Microphthalmia and Delayed Growth Syndrome in the Portuguese Water Dog

Microphthalmia and delayed growth syndrome (aka “puppy eye syndrome”) has been reported by Portuguese Water Dog breeders dating as far back as 1986. However, there is no information in the scientific literature and the majority of data concerning this syndrome has been obtained from records of breeders, which have anecdotal reports of the disease and little, if any, medical diagnostics.

Affected dogs present with microphthalmia of varying severity, other eye abnormalities, short stature and other findings. To date, the investigators have been able to collect DNA from 24 affected dogs. Males and females can be affected, although females predominate (about 70%).

Preliminary pedigree studies suggest an autosomal recessive inheritance. Human literature reports numerous syndromes associated with microphthalmia, and many genes have been identified as having a causative role.

The goals of this investigation are to better characterize the clinical syndrome seen in Portuguese Water Dogs, confirm a suspected mode of inheritance, obtain additional samples for investigation into the genetic mutation, and develop a mutation based, genetic test for breeders to eliminate this syndrome from the Portuguese Water Dog breed.

Funding for the research is provided through the collaborative efforts and generosity of the Portuguese Water Dog Foundation, Inc., and the Portuguese Water Dog Club of America. The AKC Canine Health Foundation supports the funding of this effort and will oversee administration of funds and scientific progress reports.

RESEARCHERS

Margret L. Casal, DVM, PhD
University of Pennsylvania
Amount: $12,960

Whole-genome Sequencing of non-prcd PRA in PWD

The Portuguese Water Dog Foundation will contribute $9,400 for Whole Genome Sequencing (WGS) on 4 different dogs [2 affected, 1 carriers, and 1 homozygous normal]. Samples will be tested at the WGS platform at the University of Bern, Switzerland. Dr. Aguirre’s eye lab is part of a consortium at Bern where they have WGS on 465 different dogs (at this point, none are PWDs). Bern will provide the initial filtering and data analysis, allowing Dr. Aguirre’s team to focus their analysis and to analyze the approximately 498 predicted genes in the interval in an expedited manner.

Although this proposal focuses strictly on non-prcd form of PRA, the results of the WGS studies will be critically important to other diseases of importance to PWD, for example microphthalmia/multiple congenital ocular anomalies (aka “puppy eye syndrome”) and possibly other diseases that rely on Genome Wide Association Studies (GWAS) to identify the genomic region of interest.

Any study using GWAS to map a disease interval will, much sooner than later, need high quality genomic sequence formation for the region. This comes from having access to as many different dogs/breeds as possible as well as having specific sequence information for the breed of interest from unaffected animals that can be used as disease controls. As the sequence information generated from this project will be publicly available, this resource will complement and inform research work being done on microphthalmia/multiple congenital ocular anomalies disorder as well as other diseases.

Research funded by the Portuguese Water Dog Foundation, Inc.

RESEARCHERS

Gustavo Aguirre
School of Veterinary Medicine, University of Pennsylvania
Amount: $9,400

Juvenile Cardiomyopathy

Our ultimate goal is to develop a mutation-based test for JDCM. 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 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.

Co-sponsored research with the Portuguese Water Dog Club of America, Inc.

Results

A linked marker test was developed which can use either a blood sample or a cheek swab is available from the University of Pennsylvania.

Portuguese Water Dogs: JDCM – Linked Marker Test Step by Step Submission Instructions

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RESEARCHERS

Meg Sleeper, VMD
Paula Henthorn, PhD
University of Pennsylvania

Canine Hemangiosarcoma

The main goal of this project was to develop a diagnostic test that can be used to detect hemangiosarcoma cells in blood samples from dogs. The rationale for the test is based on the fact that, as a tumor of cells that line blood vessels, hemangiosarcoma tumor cells are in intimate contact with blood and are likely to shed cells into the circulation. We can therefore use the identification of those cells to confirm a possible diagnosis in dogs that have clinical signs, and eventually to detect the disease before it becomes clinically evident (early stages when it may be more amenable to treatment) as well as to follow response to therapy (monitor remissions). Less than 50% of dogs treated with standard of care for this tumor (surgery and intensive chemotherapy) survive more than six months. Many dogs die from severe internal bleeding before there is an opportunity to institute treatment.

Results

We have further refined the system to verify we can detect malignant endothelial cells in dog blood when they represent as few as 0.01% of the nucleated cells. We are continuing to work out technical details, including cell enrichment methods, use of “positive” vs. “negative” selection, and the most reliable and reproducible format to offer the test in the field (that is, to “real” patients). The test will be licensed by Idexx Laboratories, Inc., which has now provided support for completion of the development process, including clearing regulatory hurdles and providing nationwide availability. We are much closer to a real product, and the support from the Portuguese Water Dog Club of America and the Portuguese Water Dog Foundation, Inc. allowed us to make significant progress and secure more stable funding for development from Idexx. We are indebted to the Club and the Foundation for their generosity and vision to make this happen. We truly feel this test will make a quantitative improvement in the quality of life for our dogs, by improving our ability to diagnose the disease and monitor the response to therapy.

Co-sponsored research with the Portuguese Water Dog Club of America, Inc.

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RESEARCHERS

Jaime F. Modiano, VMD, PhD
University of Colorado

NOTE: Dr. Modiano is now at the University of Minnesota

prcd Progressive Retinal Atrophy

Progressive Retinal Atrophy (PRA) is an inherited eye disease that cause blindness in dogs. In Portuguese Water Dogs, it is a form of PRA called prcd or progressive rod-cone degeneration and is inherited through an autosomal recessive gene. Because the disease can be passed on only if both dogs carry the gene, a test that identifies carriers will help breeders make appropriate choices when selecting breeding pairs.

The research approach involves using genes already identified as candidates for causing prcd. A mutation-based DNA test would single out the mutant prcd defect in every affected or carrier individual and would be unequivocally accurate. It is also less costly and easier to perform than the current linkage-based test.

Results

A mutation-based DNA test was developed and you can use blood, cheek swabs or frozen semen (semen would be used in the case of a deceased male and does not have to be submitted frozen, which greatly reduces the cost). For test information, forms, etc. visit Optigen’s website.

Research funded by the Portuguese Water Dog Foundation, Inc.

RESEARCHERS

Gustavo D. Aguirre, VMD, PhD
Gregory M. Acland, BVSc
University of Pennsylvania