomal recessive disorder and the carrier frequency has been estimated to be 4.29% within the breed. Hypomyelination is also called “Tremors” and “Shaking puppies” by dog breeders based on the fact that affected puppies have tremors when awake as early as 2 weeks of age. Clinical signs resolve in most cases by 3-4 months of age. Some of the dogs may have a mild persistent tremor of the hind legs.
Hypomyelination test information:
The VGL offers a DNA test for Hypomyelination to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal swabs thus avoiding blood collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.
The following chart details the expected outcomes of matings for all possible combinations of Hypomyelination genotypes.
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Allow 2-6 business days for results.
|N/N||100% N/N||50% N/N, 50% N/HYM||100% N/HYM|
|N/HYM||50% N/N, 50% N/HYM||25% N/N, 50% N/HYM, 25% HYM/HYM||50% N/HYM, 50% HYM/HYM|
|HYM/HYM||100% N/HYM||50% N/HYM, 50% HYM/HYM||100% HYM/HYM|
Results reported as:
N/N: no copies of hypomyelination mutation; dog is normal
N/HYM: 1 copy of hypomyelination mutation; dog is normal but is a carrier
HYM/HYM: 2 copies of hypomyelination mutation; dog is affected.
Dogs that have only one mutant copy of HYM (N/HYM) are normal but they are carriers of the disease. When two carriers are bred to each other the resulting puppies can be affected. At the time that this test was released, approximately 4.3% of Weimaraners were carriers of HYM (N/HYM); however, the number of carriers can change with each generation. Dogs that are carriers of HYM (N/HYM) are completely normal and they can be safely bred to dogs that are non-carriers of HYM (N/N) in order to maintain diversity within the breed and to select for other positive attributes in carrier dogs.
Pemberton TJ, Choi S, Mayer JA, Li FY, Gokey N, Svaren J, Safra N, Bannasch DL, Sullivan K, Breuhaus B, Patel PI, Duncan ID. (2013) A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination. Glia 62:39-51.
Shaky Puppy Syndrome
(Tremor Syndrome) Research 2011
Through a collaborative effort, the WCA Health Committee is pleased to advise the membership that the WCA is supporting Dr. Ian Duncans continuing research for a genetic marker of Hypomyelination or Shaky Puppy Syndrome in Weimaraner puppies.
Several years ago, Dr Betta Breuhaus wrote about “Shaky Puppy” in The Weimaraner Magazine in an effort to educate the membership about this disorder, and to garner support for Dr. Duncans early research. The Weimaraner Foundation Fund (WFF) and WCA members generously supported Dr. Duncans research both financially and by supplying samples. Unfortunately, that early research was uninformative.
The WCA Health Committee recently became aware that Dr. Duncan was continuing his research and had applied for an AKC/Canine Health Foundation Acorn Grant. The Health Committee reviewed the new grant request and evaluated the basis of the research. New developments and techniques in genetic studies have enabled Dr. Duncans team to continue its work in a very promising direction. The Health Committee unanimously petitioned the WCA BOD to allocate monies from the WCA AKC/CHF Donor Advised Funds to support this effort. The WCA BOD approved the committees request, and Dr. Duncans Acorn Grant was approved. We thank Dr. Duncan for providing our membership with the following synopsis of this research. points and can make finding homes for affected pups difficult as the tremor is likely to persist at least up to 10-12 weeks of age.
The disorder is caused by a delay in myelination of the brain and of specific tracts of the spinal cord. We are attempting to identify the gene responsible for this defect using a genome-wide association study. Previous studies using DNA from affected, carrier and normal dogs from across the USA, and analyzing these samples using a whole genome scan were uninformative. Our current study using a smaller cohort, but in which we are confident of the source, has allowed us to successfully map the gene. However we are left with a challenge as the area of the chromosome where the gene is located is large and contains 16 genes. Sequencing of two possible candidate genes showed no mutations. None of the remaining genes are obvious candidates that we could deduce are responsible for the defect.
Inquiries to Dr. Duncan may be made to: Ian Duncan email@example.com
Tremor syndrome in Weimaraners
Ian D. Duncan
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706 It is now 24 years since the first description of the inherited tremor syndrome in Weimaraner pups. While the exact prevalence of the disease is not known, it has been reported in all parts of the USA and Canada. In addition it has been reported in the UK, Spain, Italy and Holland. It is likely that affected dogs in Europe are related to dogs exported from North America. The disease is inherited as an autosomal recessive trait, which means that the parents are carriers of the gene (heterozygotes) and about 25% of their litter, either males and females, will be affected (homozygotes) and 50% will be carriers. As affected dogs may recover completely, it is possible for a homozygous dog to mate thus increasing the gene pool even more. The tremor is seen at 10-12 days of age and is dramatic and alarming for people who have not seen the disease. The tremor affects the entire body and may vary in intensity between littermates. In most cases the tremor dissipates over 2-3 months and usually disappears entirely though severely affected dogs may have a persistent, mild defect. The tremor can be a problem with feeding at early time current knowledge. With our latest Acorn Grant from theAKC/ Canine Health Foundation, we are planning to sequence all the genes in the mapped area of the chromosome that we have identified.
The long range goal is to identify the gene involved and the mutation so we can develop a bench test (PCR reaction) and then use this to identify heterozygous (carrier) animals. By so doing, we hope to be able to offer the breed a test that they can use to identify carriers and use this information to selectively breed dogs and reduce or eliminate the mutation from the breed. A note of caution however is that unexpected complications can arise in these analyses and based on the limited funds available to complete the project, the rate of progress will be unlikely to be fast.
We are grateful to the AKC/CHF and the WCA for their support of this research.