Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed.
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed. Data created for a genome-wide association studio of heritable osteosarcoma risk factors in dogs, including 267 racing greyhounds (153 affected (A) + 114 unaffected (U)), 135 rottweilers (80 A + 55 U), 141 IWH (76 A + 65 U) and 19 AKC greyhounds using the Illumina CanineHD array (~170,000 SNPs genomewide)
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed. Data created for a genome-wide association studio of heritable osteosarcoma risk factors in dogs, including 267 racing greyhounds (153 affected (A) + 114 unaffected (U)), 135 rottweilers (80 A + 55 U), 141 IWH (76 A + 65 U) and 19 AKC greyhounds using the Illumina CanineHD array (~170,000 SNPs genomewide)
Project description:Osteosarcoma in dogs is a spontaneously occurring disease with a global tumor gene expression signature indistinguishable from human pediatric tumors and clinical progression is remarkably similar. Unlike human OS, canine OS is a highly heritable disease with some large and giant dog breeds at >10x increased risk. We did a genome wide association study of osteosarcoma using the Illumina CanineHD genotyping array in three breeds: greyhound (mortality from OS = 26%), rottweiler (17%) and Irish wolfhound (IWH, 21%) and identified 33 inherited risk loci explaining 55 to 85% of phenotype variance in each breed. Data created for a genome-wide association studio of heritable osteosarcoma risk factors in dogs, including 267 racing greyhounds (153 affected (A) + 114 unaffected (U)), 135 rottweilers (80 A + 55 U), 141 IWH (76 A + 65 U) and 19 AKC greyhounds using the Illumina CanineHD array (~170,000 SNPs genomewide)
Project description:Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1-3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. We use genome wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin (CDH2), catenin alpha2 (CTNNA2), ataxin-1 (ATXN1), and plasma glutamate carboxypeptidase (PGCP). Two different case-only variants targeted the same approximately 500-bp highly conserved regulatory element between the cadherin genes CDH2 and DSC3. We functionally test these variants in a human neuroblastoma cell line and show that they cause significant changes in gene expression, likely due to disrupted transcription factor binding. This work demonstrates how we can use the unique genetics of dog breeds, and mechanistic similarities between human and dog diseases, to find genes and regulatory pathways underlying complex psychiatric disorders. Affymetrix SNP arrays were performed according to the manufacturer's directions. Genome wide association analysis was performed for 87 doberman pinshcers OCD cases and 63 breed-matched controls.