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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. 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
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.