Research into Bone Cancer
(Animal Health Trust)
GENETIC STUDY ON THE PREDISPOSTION OF IRISH WOLFHOUNDS
TO DEVELOP OSTEOSARCOMA
Project Update, June 2016
The IWHG are pleased to announce our continuing support of the latest development of the research by the AHT into osteosarcoma. You can read the history of this research and how it has unfolded by clicking the links on this page.
This long-running project keeps revealing snippets of the genetic puzzle that is osteosarcoma and we are hopeful that the next phase will be the most enlightening yet.
We are fortunate that the funding application from the AHT has come at the same time as an exciting new development in the world of canine genetics, which is being funded by the Kennel Club Charitable Trust, namely the Give a Dog a Genome project. You can read about it in more depth here Essentially, this is a project to sequence the entire genome of one dog from each of 75 dog breeds. The IWHG has taken advantage of the KC offer to match-fund each sequence. For this project the cost of sequencing one genome was set at £2,000; the IWHG have provided £1,000 while the KC have match -funded that amount to provide the £2,000 needed to sequence one Wolfhound genome.
Dr Starkey's funding application has requested a total amount of £7,424.32 for sequencing a further five Wolfhound genomes, four from osteosarcoma affected Wolfhounds and one from an unaffected Wolfhound which does not carry the chromosome 11 genetic marker strongly associated with osteosarcoma in US Greyhounds. This will give them the entire genome sequences of six Wolfhounds to compare 'affected by osteosarcoma' to 'unaffected by osteosarcoma', the Wolfhound sequence to the reference Boxer sequence, and also the Wolfhound genome to breeds identified as being at lower than average risk of developing osteosarcoma from the GADAG project.
Whilst we are very hopeful, we cannot emphasise enough that identifying inherited risk factors for complex diseases such as cancer is not straightforward and any DNA sequencing study attempting to do so is unlikely to deliver results quickly. That said, we have assurances from Dr Starkey that the sequences they generate will be available in the public domain and (once certain conditions are met) to other researchers. As a breed we are extremely fortunate to have Dr Mike Starkey, Head of Molecular Oncology at the AHT, as our principal investigator on this project, and Dr Cathryn Mellersh, Head of Canine Genetics at the AHT, as a co-investigator. You can read the full application by clicking this link.
IWHG, June 2016
Research paper published:
Detailed results of research into bone cancer in Greyhounds, Rottweilers and Irish Wolfhounds, with Dr Mike Starkey of the AHT a contributor.
Project Update, March 2012
Osteosarcoma is the most common bone cancer of dogs and, in 2006 a UK Kennel Club/British Small Animal Veterinary Association Purebred Dog Health Survey reported that it was the most common cause of death in Irish Wolfhounds. In September 2008, we were awarded funding by the United States-based Morris Animal Foundation to undertake a study to attempt to locate inherited genetic defects that increase the risk of Irish Wolfhounds developing osteosarcoma.
In collaboration with Dr. Kerstin Lindblad-Toh's group (divided between the University of Uppsala in Sweden and the Broad Institute in the United States), we have analysed 170,000 genetic markers (called 'SNPs') in DNA samples from 103 affected Wolfhounds and 82 unaffected veteran Wolfhounds. This analysis did not identify any SNP that has a statistically significant 'association' with osteosarcoma (that is, a SNP that is present significantly more often in the DNA of Wolfhounds with osteosarcoma than in the DNA of unaffected Wolfhounds). Consequently, we will need to analyse DNA samples from additional affected dogs and unaffected dogs, and continually reanalyse the data until we obtain statistically significant results.
An extremely generous donation of £4,000 made by the Irish Wolfhound Club in June 2011 has enabled us to collect samples from a further 2 Wolfhounds with osteosarcoma and 6 unaffected veteran Wolfhounds. We plan to continue to use the funds to finance sample collection and the isolation of DNA from the samples collected. In addition, we ultimately hope to use the funds to cover at least part of the cost of analysing (referred to as 'genotyping') the additional DNA samples. It costs around £150 to analyse the DNA sample from one dog. However, the minimum number of reagents (called 'chips' - one chip is to used to analyse one DNA sample) that can be purchased is 48, at a total cost of £7,200 (48 x £150). This means that we either have to find £7,200, or find someone else who has dog DNA samples to analyse with whom to share the £7,200 cost. At present we have a total of 7 DNA samples from affected Wolfhounds and 25 DNA samples from unaffected veteran Wolfhounds awaiting analysis, and so we are in discussions with Dr. Lindblad-Toh about splitting the £7,200 cost for analysing a further 48 Wolfhound DNA samples.
Although the comparison of 103 affected Wolfhounds and 82 unaffected Wolfhounds did not identify any genetic marker that has a statistically significant 'association' with osteosarcoma, a second comparison of 28 affected Wolfhounds (aged less than 6 years old) and 82 unaffected veteran Wolfhounds found statistically significant 'associations' between osteosarcoma and SNPs located on two different chromosomes. The motivation for this comparison was that we wondered whether Wolfhounds that developed osteosarcoma earlier than the average 6.3 years (approximately) age of onset may contain genetic risk factors additional to those carried by Wolfhounds that develop osteosarcoma later in life. Although osteosarcoma tends to occur in middle-aged to older dogs, some reports in the scientific literature have reported a 'second peak' between 18 and 24 months of age. The two SNPs that we have identified appear to pinpoint locations on two chromosomes that contain an inherited genetic abnormality that confers an increased risk of developing osteosarcoma. We have provided DNA samples to Dr. Lindblad-Toh's group (who have the necessary funds and personnel required to undertake the work) in order to assist them to attempt to identify the genetic abnormalities in the two chromosomal regions.
Dr. Mike Starkey
Oncology Research Group