Antagene's Histio Pre-test

About the Antagene Histiocytic Sarcoma Pre-Test

Histiocytic Sarcoma (HS) is a cancer that kills more than 16% of Bernese Mountain Dogs. Far too many die young from this cancer, and treatments have been of questionable help. Now we have a DNA risk test, and a tool designed to help provide probable test mating results.

Until now, the best method provided by geneticists to reduce the incidence of HS involved not breeding affected dogs or close relatives of those affected dogs. Given the fact that many Berners develop HS after they have been bred multiple times, and given the fact that nearly all Berners are near relatives of affected dogs, this advice has not been particularly helpful.

The Antagene Histio Pre-Test was developed based on nine different genetic markers that have been found to have a link to HS in the Bernese Mountain Dog. Weighting of those nine marker values provides three different results: A - four times less likely to develop HS, B - neither more nor less likely to develop HS, and C - four times more likely to develop HS. This is not a diagnostic test, as dogs with an A result may still die of HS, and dogs with a C result may live into double digits without ever getting HS. This test is best used to try to produce fewer puppies with a C result, and the advice given is to simply avoid breeding a C to another C.

Given that a mating of two dogs has 20,000 possible combinations of those nine genetic markers, Antagene now has an online tool, the Histiocytic Sarcoma Index Mate Selection (HSIMS), that allows a breeder whose dog has been tested and listed in the HSIMS database to do 'test matings' of prospective mates who have also been tested and listed in the HSIMS database. It provides the percentage chances of A's, B's, and C's for each of the puppies of a test mating. This tool is free and available to anyone who has tested their dog for the HS Pre-Test.

What is of interest is that while one might expect that an A x A mating might always give the best results, that is not the case. Some C x C matings have actually given better possible results. Pedigree study is still important, and this test - like any health test - should not be used as the one and only factor for breeding choices, but as one aspect of the whole dog. We have far too many dogs with B and C results to eliminate them from the gene pool, and many of those dogs have many excellent qualities. Working to gradually increase the number of puppies with an A or B result will be best for the overall population.

The value of a given dog, it's length or quality of life or cause of death cannot be pre-determined by A/B/C ratings given through this test. It is not a diagnostic test, and cannot be used to predict whether a dog will or won't get Histio.

Research continues in an attempt to find the genes that cause Histiocytic Sarcoma, and is being done by Dr. Jacquelyn Evans at the NIH. While the current risk test is a better tool than we have had, it's not the ultimate answer to help us eventually eliminate this disease. In addition, research for better diagnostic tools, as well as effective treatments for the disease, is ongoing.

The Antagene Histio Risk Test was developed based on nine different markers on five chromosomes that have been found to have a link to histiocytic sarcoma in the Bernese Mountain Dog. Weighting of those nine marker values provides three different results: A - four times less likely to develop histio, B - neither more nor less likely to develop histio, and C – four times more likely to develop histio. Removing all B's and C's from the gene pool would undoubtedly do tremendous harm to the gene pool, and the advice had been to avoid breeding a C to another C. But with the new HSIMS tool, even a C x C breeding might be an option.

Combining two copies of nine genes provides about 20,000 different results, so Antagene has developed a tool that can assist breeders. If two dogs are good breeding candidates for a bitch, this test can be used to determine which would give the best chance at a high percentage of A and B puppies. It is one trait in the complex determination of choosing an ideal mate.

HSIMS allows a breeder whose dog has been tested and listed in the HSIMS database to do 'test matings' of prospective mates who have also been tested and listed in the HSIMS database, to learn the statistical results of the puppies for the Histiocytic Sarcoma genetic risk test. It will show the percentage of A's, B's, and C's for those 20,000 possible results. This test is free and available to anyone who has tested their dog for the HS Pre-Test. For more information go to the Antagene website.

Julie Jackson and Pat Long

Using the Antagene Histiocytic Sarcoma (HS) Index Mate Selection (HSIMS) Tool

HSIMS Tool - Information for Breeders

Step 01

To use the tool, begin by logging into your Antagene account to access your tested dogs.
Then click on ‘My Animals’ for the list of your dogs tested:

Step 02

Next, click on the dog you want to do the test mating with, and make sure they’ve got the green light!

Step 03

Click on the red ball to turn it to ‘green’. Now your dog can be used for a test mating!
NOTE: It’s important that ALL dogs be entered into the breeding pool, even if not a breeding dog!! The HSIMS results are much more accurate than the A/B/C indexes, and much information can be gained by relatives being used for “test matings”, beyond the famous show dog! Please green light ALL your dogs that have been tested.
And now you’re ready to do a test mating. Click on “start an HSIMS simulation’. Type the call name, registered name, or identification number of the first dog in the Search box, then click on ‘Select’. NOTE: At least one of the dogs must be listed under your name, ‘My Animals

Step 04

Then select a mate, using the same search method, and click on ‘select’:

Make sure that the dog has a green light

Step 05

Results with a percent risk for each index for the puppies

And here’s the results, shown in a pie chart, with percent risk for each index for the puppies:

The HSIMS is a tool for the mating selection using the HS index of the parents. It calculates, for the next generation, in percentages, the distribution of A, B and C indexes for a specific mating, considering all of the HS genotypes possible in the next generation. Thus, the HSIMS test result is strictly specific to each couple considered. Its use requires the individual HS test of the sire and the dam.

To select the dogs for a test mating, click on the blue check mark button to select your dog, and then do the same for the mate of interest. The dogs will be shown below in the selected mating portion of the page. Click on Start the simulation, and the results will display. This probability outcome is the predicted distribution of A, B, and C indexes of the progeny of the specific mating pair. As an example, a predicted outcome of 13% As, 68% Bs, and 19% Cs means that on a large number you would expect to see this result. Keep in mind this probability can pertain to each puppy produced.

Each puppy will have (as an example) a 13% chance of being an A, a 68% chance of being a B, and a 19% chance of being a C. These percentages make excellent comparative values between different prospective matings, and the best choice (with all other factors being equal) is the mating with the probability of a highest percentage of A's and B's.

Try additional test matings to see what sort of differences there might be in various matings. And do remember, this is only one aspect of the breeding choices.

Breeders are cautioned that A x A matings are not always going to be the best solution. A's can produce C's just as C's may produce A's. A breeding program approach that uses only A x A matings or selects only A mates for their dogs without using the HSIMS tool for predicted outcome probabilities may not be making the lowest risk breedings. HSIMS calculated outcome probabilities may be used to help breeders choose lower risk matings and gradually reduce the HS risk. However, this information DOES NOT PREDICT which dogs in which index may or may not develop HS. Therefore, HSIMS is just one consideration in the complex determination of an ideal pairing. It should not be the only tool used to make breeding decisions. Once a breeder has identified several stud dogs they consider complementary for their girls, they can use the HSIMS tool to see the outcome predictions and know what is risked if all other considerations of the studs are equal. Stud dog owners can use the tool as well to see what the probable outcome of a proposed mating might be. It is important to understand that the HS test is a risk test, but the HSIMS calculated predictions for a mating are more relevant to the possible litter outcome than is each mate's individual pre-test result.