GDC KinReport™ (in detail)

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THE HOW AND WHY OF THE GDC KinReport™

by Martin E. Packard, PhD (1999)

The GDC KinReport is a new tool to provide the breeder or prospective owner with the genetic profile of a chosen dog. The report shows all the dog's relatives which are in the registry and whether or not the dogs were evaluated as affected or not affected. The report shows which diseases should be checked for each breed and which have been evaluated in the chosen dog and its relatives.

Whether a dog is clear or a carrier can best be determined by reviewing the progeny. Some insight is obtained by reviewing the siblings and half siblings, but very little useful information can be acquired from the standard AKC or breeder pedigree.

The preferred breeding animal is the one that has the fewest affected cases amongst the progeny. The affected dogs are known with certainty to have the affected genes while the 'normal' or unaffected cases can be either free of the unwanted genes or pass on the unwanted genes to their offspring.


HOW TO READ THE GDC KinReport™

The report consists of three main tables and a pedigree. The pedigree is presented to show which dogs are in the registry and whether or not they have been evaluated by GDC. The tables will show all the siblings, half siblings, and offspring of a dog, and the same for both parents. The important data are the genetic disease evaluations for each of the dogs.

The tables are assembled by a computer program which links all the dogs together on the basis of the parents. It doesn't matter if the original entries come from different owners or breeders, they will all be found and added to the record.


The Pedigree

The pedigree is not intended to replace the formal AKC pedigree. It is basically a road map. For this reason the GDC dog number precedes the dogs name, which does not include titles. Other information such as, birth dates, co-owners etc. is not included on the line. The GDC dog number is used to tie all the data together. For example, the Sire's number is given on the other tables and his name can be found by referring to the same number on the pedigree. See page 2 of Appendix A (The actual KinReport).

The asterisk, '**', shows that the dog has been evaluated and is in the registry. (It can be thought of as being a gold star.) If the dog is without an asterisk, it had been entered as an unevaluated parent.

The pedigree goes back only to great-grandparents, 3 generations, because the common genes of an ancestor are rapidly attenuated by each generation. Only 1/8 of a dog's genes are derived from a great-grandparent, because the number of genes contributed by each ancestral level is reduced by 1/2, as half come from the mother and half from the father.

However, the pedigree can be used to go deeper into the ancestors data by asking for another KinRport on a grandparent or great-grandparent. Sometimes it is helpful to look at a KinReport on siblings or progeny. If there is reason to think that the pedigree would link with other dogs in the GDC registry, dogs can be entered from a complete pedigree.

You may notice that all of the dogs in Appendix A have peculiar names with kennel names that don't match the breed. This example has been scrambled to avoid any possibility that the dog can be identified. We asked the computer to make a new three part name by random selection from the entire data base. If you recognize a breeder, that is good, as that breeder is taking advantage of the latest tools to control the genetic disease in his or her kennel. We are proud to be working with leaders in the field.

The Report Tables

The third page, Table II, gives the sibling, half siblings and off spring of the dog being considered. This table is placed first as it has the greatest significance in predicting genetic qualities. Please see the sample KinReport in Appendix A and the Glossary in Appendix B for an explanation of the codes on the entries.

The dog's names, siblings, and progeny are listed in rows down the page and the diseases in columns across the top, Appendix A, page 3. The first group of dogs listed under 1: are the siblings and half siblings, and the second, 2:, are the offspring. The selected dog will always appear in the list of siblings. The siblings and progeny are ordered by birth date, to facilitate the identification of litters. GDC asks for the number of each dog's litter mates. When this has been provided, the number appears in the last column 'Ltr Size'.

Tables III and IV on pages 4 and 5 have the same information as Table II but they relate to the Sire and Dam who is listed near the top of the page. The parents progeny will also appear in the sibling group of the dog being reviewed.

The Genetic Disease Columns

The genetic diseases which are listed and identified with the symbol ^ are those that have been selected as being important to that breed. These are chosen either by GDC's advisory panels in view of published literature or have been added at the request of a breed club. The recommended tests are breed specific and will be different for a KinReport issued for different breeds. As many as 10 genetic diseases can be listed on each KinReport.

The recommended list of genetic diseases for the breed will always show on the report. If an additional disease has been evaluated for a particular dog, that column will appear on that table, but not on the other tables. That disease column will be identified with the symbol -. None of the data in a research data base will appear on the KinReport. For example, if a dog has been evaluated for hips and epilepsy, only the hip results will be on the report.

Conclusions

The report has been designed to bring the essential information on to one form. It does not include the details of an affected elbow or eyes which appears on the GDC Evaluation report given to the owner at the time of registration. For example, the elbow may show FCP or arthrosis. If more detailed information is desired, please ask your veterinarian to contact GDC.

You may want to talk to your veterinarian about the conclusion found from the KinReport. Your veterinarian should call GDC with any questions.

A genetic report is not valid if the actual genealogy is different from the submitted pedigree. At some future time the fancy will want to use micro chips or DNA parentage testing, but until that time GDC has to depend upon the accuracy of the submitted data and its verification by the veterinarian.

We appreciate the opportunity to work with you in helping to control genetic disease in your dogs. If you have further questions or comments, please contact us at GDC, phone or fax 530-756-6773.

THE WHY OF THE GDC KinReport

The Genetic Basis of the GDC KinReport

The usefulness of the KinReport is based on the simplest of the classical genetic principals. A dog may pass on the genes for a characteristic even though that characteristic cannot be seen in that individual. This is illustrated by the example in Appendix C.

Exactly the same rules prevail for many of the canine diseases which arise from a single gene, e.g. Progressive Retinal Atrophy (PRA) or Sebaceous Adenitis (SA). Even if the disease is carried by several genes, polygenic, the principles are the same. Hip and elbow dysplasia are examples of proven polygenic diseases.

Mass Selection as Promoted by OFA

It is disappointing, but the widely practiced mass selection procedure has not produced significant reduction in the frequency of hip dysplasia over the past 30 years. Mass selection calls for breeding only normal to normal phenotypes, that is parents that do not show the disease. The problem is that a normal dog still carries hip dysplasia genes. This is why a severe case of hip dysplasia often occurs even though the breeder has been conscientious and bred only unaffected hips through several generations.

For all practical purposes all the dogs in all breeds, except perhaps sight hounds, should generally be considered to be carriers of the polygenic disease, hip dysplasia. As far as is known, no dog has ever been shown to be entirely clear of the hip dysplasia genes. The finding of such dogs would be a great blessing to any breed.

The advice of the OFA and veterinarians to breed only those dogs that do not show the disease is right, but is not enough. It is incorrect to breed dogs that are clearly affected, severe or moderate, because it is certain that the dog carries the deleterious genes. However, the absence of the disease in a parent tells us little about the genes of that dog; we can not tell from the phenotype alone, if the dog is genetically clear or is a carrier. That is we can not predict how many of the offspring will have hip dysplasia.

The Records on Affected Dogs are Very Important

Our focus needs to be on those dogs that are affected, with either a single gene or a multi-gene disease. These dogs are the ones that we are certain have the unwanted genes which can be passed on to its offspring. A major weakness in the OFA procedure of mass selection is that the information on the affected dogs is not released and is not linked through the parents to the relatives. Even if OFA, a closed registry, were to release the data, it would be incomplete because many breeders do not send in the radiographs which they believe shows their dog to be affected. The closed eye registry of CERF suffers from the same deficiency, but we don't know how seriously.

Another weakness of the current OFA and CERF closed registries is that firm data is not available on the incidence or prevalence of a disease within a breed. This information is required in assessing the progress in controlling the disease. If the disease is polygenic, the average frequency of the disease within the breed is important in selecting breeding stock. The careful breeder will try to breed only those dogs that are 'better than average'.

Although the rule of thumb to 'breed better than average' has been used since the beginning, it needs to be redefined when breeding for control of genetic diseases. The rule is most useful if the heritability of a trait is high and the trait is a simple observable, that is the relation between phenotype and genotype is high. Almost all breeding for confirmation follows this rule.

In breeding for control of genetic diseases, we can not see the genes that govern the trait or disease, except in a few cases like GCL in Cairn terriers or PRA in Irish setters. In time we will see more tests using markers or the gene itself, but to develop a test will be very difficult for polygenic diseases like hip dysplasia. The best that we can do now is to observe what the dog produces in the offspring.

Back to breeding better than average. Better means that the progeny or siblings have fewer relatives that are affected and average does not refer to the average of the general population, but rather the average of the sub -population of the breeders line or kennel. If a breeder ignores the rule of nature and adds breeding stock that is genetically inferior to her line's average the inevitable regression to the mean will occur.

The GDC KinReport will list whether or not a dog is affected or unaffected for many of the genetic diseases and with a grading for some.

It is well known that no diagnostic procedure is without the possibility of error. The practice in medical science has been to categorize a result as being 'negative' or 'positive', to simplify the use of the data. This corresponds with our use of 'affected' or 'unaffected'. A false positive is reported if the animal is actually free of the disease but the test shows it to be affected. A false negative occurs if the dog is affected but the test shows it to be disease free, that is unaffected.

It is unfortunate that the OFA has placed great significance on whether or not a dog is classified as 'normal'. If the dog is certified as normal a number is issued, and the assumption by many breeders and prospective owners is that the dog is passed for breeding, and if it is graded dysplastic the dog should not be bred. One problem with this dichotomized grading is that the dog may be bred or not bred on the basis of a result which may be a false negative or a false positive. GDC follows the practice of reporting certified dogs to respond to client requests.

The OFA has traditionally recognized this problem of inaccurate diagnosis by using three readers, knowing that not all readers will read the x-ray the same. This is not to fault the readers as we expect and know that readings can be different by one or even two grades, depending on the evaluators. A little reflection shows that the use of three readers does provide some degree of quality control but does little to improve the accuracy on a single dog. If the finding is close to a boundary, then there may be a 25 to 50% chance that the finding will be wrong. In fact the consistency provided by one reader may at times be preferable to the variation introduced by the selection of multiple readers. Some groups favor the use of a single reader, as is done in Sweden. GDC is reviewing the feasibility of providing the client with a choice of one reader rather than the traditional 3.

Although false positive or false negatives are of some concern in the genetics of hip dysplasia, the problem for many breeders is the affect on the sales of the pups. In many breeds the value of the pups is dependent on having certified parents and even grandparents. However, experience and analysis shows that a dog should not be ruled in or out of breeding solely on the basis of the phenotype of the hips, because multiple factors should influence that decision.

However, in the case of a single gene disease, PRA, a false negative is of great concern. The reason is that one affected progeny shows that the parent is a carrier and hence, a single false negative may encourage the breeding of a dog that is a carrier with the resulting wide spread dissemination of PRA genes.

Probabilities

The breeding of dogs remains an art which can be enhanced by the assiduous use of the statistical information which is available from the GDC open registry. The more information in the registry about siblings and offspring the better will be the results. If there are enough cases an analytical approach can be helpful, but can not replace a breeder's knowledge of the whole dog.

mep 5/27/95

7/25/99

 

 

Appendix B

GLOSSARY OF TERMS

_ This symbol appears in the disease columns if the test is not known to be important for that breed, but one or more dogs have been tested.
This symbol may appear for a breed even if it is known that the disease is genetic in another breed. For example, the mode of inheritance of SA is known for Standard Poodles, but has not been shown to be hereditary in Bernese Mountain Dogs. If it is shown to be genetic in BMDs and is deemed to be important the classification will be changed to ^, and the column will appear on each BMD KinReport.
^ This symbol appears in the disease columns, if the test is recommended for that breed, either by the breed club or is documented as being genetic and is generally considered to be important. Recommended test will be added to each breed as more information is available. Not all possible tests will be added to allow focus on the important diseases.
? If the question mark appears in the Litter Size column it indicates that the owner has not supplied the number of puppies.
A, B, or C The code which tells that the evaluation could not be completed and a repeat is recommended. If the test was repeated the diagnoses will replace the letter code.
Bil Bilateral Dysplasia:
Used primarily in orthopedic evaluations to indicate that the manifestations of the disease show on both joints.
Uni Unilateral Dysplasia
This usually indicates a milder classification. The joint will be classified as affected, and no certification number will be issued.
CMO Craneomandibular osteopathy.
A disease that affects some terrier breeds.
Dam Number The unique number assigned by the GDC computer for the dam of the dog. This number provides the computer linkage to progeny and to pedigree.
Dog Number The unique number assigned by the GDC computer to the dog. This number provides the computer linkage to progeny and to pedigree.
Drwf Chondrodysplasia:
Currently a research data base for dwarfism
Elbows Elbow joints:
The general category for orthopedic diseases of the elbow joints. The details of the disease have been presented on the GDC evaluation form which went to the owner and veterinarian.
Aff Affected:
The evaluation of the site shows that the dog is affected with the disease, and is certain have the deleterious genes. No further testing is required, even if the dog's age is less than the usual certification age. In some diseases, like SA, the result may be sensitive to the site of the biopsy. In this case, the diagnoses will be based on the sample that shows the disease, and will not be changed with subsequent testing. In the case of hip dysplasia, the dog will be classified as dysplastic, even if only one hip shows malformation or arthrosis. The dog will not be issued a GDC certification number.
Eplp Idiopathic Epilepsy:
Currently an all breed research data base. The affected dogs are identified by a questionnair.
Eyes Eye diseases:
The general category for eye diseases. The specific diseases, progressive retinal atrophy (PRA), cataracts (Ctrct), retinal dysplasia (RD), corneal dystrophy (CDyst), and entropian eyelids (Entrp) will be listed.
Hips Hip joints:
The general category for orthopedic diseases of the hip joints. The details of the disease and the grading have been presented on the GDC evaluation form which went to the owner.
Hist Histiocytosis:
A tumor type which is known to be genetic in the BMD. Tumor types which are in the research data base will not appear in the tumor column.
L-P Legg-Perthes disease:
An orthopedic disease of the hips
SA Sebaceous Adenitis:
A skin disease affecting the sebaceous glands.
Shld Shoulder joints:
The general category for orthopedic diseases of the shoulder joints. The details of the disease have been presented on the GDC evaluation form which went to the owner.
Sire Number Number The unique number assigned by the GDC computer for the sire of a dog. This number provides the computer linkage to progeny and to pedigree.
Mast Mastocytoma (mast cell tumors):
A tumor type which is known to be genetic in the BMD. Tumor types which are in the research data base will not appear in the tumor column.
MPL Medial patellar luxation:
A disease of the knee.
Stfls Stifles or knee joints:
The general category for orthopedic diseases of the knee joints. The details of the disease have been presented on the GDC evaluation form which went to the owner.
Tarsus Tarsus or hock joints:
The general category for orthopedic diseases of the hocks joints. The details of the disease have been presented on the GDC evaluation form which went to the owner.
Tumor Tumors or cancer:
A registry of tumors that have been diagnosed histologically. There is no unaffected category in the registry as it is not practical at this time to carry out a screening procedure. All of the tumors other than Histiocytosis and Mastocytoma are carried in the research data base and not reported on the KinReport. Seventy different tumor types are in the research data base.
Uni Unilaterally Dysplastic:
Used primarily in orthopedic evaluations to indicate that the manifestations of the disease show on only one joint. This usually indicates a milder classification. The joint will be classified as a affected and no certification number will be issued.
Unaff Unaffected:Tarsus or hock joints:
Appears in a disease column, if the test showed no evidence of the disease at the time the evaluation was preformed. The dog will have been issued an GDC certification.
Yng Young:
This dog was below the age for certification by GDC, but did not show a signs of the disease. A later examination is recommended.
5/95 Recheck Date:
An Unaffected evaluation for the late onset single gene diseases, like PRA and SA, will carry a date. This date signifies when a recheck is due, usually 1 year. An unaffected grade before the date of recheck date does not signify that the dog is currently free of the unwanted genes. It simply means that a recheck is recommended.


Appendix C

PRA TRAIT VS. PRA DISEASE

Dogs with PRA trait only do not have and will not get PRA disease, but they can pass it on to their offspring if their mate also has PRA trait or has PRA disease. The possibilities for a pup's eyes depending on the parents' traits are (1) shown below:

(Key)

*

1 -Parents: AA + A a      Genetically clear + carrier of trait
    Puppies: AA, Aa,AA Aa      2 genetically clear, 2 unaffected carriers

Case 1 shows the difficulty of identifying the genetically clear from the carriers

2 - Parents: AA + aa      Genetically clear + affected
    Puppies: Aa, Aa, Aa, Aa      4 unaffected but all carriers

Case 2 shows why an affected dog should never be bred unless the puppies are neutered or given limited AKC registration. The puppies are healthy but the carriers can spread throughout the breed.

3 - Parents: Aa + Aa       Unaffected carrier + unaffected carrier
     Puppies: AA, Aa, Aa, aa      1 clear, 2 carriers, 1 affected

Case 3 is most common, the problem is that the clear dog can not be identified from its phenotype. This is a case of breeding normal to normal, as in the mass selection procedure.

4 - Parents: Aa + aa      Carrier + Affected
     Puppies: Aa, Aa, aa, aa      2 carriers, 2 affected

Case 4 as no genetically clear dogs as offspring.This case is to avoided.

5 - Parents: aa + aa      Affected + Affected
     Puppies: aa, aa, aa, aa      4 affected

Case 5 is the worst of all possible choices.

6 - Parents: AA + AA      Clear + Clear
     Puppies: AA, AA, AA, AA      4 clear

Case 6 is the best of all possible choices and is the goal for genetic disease control.

This was modified from a chart on sickle cell anemia in humans which appeared in the March 05, 1995 Los Angles Times. Much of the science of genetics comes from human medical research and is then applied to animals. Sickle cell anemia and PRA are both autosomal recessive traits that share the same genetic rules. Polygenic diseases, e.g. hip dysplasia, do not fit this model exactly, yet there is some commonality which helps provide insight to the process.