SINCE THE ARTICLES BELOW WERE WRITTEN A MARKER WAS IDENTIFIED FOR PNA.
May 23, 2006
Dear Kerry Fancier,
I just talked to Liz Hansen, Animal Molecular Genetics Laboratory at the University of Missouri, regarding concerns of the research status and the recent AKC Canine Health Foundation communication.
Question 1 to Liz:
Answer 1: No, we are not aware of the document. Liz confirmed with Dr. O’Brien, the vet school does not consider PNA/MSD as common disorder in either breed. If it were, it would be easier to solve. Liz reiterated, the vet school research dept has not published, nor distributed any updates since the CHF conference in Oct 2005.
***(I just received the CHF DVD of the presentations and the word ‘common’ was not used in the original presentation, slide set or the summary document. The word ‘common’ does appear in the summary slide set. The error lies with the CHF documentation. Gigi)
Answer 2: The research is not stalled or stopped. The isolation to the Park2 gene is the neighborhood, but there are a lot of houses to look in. Liz said she just ordered 50 more DNA test kits to look at the samples from another direction, one that has worked for other breeds. This time of year, at the school, is busy with graduation, vacations and grant submission paperwork. She will ask Dr. Johnson to give us an update we can present at the board meeting in Chicago.
Answer 3: Liz said that they got a positive response from the NIH review committee. The research proposal was not denied, but requested further detail. This is good; Liz said most proposals are rejected on the first submittal.
***(Liz called me back; She said the NIH proposal was ranked 12th and the NIH typically grants money the top 25 proposals. They will know in June how much money they have. Gigi)
Answer 4: The vet school will not be issuing any 90-95% clear certificates due to the possibility of false positive tests, which would diminish the confidence level. They would prefer to wait for a definitive DNA marker. However, they are contacting known affected sample providers, one 12 yr old male and some puppy mill dogs, for further sampling and test breeding. The vet school is aware of mills dumping Kerries. Liz said they contact the mills directly and buy affected dogs.
PNA Research Update 7/06
USKBTC HEALTH AND GENETICS COMMITTEE NEWSLINE
submitted by Scott Kellogg DVM, Committee Chairman
UPDATE ON PNA RESEARCH PROJECT, JULY 2006
Dear USKBTC Club Members
I received the following update from Dr. O’Brien concerning their PNA gene research.
Scott Kellogg DVM, H&G Committee Chairman:
Now we wait for the review cycle to play out again, and it will probably be April before we hear anything. Meanwhile, Dr. Johnson continues to do what he can. There was another gene right next to the PARK2 that was also a potential candidate, so Dr. Johnson sequenced that one and didn’t find anything. He is looking into a different technique for finding the type of mutation we suspect is going on in the PARK2 gene, which will hopefully be easier to do than the one we were considering. We’ve also identified someone who can do RNA studies for us. That would allow us to prove that the PARK2 gene is really the culprit. Even though that still wouldn’t give us the actual mutation, at least we would know we’re barking up the right tree. Trouble is we need to collect tissues in a specific way to do that sort of study, so we have to wait for the next affected dog to come to Missouri to do so. We have found an affected Chinese Crested dog, so we’re working on getting the necessary samples on that dog.
Any way, just wanted to let you know where we were at with things. Hopefully, we’ll make the cut this time and be able to move forward with this. Meanwhile, if any other affected dogs surface, please let us know.
Thanks to Dr. O’Brien for his update, and let’s hope their grant is approved. If any PNA puppies happen to come along, please contact Dr. O’Brien at the University of Missouri School of Veterinary Medicine.
(The following great news was originally viewed on the USKBTC elist. Permission was given by Scott Kellogg to post to the website.)
September 14, 2004
I am VERY excited to announce that the SPECIFIC DEFECTIVE GENE, that produces PNA (progressive neuronal abiotrophy), HAS BEEN DISCOVERED by researchers at the University of Missouri’s School of Veterinary Medicine.
Dr. Gary Johnson contacted me this evening and announced the news, and authorized its dissemination. Drs. Johnson and Dennis O’Brien have been working on the search for this defect, and have found the EXACT DEFECTIVE GENE, as confirmatory research concluded today. They will begin testing for PNA immediately. A 3 ml EDTA blood sample is required for the PNA test.
Submission instructions can be found at the following website, (They do not have a PNA website as of yet.): www.canine-epilepsy.net Click on the sample submission button on the left side of the margin, and follow the directions, as if sending a blood sample for epilepsy submissions. (The lab will set up a separate PNA website later on.)
Liz Hanson of their lab will be handling blood submissions. There is no charge (at this time) for testing, due to the fact that the United States Kerry Blue Terrier Club is participating in the Canine Phenome project being conducted by the University.
If you are interested in donating to the Canine Phenome project fund, go to the Charitable Funds section of www.uskbtc.com
This PNA test will determine if your dog is a carrier of the defective gene that produces PNA–thus determining if your dog is a carrier or not. By careful breeding of either 1)carrier to non-carrier, or 2) non-carrier to non-carrier, the production of the PNA disease can be stopped. Since this is a simple recessive gene, PNA is produced only when a carrier animal is bred to a carrier animal. Carrier animals can be bred with no possibility of PNA being produced, as long as they are bred to non-carrier animals.
Many thanks are to be extended to Drs. Johnson and O’Brien and their laboratory staff, club member Jana Deaton, for her work with PNA in the recent years, Zippy Fleischer for her many years of work previously, Dr. de La Hunta of Cornell for his initial research of the disease and pathology work thereafter, and Kerry and Chinese Crested breeders who have assisted with PNA research.
Additional information will be posted at the United States Kerry Blue Terrier Club website in the coming days.
Dr. Johnson will be presenting a seminar sponsored by the USKBTC on Saturday, October 2nd following the USKBTC Futurity in Gwynedd, Pennsylvania. He will talking about the Canine Phenome Project and PNA research and testing. The seminar is free. For more information, consult www.uskbtc.com and look under Montgomery County events.
The USKBTC is working to have blood collection for PNA testing available at the Futurity for interested parties. More information will be posted at the www.uskbtc.com website. This is a GREAT, GREAT day for the Kerry Blue Terrier and its fanciers!
Scott Kellogg DVM
PNA Research & Funding Update 1/05
USKBTC Health and Genetics Committee
PNA Research & Update
Dear Fellow USKBTC Club members: Dr. Gary Johnson, co-primary PNA researcher from the University of Missouri School of Veterinary Medicine, has provided this PNA research update (as of December 31, 2004) for our club. Dr. Johnson gave an excellent presentation for the USKBTC at Montgomery County, and the club is grateful for him taking the time out of his busy schedule to speak to our group. He and Dr. Dennis O’Brien are continuously working on finding the exact location of the PNA genetic mutation.
A linkage test is currently available, and hopefully soon there will be a test for the exact mutuation. Club members interested in donating monies towards this research can do so through the USKBTC Charitable Funds program, which can be found in the report by the Funds committee. We will post updates on the progress of PNA research as things develop.
Thanks to all club members for their continued support.
USKBTC Health and Genetics Committee
Dr. Johnson’s letter to the USKBTC H&G Committee is below.
I want you and the Kerry Blue Terrier Club members to know that we at the University of Missouri are continuing our work on PNA. When I spoke at the Kerry Blue Terrier National Specialty in Philadelphia, we had identified the canine chromosome containing the mutant PNA gene and narrowed the search to a twenty million base pair segment of that chromosome which contains approximately 100 genes. Among these hundred or so genes was a gene that caused a similar neurodegenerative disease in people. We had identified a mutation within the canine version of that gene and for a while there, we thought we had found the cause of PNA; however, as we began testing for this mutation, we found that it appeared in some known normal dogs, indicating that this mutation was not the cause of PNA.
Since then we have narrowed the target region to eleven million base pairs containing 41 genes. Thus, we have narrowed the search to about four tenths of one percent of the canine DNA code. The suspect gene is still in the target region, and we are continuing the search for the causative mutation within this gene. Unfortunately, the gene is very large and it isn’t financially feasible for us to sequence the entire gene. Early in 2005 we are planning to employ a new technique which we hope will lead us to the mutation causing the disease. While we continue to look for the mutation, we plan to develop and use what is known as a “linked marker” to evaluate the approximately 200 Kerry Blue Terrier samples sent to us for testing.
Linked markers are not as reliable as the so-called “disease” markers which directly test for mutation; nonetheless, they can be very useful. For instance, a linked marker offered by VetGen was used to greatly reduce the incidence of heritable copper toxicosis in Bedlington Terriers. Our linked marker will consist of a pattern of sequences known as a haplotype in the target region. Dogs with the mutant haplotype on one chromosome are probable carriers of the disease. Dogs that lack the mutant haplotype are considered normal. Our first attempt at a linked marker involved a haplotype region that was too broad and misidentified some dogs. In the next few weeks, we will evaluate a more focused haplotype. Hopefully, this more focused haplotype will provide us with a sufficiently accurate test, and we can provide interim results while we continue to search for the mutation causing the disease.
One reason that research has gone so slow is that we only have samples from four affected Kerry Blue Terriers. Samples from additional affected dogs or their close relatives would be of great help. If you know of any affected dogs or relatives and would like to help, please contact project coordinator Liz Hansen by email at HansenL@missouri.edu, or by phone 573-884-3712. Forms and instructions for sending samples are found on our website, www.CanineGeneticDiseases.net, in the “Ataxia” section.
USKBTC FULLFILLS INITIAL COMMITMENT TO PNA PROJECT
On December 30 the USKBTC, through its Charitable Funds, sent a check for $7,500 to the University of Missouri in support of Dr. Gary S. Johnson’s on-going research on PNA. As many of you know, the specific marker has not yet been identified.
As a result, Dr. Johnson has requested the remaining $2,500 of the committed $10,000 be retained for one of the AKC/Canine Health Foundation “Acorn” grants. The “Acorn” proposal will be submitted by Dr. Johnson when a linked marker is ready for testing and the funds utilized for DNA testing. Through Dr. Scott Kellogg, Chair of the USKBTC Health and Genetics Committee, on-going dialogue continues with Dr. Johnson on his progress.
Tax deductible donations to the USKBTC’s Charitable Funds (501c3 non-profit status) to support Health and Genetics Research, Rescue and Education may be sent to:
PNA (CMSD) Update 10/05
The following information by Dr. Johnson wa sent to the USKBTC and is the most recent update on the reseach being done on CMSD (PNA).
At the University of Missouri-Columbia we (Dennis O’Brien, Joan Coates, Liz Hansen, and Gary Johnson) are continuing our search to find the mutation responsible for the mutation responsible for Canine Muliti-System Degeneration (CMSD, also known as PNA) in Kerry Blue Terriers. The research reported at the Kerry Blue Terrier Specialty has been published.
At that time we had used pedigree/marker analysis to localize the mutation to a fifteen million base pair segment of canine chromosome 1. Since then we have produced 11 new markers in the target region. In addition we have analyzed DNA from two additional affected Kerry Blue Terrier DNA samples. One was a rescue dog. The other DNA sample was extracted from formalin fixed tissue in a paraffin block supplied by Dr. deLahunta. Actually Dr. deLahunta sent us blocks from three affected Kerrys, but we were only able to extract usable DNA from one of them. With these new samples we were able to use haplotype analysis to narrow the target region to 5.1 million base pair segment.
Among the genes within this target segment is PARK2. Mutations in human PARK2 cause a recessive neurodegenerative disease that resembles CMSD. Three types of mutations in PARK2 cause the human disease: point mutations, exon deletions, and exon duplications. We have been able to rule out point mutations and exon deletions in canine PARK2 as the cause of CMSD; however, ruling out exon duplications in PARK2 is technically much more difficult. The technique used to detect human exon duplications is called multiplex amplifiable probe hybridization or MAPH. So far this technique has only been used to analyze human DNA.
We are in the process of adapting the method to determine if CMSD results from exon duplication in the canine PARK2 gene. If this is successful we will be able to determine which of the 270 Kerry Blue Terrier samples submitted to us are CMSD carriers and which are clear.
In addition to the support received from the Kerry Blue Terrier Clubs, the University of Missouri College of Veterinary Medicine provide $13,000 to support the work. We have also submitted a $400,000 R21 grant proposal to NIH to study CMSD.
The Canine Phenome Project website is now being beta-tested by the Basenji club. We anticipate being able to begin enrolling Kerry Blue Terriers by the end of this year.