Originally published in Kittens USA 2011
In 1953, James Watson and Francis Crick reported their discovery of the double helical structure of DNA in the journal Nature. Their discovery finally provided a model to explain the molecular basis of inheritance and revolutionized the medical and scientific world. However, no one would have guessed that in 50 years, the role of DNA would become so widespread that the word DNA would enter our popular vocabulary and would no longer be confined to science textbooks and academic circles. Today, doctors both in real-life and in television shows like House can order DNA tests to diagnose hereditary diseases. DNA has also become an important piece of forensic evidence, as seen in popular shows like C.S.I., and in actual courtrooms, where it can be used to convict the guilty and exonerate the innocent. More recently, DNA tests have even become available for pet parents to test their dogs or cats. Unfortunately, there is much confusion about what these tests can accomplish, especially in regards to cats. To better understand their uses and limitations, cat parents need to understand a little about DNA and what DNA tests actually do.
DNA, short for deoxyribonucleic acid, exists as two strands wound together in a double helix. DNA contains chemical groups called bases that hold the strands together and more importantly, encode genetic information. To understand how DNA holds the genetic code and how genetic information is organized, it helps to use the analogy of a cookbook. The sequence of bases encodes genetic information much like the order of letters make words. A gene is analogous to a recipe and represents a segment of DNA that contains the genetic information necessary to make a protein. Mutations are changes in the instructions that alter the structure or function of the protein and cause disease. Polymorphisms are variations of the gene that do not cause disease, like the differences in the color of your eyes.
Genetic testing uses various molecular techniques to examine DNA for mutations or polymorphisms. In cats, DNA testing can be used to diagnose inherited diseases, to look for specific traits, and to establish lineage. A mouth swab is used to collect DNA, and the small amount of DNA is amplified using a molecular technique called polymerase chain reaction (PCR). Currently, commercially available feline genetic tests can test for mutations that cause hypertrophic cardiomyopathy (HCM), polycystic kidney disease (PKD), and mucopolysaccharidoses. Genetic tests also look for specific traits, like the color albino, cinnamon-red, and color points in Siamese and Burmese cats.
HCM is a good example of the uses, and limitations, of genetic testing. HCM is the most common form of heart disease in cats. It causes hypertrophy, or thickening, of the heart wall and ultimately causes heart failure and death. The inherited form of HCM can be caused by mutations in the MYBPC3 gene and is common in certain breeds, such as the Ragdoll and Maine Coon cat. However, HCM is caused by different mutations of the same gene in the Ragdoll and Maine Coon breeds. So what does it mean if you order a genetic test for MYBPC3 and the results are negative? To begin with, there are many forms and causes of HCM, so a “negative” test does not necessarily mean that a cat does not have HCM. Instead, it simply means that the cat does not have the tested mutation in the tested gene MYBPC3. “DNA tests identify the mutation, not a functioning gene,” says Jerold S. Bell, DVM, Clinical Associate Professor of Genetics at Tufts Cummings School of Veterinary Medicine. While a positive test can make a definitive diagnosis, a negative test does not always exclude a genetic disease. Likewise, finding a polymorphism, which is an alteration of the DNA not associated with disease, leads to an inconclusive result since it neither excludes nor diagnoses a disease. Finally, depending on the molecular technique used in the test, some types of mutations, like having a large deletion of DNA from a gene, may be entirely missed.
However, genetic testing can be instrumental in the right context. In breeds with known predispositions to inherited diseases, genetic testing can be used to specifically look for these genetic disorders. These test results can help breeders make informed decisions about their breeding program and may help them eliminate these genetic disorders from a particular breed. For example, PKD is an inherited kidney disease that is more common in Persians and Exotic Shorthairs. With PKD, cysts develop in the kidney and ultimately cause kidney failure as they enlarge and compromise kidney function. Breeders of Persians and Exotic Shorthairs can insure their breeding program is PKD-free by testing their cats for the PKD gene mutation. Likewise, a pet parent of a cat from a breed with a known predisposition to a genetic disease can test their cat for the genetic mutation. The discovery of a mutation like MYBPC3 in Maine Coon cats may prompt their veterinarian to screen the cat for congestive heart failure earlier and more frequently. According to Leslie A. Lyons, PhD, Associate Professor of Population Health and Reproduction from the University of California, Davis, “DNA testing can really help breeders make better breeding decisions and give their clients more information about their cats, whether that be about PKD or other disease mutations.” Dr. Bell agrees and says, “DNA testing should be used in all cats from breeds where a mutation has been identified.”
Besides testing for genetic diseases, DNA can be used to establish paternity. Every individual has a unique set of genetic markers that act like a genetic fingerprint, with 50% of these markers being paternally-derived and 50% maternally-derived. Looking at the genetic fingerprint of two cats can determine their relatedness. This can be useful for cat breeders when there is doubt about the parentage of a litter, if a mating was not witnessed, or if they are concerned that the female cat was exposed to multiple males during her heat cycle.
Finally, many pet parents wish to test their pet’s DNA to determine their breed make-up. While Mars has a DNA test available for dogs to determine their breed make-up, a similar test for cats is currently not available. However, Mars has plans to develop such a test for cats. You may one day find out if your cat’s vocal personality is due to his Siamese “genes”. The future of genetic testing is even more promising. According to Dr. Lyons, “In the near future, DNA tests will be able to screen for diseases like hyperthyroid disease, obesity, asthma, diabetes and even susceptibility towards infectious diseases.” Pet parents will be able to use this information to tailor their pet’s healthcare and lifestyle based on their genetic risk profile. Genetic markers may even be used to determine which particular therapies are likely to work best for your particular pet. For now, DNA testing is a useful tool for breeders and cat parents of high-risk breeds, like Persians, Ragdolls and Maine Coon cats, and will help them make informed decisions about possible breedings and their cat’s healthcare. If you are getting a breed of cat predisposed to genetic diseases, ask the breeder if they have tested their cats to insure that they are disease free.
For more information about whether DNA testing may be beneficial for your cat’s health speak to your veterinarian and go to: www.catgenes.org.