Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia. 82 canine samples representing 9 dog breeds
Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia. 51 canine samples representing 12 dog breeds
Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia.
Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia.
Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia.
Project description:The Italian island of Sardinia is well known in studies of human population isolates. It is also home to the Fonni's Dog, a breed of canine whose development was reliant on the functionality of the dog. Using genome-wide variant and sequence analyses, we have characterized the Fonni's Dog relative to 27 other dog breeds from the Mediterranean region. We determine introgression events relevant to Mediterranean breed development and describe how the Fonni's dog presents an intriguing model demonstrating the characteristics of traditional human population isolates and, in particular, exhibiting the unique demographic composition of the people of Sardinia. 4 canine samples representing 1 dog breed
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.