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  • Memorandum of Agreement (Required)                                                           
  • ANTAGENE Sampling Certificate (Required)                                                 
  • OptiGen Order Form (Required) Online or printed                                                                  
  • ANTAGENE HS Health Questionnaire (Optional)                                           
  • Research sample/Expanded Validation application                                           
    (Required for any Free Testing Research samples)              


*8/3/17 - Update on research sample interest: Any/all cases of Systemic Histiocytosis are being sought by the University of Rennes research team and will be accepted at OptiGen for shipment to Antagene--comparable to the cases of Histiocytic Sarcoma submitted for validation/free testing.

Please note that due to ongoing research on this disease, Antagene and CNRS REQUIRE A BLOOD SAMPLE for all HS tests. An exception is made and cheek swabs will be accepted for puppies less than 3 months old.


August 1, 2016                     

ANTAGENE Genetic risk test for Histiocytic Sarcoma    Pre-Test SH    Code 150

For Breed: Bernese Mt. Dogs

PLEASE NOTE: The Histiocytic Sarcoma Pre-Test (Pre-Test SH) is performed by ANTAGENE in France. OptiGen does not provide test results for this genetic test. All test certificates for Pre-Test SH are sent to clients directly by ANTAGENE. Other than providing DNA services to ANTAGENE, OptiGen is in no way involved in the testing, analysis or reporting of the Pre-Test SH results. OptiGen and its internal scientific advisors have evaluated the Pre-Test and have decided that it is an important first step in identifying the specific genetic defect(s) responsible for HS. OptiGen agrees with Antagene that, "The Pre-Test SH for Histiocytic Sarcoma is not an end point but a continuation of the research on Histiocytic Sarcoma. The test will be optimized and refined with advanced research.” 

Disease description:
Histiocytic Sarcoma (HS) is a highly aggressive and lethal form of cancer that affects 15-25% of Bernese Mountain Dogs (BMD) and is a major cause of death due to a genetic predisposition in this breed. It is a cancer of histiocytes, cells responsible for immune functions, which are present in the lymph nodes and in numerous organs, including the spleen, liver and lungs. The typical age of onset in the BMD is 6.5 years, and the progression of disease is usually rapid, with a mean survival time following diagnosis of only 49 days (Abadie et al., J.Hered, 2009). To date, there is no effective treatment, and the disease outcome is fatal.

Genetic risk test for Histiocytic Sarcoma: Pre-Test SH:
ANTAGENE, an ISO9001-accredited DNA testing laboratory in France, has commercialized a DNA test that evaluates the risk of developing and passing on to a dog's progeny genetic factors that cause and influence development of Histiocytic Sarcoma (HS) in the Bernese Mountain Dog (BMD). The genetic research on HS predisposition is performed in the frame of an international collaboration. The research that led to the development of this genetic risk test is being conducted by Drs Catherine Andre and Benoit Hedan from the Canine Genetics team of the Institute of Genetics & Development of the CNRS (National Centre for Scientific Research) at the University of Rennes, France ( Due to the complexity of HS's multifactorial mode of inheritance, this genetic risk test offers an estimate of probability or risk of developing and transmitting HS. It is named Pre-Test SH, to reflect its early stage of use, especially in regards to the North American population of BMDs, and also to emphasize that the test is still under development as part of an active research program of the Canine Genetics team in CNRS, France.

In order to enable breeders to take advantage of the CNRS research findings, ANTAGENE, in collaboration with the CNRS Canine Genetics team, has made the Pre-Test SH available to BMD breeders. The Pre-Test SH was first offered to BMD breeders in France, where the majority of research samples used to develop this genetic risk test originated. A two step validation process has been performed, first on BMDs from Europe, then on BMDs from the USA (91 dogs from the Berner-Garde's repository) by Dr Andre's team and ANTAGENE. OptiGen, as of August 1, 2016, has begun sale of the Pre-Test SH in North & South America.

OptiGen's role in the sale of the Pre-Test SH is to provide DNA extraction services as well as to assist in communications between the USA BMD community and ANTAGENE and Dr Andre's team, especially with the aim of promoting further research and refinement of the Pre-Test SH. Information obtained from the sale of the Pre-Test SH contributes to the ongoing research being undertaken by the CNRS Canine Genetics team and its partners. For this reason, there are extra steps required in ordering ANTAGENE's Pre-Test SH compared to other routine DNA tests available at OptiGen. See the "How to Place an order via OptiGen for ANTAGENE's Pre-Test for Histiocytic Sarcoma" section below for further details.

Characteristics of the Pre-Test SH:
Interpretation of ANTAGENE's Pre-Test SH result is not trivial due to the multifactorial nature of this genetic risk test. Statistical analysis of the predictive genetic markers of this genetic risk test has been used to produce a genetic index. The calculation of the index has been developed based on a population of 1081 French Bernese Mountain Dogs. This index estimates a probability of a BMD developing HS and of transmitting the predictive genetic factors on to progeny. The Pre-Test SH is a genetic tool designed to assist breeders in the management of their kennels and in making decisions on matings, with the aim of eventually lowering the incidence of this devastating disease in the population of Bernese Mountain Dogs.

Expected results using ANTAGENE’s Pre-Test SH for
Histiocytic Sarcoma


Based on data analysis of BMD research population
(by the Canine Genetics team of CNRS and ANTAGENE)


The individuals tested have a four times LOWER risk of developing Histiocytic Sarcoma


Neutral—not predictive of higher or lower risk of developing Histiocytic Sarcoma


The individuals tested have a four times HIGHER risk of developing Histiocytic Sarcoma. The risk of the markers associated with the disease being transmitted to offspring is increased.


Validation steps of the Pre-Test SH; Correlation of Index Results and clinical status:
in 2015, two validation steps have been performed on new populations (718 samples): a European BMD population (656 samples) and a North American BMD population (91 samples). These samples had a well defined status: Affected BMDs had definitive pathology diagnoses of HS and Healthy BMDs were older than 10 years of age, with no diagnosis of cancer.

The correlation between the index and the clinical status of the dogs was calculated. No significant difference of this correlation has been observed between these populations and the French research population, the test was validated on a European BMD population and on North American BMDs.

Healthy dogs, of more than 10 years old (total validation n=303)
- Index A: 41.5%
- Index B: 46.5%
- Index C: 12%

Dogs clinically diagnosed as Histiocytic Sarcoma affected (total validation n=415)
- Index A: 14%
- Index B: 43%
- Index C: 43%

As observed in the above percentages, the A and C index categories of the Pre-Test SH are correlated to  the disease status, showing that A dogs are more likely to be healthy and C dogs more likely to be affected. This genetic risk test should not in any way be regarded as diagnostic of HS disease. Rather, the Pre-Test SH should be used as a breeding tool that estimates the probability for a given dog to develop HS and of passing HS risk factors on to its offspring.

Based on the results of the validation population:
- the probability that an A index dog is healthy is 68.3%
- the probability that an affected dog is not A index type is 86%
- the probability that a C index dog is affected is 82.8%
- the probability that a healthy dog is not C index type is 87.8%

Frequency of A, B, C indexes observed in European population (2013-2016):
Based on samples received at ANTAGENE to perform the Pre-Test SH, from the European population (n=757), without clinical status, (note they present a sampling bias), the results give information regarding frequencies observed in Europe.
- Dogs that scored A: 23%
- Dogs that scored B: 44%
- Dogs that scored C: 33%

Recommendations on the use of the Pre-Test SH:
OptiGen strongly recommends that breeders consult BMD breed clubs and health organizations, such as the Berner-Garde Foundation, when making use of ANTAGENE's Pre-Test SH.  Although it is obvious that breeders will strive to lower the risk of producing dogs that develop HS, it is also of the utmost importance when selecting breeding pairs that sufficient genetic diversity is maintained in the breed. OptiGen, ANTAGENE and CNRS Canine Genetics team insist on the fact that ANTAGENE Pre-Test SH should be just one of many selection criteria.

An index C dog should not be removed from a breeding program based on its Pre-Test SH status alone, rather it should be mated with the individuals showing Index A or B results. Mating programs should be planned to avoid C x C matings - however even these matings are capable of producing Index A offspring (but with a lower frequency than other matings).

How to Place an order via OptiGen for ANTAGENE's Histiocytic Sarcoma Pre-Test SH:
Due to the early stage of understanding and the need for continued research on the genetic bases of HS in the BMD, multiple signed forms are required in placing an order for the ANTAGENE Pre-Test SH:

- One signed copy of the Memorandum of Agreement (Required for the first order placed by an individual):

- ANTAGENE Sampling Certificate (Required for all orders; includes veterinarian's certification and email address)

- OptiGen Order form - either online or printed (Required)

- ANTAGENE HS Health Questionnaire (optional). The questionnaire is available on ANTAGENE's website at

Please note that in order to receive an authenticated result certificate, the animal must be sampled and it's identity certified by a veterinarian, so Veterinarian's involvement is required

In contrast to the other tests that OptiGen currently offers, the veterinarian's role is to:

- Sampling can be done by 1-3 ml whole unclotted blood in EDTA (preferred), sterile cheek swabs (2/dog) or semen sample for the Pre-Test SH. See OptiGen information page for guidelines.

- Certify sample's identity (by providing clinician's signature and veterinary license number on ANTAGENE Sampling Certificate)

- Provide clinician's email address to allow for direct reporting and communications with ANTAGENE.


Steps to placing an Order for the ANTAGENE Pre-Test SH:

1. Go to the OptiGen Order Test page to place an online order or download a printable form.

2. Download and sign the ANTAGENE Memorandum of Agreement and the ANTAGENE Sampling Certificate.

3. Take the ANTAGENE Sampling Certificate and the OptiGen order form to the veterinarian's clinic.

4. Make sure the veterinarian signs and certifies the ANTAGENE sampling certificate and also provides an email address on that form

5. Include all required forms in the same shipment with the blood samples. Ship samples to:

OptiGen, LLC
Cornell Business and Technology Park
767 Warren Road, Suite 300
Ithaca, NY 14850

The Pre-Test SH results will be sent by ANTAGENE by email (in PDF format) within 10 to 15 days from the reception of the DNA sample at ANTAGENE. Hard copy certificates of the Pre-Test SH will not be mailed to the owner.

Free DNA testing to support continued research and an expanded validation study of HS in the North American BMD population:
OptiGen, in collaboration with ANTAGENE and researchers at the Canine Genetics team of CNRS, Rennes, France, will accept blood and/or tissue samples from 50 Affected BMDs with confirmed diagnoses of HS and 50 Healthy BMDs, for research/expanded validation study.

In brief, all AFFECTED dogs that are being submitted for research, must have a definitive HS diagnosis verified by a pathology report; dogs must be less than 10 years old, have a pedigree and have permanent identification (tattoo or chip).

All NORMAL dogs must be more than 10 years old (born before 2006), with no cancer record as confirmed by licensed veterinarian; pedigree record and tattoo or chip ID must also be provided.

Samples that are approved for the research study will be tested using the Pre-Test SH, free of charge, and the test results will be provided to the clients and their veterinarians and will be included in the research process.

Learn more about the ongoing HS research projects by visiting the Berner International Working Group (IWG).





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