00757A: Hereditary Mutations in Genes Associated with Osteosarcoma in Large Dog Breeds

Grant Status: Closed

Grant Amount: $91,481
Kerstin Lindblad-Toh, PhD; Broad Institute
April 1, 2007 - September 30, 2009

Sponsor(s): American Bullmastiff Association, Bernese Mountain Dog Club of America, Flat-Coated Retriever Foundation, Golden Retriever Foundation, Hoffman Miniature Schnauzer Donor Advised Fund, Orthopedic Foundation for Animals, Portuguese Water Dog Foundation, Rottweiler Health Foundation, Scottish Terrier Club of America, Starlight Fund, Tualatin Kennel Club

Breed(s): Greyhound, Rottweiler
Research Program Area: Oncology - Osteosarcoma
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Project Summary

In the completed CHF study "Mapping Genes Associated with OSA in Large Breed Dogs", the investigators have identified genomic regions associated with OSA in Rottweilers and Greyhounds using genome-wide association with the newly developed ~27,000 SNP array. Results of genome-wide scans show that three regions are associated with OSA from the genome-wide screen in Rottweilers and three different and non-overlapping regions are associated with OSA in Greyhounds. In this study, they conducted further fine-mapping of these candidate regions using additional Rottweiler samples paired with Mastiff-type breeds (Golden Retrievers and Leonbergers) and, likewise, additional Greyhound samples paired with Long-limbed Hound type breeds (Irish Wolfhounds and Great Danes). They have now performed fine-mapping in nine breeds (Rottweilers, Golden Retrievers, Labrador retrievers, Leonbergers, Great Pyrenees, Mastiffs, Greyhounds, Great Danes and Irish Wolfhounds.) All six loci are supported, and several candidate genes have been interrogated for mutations. Since no coding candidate mutations have been identified so far, the researchers believe that regional resequencing will be necessary and the methodology to do this has been developed. They have also continued to fine-map in larger sample numbers to identify the most highly associated regions in preparation for regional resequencing to identify mutations. Regional resequencing is now ongoing to identify mutations. This project is continuing under CHF Grant 1317.


Karlsson, E. K., Baranowska, I., Wade, C. M., Salmon Hillbertz, N. H. C., Zody, M. C., Anderson, N., … Lindblad-Toh, K. (2007). Efficient mapping of mendelian traits in dogs through genome-wide association. Nature Genetics, 39(11), 1321–1328. https://doi.org/10.1038/ng.2007.10

Karlsson, E. K., Sigurdsson, S., Ivansson, E., Thomas, R., Elvers, I., Wright, J., … Lindblad-Toh, K. (2013). Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B. Genome Biology, 14(12), R132. https://doi.org/10.1186/gb-2013-14-12-r132

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