SHIH TZU FANCIERS OF SOUTHERN CA

FREQUENTLY ASKED QUESTIONS

What is a gene? The gene is the basic unit of heredity. Each gene, acting alone or with other genes, determines one or more canine characteristic. All of the genes that constitute the hereditary makeup of an organism are called the genome. Genes occur in strands of genetic material within the cell called chromosomes. A dog is composed of a large number of cells that are genetically identical. The first cell of a particular dog formed when egg and sperm united contains one set of chromosomes form each parent. The canine genome is made up of 39 pairs of chromosomes (one set form each parent) that contain approximately 3 billion base pairs of DNA, or about 100,000 or so genes. Each gene generally occupies a particular position within a particular chromosome.

What is DNA? The chromosome is made up of two very long single strands of a chemical called DNA (deoxyribonucleic acid) that are wrapped around each other to form a double helix. This DNA never leaves the nucleus of the cell--it is like a reference library that contains the genes (functional) regions) that determine how the organism will develop. DNA strands are made up of 4 basic units linked together in pairs. The entire canine genome contains about 3 billion base pairs. A small gene may contain 100 of these base pairs; a larger one may contain 10,000 base pairs.

What is a genetic marker? Scattered throughout the chromosome are short repeated groups of these base pairs known as micro-satellites, or markers, that can be used to track defective genes. Hundreds of these distinctive sequences have been isolated along the canine genome for use in mapping genes. To find a marker that is "linked" to a disease, researchers may examine hundreds of markers from animals with and without the disease before they find one that is located so close to a disease gene that it is almost always inherited along with the disease caused by that gene. The closer the marker is to the disease gene itself, the more accurate the test. Finding such a marker narrows down where to look for the disease-causing gene, which could ultimately lead to a more specific test for the gene itself. 

What is a mutation? A mutation is a genetic mistake that scrambles the instructions given by a gene. Mutations may be good, bad, or indifferent. In the case of renal dysplasia, it is believed the presence of mutations in one or perhaps two different genes causes the glomerule of the kidney to stop developing.

What are dominant and recessive genes? A dominant gene will express itself when the puppy inherits only one copy of the gene (from sire or dam). If a disease-causing gene is recessive, a dog with the gene can be bred to a dog without it and will not produce the disease, although it will produce carriers of the gene. If the gene is dormant, both parents must be free of it to avoid producing affected puppies. Again, more than one defective gene may be needed to produce a disease.

What is the two gene theory of renal dysplasia inheritance? Researchers believe that renal dysplasia is probably caused by the presence of two defective genes rather than one (although it may be cause by a single dominant gene that is affected by other factors--i.e. has incomplete penetrance.) The two-gene theory, with one of the genes being dominant and the other recessive, would explain many of the mysteries of RD. Imagine that RD is a door with two locks, the regular door lock and a deadbolt lock. In order to open the door, you will need two keys. But you need the right two keys. Two door keys or two deadbolt keys will not do it. If you mate a dog with RD1 to a bitch with RD1, the puppies will have normal kidneys. If your dogs are highly line bred, and therefore highly homozygous for RD1, you will not have a problem until you outcross to a line with RD2. This would explain how a breeder can go along with healthy dogs for many years and suddenly have a whole litter with renal dysplasia. It would also explain the rare case in which two dogs were biopsied clear produced affected puppies. Even if two defective genes are involved, we only need to identify and eliminate one of these genes to avoid producing any affected Shih Tzu. The new VetGen linked marker test for one of these defective genes is a major step in that direction.

What about the genetics of JRD? Shouldn't the actual underlying genetic situation be known before breeders act? The underlying genetics of JRD is not known at present, and may not be known for some time. Theories include:

1) That abnormalities in two genes, one dominant and one recessive, must simultaneously be present.

2) That a common dominant gene with incomplete penetrance is responsible, but it is affected by other factors (called incomplete penetrance).

3. That an even more common recessive gene, again with incomplete penetrance is responsible.

Any of these theories could be correct because once you invoke incomplete penetrance, differentiation between theories becomes difficult. However, for purposes of using this test, the underlying genetic mechanism is not relevant. What you have is a marker that when present indicates a greatly increased risk, and when absent, indicates a greatly reduced risk. It does not matter at this point whether it is predicting a mutation in one of two required genes, a mutation in a dominant gene, or a mutation in a recessive gene. Its applicability is exactly the same.

If we reduce the M allele frequency significantly, would we have a significant negative impact on genetic diversity in any of the breeds? A gradual reduction of an allele that has about a 30% frequency is not a risk to diversity. Also it is unlikely that all breeders will embrace the test simultaneously. Some breeders will eliminate or greatly reduce the M marker; others will do this to some extent, while others will ignore it. This mix of responses will minimize any impact. Keep in mind that when the genetic defect is found, it will probably have a relatively high frequency, putting the breed in exactly the same situation.

What about the cost of the test? Why should as marker test that is 80% predictive cost as much as a direct test of the mutation that is 100% predictive? The cost is not based on a differential value to the breeder, but on the costs of providing the service and the cost of research to develop the information to develop the test. VetGen has yet to make a profit on any test it has offered. 

For individual tests contact VetGen at HealthyDog@bizserv.com or 1-800-483-8436, or go to the VetGen website http://www.VetGen.com for an order form and more information. Every DNA sample sent directly to VetGen is coded upon receipt, making references to specific dog's identity and genetic status entirely confidential between VetGen and the owner of the dog.

For additional information go to the ASTC website: http://www.shihtzu.org

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