Inherited traits, desirable or not, are controlled by the genetic make- up (genotype) of the individual dog or cat. The genotype is determined by the genes received from the parents, one-half from the sire and one-half from the dam. Most inherited traits in animals are polygenic. Some examples are: conformation, type, size, longevity, disease resistance, temperament, speed, milk and egg production, growth rate, maturation and sexual maturity rate, and numerous inherited diseases.
Intuitively, it is recognized that these traits do not follow inheritance patterns based on simple Mendelian genetics. Mendelian genetics usually uses one pair of genes to explain basic genetic principles. For example, assume that:
1) The color black is dominant to brown,
2) The black gene is represented by B and the brown gene by b, and
3) a homozygous black (BB) is mated with a brown (bb). All of the offspring will be black, but will have the heterozygous Bb genotype. If two heterozygous blacks (Bb) are mated, Mendelian genetics predicts the offspring are expected to be three black (1 BB and 2 Bb) and one brown (bb).
The ratio of 1:2:1 for the genotypes is based on probability. If only a small number of offspring are available from this type of mating, they may not fall within the ratio, but larger numbers will produce the predicted results. In addition, the finding of one brown offspring from the mating of black parents indicates that both parents are carriers (heterozygous Bb) of the recessive brown gene. In such a case, two out of three black offspring are also carriers, but until they are bred it is uncertain which are the carriers. In the above example of simple Mendelian genetics, the probable genotype of the parents can be determined by examination of the progeny.
However, polygenic traits, such as most characteristics that breeders are concerned with, are defined as those affected by multiple gene pairs. An oversimplified example is two genes affecting the same trait. Assume the mating of two dogs with genotypes of AaBb where the dominant alleles "A" and "B" are desirable. The expected genotypic outcome is nine different genotypes with the following frequencies:
Only 25% of the progeny from this mating are expected to have the same genotype for the trait as the parents. Some of the remaining progeny will have a more desirable genotype (AABB, AABb, AaBB) while others will have a less desirable genotype for the trait (Aabb, AAbb, aaBB, aaBb, aabb). As the number of genes involved increases, the possible combinations soar. The problem is further magnified if each gene pair exerts a different degree of influence on a trait to produce an "additive" result. It is currently impossible to precisely predict the specific outcome of a particular mating with regard to polygenic (additive) traits and probabilities can only be generally estimated.
However, animal geneticists have developed successful breeding programs to improve milk production in cows, egg production in hens, speed in horses, growth rate in food animals, etc. They use basic genetic principles that have also been demonstrated effective in the dog. Some of the following aspects of polygenic traits considered in arriving at these principles include:
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Polygenic traits have a range of manifestations from the most desirable to the least desirable characteristic under consideration.
For example, mating two dogs of ideal conformation can be expected to result in a larger number of offspring with ideal conformation when compared with offspring of a mating where one or both parents have less than ideal conformation. However, both litters will present a range of conformational characteristics.
Polygenic traits are influenced by environmental factors which may minimize or maximize genetic potential.
For example, a horse with a respiratory infection will not be able to achieve its genetic speed capability, or a cow on a starvation diet will not produce milk to its full genetic potential.
Heritability measures the phenotypic expression of multiple genes as possibly modified by environmental influences and the degree to which the resulting phenotype predicts the genotype. The equation P (phenotype) = G (genetics) + E (environment) is a starting point. This equation means the variation in phenotype presented comes about from the complex interaction of the animal's own inherited genotype with the environment to which it has been exposed. Using hip dysplasia (HD) as an example, some environmental factors include, but are not limited to, overweight, rapid growth rate, early maturation, sex of the animal, etc. The most studied environmental influence on HD is caloric intake.
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It is important to understand that heritability estimates do not refer to the degree of inheritance, but rather to the degree that the additive genetic component is reflected in the phenotype.
This is easier to understand using a trait for which most people have a greater intuitive grasp. In dogs, wither height is a polygenic trait that may be modified by the environment. Height may be influenced by restricting calorie or vitamin intake, certain environmental effects on hormones (such as early spay/neuter), and other environmental factors. Despite those potential environmental influences, height is recognized to be an inherited trait. However, one cannot accurately predict the height of an offspring by knowing the height of parents or siblings. This is because polygenic traits have many complex genetic interactions, in addition to their interactions with the environment. Thus, when one is only able to measure the height of parents or siblings, one is measuring their phenotypes, and not able to consider their genotypes and the various possible interactions of those genes. It may be helpful to substitute "predictability" for "heritability" to further clarify this concept.
Heritability estimates are usually determined through mid-parent offspring analysis using statistical methods and express the reliability of the phenotype as a guide to the predictive breeding value of the animal. Heritability estimates are reported on a scale from 0 to 1.0 (0-100%). These are expected to vary depending on the genetic background of the studied breed population and will change over time through selective breeding.
If the heritability estimate for a given trait is 0.1, it is generally considered low and the animal's phenotype is not a good indicator of the genotype (breeding value). Genetic selection based on a single phenotype would yield poor results. Although difficult to obtain for most hobby breeders, phenotypic information on many offspring raised in different environments (progeny testing) would offer additional insight into the parent's genotype.
If it is between 0.2 and 0.3, the heritability estimate is generally considered moderate. The animal's phenotype predicts its genetic makeup to a reasonable degree, and genetic selection based on the individual animal's phenotype is expected to yield slow yet substantial results. However, more rapid results can be achieved if phenotypic information on relatives (pedigree depth and breadth) is also considered. This also increases the accuracy in predicting the animal's breeding value and aids in identifying carrier animals.
If the heritability estimate is between 0.4 and 1.0, it is generally considered high and the animal's phenotype is a good predictor of its genetic makeup. In this case, rapid results can be obtained with genetic selection based on phenotype.
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Breeding based on individual phenotypes appears to be the method used by most breeders, as available information on relatives is somewhat limited. For traits considered to have moderate heritability, this approach will reduce the frequency of an undesirable trait in the progeny, but progress, while substantial, will be slow.
Information on siblings of an individual animal, plus information on the siblings of parents and grandparents, makes it possible for the breeder to apply greater selection pressure against the disease. This results in selection of animals with more ideal breeding values and provides a more rapid reduction of the undesirable trait in the breeding program.
The following breeding selection criteria have been demonstrated to more rapidly and effectively reduce the frequency of undesirable traits:
1. Breed only normal dogs to normal dogs
Using hip dysplasia as an example, Table 1 illustrates the outcome of matings based on information extracted from the OFA database. A total of 152,589 progeny were identified where both parents had hip conformation ratings. The percentage of dysplastic progeny increased as the sire's and dam's phenotypic hip ratings decreased from excellent through dysplastic. Reed (2000) reported equal genetic contribution on progeny hip scores from the sire and dam.
Table 1: Mating Probability
Based on 152,589 progeny in the OFA Hip database with known sire and dam hip scores:
||T = 5,835
N = 5,630 (96.5%)
D = 205 (3.5%)
|T = 16,315
N = 15,481 (94.9%)
D = 834 (5.1%)
|T = 1,931
N = 1,782 (92.3%)
D = 149 (7.7%)
|T = 362
N = 308 (85.1%)
D = 54 (14.9%)
||T = 17,281
N = 16,291 (94.3%)
D = 990 (5.7%)
|T = 69,041
N = 63,346 (91.8%)
D = 5,695 (8.2%)
|T = 12,008
N = 10,566 (88.0%)
D = 1,442 (12.0%)
|T = 1,826
N = 1,525 (83.5%)
D = 301 (16.5%)
||T = 3,146
N = 2,888 (91.8%)
D = 258 (8.2%)
|T = 15,475
N = 13,581 (87.8%)
D = 1,894 (12.2%)
|T = 3,957
N = 3,311 (83.7%)
D = 646 (16.3%)
|T = 632
N = 456 (72.2%)
D = 176 (27.8%)
||T = 595
N = 528 (88.7%)
D = 67 (11.3%)
|T = 2,941
N = 2,394 (81.4%)
D = 547 (18.6%)
|T = 935
N = 698 (74.7%)
D = 237 (25.3%)
|T = 309
N = 197 (63.8%)
D = 112 (36.2%)
T = total number of progeny; N = number and percent of normal progeny; D = the number and percent dysplastic progeny.
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2. Breed normal dogs that come from normal parents and grandparents
This employs the traditional horizontal pedigree with emphasis on the most immediate three generations (50% genetic contribution from each parent, 25% from each grandparent and 12.5% from each great grandparent)
3. Breed normal dogs that have more than 75% normal siblings
This information is usually not available since most animals in a litter become pets and are not screened for undesirable traits. Breeders can add incentives to purchase contracts in an attempt to gather this information, such as offering reimbursement for a preliminary hip radiograph taken when the pet dog is spayed/neutered.
4. Select a dog that has a record of producing a higher than breed average percentage of normal progeny
If known, the comparison of production performance between individuals is an important criterion. For example, a stud dog with a track record of producing 90% normal progeny is far superior to another dog producing only 50% normal progeny.
5. Choose replacement animals that exceed the breed average
Exert constant, consistent pressure to ensure overall breed improvement.
In summary, achieving goals in breeding program depends upon the ability to assess an animal's predictive breeding value. Important information to assist breeders in achieving their goals is available on the OFA website through the database search option (www.offa.org)
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DNA genetic databases
DNA testing based on identification of a specific genetic mutation is the most accurate method of identification of an animal's genotype, and knowledge of the genotypic status is the breeder's most powerful tool for elimination of a genetic disease. There are several broad categories into which DNA tests may fall. The most straightforward are tests which definitively predict whether or not a dog will manifest a certain disease, and also predict the risk to its offspring. These include tests for simple recessive genes without complex modifiers (incomplete penetrance) or environmental interaction. Most current DNA tests fall into this category. Such tests can identify affected (homozygous for the disease alleles), carrier (phenotypically normal, but heterozygous with one disease allele and one normal allele), or clear (homozygous normal) dogs, both in adults for breeding purposes, and within litters to help determine the appropriate placement of a puppy. In the case of diseases caused by recessive genes, careful and knowledge- able breeding decisions and strategies may permit the use of carrier, or rarely, affected, animals in breeding programs for a short period of time. This enables the breeder to maintain desirable breed traits within a breeding program, while being assured of producing offspring that are phenotypically normal, and making rapid progress toward the goal of producing offspring that are genotypically normal.
DNA tests can also be used to detect genes that do have modifiers such as incomplete penetrance or environmental influences. In the case of dominant genes with modifiers, DNA tests could definitively detect which dogs have the abnormal gene, but this would not predict with certainty whether such a dog would actually develop the disease. It would, however, give accurate information with regard to the odds of the disease gene being passed to the next generation (although once again, not with certainty whether offspring will develop the disease). Perhaps equally as important, DNA tests could be done with litter age pups. This would enable breeders to place only pups who do not carry the disease gene at all into potential breeding situations, while those who test positive could be placed into non breeding homes. Remember, however, that when a dominant gene is involved, such a pup may develop the disease and have a compromised quality of life. The ability to use DNA testing to keep pups with abnormal genes out of breeding homes should never be thought of as a way to excuse breeding a dog that is capable of producing clinical disease, and the possibility of producing affected pups with these types of breedings must be given appropriate and compassionate weight. In the rare instance where desirable traits of an individual capable of producing disease, outweigh the undesirable genetic trait, a breeding should only be undertaken with a clear commitment to eliminate the disease gene in the next generation through diligent DNA testing.
DNA testing by linkage is not as accurate as that for identification of a specific genetic mutation, but it is still more desirable than existing tests based on phenotypic evaluations. While some minor degree of false positives and false negatives is possible, accuracy rates are usually above 95%.
The financial advantages of DNA testing and associated DNA profiling are clear. Tests are accurate, can be done at an early age, only one test is required and progeny can be cleared by parentage if DNA profiles are available for determination of parentage.
There are multiple genetic registries that utilize DNA based testing. All of these tests are more sensitive and specific for the detection of genetic disease traits than are phenotypic based tests. At this time, there are a limited number of breed-specific genetic tests. However, more and more tests will become available in the future. Call or check the OFA web site for breed specific DNA test availability.
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Currently available tests
Copper Toxicosis- A genetic disorder that affects several breeds and causes copper accumulation in the body which leads to liver disease.
von Willebrand's Disease- An inherited disease which causes dogs to be susceptible to abnormal bleeding following injuries or surgical procedures.
Phosphofructokinase Deficiency- A genetic deficiency which causes mild to moderate anemia with severe episodes of bleeding.
Progressive Retinal Atrophy- An inherited degenerative eye disorder that leads to blindness.
Pyruvate Kinase Deficiency- Pyruvate kinase is an enzyme that is normally found in red blood cells. When there is a deficiency of this enzyme red blood cells break down prematurely. This causes the dog to become anemic, exhibit a lack of energy, low exercise tolerance and probably reduced fertility.
Cystinuria- An inherited disorder which is characterized by stone formation in the kidney, urinary bladder, and urethra.
Globoid Cell Leukodystrophy- An inherited disorder which is characterized by progressive neurologic abnormalities occurring predominantly in the hind legs.
Congenital Stationary Night Blindness- Nonprogressive night blindness which is apparent by 5 to 6 weeks of age.
Renal Dysplasia- Inappropriate structures within the renal parenchyma resulting in renal failure as early as 3 to 6 months of age.
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Please contact the desired laboratory for testing procedures and fees.
Optigen 607-257-0301 www.optigen.com
PennGen 215-898-3375 www.vet.upenn.edu/penngen
VetGen 800-483-8436 www.VetGen.com
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The OFA serves as the central repository of DNA test results from approved laboratories for purposes of monitoring the disease and as a source of information for breeders, breed clubs, owners, prospective owners, and researchers. DNA application forms can be downloaded from the OFA website (www.offa.org). The owner or agent should complete and sign the OFA application form, and the information is best obtained directly from the animal's certificate or registration papers. It is also important to record the animal's tattoo or microchip number, and registration numbers of the sire and dam. The signed application form (which should include the owner's choice of open or semi-open database), a photocopy of the DNA test result and the service fee should be mailed to: Orthopedic Foundation for Animals, Inc., 2300 E. Nifong Blvd., Columbia, MO 65201-3856. There is a minimal cost to enter a clear or carrier in the data bank and sibling discount rates (3 or more sibs) are available. There is no charge to enter an affected individual as it is important for scientific analysis that affected information be entered into the database.
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