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 and is available on line at http://jhered.oxfordjournals.org/cgi/reprint/esi086v1

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.

Last Updated: 10/16/2005, 9:35 am