Over the course of the past few years Mars Veterinary, Inc., has unveiled an array of commercial canine genetic tests that have the potential to alter drastically the dynamics of the world of purebred dogs. The five tests are: Wisdom Panel® Insights, a test intended to reveal the breed background of mixed-breed dogs; Wisdom Panel® Designer Dog, a similar test intended to confirm whether a presumed crossbred or "designer dog" is actually the progeny of two distinct purebred parents (versus a mongrel of undetermined parentage); Wisdom Panel® Professional, a veterinarian marketed and administered test intended to provide information on probable genetic origins and to reveal predispositions to genetic diseases; Wisdom Panel® Purebred, intended to confirm purebred status of a dog and to identify its breed; and Optimal Selection, a breeder-oriented test intended to evaluate heterozygosity and to help suggest advantageous matings.
Obviously this is a radically different style of genetic testing from the narrowly-focussed DNA marker tests already familiar to some of us, used to detect specific genetic disorders, or the microsatellite-based individual dog ID and parentage verification tests that have been familiar in the dog world for the last fifteen years or more. These new tests, based on SNP (single nucleotide polymorphism) markers, although they do not test the dog's entire genome, target broad arrays of SNP markers across as many as 25 chromosomes and use them to compare individual dogs with typical breed signatures of anywhere from 150 to 200+ dog breeds.
The Wisdom Panel® Purebred test is based upon a do-it-yourself cheek swab sampling procedure. A small nylon brush collects epithelial cells from the inside of your dog's mouth; the brush is mailed to Mars Veterinary where DNA from the collected cells is harvested and analysed by an automated procedure. A report is emailed back to the owner.
Wisdom Panel® Purebred performs what the company calls a Principal Component Analysis of an individual marker array and compares the result with the SNP markers found in a "cluster" of dogs typical of the breed to which the candidate animal is compared, to see if the animal's marker signature falls within the cluster typical of the breed as compared with an outgroup. Next, the sample is compared to the two next best matched breeds. Next, a pairwise comparison analysis is performed between the dog's DNA data and all other purebred dogs in the Wisdom Panel® database, to determine the most closely-matching breed in the top twenty best matches, out of some ten thousand dogs in the database. Finally the observed homozygosity of the candidate animal's DNA data is compared with the expected range of homozygosity for the breed requested.
The result, if the dog is confirmed as a purebred, is a strongly convincing body of DNA evidence associating the individual dog's DNA signature with that of a particular purebred dog breed. It should be pointed out that this is far more detailed and persuasive evidence than anything that can be provided by a kennel-club certificate of registration. If the conformity of an individual dog's DNA marker array with the unique signature of a single breed is close enough to cause Wisdom Panel®'s computer algorithms to confirm breed membership, what other evidence could possibly be produced to suggest that the animal in question is not a member of the breed suggested by the DNA evidence?
This test is currently priced at US$69.99 and at the time of writing is offered at a $20 discount. The price includes a breed ancestry chart, a detailed PCA analysis breakdown, an observed homozygosity estimate plotted against average homozygosity for the breed in question, a statement of authentication, and a breed information summary.
This test is intended for owners of mixed-breed dogs who would like to know something about the genetic makeup and probable breed origins of their pets. Using a cheek swab sample, it compares an individual dog's SNP marker profile with over 190 breeds in the Wisdom Panel® database in order to produce a pedigree profile showing the probable purebred breed (or mixed breed) great grandparents, grandparents and parents. It further breaks down the mixed-breed component (if any) into the five most probable purebred ancestry sources. The report also includes a good summary of breed information for purebred ancestors identified in the last three generations. In some cases notes on the level of confidence in the analysis may be included. This is an impressive level of detailed information for a mixed breed pet; quite a far cry from "our vet said she might be a husky-shepherd cross"!
The Insights™ test usually costs US$69.99; at the time this article was written it was offered at a $20.00 discount.
This is a blood-based test marketed solely through veterinary clinics. Similar to Insights™ in concept and intended purpose, it operates at a higher level of accuracy and detail than the cheek swab test and compares the sample to a database of 235+ breeds and varieties. It is intended to give both veterinarian and owner of mixed breed dogs a better idea of the dog's probable adult size, vulnerability to certain breed-based genetic diseases, and special needs stemming from its breed origins. No price is listed on the website inasmuch as the test is sold only through vet clinics, so presumably you'll need to ask your vet about price and availability.
This cheek-swab based test is similar to Insights™ but targets the owners of "Designer Dogs" specifically. It is primarily designed to confirm that the dog tested is in fact an F1 crossbred from two purebred parents, as opposed to a mixed breed animal. The report includes a breed-ancestry pedigree similar to the one generated by Insights™, along with a similar breed information package, a certificate of authenticity, and a PCA breed cluster analysis.
The Designer Dog test usually costs US$69.99; at the time this article was written it was also offered at a $20.00 discount.
There are many possible applications for the three tests I have just described. Primarily, of course, owners of rescue or animal shelter dogs, owners of designer dogs, and owners of mixed breed dogs will use these tests to confirm the breed origins of their pets. The possibilities, however, don't necessarily stop there. The Purebred test could be used to monitor the progress of outcross/backcross breeding programmes. It might also see use to confirm purebred status in those occasional cases in which a registered purebred displays traits of appearance or behaviour that do not accord with its stated breed. It is even possible that these tests could be used some day to guide breeding programmes designed to restore extinct breeds like the Tahltan Bear Dog, in cases when museum specimens or study skins are available for initial DNA cluster profiling.
Optimal Selection™ targets dog breeders, unlike the other tests in the Mars stable which are all aimed primarily at owners. The avowed purpose of the Optimal Selection™ test is "to help breeders choose more optimal pairings by using cutting edge genetic technology to look beyond pedigrees, examine the chromosomes of potential breeding matches, and make more educated selections." It is intended as a tool to help breeders make better mating choices by incorporating a direct test of heterozygosity and chromosomal haplotypes in addition to more traditional selection criteria.
If this sounds startling, ambitious and quite forward-looking -- it is. I doubt that very many of us in the diversity-breeding movement expected to see anything of this nature available commercially for another ten or fifteen years. Yet Optimal Selection™ is available now. A blood-based test (this is necessary for the highest-quality DNA information), Optimal Selection™ has been field-tested in a two-year pilot study with the Dandie Dinmont Terrier Club of America, where its Breeding Scores were proven to be directly correlated with average litter size and health. Using this tool, participating Dandie breeders were able to increase average litter size to 3.75 registered pups per litter from the historical breed average of 2.75 pups per litter, convincing evidence not only of the value of the test itself but also of the effectiveness of diversity breeding.
Optimal Selection™, like Wisdom Panel® Purebred, yields a direct estimate of an individual dog's homozygosity for comparison with other individuals and with the breed average. More significantly, it offers a detailed analysis of 25 of the 38 canine autosomal (non-sex) chromosomes. The resulting haplotype profile may then be directly compared with potential mates for the dog in question. The idea is that, once your dog has been profiled, after a preliminary narrowing of the field by traditional selection criteria (working qualities, temperament, conformation or whatever), the final choice of a mate can then be made with a view to conserving genetic diversity by avoiding undesired and inadvertent haplotype overlap (and therefore a probable corresponding diminution of genetic diversity).
This is sophisticated stuff; don't be surprised if you don't understand it on first hearing. Let me try, though, to explain how it works. The individual dog report contains bar graphs of haplotypes -- unique arrays of SNP markers -- on 25 of the 38 canine autosomes. There may be anywhere from six or eight to forty or more haplotypes identified for a given chromosome in a given breed. The bar graph shows them all, along with their relative frequency in the Mars Veterinary database. It also shows which two of these possible haplotypes are found on your dog's two matching chromosomes. The matching reports issued on request for possible matings of your dog with other tested dogs of the same breed in the Optimal Selection database lists the 25 tested chromosomes along with a predicted "breeding score" for each which will be either 0.00 (no chance of "haplotype overlap", that is, of your dog and its candidate mate contributing the same haplotype), 0.25 (25% chance of an overlap because each dog has one copy of the same haplotype), 0.50 (50% chance of an overlap because one mate has one copy and the other has two copies of the same haplotype or alternatively both mates carry the same two haplotypes), or 1.00 (100% chance of overlap because both mates have two copies of the same haplotype). Individual chromosome breeding scores are then added up to generate an overall breeding score for the mating in question, thus allowing overall comparison between several possible matings. The company's sample reports and FAQs do a good job of explaining the concept and its application. This is a powerful tool for the conservation of genetic diversity both within a breed and in one's own kennel population, the likes of which has never before been available to breeders.
The test costs US$95.00 for profiling each individual animal. Once animals have been profiled, match reports for potential matings are available without further payment. Match reports for already-profiled stud dogs owned by others may be obtained once the owner's permission has been obtained.
I would like to stress just how important this new tool could be to dog breeders. Closed stud books, genetic drift, bottlenecking, and constant artificial selection exact a terrible toll in lost genetic diversity in domestic dog breeds. Various veterinary academic studies have made this clear enough, documenting losses up to 97% in some breed genomes. The Optimal Selection™ test is the first tool ever to be made commercially available to dog breeders that is capable of looking directly at canine genetic diversity at the practical level, the chromosomal level, which is the only level at which the problem of diversity losses can be addressed directly by the breeder.
Wright's Coefficient of Inbreeding is a useful tool as far as it goes; but it is only a statistical predictor. It tells us what proportion of multiple-allele loci are likely to demonstrate homozygosity at specific levels of pedigree inbreeding. It cannot tell us that one particular dog is definitely more homozygous than another dog. Yet that knowledge is crucial when we attempt to select the most advantageous matings. Inbred littermates can vary quite markedly in actual homozygosity even though they have exactly the same COI. Double first cousins also have exactly the same COI and can vary even more in actual homozygosity. Optimal Selection™ can differentiate accurately between dogs having the same COI, revealing to the breeder which individuals are more homozygous or heterozygous, thus allowing the breeder to plan matings that will make the best use of whatever diversity is available within the overall breeding pool and therefore maximising genetic diversity in the next generation. A tool of this nature, intelligently and consistently applied over time to many litters, can make a tremendous difference in retained genetic diversity in a bloodline, and therefore in overall genetic health of the animals produced by that bloodline. Many of our failures as dog breeders are in the area of not making the best use of what we have; Optimal Selection™ can help us improve in this area.
I think it is reasonable to expect that this tool will be refined and improved with the the passage of time, with additional research and improved DNA marker technology. Already in its pilot testing phase it has shown that its use can bring immediate benefits in the critical areas of fertility, fecundity and nestling survival, allowing breeders to produce larger, healthier litters from existing lines. As additional chromosomes are analysed and more haplotypes discovered and studied, it is highly likely that specific haplotypes will be found to be associated with desirable and undesirable traits in specific dog breeds, making these tests that much more useful to the breeder. The tests will not replace conventional breeder selection, but they may make it much more effective and turn it into a process that no longer erodes genetic health.
More detailed information on each of these genetic tests, including FAQs and PDF files of sample reports, are available on the Wisdom Panel® website.
My thanks to Angela Hughes DVM PhD, Veterinary Genetics Research Manager at Mars Veterinary, for generously giving her time to explain various technical issues to me to facilitate the writing of this article and for supplying example image files from Mars Veterinary sample reports.
