Update on Osteosarcoma, June 2005
By John Dillberger, DVM
In 2004 the SDCA Board approved funding of an $18, 246 grant to support this research, using money from the Canine Health Foundation (CHF) Donor-Advised “Bunnie Austin” Fund. The first installment of $9, 123 was paid in July 2004.
In December 2004, Dr. Hauck provided a progress report to the CHF. I received a copy in April 2005, which is attached to this report as Appendix B. The summary of recent progress reads:
“During the initial 5 months of the grant, the Scottish Deerhound pedigree information was expanded to a total of 1,490 individuals, representing at least 10 generations. This group includes 123 dogs that developed osteosarcoma. The health information on these dogs was validated via contact with the primary veterinarians. Confirmation was obtained concerning what diagnostics had been performed and the probable disease status (whether or not the dog developed probably osteosarcoma). Birth and death dates were confirmed with owners. This database has been reformatted to be analyzed using SAGE 5.0 software, and this has required the reclassification of 186 inbreeding loops and 192 marriage loops (marriage loop identification and reclassification is ongoing). Once all the loops have been handled appropriately, an analysis of the pedigrees will be completed to determine the most likely mode of inheritance. We expect this portion of the project to be completed within the next 3 months.
"The health status validation resulted in the submission of additional DNA samples. The current DNA database consists of 325 DNA samples, including 53 dogs affected with osteosarcoma. The initial whole-genome screen has been performed on DNA from 8 carefully selected affected dogs. This required over 2,600 PCR reactions. Analysis of the genotypes (which requires manual review of each microsatellite analysis) is currently underway and will take 3-5 months. The results of this initial screen may allow a more directed approach (use of fewer satellite markers) to be utilized with the next cohort of Scottish Deerhounds tested.”
In late April 2005, I spoke by phone with Dr. Phillips and learned the following:
The pedigree information has expanded to approximately 3000 dogs, which includes approximately 400 dogs that developed osteosarcoma.
The male:female ratio of affected dogs is about 1:2, suggesting that females are more likely to be affected than males. This mirrors our findings in the Deerhound Health Survey done in the 1990s, which included data from about 400 dogs.
The average age of onset is about 8 years old. Again, this mirrors prior results from various surveys, including ones done by the Deerhound Club in the UK and our own Deerhound Health Survey. This late age of onset may indirectly explain the difference in osteosarcoma risk between males and females. If males are more likely than females to die of other causes at a relatively young age, then that would leave more older females than males at risk for osteosarcoma. The Deerhound Health Survey suggested that males are more likely than females to die of cardiomyopathy at a relatively young age.
Analysis of inbreeding and marriage loops reveals a strong inter-sibling correlation, which suggests a high likelihood that osteosarcoma risk is governed by a single gene in Deerhounds. There is also a strong mother-son correlation, but the father-son correlation is much weaker. Taken together, these findings suggest that the mode of inheritance may be more complicated than a simple dominant or recessive. In other words, the story of how osteosarcoma risk is inherited is not as simple as hoped.
Further DNA analysis is not prudent until the mode of inheritance can be pinned down with more certainty. If the mode of inheritance is known, then it probably would take only a small number of additional DNA analyses to identify a genetic marker. If the mode of inheritance is unknown, one can still search for a marker, but doing so requires a large number of additional DNA analyses and a correspondingly larger amount of time and money. Indeed, our database, large as it is, may be inadequate to identify a genetic marker unless we can work out the mode of inheritance.
Dr. Phillips is leaving NC State University this month to take a position as Assistant Professor at the University of Tennessee. He would like to continue as part of the research team, but that is up to Dr. Hauck, who is the principle investigator. When I spoke with Dr. Hauck in May 2005, she seemed reluctant to keep Dr. Phillips on the team, preferring to replace him with another geneticist at NC State. On May 22, 2005 I wrote to Erika Werne at the CHF asking that the CHF investigate the situation and provide the SDCA with a report of how Dr. Phillips departure might affect the project—particularly the timetable and likelihood of success. When I spoke with Erika Werne on June 7, 2005, she said she had forwarded my concerns to Dr. Hauck and asked for a response.
Copyright 2005 by Dr. John Dillberger, P.O. Box 910, Creedmoor, NC 27522-0910. Reprinted with permission. All rights reserved.
For more information on osteosarcoma in Scottish Deerhounds, or in other breeds of dog, please click on the links on the right.