Your Money at Work

Kimberly Greer, Ph.D.

Determining the cause of PDE:

What have we accomplished?

The goals for this project included the collection of detailed veterinary information from multiple pedigrees containing PDE affected dogs and sample collection from pedigree members, followed by DNA isolation. The medical information included full clinical examination notes, blood chemistry panels, laboratory culture results, CSF analyses, MRI and/ or CT reports together with histopathology. From this information, we wanted to determine three primary points of importance:
1) if a genetic component to PDE could be established
2) the mode of transmission if genetic origins exist and
3) sample sizes required for further analyses. The collection of this extensive information set and its review was vital to set the stage for future detailed research.

As of July 2004, the primary goals of the research grant are completed. We now have in hand, the largest sample set in existence for information regarding PDE. We also have the largest sample set of prepared DNA from multiple pedigrees currently available. Within the set, we have data points that can be segregated out for individual statistical analyses. Most recently, a computer database was built for storing and sorting our extensive set of information. The entire sample set is in the process of entry. Once it’s entered, we will generate the data book required for statistical analysis of transmission. So, when the computer tallies our Pugs and sorts them by relation, we will know if there is a direct genetic transmission of PDE. This piece of information should be available by Nationals. Lastly, and importantly, biological samples needed for initial molecular analyses are available.

This extraordinary dataset has made a few points clear that were not necessarily clear previously. We now know that black pugs are affected with PDE along with fawns. We also have a better idea of the ratio of males to females (1:5). As the number of study participants increases, however, this number may become more equal. We learned that the average age of onset is 16 months and although several Pugs have displayed PDE shortly after vaccination, we do not have enough evidence at this time to conclude that vaccination is a contributing factor. Considering our new information, two theories remain as to the cause of PDE:
1) PDE is a genetically inherited disorder
2) PDE has genetic contributions, but is triggered by an environmental exposure.

After our significant investment in collecting this extensive data set, we now want to use the data for resolving the remaining theories. First, the statistical analysis of Pug relationships will be completed soon and it will tell us if PDE is strictly inherited in a genetic fashion that we could manipulate with choice breeding. Second, although there is no obvious genetic and environmental combination currently apparent, I am continuing to collect information regarding affected Pugs and their relatives. The statistical associations are calculated periodically to see if new associations have become apparent.

What does our future hold? Well, we have established the primary resource we needed to determine the cause of PDE in our pugs: DNA and collated information. We are at last in a prime position to search in detail for the cause(s) and we have gained valuable insight along the way.