Project acronym DOGPSYCH
Project Canine models of human psychiatric disease: identifying novel anxiety genes with the help of man's best friend
Researcher (PI) Hannes Tapani Lohi
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Anxiety disorders include different forms of pathological fear and anxiety and rank among the most common health concerns in human medicine. Millions of people become affected every year, and many of them do not respond to treatments. Anxiety disorders are heritable, but genetically complex. As a result, traditional gene mapping methods in the human population with prominent locus and allelic heterogeneity have not succeeded. Similarly, rodents have provided some insights into the circuitry of anxiety, but naturally occurring versions do not exist and gene deletion studies have not provided adequate models. To break through and identify new anxiety genes, I propose a novel and unique approach that resorts to man s best friend, dog. Taking advantage of the exaggerated genetic homogeneity characteristic of purebred dogs, recent genomics tools and the existence of naturally occurring heritable behaviour disorders in dogs can remedy the current lack of a suitable animal model of human psychiatric disorders. I propose to collect and perform a genome-wide association study in four breed-specific anxiety traits in dogs representing the three major forms of human anxiety: compulsive pacing and tail-chasing, noise phobia, and shyness corresponding to human OCD, panic disorder and social phobia, respectively. Canine anxiety disorders respond to human medications and other phenomenological studies suggest a share biological mechanism in both species. The proposed research has the potential to discover new genetic risk factors, which eventually will shed light on the biological basis of common neuropsychiatric disorders in both dog and human, provide insight into etiological mechanisms, enable identification of individuals at high-risk for adverse health outcomes, and facilitate development of tailored treatments.
Summary
Anxiety disorders include different forms of pathological fear and anxiety and rank among the most common health concerns in human medicine. Millions of people become affected every year, and many of them do not respond to treatments. Anxiety disorders are heritable, but genetically complex. As a result, traditional gene mapping methods in the human population with prominent locus and allelic heterogeneity have not succeeded. Similarly, rodents have provided some insights into the circuitry of anxiety, but naturally occurring versions do not exist and gene deletion studies have not provided adequate models. To break through and identify new anxiety genes, I propose a novel and unique approach that resorts to man s best friend, dog. Taking advantage of the exaggerated genetic homogeneity characteristic of purebred dogs, recent genomics tools and the existence of naturally occurring heritable behaviour disorders in dogs can remedy the current lack of a suitable animal model of human psychiatric disorders. I propose to collect and perform a genome-wide association study in four breed-specific anxiety traits in dogs representing the three major forms of human anxiety: compulsive pacing and tail-chasing, noise phobia, and shyness corresponding to human OCD, panic disorder and social phobia, respectively. Canine anxiety disorders respond to human medications and other phenomenological studies suggest a share biological mechanism in both species. The proposed research has the potential to discover new genetic risk factors, which eventually will shed light on the biological basis of common neuropsychiatric disorders in both dog and human, provide insight into etiological mechanisms, enable identification of individuals at high-risk for adverse health outcomes, and facilitate development of tailored treatments.
Max ERC Funding
1 381 807 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym GENANX
Project A cross-species neurogenomics approach to anxiety
Researcher (PI) Iiris Maaria Hovatta
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS2, ERC-2011-StG_20101109
Summary My goal is to identify novel genetic factors that regulate normal and pathological anxiety. Anxiety disorders are complex diseases with genetic and environmental susceptibility factors. Stressful life events, especially in childhood are well-known risk factors for anxiety disorders. We have previously used inbred mouse strains to identify genes underlying innate anxiety. Here I propose a new approach using a mouse model of anxiety induced by social stress to identify gene regulatory networks, to show the causality of the selected networks in vivo, and to investigate involvement of these networks in the genetic predisposition to human anxiety disorders. Gene regulatory networks will be identified by using massively parallel sequencing methods (i.e. miRNA-seq and mRNA-seq). We will generate from four brain regions known to regulate anxiety a complete gene and miRNA expression atlas, which is used to identify genes, transcripts, miRNAs and isomiRs differentially expressed between anxious and control animals. Pathway and network analysis tools are employed to identify molecular pathways affected by induced anxiety. Datasets consisting of different levels of data from individual brain regions will then be integrated in light of existing molecular and anatomical information to construct draft network models that will be curated, filtered and enhanced. On the basis of these models, we will generate specific hypotheses that are tested in vivo in mice to show the causality of the most interesting networks. To identify the networks important for human anxiety disorders, we have access to a unique population-based cohort from Finland characterized for anxiety disorders. Candidate genes and miRNAs from selected networks are tested in a genetic association analysis. This multidisciplinary project will increase understanding of the genetic and neurobiological basis of anxiety in mouse and human, and has potential to provide targets for the development of improved anxiolytics.
Summary
My goal is to identify novel genetic factors that regulate normal and pathological anxiety. Anxiety disorders are complex diseases with genetic and environmental susceptibility factors. Stressful life events, especially in childhood are well-known risk factors for anxiety disorders. We have previously used inbred mouse strains to identify genes underlying innate anxiety. Here I propose a new approach using a mouse model of anxiety induced by social stress to identify gene regulatory networks, to show the causality of the selected networks in vivo, and to investigate involvement of these networks in the genetic predisposition to human anxiety disorders. Gene regulatory networks will be identified by using massively parallel sequencing methods (i.e. miRNA-seq and mRNA-seq). We will generate from four brain regions known to regulate anxiety a complete gene and miRNA expression atlas, which is used to identify genes, transcripts, miRNAs and isomiRs differentially expressed between anxious and control animals. Pathway and network analysis tools are employed to identify molecular pathways affected by induced anxiety. Datasets consisting of different levels of data from individual brain regions will then be integrated in light of existing molecular and anatomical information to construct draft network models that will be curated, filtered and enhanced. On the basis of these models, we will generate specific hypotheses that are tested in vivo in mice to show the causality of the most interesting networks. To identify the networks important for human anxiety disorders, we have access to a unique population-based cohort from Finland characterized for anxiety disorders. Candidate genes and miRNAs from selected networks are tested in a genetic association analysis. This multidisciplinary project will increase understanding of the genetic and neurobiological basis of anxiety in mouse and human, and has potential to provide targets for the development of improved anxiolytics.
Max ERC Funding
1 499 863 €
Duration
Start date: 2012-02-01, End date: 2017-07-31
