Research Objective:

Finding the gene responsible for juvenile cardiomyopathy in the Portuguese Water Dog breed and develop a test to detect carriers.

Principal Investigators:

Meg Sleeper VMD
Paula Henthorn, Ph.D.
Sections of Cardiology and Medical Genetics
Department of Clinical Studies
University of Pennsylvania Veterinary Hospital

Abstract:

Below is a reprint of a letter the Foundation received from the researchers at Penn:

Penn Veterinary Medicine
Section of Medical Grenetics
Department of Clinical Studies-Philadelphia

September 22, 2006

Dear Members of the Board of the Portuguese Water Dog foundation

Let us start by thanking you for your past generous support. We have wonderful news, a new request, and a cautionary message for you! First we’ll give you the good news. Our whole genome scan to look for the cause of Juvenile Dilated Cardiomyopathy (JDCM) has yielded a linked marker. We now have the toehold we need to be able to find the gene and mutation and to develop a useful test that will allow you to avoid producing pups that succumb to this disease. We are all very excited and working very hard to advance the project. Now comes the request. We hope it comes as no great surprise when we tell you that the harder we can work on the project, the faster we will be able to provide a test. Additional fund of $16,870 would be extremely helpful, particularly to provide salary support for a very experienced technician to work on this project. (Note: The Foundation has pledged to provide these funds.)

We assume your first response is: “When will we have the test?” which prompts our cautionary remarks. What we have today is a single genetic marker that is NOT informative for every known carrier that we have examined. So putting it in genetic test terms that you have heard before because of your experience with prcd, we already know that we have a false allele, and this just from examining families that we know segregate the mutant JDCM gene. This may be higher in the general population. We have also observed recombination between the marker and the disease locus. So it would be putting it in too optimistic terms to say that we have a test. What we have is a result that make us certain that a test is truly on the way. Before we can even think about using a particular marker as a test, we need to identify a marker that has not recombined, and to have some understanding of the frequency of any “false” alleles. This is the work that the additional funds we request will partially support.

Our ultimate goal is to develop a mutation-based test for JDCM. Unfortunately, we again cannot predict how long that may take. There are  several difficulties with JDCM, especially compared with other genetic diseases that affect your breed. Because the diagnosis of affected animals is often made after it is no longer possible to obtain blood or tissue, the most useful DNA samples cannot be obtained and therefore the strength of the pedigrees we have to work with is diminished. Disease gene determination is often aided by finding the disease in other breeds, but this is not the case with JDCM. Despite these limitations, our goal is that by your National Specialty in 2007, we will have identified one or a battery of markers that can be used to detect the chromosomal region that contains the JDCM disease-causing allele, however, we have no way to anticipate what the “false allele” frequency will be. That has been predetermined by the breeding history of Portuguese water dogs and the situation may exist that we will not be able to provide a specific test until we find the mutation itself.

So, we’ll close by saying that, despite the cautionary remarks above, we are very excited by our recent findings, and hope you are also pleased. The work we ask you to support is absolutely necessary to get you a test, whether it is a linked-marker test, or a mutation-based test. We are doing our utmost to advance the work as quickly as possible and look forward to a day when no Portuguese water dog dies from JDCM.

With best regards,

Paula S. Henthorn, PhD and Meg Sleeper, DVM