Thank you for collaborating with the scientists at the University of Utah. The Georgie Project is studying both anatomy and specific diseases found in this breed to help provide a better understanding of the genetics of the Portuguese Water Dog. We are very hopeful that this knowledge will help breeding practices and the health of the breed. Genotyping is an arduous process that consists of extracting DNA from blood that we receive and then testing that DNA for hundreds of genetic markers. If we can genotype each dog with about 600 markers, we will have a good chance of identifying some genes responsible for the size and shape of the dogs. We also may find some of the genes responsible for a number of genetic diseases such as canine hip dysplasia (CHD), epilepsy (seizures), Addison’s disease, cardio myopathy, and possibly others.

We felt that it was time to update you on the progress of the project and to provide you with some individual data on your dog(s). At present we have received about 250 sets of x-rays from which we have learned a great deal. From the x-rays we determine the size of individual bones and when these data are examined collectively (by a process known as principal component analysis) we obtain quantitative measures of size and shape that relate to the overall structure of the dog. When we have reached our goal of 500 x-rays we should have about 10 independent such aspects of the breed.

With the analysis of 230 (of the 250 received) we have established 3 of these aspects: 1) The overall size of the PWD skeleton (including the length, width and thickness of bones). This, is one of the factors that determines the amount of muscle a dog can support. 2) A measure of the overall length of bones vs. their thickness. Dogs tend to have either long "skinny" bones or shorter, thicker bones. This is a trade off between speed and motion (long bones) vs. strength and sturdiness (thicker bones). 3) The size of the head relative to the body. The ranking(s) of your dog(s) in these three categories, relative to the other ~230 dogs, is indicated on the accompanying pedigree/data sheet(s).

We have identified genetic loci for some of these characters. Of these, one most likely to be of interest to owners or breeders, is a locus for size. At stake, appears to be an allele that gives rise to smaller dogs. This genetic marker allele for small size is the "A" allele. Homozygotes (2 copies) of the A allele are smallest, heterozygotes (1 copy) are intermediate in size. Other alleles "B" through "H" are either neutral or may produce larger dogs. Although this appears to be an important locus for determining the size of your dog, it is not the only genetic locus for size. Thus, a dog may be homozygous for the "A" allele, but have an average build or even be large as a result of other genes that we have not yet identified. Nevertheless, dogs homozygous for this allele on the average will tend to be smaller. Matings between two heterozygous dogs, each carrying the "A" allele can produce litters that may vary widely in size when full grown, from small "AA" dogs to larger "**" dogs where "*" indicates any allele that is not "A" (i.e. "B" to "H"). In the accompanying data sheet, we have included the genetic rating of your dog "AA", "A*" or "**".

From your x-rays we have also measured laxity in the hip (coxofemoral) joint. For a quantitative measure of laxity we have used a measure known as the Norberg Angle. The Norberg Angle is the angle that the head of the thighbone (femur) makes with the hip socket. (This measure is explained in detail on our web site at: www.georgieproject.com/disease/norberg.htm). The Norberg Angle for your dog(s) also is on the accompanying data/pedigree sheet(s) see page 5. As a breed, we found that this joint is more lax in Portuguese Water Dogs than in most other breeds, including Labradors and German Shepherds. Therefore, OFA ratings in the breed will tend to be less good. Another interesting aspect of the study on hip laxity was the finding that the left hip of Portuguese Water Dogs is, on average, more lax than the right.

A number of published studies indicate that osteo-arthritis is more frequent in dogs with greater hip laxity. We searched for evidence of osteo-arthritis in the x-rays. Osteo-arthritis was classified as Sclerosis or as bone spurs (cranial, caudal or femoral). An explanation of these classifications also is given on pages 3 and 4. Despite the greater hip laxity, there was very little evidence for osteo-arthritis in the breed as a whole, although there appears to be a tendency to find more osteo-arthritis in the left joint than the right. Your dog(s) scores for osteo are included in the data sheet(s) see page 5. One problem with the osteo data is that arthritis is found in older dogs and we have fewer x-rays from such dogs (see below). To confirm or reject the supposition that there is little correlation in PW Dogs between hip laxity and osteo-arthritis of the coxofemoral joint we will need more data from older dogs.

Previous Georgie Project research on Cardiomyapathy, defined the genetic transmission of the disease (simple recessive) and the ancestor that carried the gene (Taro). That work was made available on a web site (www.larklab.4biz.net/cardioM.htm) and will appear in the American Journal of medical Genetics as a collaborative publication with Dr. Joseph Alroy's group at Tufts University. The Georgie Project is currently active in three other areas of disease: Canine Hip Dysplasia (CHD), Seizures (Epilepsy), and Addison’s disease.

We have already described our interest in CHD and are beginning to work with the PWDCA CHD committee to try and establish the heritability of CHD in the breed. If this heritability is high, we plan to follow dogs on which we have Norberg Angle measurements to determine if they develop osteoarthritis as they get older and if so the degree of the disease. From these data together with genotyping of dogs we hope to identify genes responsible for osteo in our breed.

Seizures in PWD are probably a form of epilepsy. Records of dogs that have seizures indicate that there is a high heritability (strong genetic component) for this disease, confined to a narrow portion of the PWD pedigree. The data support the hypothesis that the disease was introduced by Tabu, the ancestor probably responsible for GM-1. We have blood from 13 dogs that are affected and from a number of parents of affecteds. At present, reports of the disease are infrequent, making it difficult to establish a clear mode of inheritance. However, the high heritability has made it clear that given DNA from more affected dogs and their normal siblings or close relations, we stand a good chance of identifying the gene(s) responsible for the disease. Our goal is to determine if there is a diagnostic test for the disease other than the appearance of actual seizures and to obtain DNA from many more animals so that we may identify the gene(s) responsible. Currently we are working with the PWDCA seizure committee to achieve these goals.

Georgie Project research on Addison’s disease has suggested that it is probably an autoimmune disease that may be part of the complex of diseases known as Autoimmune Polyglandular Syndrome or APS (see "The three awful A's by Karen Miller in the Courier). It is genetic in origin, and has a low penetrance, but unlike Epilepsy is widely distributed throughout the PWD population with a low heritability. This makes it very difficult to analyze. We have begun a study in collaboration with the Endocrinology group in UC Davis to see if we can detect animals predisposed to the disease from the levels of hormone in their blood. This study, that has just begun, will require many more participants. However, it has been well supported with donations of money and of expensive reagents. If we succeed in our goal, we should achieve a better definition of the preclinical disease or even an assay for preclinical Addison's which may be a necessary condition for finding the genes involved.

To date the accomplishments of the Georgie Project are encouraging. They demonstrate that we can find genes that affect the appearance and performance of the breed. We are well on the way to finding genes for disease and providing estimates of disease risk based on DNA analysis. However, to achieve our goals we need a minimum of about 500 dogs, chosen from "all walks of life", i.e. not heavily weighted toward one particular breeder or owner. Moreover, genotyping is not enough. We also need phenotypes. For the anatomy of the Portuguese Water Dog (and for CHD), this means the set of five x-rays that we have been requesting. For work on disease, it means receiving blood (for DNA) from animals (and relatives of animals, e.g. parents or litter mates) that have been diagnosed with a disease and for economy as well as efficiency, x-rays on these animals as well. (It costs approximately $1000 to genotype each dog. X-rays cost an additional $175. Therefore it is wasteful to genotype a dog without also collecting a set of x-rays).

To date about 300 owners from 37 states and Canada have agreed (in writing) to participate in the project providing blood and x-rays on about 600 dogs. We have received blood from about 500 dogs but x-rays from only 250. The list shows the distribution of commitments, DNA samples and x-rays received. We are unable to supply a data sheet for those dogs from which we have no X-rays.

Data and materials (x-rays and DNA) from individual dogs are maintained at the University of Utah and remain strictly confidential. Raw data and materials from any dog as well as the results of data analysis on that dog will not be released to any other party without a specific request from the owner that also must be initiated by the owner. Within the project, data pertaining to any specific dog is only seen by Kevin Chase and all data are coded within the data files by a number assigned to each dog. Others, working in the project are able to view results on the population of dogs as a whole, but not on individual dogs. Information on the PWD population is released in the form of general results, not as information on individuals. If results are obtained that suggest a possible health problem involving an individual dog, that information is reported directly to the veterinarian that provides health care for the dog and/or provided the data that suggests that a problem might exist (x-rays, blood, or blood chemistry for Addison tests).

PC1 is the overall skeletal size of the dog. Higher ranks indicate dogs that are larger relative to the rest of the population. These rankings have been corrected for sex; therefore, female dogs with a high rank will be larger than most females but not necessarily larger than most males.

PC2 is the trade-off between long thin bones (low rank) and short stout bones (high rank).

PC3 measures the relationship between the body and the head. Low ranks indicate a big body and small head. High ranks indicate a small body and big head.

The Norberg angle measures laxity using the same x-ray view as that used for OFA evaluation. However it represents a more objective evaluation of the radiograph and has been used in a number of scientific publications. This measurement provides us with an estimate of laxity in the breed as a whole. Norberg angles ranged from 82 - 120 in the population with an average of 107.

The measurements of osteo-arthritis taken from the x-rays are more difficult to interpret. Normally sclerosis and spurs are not measured on non-symptomatic dogs. Thus, their relation to clinical disease as opposed to their presence in healthy dogs is unknown. Therefore, osteo data on your particular dog may not be relevant to clinical disease. Indeed many owners have informed us of their dogs’ ability to run, dodge or jump well despite the presence of sclerosis or spurs. Average values for this population are Sclerosis 0.48, Cranial Spurs 0.1, Caudal Spurs 0.05, Femoral Spurs 0.25.

From this study, we hope to understand how the osteo x-ray data relate to performance and can be predicted from laxity. We would be grateful for any comments on your dogs’ agility that you can provide to us by e-mail or by snail mail. Please include your dogs registered name and AKC number.

"Snail Mail"

Georgie Project, c/o Lark Laboratory
University of Utah
Department of Biology
257 South 1400 East, Room 201
Salt Lake City, UT 84112-0840
E-mail: Georgieproject@bioscience.utah.edu
Toll free telephone: 866-578-5835