1317: Mutation Detection and Functional Analysis of Multiple Loci for Osteosarcoma

Grant Status: Closed

Grant Amount: $80,692.2
Dr. Kerstin Lindblad-Toh, PhD, Broad Institute
January 1, 2010 - March 31, 2012
Sponsor(s): American Boxer Charitable Foundation, American Shetland Sheepdog Association, American Shih Tzu Club, Inc., Bernese Mountain Dog Club of America, Border Terrier Club of America, Collie Health Foundation, Golden Retriever Foundation, Greyhound Club of America, Labrador Retriever Club, National Amateur Retriever Club, National Beagle Club, Poodle Club of America Foundation, Siberian Husky Club of America
Breed(s): Greyhound, Rottweiler, Leonberger, Great Pyrenees, Great Dane, Irish Wolfhound, Labrador Retriever, Boxer, Golden Retriever, Mastiff
Research Program Area: Oncology - Osteosarcoma

Abstract

Background: Osteosarcoma (OSA) is a considerable canine health concern, affecting 8,000-10,000 dogs in the United States annually. In the completed CHF study "Mapping Genes Associated with OSA in Large Breed Dogs", the researchers identified six genomic regions associated with osteosarcoma (OSA) in Rottweilers and Greyhounds. In study 758, they conducted fine-mapping of these candidate regions using additional Rottweiler and Greyhound samples as well as samples from eight other breeds (Golden Retrievers, Labrador retrievers, Leonbergers, Great Pyrenees, Mastiffs, Great Danes, Irish Wolfhounds and boxers). All six loci are supported and have been narrowed to a discreet size. Some loci are present in some breeds, some in others. The majority of candidate genes in associated regions have been re-sequenced, but no associated protein changes identified. Objective: The researchers will re-sequence the whole regions of association in cases and controls to identify candidate mutations. Once mutations have been found they aim to survey multiple breeds to see if they share the same mutations. This will make it possible to develop and apply genetic tests for OSA. The researchers will also study the functional consequences of the mutations, which will lead to a better understanding of the disease, enabling development of more targeted treatment options.

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