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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5875
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pubmed:dateCreated |
2008-4-25
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pubmed:abstractText |
Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:AddingtonAnjené MAM,
pubmed-author:BakerCarlC,
pubmed-author:BhandariAbhishekA,
pubmed-author:ButlerPhilipP,
pubmed-author:ChenZugenZ,
pubmed-author:CooperGreg MGM,
pubmed-author:DavisSeanS,
pubmed-author:EckstrandKristenK,
pubmed-author:EichlerEvan EEE,
pubmed-author:FindlingRobert LRL,
pubmed-author:GochmanPeterP,
pubmed-author:GogtayNitinN,
pubmed-author:KingMary-ClaireMC,
pubmed-author:KusendaMaryM,
pubmed-author:LakshmiBB,
pubmed-author:LeeMing KMK,
pubmed-author:LongRobertR,
pubmed-author:MakarovVladV,
pubmed-author:MalhotraDheerajD,
pubmed-author:McCarthyShane ESE,
pubmed-author:McClellanJon MJM,
pubmed-author:MeltzerPaul SPS,
pubmed-author:MerrimanBarryB,
pubmed-author:NelsonStanley FSF,
pubmed-author:NooryLailaL,
pubmed-author:NordAlex SAS,
pubmed-author:PierceSarah BSB,
pubmed-author:RapoportJudith LJL,
pubmed-author:RippeyCaitlin FCF,
pubmed-author:RoccanovaPatriciaP,
pubmed-author:SebatJonathanJ,
pubmed-author:SikichLinmarieL,
pubmed-author:SingletonAndrew BAB,
pubmed-author:StraySunday MSM,
pubmed-author:StrombergThomasT,
pubmed-author:WalshTomT
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
320
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
539-43
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:18369103-Adolescent,
pubmed-meshheading:18369103-Adult,
pubmed-meshheading:18369103-Age of Onset,
pubmed-meshheading:18369103-Amino Acid Sequence,
pubmed-meshheading:18369103-Brain,
pubmed-meshheading:18369103-Case-Control Studies,
pubmed-meshheading:18369103-Child,
pubmed-meshheading:18369103-Excitatory Amino Acid Transporter 1,
pubmed-meshheading:18369103-Female,
pubmed-meshheading:18369103-Gene Deletion,
pubmed-meshheading:18369103-Gene Duplication,
pubmed-meshheading:18369103-Genetic Predisposition to Disease,
pubmed-meshheading:18369103-Genome, Human,
pubmed-meshheading:18369103-Humans,
pubmed-meshheading:18369103-Male,
pubmed-meshheading:18369103-Molecular Sequence Data,
pubmed-meshheading:18369103-Mutation,
pubmed-meshheading:18369103-Neurons,
pubmed-meshheading:18369103-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18369103-Polymorphism, Single Nucleotide,
pubmed-meshheading:18369103-Receptor, Epidermal Growth Factor,
pubmed-meshheading:18369103-Schizophrenia,
pubmed-meshheading:18369103-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.
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pubmed:affiliation |
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
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