Research Updates

Health and Genetics

August 2008

Dr. Gary Johnson’s lab at the University of Missouri ran 30 samples from the purebred population of Chinooks stored at UMO looking for the mutation responsible for degenerative myelopathy (DM). This mutation has recently been identified in other breeds and UMO has developed testing to identify the mutation causing DM.

The results of the Chinook testing are encouraging: None of the Chinook samples tested had the mutation. Dr. Johnson points out that this sampling is from the population of Chinooks submitted for the UMO seizure study and therefore all lines and families may not be represented in the testing (including cross bred lines). Dr. Johnson advises if any Chinook shows signs of DM, or has been diagnosed with DM, his lab will accept a blood sample from the Chinook and run the DM test at no cost to the owner.

CCA thanks Dr. Johnson and his lab for testing our Chinooks for degenerative myelopathy. A link to the UMO research may be found at:
http://www.caninegeneticdiseases.net/DM/ancmntDM.htm

June 2008

In June, Dr. Gary Johnson will start running samples on Chinook dogs to find out if the Chinook has the mutation for Degenerative Myelopathy:

The AKC Canine Health Foundation and the University of Missouri recently announced an exciting genetic discovery: Drs. Gary Johnson and Joan Coates at the Animal Molecular Genetics Laboratory of the University of Missouri and Drs. Claire Wade and Kerstin Lindblad-Toh at the Broad Institute of MIT/Harvard and their colleagues have identified a DNA mutation that is a major risk factor for development of Degenerative Myelopathy (DM) in dogs.

DM is a progressive disease of the spinal cord in older dogs. The age of onset is typically between 8 and 14 years of age. DM begins with a loss of coordination (ataxia) in the hind limbs. The affected dog will wobble when walking, knuckle over or drag the feet. As the disease progresses, the limbs become weak and the dog begins to buckle and has difficulty standing. The weakness is progressive until the dog is unable to walk. Loss of urinary and fecal continence may occur, and eventually weakness will develop in the front limbs. A key feature is that DM is not a painful disease.

The research has found that a relatively high percentage of dogs in several different breeds have the predisposing mutation including: Boxers, Pembroke Welsh Corgis, Chesapeake Bay Retrievers, and Rhodesian Ridgebacks. To date, there is little information that indicates the Chinook is affected with degenerative myelopathy though there have been several Chinooks who have some of the symptoms of DM. Because of the different breeds that make up the Chinook dog, the researchers at the University of Missouri and the Chinook Club of America are both interested in learning if the Chinook carries the DM mutation. We hope to have this answer very shortly!
 

March 2008

Chinook DNA is on its way this March to Helsinki, Finland to Dr. Hannes Lohi's lab.  Dr Lohi is collaborating with principal investigator Dr. Gary Johnson of the University of Missouri on the Chinook *dyskinesia* condition, often referred to by those in the fancy as Chinook type seizures.   Dr. Lohi’s lab will start the mapping process and Dr. Johnson thinks that the uniqueness of the Chinook movement disorder puts us in a good position to find the mutation causing the problem.  Look for updates in our next newsletter or on our website.

NEW SAMPLES ARE NEEDED!  If you have a Chinook experiencing the Chinook type seizures and haven’t yet done so, please send in a blood sample to UMO.  Samples from affected Chinooks as well as their close relatives – parents, and siblings – are still being sought.  For info on how to participate you may contact me at Bartol@charter.net or UMO at:  Liz Hansen at hansenl@missouri.edu  You and your Chinook CAN make the difference and help us find a cure!  An added benefit of sending a sample is the fact that your Chinook will have DNA stored at UMO (at no cost) to potentially be used for other Chinook research studies.

*Definition of dyskinesia from wemove.org:  Dyskinesias: Abnormal neuromuscular conditions characterized by disorganized or excessive movement (also known as hyperkinesia). Forms of dyskinesia include sudden, brief, "shock-like" muscle contractions (myoclonus); involuntary, rhythmic, oscillatory movements of a body part (tremor); rapid involuntary jerky movements (chorea); relatively slow writhing motions (athetosis); or abrupt, purposeless, simple or complex muscle movements or vocalizations (motor or vocal tics).

January 2008

The AKC Canine Health Foundation recently approved Grant No. 847-A: Mapping and Identification of the Mutation Responsible for Epilepsy in the Chinook.  The principal investigator is Gary S. Johnson, DVM, PhD from the University of Missouri.  Samples from affected Chinooks and family are still being sought.  A description of the grant follows. 

Abstract:
Episodic dyskinesias (EDs) are episodes of abnormal movement or tone, distinguished from seizures by the character of the episode and a lack of EEG spikes and waves typical of seizure activity. We have identified what appears to be an autosomal recessive ED that is prevalent in the Chinook breed. Typical episodes are characterized by an inability to stand or ambulate, head tremor, and involuntary flexion of one or multiple limbs, without loss of consciousness or autonomic signs. Episodes were variable in duration, ranging from seconds to hours. Interictal EEGs recorded on two dogs with ED were normal. Most affected dogs exhibit only ED, others experience only generalized tonic-clonic seizures, and still others had both ED and generalized tonic-clonic seizures. We have collected DNA from 34 affected Chinooks and over 200 clinically normal relatives in preparation for whole genome mapping of the ED locus by genotype association analysis using the Affymetrix 27,000-marker canine SNP chip. After mapping this locus to a small chromosomal interval, we will resequence regional candidate genes to identify the causative mutation. DNA tests for suspect mutations will be evaluated by genotyping all Chinook DNA samples in our collection. A validated DNA test will be offered to Chinook breeders.

May 2006

UPDATE ON THE CHINOOK “SEIZURES” STUDY AT THE UNIVERSITY OF MISSOURI

Dr. Dennis O’Brien, Dr. Rebecca Packer, Dr. Joan Coates

Research on Chinook “seizures” has been conducted at the University of Missouri, College of Veterinary Medicine for a number of years.  We place the “seizures” in quotation marks because Chinooks have different types of episodes, some of which appear to be classic seizures while others are different.  See http://www.canine-epilepsy.net/Chinook/chinooks.html for additional discussion of the disease and description of these “seizure-like” episodes.

We began banking DNA samples when the condition was first recognized.  The response of the breeders and owners to our efforts to address this problem has been excellent, and we thank you for your participation.  We appear to have now collected enough samples to start our gene mapping analysis, which began several months ago.  There are over 30,000 genes in the canine chromosome, so mapping a disease to a gene or combination of genes is a long and arduous process.  Although the study is progressing, please be aware that these mapping studies can take several months to several years to complete.  The amount of time needed for completion of these gene mapping studies depends on a number of factors: 1) sample size (the greater number of whole families participating, the easier it is to identify the gene or genes involved), 2) whether the disease of interest is a result of one gene or a complex interaction of multiple genes (the more complex, the harder it is to identify), 3) the specific genetic information generated by the assays, and perhaps most importantly 4) the accuracy of the information we are provided by the owners.  The genetic information gained through this study would allow us to identify a mode of inheritance, and to identify affected and carrier dogs prior to breeding age or placement into homes.  This information also would allow us to reduce the prevalence of epilepsy through modifications in breeding regimes.  For those Chinooks that already have developed epilepsy, we may be better able to identify the specific mechanism of “seizure” activity, and design more effective treatment protocols.  These are all long-term goals; however, they will be attainable provided that we are able to identify the gene or genes responsible for the Chinook “seizure” disorder. 

Until we identify the mode of inheritance of this disorder, it is difficult to provide interim breeding recommendations.  At this time, our only recommendation to reduce the frequency of “seizures” in Chinooks is not to breed affected dogs (an “affected dog” being defined as any dog that has a history of seizures or the “seizure-like” episodes described in the website during their life, regardless of if the seizures ceased later in life).  Since some dogs do not begin having episodes until late in life, it is difficult to determine who may become affected until after several breedings.  It is also difficult to provide recommendations for those dogs who are unaffected, but who have given rise to affected offspring.  It is possible that they are carriers of the disease who were bred to other carriers, but until we identify the gene we are unable to determine who is actually a carrier or affected.  Regardless, it is important that we do not create another genetic bottleneck by limiting the gene pool too severely, or we risk creating additional genetic diseases.  Thus, in some genetic diseases of autosomal recessive inheritance, it may be appropriate to continue breeding a carrier to an unaffected (non-carrier) dog on a limited basis provided they possess other desirable breed characteristics.  Carrier to carrier breedings, however, would not be desirable in such situations.  We will be able to provide more information on breeding recommendations once we have more genetic information available.  For more information on breeding strategies, Dr. Jerold Bell has written several articles for the AKC Gazette magazine regarding inherited genetic diseases and how to maintain responsible breeding practices without creating further genetic bottlenecks.  For more information on seizure disorders and the basis of molecular genetics testing, a CD-ROM of Dr. Dennis O’Brien’s seminar ”Chinook ‘Seizures’: of Diseases & Genes” should be available through your breed club, or you can view similar information from the website http://www.canine-epilepsy.net/Chinook/chinooks.html.

Since a lot of time has passed since our first DNA samples started arriving, we are in need of updating our records for those Chinooks enrolled in the study.  We must verify that dogs previously reported as unaffected remain unaffected to-date.  For those dogs that are affected by seizures or seizure-like episodes, we would like to characterize the appearance of these episodes.  In addition, we are also collecting information on cryptorchidism for male Chinooks in our study.  This was a problem of interest to many Chinook owners and breeders, and we are happy to include this information in our analysis.  We do not have current contact information for some participants who have changed email addresses or relocated since the study began.  If you have not recently been contacted by the University of Missouri regarding this study, please contact Liz Hansen at HansenL@missouri.edu so that we can update our information. 

Although we have started the analysis phase of the study, we still need DNA samples from additional participants to ensure that we find the gene responsible.  We are particularly interested in receiving DNA from affected dogs and their relatives.  DNA from whole families (siblings, parents, grandparents) is most useful, as this allows us to perform the gene mapping studies and analyze patterns of inheritance.  If you wish to participate in this study, please email Liz Hansen (HansenL@missouri.edu), or visit http://www.canine-epilepsy.net for more information on sample submission.

NOTE THAT ALL INFORMATION PROVIDED TO US FOR THIS STUDY WILL BE KEPT STRICTLY CONFIDENTIAL