Genetic Studies for SAS and SCARF
By Margaret Black | January 1, 2019
SCARF has a long-standing interest in supporting research opportunities that seek to identify the genetic basis of diseases that afflict Samoyeds. In spring 2018 SCARF was contacted about Samoyeds from a shelter in Iowa who had heart murmurs, a possible indicator of subvalvular aortic stenosis (SAS), a congenital heart defect in dogs. We were told that dogs from this shelter were notorious for sudden cardiac death and accurate pedigrees were not available. While it is unclear at this time whether those deaths were caused by SAS, it cannot be ruled out either.
What is subvalvular aortic stenosis or SAS?
“Subaortic stenosis is a common, potentially devastating birth defect of the heart in dogs. It consists of excessive tissue that partially blocks the path for outflow of blood from the heart to the circulation, creating a partial obstruction. The result is an increase in strain on the main pumping chamber of the heart, the left ventricle, as the heart works harder to maintain a normal circulation. In severe cases, subaortic stenosis can be fatal, but in mild cases it produces no problems (no symptoms, no need for treatment) in the affected dog. Subaortic stenosis is almost always inherited, so all affected dogs, whether mild or severe, should be removed from the breeding pool.”
For an excellent overview of congenital heart diseases in the Samoyed please see: http://www.mirage-samoyeds.com/heart.htm by Cheri Hollenback (1998).
What is known about genetic mutations that lead to SAS?
An article by Dr. Joshua Stern (UC Davis) et al. published in Human Genetics (133:1139-1148 (2014)) suggests the genetic cause of SAS using one family of Newfoundlands has a complex inheritance pattern. He further describes the identification of a single genetic mutation that is strongly associated with SAS using one method but results from the other methods employed were less conclusive. The mutation was found in a gene called PICALM and encodes a protein important in the development of the heart during embryogenesis, as well as involvement in other developmental and cellular processes. A different group, however, was unable to substantiate that PICALM mutations cause SAS in Newfoundlands and raised concerns about the type and number of samples in the Stern study (Droegemueller et al., Human Genetics 134:127-129 (2015)). While the amount of scientific literature about this topic is small and contradictory, it highlights the need for additional studies to validate a genetic marker for SAS. Future studies using a larger sample size of DNA from unrelated dogs diagnosed with SAS will help to confirm the causative gene or genes responsible for SAS. We all know that pedigrees play a vital role in making informed decisions regarding breeding programs. While the use of dogs without accurate pedigrees (such as the Iowa dogs) may aid in the identification of the genetic marker for SAS, it would not properly inform which lineage of dogs may carry the causative genetic mutation and thus is likely to significantly delay the opportunity to eliminate the genetic cause for SAS in the Samoyed breed.
Should SCARF support finding a genetic marker for SAS in Samoyeds?
When SCARF was approached last spring, we were asked to urgently fund echo-cardiographs ($200/dog) on up to 20 of the Iowa shelter dogs, and blood samples would also need to be collected. As we were told, the Iowa dogs were unsocialized and were likely to be reluctant to being subjected to echocardiography. Furthermore, they were already being slowly placed in rescues, some long distances from veterinary cardiologists, making getting the echocardiographs challenging, if not impossible. Cheri Hollenback (SCA President) had contacted Dr. Stern from UC Davis to find out if he would be interested in a study to look for a genetic mutation for SAS in the Samoyed breed. It was posed that if SCARF could finance the echocardiographs and blood draws, it would encourage Dr. Stern to initiate the genetic mapping study. The SCARF Board seriously considered this request and sought further clarification about this research project.
When SCARF funds a research study, proposals come to us detailed with specific aims, background information, justification, scientific methods, budgets and potential outcomes through established funding agencies such as the AKC Canine Health Fund that have already vetted and found merit in the proposed studies. The SCARF Board also recognizes that our funds come from donations from Samoyed breeders and friends of the breed and thus it is the Board’s responsibility to ensure that there is accountability for any study we provide support for. I reached out to Cheri Hollenback and she was able to put me in contact with Dr. Stern. After explaining SCARF’s position and interest, Dr. Stern said his lab would start collecting samples (at no cost to the club) and, once sufficient numbers of affected samples and their information/DNA had been obtained, he would then be back in touch about the best way to propose a full genome wide association study for funding consideration. They would like to collect 48 affected and 48 control samples before initiating their genetic mapping studies. The SCARF Board is very interested in funding the identification of SAS in Samoyeds and is keen to receive suitable proposals for such studies. Cheri Hollenback has been instrumental in driving this research avenue forward and at this time the best way you can help is by providing samples. For more information about the SAS-Samoyed sample collection and to download the sample submission form from Dr. Stern’s lab please visit:
Please also consider donating DNA samples (cheek swabs) to the SCARF DNA Bank so that other researchers can access the materials and additional dog specific information can be gathered. To learn more about the SCARF DNA database please go to:
Margaret Black, Ph.D.
Director, SCARF Board