Amy Young

Amy Young is a geneticist at the University of California, Davis; her article on commercial DNA breed tests appeared in the Sept/Oct '08 issue of Bark.

Culture: Science & History
DNA Testing
Which DNA test should you choose to settle the “what’s in the mix” question?

For years, you’ve argued with your spouse that the 60-pound, black-and-tan tennis ball–chaser who takes you for walks and sweeps the coffee table clean with his tail is a German Shepherd mix, and that there is absolutely no Doberman Pinscher in there. Finally, in order to end the breed debate once and for all and restore peace to your household, you’ve decided to settle the question with a mixed-breed analysis test.

You’ve heard of the “swab test” and the “blood test” and know that both claim to unravel breed ancestry. With a little more research, you discover that the world of canine heritage tests has expanded since the first tests became available in 2007. Having a choice is great, but how do you go about comparing them and choosing the one that’s right for you?

There are several factors to consider, including the type of sample required, the number of breeds that can be identified, costs, turnaround times and the way the results are reported. Before you commit to a test that will decide the outcome of the German Shepherd/Doberman Pinscher battle, be sure you understand what you’ll be getting.

MetaMorphix Inc. (MMI) Genomics administers the Canine HeritageTM Breed Test, commonly referred to as “the swab test,” and Mars Veterinary provides “the blood test,” the Wisdom PanelTM MX Mixed Breed Analysis. These two companies have been considered the main players in this market, but new contenders are flocking to the scene. The most recent challengers are DNA Print Genomics, which offers the Doggie DNA Print, and BioPet Vet Lab, which recently unveiled the Dog DNA Breed Identification Test. Both use cheek swab samples.

The swab sample has the advantage of a collection procedure that is simple enough to be done by the owner at home. It does have some drawbacks, however, including a risk of contamination and too few cells being obtained for successful testing. To avoid the latter, BioPet Vet Lab includes a card that changes color to indicate that a sufficient sample is present. Blood samples are collected by a veterinarian and the chances of contamination and inadequate sample size are greatly reduced.

Tests also differ in the number of breeds available for comparison. Mars Veterinary interrogates the genetic signatures of more than 130 of the 159 breeds recognized by the American Kennel Club (AKC).* MMI Genomics recently announced the XL version of their test, which has a database of more than 100 breeds. The breed list available for BioPet Vet Lab contains 58 breeds. DNA Print Genomics does not report specific breed matches; rather, “15 elements of dog ancestry” are revealed, and the customer performs a search of the company’s online database to identify matches to particular breeds. Since each test interrogates a different set of breeds, sending your dog’s sample to more than one company may not return identical results.

Cost and turnaround times vary from test to test. In the past, the cost of the Wisdom Panel MX Mixed Breed Analysis test was determined solely by individual veterinary clinics, but the test can now be purchased online for $124.99, and test results are available within three to four weeks. (Your veterinarian will still have to draw the blood sample.) The swab tests are sent directly to the owners for sample collection, and prices and turnaround times vary: Doggie DNA Print, $199, six to nine weeks; Canine Heritage XL Breed Test, $119.95, four weeks (if you submitted a sample for the original version of the Canine Heritage Breed Test, you can purchase an upgrade to the XL version for $55 online); and the Dog DNA Breed Identification Test, $57.95 to $59.99, two weeks. (Prices current at press time.)

Results are presented as a certificate or report, depending on the company. MMI Genomics provides owners with a Certificate of DNA Breed Analysis. Three breed categories are included in the results: Primary, Secondary and In the Mix. BioPet Vet Lab’s Ancestry Analysis Certificate reports breeds in your dog’s genetic background in order of prevalence; a paragraph about each breed as well as a behavior, health and personality summary are included.

A report from DNA Print Genomics includes genotypes, ancestral population results and 15-N population results. Ancestral population results indicate your dog’s relationship to each of the four most basic branches of the canine family tree—wolf-like, hunters, herders and Mastiffs—while 15-N population results are a set of numbers that compare a sample to groups of breed signatures in the database. Each owner is given an ID and password that are used to query the online database for matches to specific breeds.

The Mars Veterinary report presents images of the breeds present in your dog’s ancestry, with the relative size of the image indicating the prevalence of each breed. An appearance, behavior and history section describes characteristics of each identified breed that might be seen in your dog.

As the companies run more tests and add breeds to their databases, the accuracy of the results may improve. It is also possible that even more companies will enter the canine breed ancestry DNA test field. When deciding where your dog’s sample will be submitted, determine what you want to learn and educate yourself about each of the tests. All of the companies agree that working with your veterinarian will ensure that you get the most out of your results. Who knows, choosing the test that best matches your needs could do more than just earn you a victory in the great German Shepherd/Doberman Pinscher debate!

*None of these tests are designed to identify purebred dogs, and the AKC will not accept test results for registration purposes.

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Culture: Science & History
DNA Test Helps Dalmatians
Researchers identify gene that causes bladder stones

How do you recognize a Dalmatian? If you think of the movie 101 Dalmatians or the dog who traditionally rides on the fire engine, it’s easy. Dalmatians are, of course, known for their characteristic spots— breeders have spent many years selecting for dogs with spotting patterns that fit the ideal breed standard: evenly distributed, distinct, well-defined round spots that are larger than a dime but smaller than a half dollar. However, sometimes the bad unexpectedly comes along with the good. Breeding for these patterns has brought with it a predisposition to form bladder stones, a condition that is potentially life threatening. Now, with the help of a special group of Dalmatians and some dedicated breeders, scientists have unearthed the cause of this condition and designed a DNA test that will not only improve Dalmatian health, but will benefit other dogs as well.

In most dogs, the proteins in food are broken down in the liver, and the byproduct, allantoin, is excreted by the kidneys into the urine, where it dissolves. In Dalmatians, the process stops at the step before the production of allantoin; instead, uric acid is produced. Because uric acid does not dissolve well in urine, it can form urate stones in the bladder, and these stones can block the urethra; in serious cases, this condition requires surgery to resolve. The accumulation of high levels of uric acid in the urine is called hyperuricosuria (huu).

Huu, which was first described in 1916, was shown in 1938 to have a recessive mode of inheritance (an individual must have two copies of the mutation to be affected). All Dalmatians carry two copies of the huu mutation, meaning that within the purebred Dalmatian population, there is no way to breed dogs with low levels of uric acid because the trait does not exist in their gene pool. Consequently, Dalmatians produce 20 times more uric acid per day than other dogs and are prone to urate stones. (Interestingly, although all Dalmatians have high levels of uric acid, not all exhibit clinical disease. The reason for this is unknown.)

In order to correct this condition, a normal, low-uric-acid copy of the gene had to be introduced into the gene pool. In 1973, Dr. Robert Schaible, a medical geneticist and Dalmatian breeder, bred a Dalmatian to a Pointer and then bred the offspring back to purebred Dalmatians. The goal of this backcross was to produce dogs who looked and acted like Dalmatians, but who had normal (i.e., low) uric acid levels in their urine and therefore would not produce bladder stones. Each time one of these backcross Dalmatians (with low levels of uric acid, or LUA dogs) is bred to a purebred Dalmatian (with high levels of uric acid, or HUA dogs), about 50 percent of the puppies are LUA and 50 percent are HUA.

LUA dogs tend to have smaller spots than HUA dogs, providing further evidence that the huu mutation was unintentionally selected for along with the deliberate selection for spot patterns. Although the spots on LUA dogs are generally smaller, they still fall within the guidelines of the Dalmatian standard as outlined by the American Kennel Club (AKC).

Two backcross Dalmatian puppies from the fifth generation were registered with the AKC, which meant that they could be shown in AKC-recognized events. The registration was later opposed, and further registration of backcross dogs was prohibited. The issue of AKC backcross Dalmatian registration continues to be controversial and emotional. Backcross Dalmatians can be registered with the United Kennel Club.

Since most serious breeders register their dogs with the AKC, the number of purebred Dalmatians available to backcross breeders became severely limited because the puppies were not eligible for AKC registration. By 2005, after 30 years of work, few breeders were using backcross dogs in their programs, and Dr. Schaible was limited by the number of dogs he could keep himself, factors that suggested the project was nearing an end. Around that time, Denise Powell, a northern California Dalmatian breeder for more than 20 years, contacted Dr. Schaible to inquire about breeding backcross Dalmatians. “I was shocked to learn that he had just two aging stud dogs and two infant female pups,” says Powell. “I decided then and there to do what I could to help preserve the only line of LUA Dalmatians in the world from dying out. I asked, and Bob agreed to let me have one of the two pups.”

Powell’s dedication led to the creation of the Dalmatian Heritage Project, which in turn sparked the involvement of other Dalmatian breeders and the expansion of the backcross population. Current descendants of the original cross represent the 12th generation of the family. There is only one Pointer out of more than 4,000 relatives in the pedigrees of the backcross dogs, which makes them more than 99 percent Dalmatian.

Backcross dogs undergo all the health screenings recommended for AKCregistered Dalmatians, including Brainstem Auditory Evoked Response (BAER) hearing testing, temperament analysis, conformational analysis and, in some cases, Orthopedic Foundation for Animals (OFA) hip exams and Canine Eye Registration Foundation (CERF) eye evaluations.

Danika L. Bannasch, DVM, PhD, associate professor of genetics at the University of California, Davis, School of Veterinary Medicine—and Dalmatian owner and former breeder—became involved with the project in 1998. Using blood samples and pedigree information from generations of backcross Dalmatians, Dr. Bannasch and her colleagues recently identified a mutation in the SLC2A9 gene that causes huu in Dalmatians. The mutation correlates perfectly with a dog’s huu status: Only HUA dogs have two copies of the mutation. “The biggest challenge to finding the genetic cause for huu in Dalmatians was the fact that the trait is fixed in the breed,” says Bannasch.“If we didn’t have the backcross, it would have been impossible to do.”

The scientific data reporting the identification of the huu mutation has been published in the peer-reviewed genetics journal of the Public Library of Science (PLoS), and a DNA test for the mutation is now available through the Veterinary Genetics Laboratory at UC Davis. Previously, a laborious and expensive urine test was required to determine whether a dog was LUA or HUA. The DNA test eliminates the need for the urine test and makes selection easier in the backcross Dalmatians.

The positive impact of this genetic discovery extends beyond Dalmatians. High levels of uric acid and urate stone formation have been reported in individuals from other breeds, including Bulldogs and Black Russian Terriers. Testing in Dr. Bannasch’s laboratory has confirmed that the mutation responsible for huu in these breeds is the same one identified in Dalmatians.

“Now we have a means for identifying the probable major cause for urate disease in dogs,”says Bannasch.“If you know your dog is predisposed to form bladder stones, you can alter things about their management and be aware of the signs of stone disease.”

The huu mystery described in Dalmatians more than 90 years ago has been solved through visionary thinking and tireless dedication. Advances in genetics enabled the creation of a DNA test that will benefit not only Dalmatians, but other dogs as well. The story of the backcross Dalmatians exemplifies the profound impact on canine health that breeders, owners, veterinarians and scientists can achieve by working together.