Project description:Through thousands of years of breeding and strong human selection, the dog (Canis lupus familiaris) exists today within hundreds of closed populations throughout the world, each with defined phenotypes. A singular geographic region with broad diversity in dog breeds presents an interesting opportunity to observe potential mechanisms of breed formation. Italy claims 14 internationally recognized dog breeds, with numerous additional local varieties. To determine the relationship among Italian dog populations, we integrated genetic data from 263 dogs representing 23 closed dog populations from Italy, seven Apennine gray wolves. Using 142,840 genome-wide SNPs, this dataset was used in the identification of breed development routes for the Italian breeds that included divergence from common populations for a specific purpose, admixture of regional stock with that from other regions, and isolated selection of local stock with specific attributes.
Project description:In this study, beta-TCP was implanted in dog mandibles, after which the gene expression profiles and signaling pathways were monitored using microarray and Ingenuity Pathways Analysis (IPA). Following the extraction of premolars and subsequent bone healing, betaâTCP was implanted into the artificial osseous defect. Total RNA was isolated from bone tissues and gene expression profiles were examined using microarray analysis. We used microarrays to detail the global programme of gene expression and identified distinct classes of up- and down- regulated genes during this process. Waiting 3 months healing after tooth extraction from beagle dog mandibles, we drilled the holes in the dog mandibles, and implanted without and with beta-TCP. And these dog mandibles were selected for RNA extraction and hybridization on Affymetrix microarrays. After implanting beta-TCP in the dog mandibles 4, 7, 14 days, we selected sample at 3 time points: Control_4d, beta-TCP_4d, Control_7d, beta-TCP_7d, Control_14d, beta-TCP_14d.
Project description:Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Keywords: Expression profiling by array
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.
Project description:Dogs have become a valuable model in exploring multifaceted diseases and biology relevant to human health. Despite large-scale dog genome projects producing high-quality draft references, a comprehensive annotation of functional elements is still lacking. We addressed this through integrative next-generation sequencing of transcriptomes paired with five histone marks and DNA methylome profiling across 11 tissue types, deciphering the dog’s epigenetic code by defining distinct chromatin states, super-enhancer and methylome landscapes, and thus showed that these regions are associated with a wide range of biological functions and cell/tissue identity. In addition, we confirmed that the phenotype-associated variants are enriched in tissue-specific regulatory regions and, therefore, the tissue of origin of the variants can be traced. Ultimately, we delineated conserved and dynamic epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog that can be used for comparative biology and medical research.
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.
Project description:Selective breeding of domestic dogs has generated diverse breeds often optimized for performing specialized tasks. Despite the heritability of breed-typical behavioral traits, identification of causal loci has proven challenging due to the complexity of canine population structure. We overcome longstanding difficulties in identifying genetic drivers of canine behavior by developing an innovative framework for understanding relationships between breeds and the behaviors that define them utilizing genetic data for over 4,000 domestic, semi-feral and wild canids and behavioral survey data for over 46,000 dogs. We identify ten major canine genetic lineages and their behavioral correlates and show that breed diversification is predominantly driven by non-coding regulatory variation. We determine that lineage-associated genes converge in neurodevelopmental co-expression networks, identifying a sheepdog-associated enrichment for interrelated axon guidance functions. This work presents a scaffold for canine diversification that positions the domestic dog as an unparalleled system for revealing the genetic origins of behavioral diversity.