Susan E. Johnson, DVM
MS Associate Professor Dept. of Veterinary Clinical Sciences
Ohio State University
Re: Canine Health Foundation Grant No. l943: Congenital Portosystemic Shunts and Hepatoportal Microvascular Dysplasia in Cairn Terriers and Yorkshire Terriers: Clinical Characterization and DNA Linkage Studies.
This is a progress report for the above research proposal. We have spent the past year collecting DNA samples from families of Cairn terriers and Yorkshire terriers with congenital PSS. Many family members also have hepatic microvascular dysplasia. DNA samples, clinical evaluation records, and pedigrees have been sent from all over the country (and some from Canada) to Dr. Yuzbasiyan-Gurkan’s lab at MSU for DNA extraction and record keeping. I have requested copies of the submitted information from Dr. Yuzbasiyan-Gurkan and have not yet received information on every sample sent. Based on my review of the copies I have been able to obtain, I have summarized the following information: 57 DNA samples from Cairn terriers have been submitted. Out of the 57 samples, 11 samples are from dogs with PSS, 8 samples are from dogs with microvascular dysplasia, 12 dogs have been confirmed normal, and 26 dogs have incomplete information to know their clinical status. It is clear from the information that simply sending DNA samples; without any serum bile acid results or veterinary evaluation hinders our ability to use information in a large number of these dogs. More work needs to be done including further evaluation of those dogs with incomplete information and continued efforts to locate, evaluate, and obtain DNA samples on missing family members.
There have been some new developments that significantly impact on our plan to initiate DNA linkage studies, which is the primary objective for year 2. Recent information suggests that PSS is inherited as a polygenic trait in Cairn terriers. Drs. Yuzbasiyan and Schall have been in touch with colleagues in the Netherlands who have studied nearly all the Cairn terrier population in that country. Based on the extensive family data they have accumulated, they have confirmed that PSS is an inherited disease in Cairn terriers. However, their results suggest that a polygenic mode of inheritance is most likely. A preliminary report was presented by Dr. Rothuizen at the recent ACVIM Veterinary Medical Forum. He described the results of two test breedings of Cairn terriers. In the first breeding, an affected female with surgically corrected PSS was bred to her phenotypically healthy father. This breeding produced a litter of 6 pups; 3 pups with PSS and 3 healthy pups. The same bitch was mated with a non-related male with corrected PSS. In the litter of 6 pups, 4 pups had a PSS and 2 were healthy. They concluded that the mode of inheritance for extrahepatic PSS in Cairn terriers is most likely polygenic rather than a single recessive gene. Microvascular dysplasia was not specifically addressed in this study and remains an unknown issue.
These results have important implications for our own study, since it is likely that the results of the Cairn PSS studies in the Netherlands are representative of the situation in our own Cairn terriers. Our second year objective was to start DNA linkage studies when sufficient DNA samples had been collected. However, if the mode of inheritance is polygenic rather than a simple recessive disorder, our chances for a fruitful DNA linkage study may be substantially diminished. Dr. Yuzbasiyan - Gurkan is concerned that it may require a much larger number of PSS dogs (in the order of hundreds) to get significant information. I have asked Dr. Terry King, a population geneticist who is involved with this project, whether she also feels this is true. She indicated to me that it is not necessarily “hopeless”, that it really depends on the pedigrees. Consequently, I have recently mailed -2- copies of all the information I received to date from Dr. Yuzbasiyan-Gurkan on the dogs with known clinical status so Dr. King can review this information and give me an opinion. Until I have better information that there is some hope for success with this project, I have stopped soliciting samples and asked the CHF for a 6 month no-cost extension of the first year proposal. I am reluctant to spend scarce resources on a project, if it is not likely to provide useful information.
On an unfortunate note, in January, Dr. Yuzbasiyan-Gurkan notified me that she has declined to be a part of this or any other research project involving the Canine Health Foundation. This “falling-out” with the CHF has nothing to do with this project but Dr. Yuzbasiyan-Gurkan feels because of her relationship with the CHF, her continued participation in this project would jeopardize the project. She has been very helpful to me and is willing to advise me on locating another molecular biologist who could perform the DNA linkage studies. Before pursuing this aspect, which would involve rewriting the budget for year 2, I want to be sure further pursuit of this project is warranted. Even if the project is halted at this stage, I believe it is still valuable to have these DNA samples banked for the future, since linkage studies in Irish Wolfhounds could yield a marker which could be tested in Cairn terriers.
