Diverse dog breeds genotyped on Affymetrix Canine v2 Arrays
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ABSTRACT:
PROVIDER: PRJNA268030 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Diverse dataset of 1247 dogs from many breeds and wolves used to investigate the origins of dog domestication DNA for 1228 dogs from 35 breeds and 19 wolves was extracted from whole blood samples and genotyped on the Affymetrix Canine v2 Arrays. Genotypes were called using Affymetrix's snp5-probeset-genotype software and the BRLMM-P calling algorithm. The included breed designations are owner reported.
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Project description:This study used the NimbleGen dog whole genome CGH 2.1M tiling array to assay copy number variants in the dog genome in multiple breeds and wolf.
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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.
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