The DISC1 Pathway Modulates Expression of Neurodevelopmental, Synaptogenic and Sensory Perception Genes
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{"title"=>"The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes", "type"=>"journal", "authors"=>[{"first_name"=>"William", "last_name"=>"Hennah", "scopus_author_id"=>"6506305368"}, {"first_name"=>"David", "last_name"=>"Porteous", "scopus_author_id"=>"7006940003"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"354438375", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0004906", "scopus"=>"2-s2.0-64049088120", "pmid"=>"19300510", "sgr"=>"64049088120"}, "id"=>"0c5d840f-0bec-3d8e-828f-ee32954d1ee6", "abstract"=>"BACKGROUND: Genetic and biological evidence supports a role for DISC1 across a spectrum of major mental illnesses, including schizophrenia and bipolar disorder. There is evidence for genetic interplay between variants in DISC1 and in biologically interacting loci in psychiatric illness. DISC1 also associates with normal variance in behavioral and brain imaging phenotypes. METHODOLOGY: Here, we analyze public domain datasets and demonstrate correlations between variants in the DISC1 pathway genes and levels of gene expression. Genetic variants of DISC1, NDE1, PDE4B and PDE4D regulate the expression of cytoskeletal, synaptogenic, neurodevelopmental and sensory perception proteins. Interestingly, these regulated genes include existing targets for drug development in depression and psychosis. CONCLUSIONS: Our systematic analysis provides further evidence for the relevance of the DISC1 pathway to major mental illness, identifies additional potential targets for therapeutic intervention and establishes a general strategy to mine public datasets for insights into disease pathways.", "link"=>"http://www.mendeley.com/research/disc1-pathway-modulates-expression-neurodevelopmental-synaptogenic-sensory-perception-genes", "reader_count"=>64, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>9, "Researcher"=>18, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>4, "Student > Bachelor"=>10, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>9, "Researcher"=>18, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>4, "Student > Bachelor"=>10, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>34, "Medicine and Dentistry"=>14, "Neuroscience"=>5, "Chemistry"=>1, "Psychology"=>4, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>14}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>34}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Austria"=>1, "Turkey"=>1, "United States"=>2, "Japan"=>1, "Italy"=>2, "United Kingdom"=>2, "Chile"=>1, "Germany"=>1, "Spain"=>2, "Russia"=>1}, "group_count"=>3}

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  • {"files"=>["https://ndownloader.figshare.com/files/904172"], "description"=>"<p>Psychiatric drug target genes that display DISC1 pathway mediated differential expression.</p>", "links"=>[], "tags"=>["genes", "disc1", "pathway", "mediated", "differential"], "article_id"=>574628, "categories"=>["Genetics", "Infectious Diseases", "Mental Health"], "users"=>["William Hennah", "David Porteous"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004906.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Psychiatric_drug_target_genes_that_display_DISC1_pathway_mediated_differential_expression_/574628", "title"=>"Psychiatric drug target genes that display DISC1 pathway mediated differential expression.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:17:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/904213"], "description"=>"*<p>Haplotype of SNPs rs2503166, rs583018 and rs526772.</p>", "links"=>[], "tags"=>["ontology", "biologically", "disc1", "pathway"], "article_id"=>574675, "categories"=>["Genetics", "Infectious Diseases", "Mental Health"], "users"=>["William Hennah", "David Porteous"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004906.t002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Table_of_significant_gene_ontology_terms_that_are_biologically_relevant_to_the_DISC1_pathway_or_major_mental_illness_/574675", "title"=>"Table of significant gene ontology terms that are biologically relevant to the DISC1 pathway or major mental illness.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-20 01:17:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/904003"], "description"=>"<p>This protocol can be adapted to any chosen gene, pathway and disorder by simply replacing DISC1 with the gene of primary interest.</p>", "links"=>[], "tags"=>["performed"], "article_id"=>574468, "categories"=>["Genetics", "Infectious Diseases", "Mental Health"], "users"=>["William Hennah", "David Porteous"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004906.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_chart_to_demonstrate_the_analysis_performed_here_/574468", "title"=>"Flow chart to demonstrate the analysis performed here.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-20 01:14:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/904071"], "description"=>"<p>Network generated through the use of Ingenuity Pathway Analysis (Ingenuity Systems®, <a href=\"http://www.ingenuity.com\" target=\"_blank\">www.ingenuity.com</a>), using the build function and connecting the identified genes to the core DISC1 interactome, only allowing for direct interaction. Relationships are supported by at least 1 reference from the literature, from a textbook, or from canonical information stored in the Ingenuity knowledge base.</p>", "links"=>[], "tags"=>["100", "528", "genes", "differential", "disc1and"], "article_id"=>574525, "categories"=>["Genetics", "Infectious Diseases", "Mental Health"], "users"=>["William Hennah", "David Porteous"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004906.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Network_of_how_100_of_the_528_genes_identified_with_significant_differential_expression_relate_to_DISC1and_its_core_interactors_/574525", "title"=>"Network of how 100 of the 528 genes identified with significant differential expression relate to DISC1and its core interactors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-20 01:15:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/447323", "https://ndownloader.figshare.com/files/447357", "https://ndownloader.figshare.com/files/447392", "https://ndownloader.figshare.com/files/447413", "https://ndownloader.figshare.com/files/447431", "https://ndownloader.figshare.com/files/447446", "https://ndownloader.figshare.com/files/447463", "https://ndownloader.figshare.com/files/447475"], "description"=>"<div><h3>Background</h3><p>Genetic and biological evidence supports a role for DISC1 across a spectrum of major mental illnesses, including schizophrenia and bipolar disorder. There is evidence for genetic interplay between variants in DISC1 and in biologically interacting loci in psychiatric illness. DISC1 also associates with normal variance in behavioral and brain imaging phenotypes.</p><h3>Methodology</h3><p>Here, we analyze public domain datasets and demonstrate correlations between variants in the DISC1 pathway genes and levels of gene expression. Genetic variants of DISC1, NDE1, PDE4B and PDE4D regulate the expression of cytoskeletal, synaptogenic, neurodevelopmental and sensory perception proteins. Interestingly, these regulated genes include existing targets for drug development in depression and psychosis.</p><h3>Conclusions</h3><p>Our systematic analysis provides further evidence for the relevance of the DISC1 pathway to major mental illness, identifies additional potential targets for therapeutic intervention and establishes a general strategy to mine public datasets for insights into disease pathways.</p></div>", "links"=>[], "tags"=>["disc1", "pathway", "modulates", "synaptogenic", "sensory", "genes"], "article_id"=>148158, "categories"=>["Genetics", "Cancer", "Mental Health"], "users"=>["William Hennah", "David Porteous"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0004906.s001", "https://dx.doi.org/10.1371/journal.pone.0004906.s002", "https://dx.doi.org/10.1371/journal.pone.0004906.s003", "https://dx.doi.org/10.1371/journal.pone.0004906.s004", "https://dx.doi.org/10.1371/journal.pone.0004906.s005", "https://dx.doi.org/10.1371/journal.pone.0004906.s006", "https://dx.doi.org/10.1371/journal.pone.0004906.s007", "https://dx.doi.org/10.1371/journal.pone.0004906.s008"], "stats"=>{"downloads"=>25, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_DISC1_Pathway_Modulates_Expression_of_Neurodevelopmental_Synaptogenic_and_Sensory_Perception_Genes/148158", "title"=>"The DISC1 Pathway Modulates Expression of Neurodevelopmental, Synaptogenic and Sensory Perception Genes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-03-20 02:15:58"}

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