Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.
Identifieur interne : 001674 ( Main/Exploration ); précédent : 001673; suivant : 001675Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.
Auteurs : Michael R. Johnson [Royaume-Uni] ; Kirill Shkura [Royaume-Uni] ; Sarah R. Langley [Royaume-Uni] ; Andree Delahaye-Duriez [Royaume-Uni] ; Prashant Srivastava [Royaume-Uni] ; W David Hill [Royaume-Uni] ; Owen J L. Rackham ; Gail Davies [Royaume-Uni] ; Sarah E. Harris [Royaume-Uni] ; Aida Moreno-Moral [Royaume-Uni] ; Maxime Rotival [Royaume-Uni] ; Doug Speed [Royaume-Uni] ; Slavé Petrovski [Australie] ; Anaïs Katz [Royaume-Uni] ; Caroline Hayward [Royaume-Uni] ; David J. Porteous [Royaume-Uni] ; Blair H. Smith [Royaume-Uni] ; Sandosh Padmanabhan [Royaume-Uni] ; Lynne J. Hocking [Royaume-Uni] ; John M. Starr [Royaume-Uni] ; David C. Liewald [Royaume-Uni] ; Alessia Visconti [Royaume-Uni] ; Mario Falchi [Royaume-Uni] ; Leonardo Bottolo [Royaume-Uni] ; Tiziana Rossetti [Royaume-Uni] ; Bénédicte Danis [Belgique] ; Manuela Mazzuferi [Belgique] ; Patrik Foerch [Belgique] ; Alexander Grote [Allemagne] ; Christoph Helmstaedter [Allemagne] ; Albert J. Becker [Allemagne] ; Rafal M. Kaminski [Belgique] ; Ian J. Deary [Royaume-Uni] ; Enrico Petretto [Royaume-Uni]Source :
- Nature neuroscience [ 1546-1726 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Biochimie de l'encéphale (génétique), Cognition, Expression des gènes, Hippocampe (), Humains, Incapacités de développement (génétique), Incapacités de développement (physiopathologie), Incapacités de développement (psychologie), Réseaux de régulation génique (génétique), Synapses (génétique), Système nerveux (croissance et développement), Système nerveux (physiopathologie), Variation génétique, Épilepsie temporale (), Épilepsie temporale (génétique), Étude d'association pangénomique.
- MESH :
- croissance et développement : Système nerveux.
- génétique : Biochimie de l'encéphale, Incapacités de développement, Réseaux de régulation génique, Synapses, Épilepsie temporale.
- physiopathologie : Incapacités de développement, Système nerveux.
- psychologie : Incapacités de développement.
- Animaux, Cognition, Expression des gènes, Hippocampe, Humains, Variation génétique, Épilepsie temporale, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Animals, Brain Chemistry (genetics), Cognition, Developmental Disabilities (genetics), Developmental Disabilities (physiopathology), Developmental Disabilities (psychology), Epilepsy, Temporal Lobe (genetics), Epilepsy, Temporal Lobe (surgery), Gene Expression, Gene Regulatory Networks (genetics), Genetic Variation, Genome-Wide Association Study, Hippocampus (surgery), Humans, Nervous System (growth & development), Nervous System (physiopathology), Synapses (genetics).
- MESH :
- genetics : Brain Chemistry, Developmental Disabilities, Epilepsy, Temporal Lobe, Gene Regulatory Networks, Synapses.
- growth & development : Nervous System.
- physiopathology : Developmental Disabilities, Nervous System.
- psychology : Developmental Disabilities.
- surgery : Epilepsy, Temporal Lobe, Hippocampus.
- Animals, Cognition, Gene Expression, Genetic Variation, Genome-Wide Association Study, Humans.
Abstract
Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.
DOI: 10.1038/nn.4205
PubMed: 26691832
Affiliations:
- Allemagne, Australie, Belgique, Royaume-Uni
- Angleterre, District de Cologne, Grand Londres, Rhénanie-du-Nord-Westphalie, Victoria (État), Écosse
- Bonn, Glasgow, Londres, Melbourne, Édimbourg
- Université d'Édimbourg, Université de Glasgow, Université de Melbourne
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Le document en format XML
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Hocking</name><affiliation wicri:level="1"><nlm:affiliation>Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Applied Health Sciences, University of Aberdeen, Aberdeen</wicri:regionArea><wicri:noRegion>Aberdeen</wicri:noRegion></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Liewald, David C" sort="Liewald, David C" uniqKey="Liewald D" first="David C" last="Liewald">David C. Liewald</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Visconti, Alessia" sort="Visconti, Alessia" uniqKey="Visconti A" first="Alessia" last="Visconti">Alessia Visconti</name><affiliation wicri:level="3"><nlm:affiliation>Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, Kings College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Falchi, Mario" sort="Falchi, Mario" uniqKey="Falchi M" first="Mario" last="Falchi">Mario Falchi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, Kings College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Bottolo, Leonardo" sort="Bottolo, Leonardo" uniqKey="Bottolo L" first="Leonardo" last="Bottolo">Leonardo Bottolo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Mathematics, Imperial College, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Mathematics, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Rossetti, Tiziana" sort="Rossetti, Tiziana" uniqKey="Rossetti T" first="Tiziana" last="Rossetti">Tiziana Rossetti</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Danis, Benedicte" sort="Danis, Benedicte" uniqKey="Danis B" first="Bénédicte" last="Danis">Bénédicte Danis</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Mazzuferi, Manuela" sort="Mazzuferi, Manuela" uniqKey="Mazzuferi M" first="Manuela" last="Mazzuferi">Manuela Mazzuferi</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Foerch, Patrik" sort="Foerch, Patrik" uniqKey="Foerch P" first="Patrik" last="Foerch">Patrik Foerch</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Grote, Alexander" sort="Grote, Alexander" uniqKey="Grote A" first="Alexander" last="Grote">Alexander Grote</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurosurgery, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurosurgery, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Helmstaedter, Christoph" sort="Helmstaedter, Christoph" uniqKey="Helmstaedter C" first="Christoph" last="Helmstaedter">Christoph Helmstaedter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neuropsychology, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neuropsychology, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Becker, Albert J" sort="Becker, Albert J" uniqKey="Becker A" first="Albert J" last="Becker">Albert J. Becker</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neuropathology, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neuropathology, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Kaminski, Rafal M" sort="Kaminski, Rafal M" uniqKey="Kaminski R" first="Rafal M" last="Kaminski">Rafal M. Kaminski</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Petretto, Enrico" sort="Petretto, Enrico" uniqKey="Petretto E" first="Enrico" last="Petretto">Enrico Petretto</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26691832</idno><idno type="pmid">26691832</idno><idno type="doi">10.1038/nn.4205</idno><idno type="wicri:Area/PubMed/Corpus">002260</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002260</idno><idno type="wicri:Area/PubMed/Curation">002234</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002234</idno><idno type="wicri:Area/PubMed/Checkpoint">002234</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002234</idno><idno type="wicri:Area/Ncbi/Merge">002F00</idno><idno type="wicri:Area/Ncbi/Curation">002F00</idno><idno type="wicri:Area/Ncbi/Checkpoint">002F00</idno><idno type="wicri:Area/Main/Merge">001669</idno><idno type="wicri:Area/Main/Curation">001674</idno><idno type="wicri:Area/Main/Exploration">001674</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.</title><author><name sortKey="Johnson, Michael R" sort="Johnson, Michael R" uniqKey="Johnson M" first="Michael R" last="Johnson">Michael R. Johnson</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Shkura, Kirill" sort="Shkura, Kirill" uniqKey="Shkura K" first="Kirill" last="Shkura">Kirill Shkura</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Langley, Sarah R" sort="Langley, Sarah R" uniqKey="Langley S" first="Sarah R" last="Langley">Sarah R. Langley</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Delahaye Duriez, Andree" sort="Delahaye Duriez, Andree" uniqKey="Delahaye Duriez A" first="Andree" last="Delahaye-Duriez">Andree Delahaye-Duriez</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Srivastava, Prashant" sort="Srivastava, Prashant" uniqKey="Srivastava P" first="Prashant" last="Srivastava">Prashant Srivastava</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hill, W David" sort="Hill, W David" uniqKey="Hill W" first="W David" last="Hill">W David Hill</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Rackham, Owen J L" sort="Rackham, Owen J L" uniqKey="Rackham O" first="Owen J L" last="Rackham">Owen J L. Rackham</name><affiliation><nlm:affiliation>Duke-NUS Medical School, Singapore, Republic of Singapore.</nlm:affiliation><wicri:noCountry code="subField">Republic of Singapore</wicri:noCountry></affiliation></author><author><name sortKey="Davies, Gail" sort="Davies, Gail" uniqKey="Davies G" first="Gail" last="Davies">Gail Davies</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Moreno Moral, Aida" sort="Moreno Moral, Aida" uniqKey="Moreno Moral A" first="Aida" last="Moreno-Moral">Aida Moreno-Moral</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Rotival, Maxime" sort="Rotival, Maxime" uniqKey="Rotival M" first="Maxime" last="Rotival">Maxime Rotival</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Speed, Doug" sort="Speed, Doug" uniqKey="Speed D" first="Doug" last="Speed">Doug Speed</name><affiliation wicri:level="3"><nlm:affiliation>University College London Genetics Institute, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University College London Genetics Institute, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Petrovski, Slave" sort="Petrovski, Slave" uniqKey="Petrovski S" first="Slavé" last="Petrovski">Slavé Petrovski</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Austin Hospital and Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, Austin Hospital and Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Katz, Anais" sort="Katz, Anais" uniqKey="Katz A" first="Anaïs" last="Katz">Anaïs Katz</name><affiliation wicri:level="3"><nlm:affiliation>Division of Brain Sciences, Imperial College Faculty of Medicine, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Brain Sciences, Imperial College Faculty of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><affiliation wicri:level="4"><nlm:affiliation>Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Porteous, David J" sort="Porteous, David J" uniqKey="Porteous D" first="David J" last="Porteous">David J. Porteous</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Smith, Blair H" sort="Smith, Blair H" uniqKey="Smith B" first="Blair H" last="Smith">Blair H. Smith</name><affiliation wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Population Health Sciences, University of Dundee, Dundee</wicri:regionArea><wicri:noRegion>Dundee</wicri:noRegion></affiliation></author><author><name sortKey="Padmanabhan, Sandosh" sort="Padmanabhan, Sandosh" uniqKey="Padmanabhan S" first="Sandosh" last="Padmanabhan">Sandosh Padmanabhan</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea><orgName type="university">Université de Glasgow</orgName><placeName><settlement type="city">Glasgow</settlement><region type="country">Écosse</region></placeName></affiliation></author><author><name sortKey="Hocking, Lynne J" sort="Hocking, Lynne J" uniqKey="Hocking L" first="Lynne J" last="Hocking">Lynne J. Hocking</name><affiliation wicri:level="1"><nlm:affiliation>Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Applied Health Sciences, University of Aberdeen, Aberdeen</wicri:regionArea><wicri:noRegion>Aberdeen</wicri:noRegion></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Liewald, David C" sort="Liewald, David C" uniqKey="Liewald D" first="David C" last="Liewald">David C. Liewald</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Visconti, Alessia" sort="Visconti, Alessia" uniqKey="Visconti A" first="Alessia" last="Visconti">Alessia Visconti</name><affiliation wicri:level="3"><nlm:affiliation>Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, Kings College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Falchi, Mario" sort="Falchi, Mario" uniqKey="Falchi M" first="Mario" last="Falchi">Mario Falchi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, Kings College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Bottolo, Leonardo" sort="Bottolo, Leonardo" uniqKey="Bottolo L" first="Leonardo" last="Bottolo">Leonardo Bottolo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Mathematics, Imperial College, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Mathematics, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Rossetti, Tiziana" sort="Rossetti, Tiziana" uniqKey="Rossetti T" first="Tiziana" last="Rossetti">Tiziana Rossetti</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Danis, Benedicte" sort="Danis, Benedicte" uniqKey="Danis B" first="Bénédicte" last="Danis">Bénédicte Danis</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Mazzuferi, Manuela" sort="Mazzuferi, Manuela" uniqKey="Mazzuferi M" first="Manuela" last="Mazzuferi">Manuela Mazzuferi</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Foerch, Patrik" sort="Foerch, Patrik" uniqKey="Foerch P" first="Patrik" last="Foerch">Patrik Foerch</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Grote, Alexander" sort="Grote, Alexander" uniqKey="Grote A" first="Alexander" last="Grote">Alexander Grote</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurosurgery, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurosurgery, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Helmstaedter, Christoph" sort="Helmstaedter, Christoph" uniqKey="Helmstaedter C" first="Christoph" last="Helmstaedter">Christoph Helmstaedter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neuropsychology, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neuropsychology, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Becker, Albert J" sort="Becker, Albert J" uniqKey="Becker A" first="Albert J" last="Becker">Albert J. Becker</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neuropathology, University of Bonn, Bonn, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neuropathology, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Kaminski, Rafal M" sort="Kaminski, Rafal M" uniqKey="Kaminski R" first="Rafal M" last="Kaminski">Rafal M. Kaminski</name><affiliation wicri:level="1"><nlm:affiliation>Neuroscience TA, UCB Pharma, Braine-l'Alleud, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Neuroscience TA, UCB Pharma, Braine-l'Alleud</wicri:regionArea><wicri:noRegion>Braine-l'Alleud</wicri:noRegion></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></affiliation></author><author><name sortKey="Petretto, Enrico" sort="Petretto, Enrico" uniqKey="Petretto E" first="Enrico" last="Petretto">Enrico Petretto</name><affiliation wicri:level="3"><nlm:affiliation>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">Nature neuroscience</title><idno type="eISSN">1546-1726</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain Chemistry (genetics)</term><term>Cognition</term><term>Developmental Disabilities (genetics)</term><term>Developmental Disabilities (physiopathology)</term><term>Developmental Disabilities (psychology)</term><term>Epilepsy, Temporal Lobe (genetics)</term><term>Epilepsy, Temporal Lobe (surgery)</term><term>Gene Expression</term><term>Gene Regulatory Networks (genetics)</term><term>Genetic Variation</term><term>Genome-Wide Association Study</term><term>Hippocampus (surgery)</term><term>Humans</term><term>Nervous System (growth & development)</term><term>Nervous System (physiopathology)</term><term>Synapses (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Biochimie de l'encéphale (génétique)</term><term>Cognition</term><term>Expression des gènes</term><term>Hippocampe ()</term><term>Humains</term><term>Incapacités de développement (génétique)</term><term>Incapacités de développement (physiopathologie)</term><term>Incapacités de développement (psychologie)</term><term>Réseaux de régulation génique (génétique)</term><term>Synapses (génétique)</term><term>Système nerveux (croissance et développement)</term><term>Système nerveux (physiopathologie)</term><term>Variation génétique</term><term>Épilepsie temporale ()</term><term>Épilepsie temporale (génétique)</term><term>Étude d'association pangénomique</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Système nerveux</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Brain Chemistry</term><term>Developmental Disabilities</term><term>Epilepsy, Temporal Lobe</term><term>Gene Regulatory Networks</term><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Nervous System</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Biochimie de l'encéphale</term><term>Incapacités de développement</term><term>Réseaux de régulation génique</term><term>Synapses</term><term>Épilepsie temporale</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Incapacités de développement</term><term>Système nerveux</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Developmental Disabilities</term><term>Nervous System</term></keywords><keywords scheme="MESH" qualifier="psychologie" xml:lang="fr"><term>Incapacités de développement</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Developmental Disabilities</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Epilepsy, Temporal Lobe</term><term>Hippocampus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cognition</term><term>Gene Expression</term><term>Genetic Variation</term><term>Genome-Wide Association Study</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cognition</term><term>Expression des gènes</term><term>Hippocampe</term><term>Humains</term><term>Variation génétique</term><term>Épilepsie temporale</term><term>Étude d'association pangénomique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Belgique</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>District de Cologne</li><li>Grand Londres</li><li>Rhénanie-du-Nord-Westphalie</li><li>Victoria (État)</li><li>Écosse</li></region><settlement><li>Bonn</li><li>Glasgow</li><li>Londres</li><li>Melbourne</li><li>Édimbourg</li></settlement><orgName><li>Université d'Édimbourg</li><li>Université de Glasgow</li><li>Université de Melbourne</li></orgName></list><tree><noCountry><name sortKey="Rackham, Owen J L" sort="Rackham, Owen J L" uniqKey="Rackham O" first="Owen J L" last="Rackham">Owen J L. Rackham</name></noCountry><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Johnson, Michael R" sort="Johnson, Michael R" uniqKey="Johnson M" first="Michael R" last="Johnson">Michael R. Johnson</name></region><name sortKey="Bottolo, Leonardo" sort="Bottolo, Leonardo" uniqKey="Bottolo L" first="Leonardo" last="Bottolo">Leonardo Bottolo</name><name sortKey="Davies, Gail" sort="Davies, Gail" uniqKey="Davies G" first="Gail" last="Davies">Gail Davies</name><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><name sortKey="Delahaye Duriez, Andree" sort="Delahaye Duriez, Andree" uniqKey="Delahaye Duriez A" first="Andree" last="Delahaye-Duriez">Andree Delahaye-Duriez</name><name sortKey="Falchi, Mario" sort="Falchi, Mario" uniqKey="Falchi M" first="Mario" last="Falchi">Mario Falchi</name><name sortKey="Harris, Sarah E" sort="Harris, Sarah E" uniqKey="Harris S" first="Sarah E" last="Harris">Sarah E. Harris</name><name sortKey="Hayward, Caroline" sort="Hayward, Caroline" uniqKey="Hayward C" first="Caroline" last="Hayward">Caroline Hayward</name><name sortKey="Hill, W David" sort="Hill, W David" uniqKey="Hill W" first="W David" last="Hill">W David Hill</name><name sortKey="Hocking, Lynne J" sort="Hocking, Lynne J" uniqKey="Hocking L" first="Lynne J" last="Hocking">Lynne J. Hocking</name><name sortKey="Katz, Anais" sort="Katz, Anais" uniqKey="Katz A" first="Anaïs" last="Katz">Anaïs Katz</name><name sortKey="Langley, Sarah R" sort="Langley, Sarah R" uniqKey="Langley S" first="Sarah R" last="Langley">Sarah R. Langley</name><name sortKey="Liewald, David C" sort="Liewald, David C" uniqKey="Liewald D" first="David C" last="Liewald">David C. Liewald</name><name sortKey="Moreno Moral, Aida" sort="Moreno Moral, Aida" uniqKey="Moreno Moral A" first="Aida" last="Moreno-Moral">Aida Moreno-Moral</name><name sortKey="Padmanabhan, Sandosh" sort="Padmanabhan, Sandosh" uniqKey="Padmanabhan S" first="Sandosh" last="Padmanabhan">Sandosh Padmanabhan</name><name sortKey="Petretto, Enrico" sort="Petretto, Enrico" uniqKey="Petretto E" first="Enrico" last="Petretto">Enrico Petretto</name><name sortKey="Porteous, David J" sort="Porteous, David J" uniqKey="Porteous D" first="David J" last="Porteous">David J. Porteous</name><name sortKey="Rossetti, Tiziana" sort="Rossetti, Tiziana" uniqKey="Rossetti T" first="Tiziana" last="Rossetti">Tiziana Rossetti</name><name sortKey="Rotival, Maxime" sort="Rotival, Maxime" uniqKey="Rotival M" first="Maxime" last="Rotival">Maxime Rotival</name><name sortKey="Shkura, Kirill" sort="Shkura, Kirill" uniqKey="Shkura K" first="Kirill" last="Shkura">Kirill Shkura</name><name sortKey="Smith, Blair H" sort="Smith, Blair H" uniqKey="Smith B" first="Blair H" last="Smith">Blair H. Smith</name><name sortKey="Speed, Doug" sort="Speed, Doug" uniqKey="Speed D" first="Doug" last="Speed">Doug Speed</name><name sortKey="Srivastava, Prashant" sort="Srivastava, Prashant" uniqKey="Srivastava P" first="Prashant" last="Srivastava">Prashant Srivastava</name><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><name sortKey="Visconti, Alessia" sort="Visconti, Alessia" uniqKey="Visconti A" first="Alessia" last="Visconti">Alessia Visconti</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Petrovski, Slave" sort="Petrovski, Slave" uniqKey="Petrovski S" first="Slavé" last="Petrovski">Slavé Petrovski</name></region></country><country name="Belgique"><noRegion><name sortKey="Danis, Benedicte" sort="Danis, Benedicte" uniqKey="Danis B" first="Bénédicte" last="Danis">Bénédicte Danis</name></noRegion><name sortKey="Foerch, Patrik" sort="Foerch, Patrik" uniqKey="Foerch P" first="Patrik" last="Foerch">Patrik Foerch</name><name sortKey="Kaminski, Rafal M" sort="Kaminski, Rafal M" uniqKey="Kaminski R" first="Rafal M" last="Kaminski">Rafal M. Kaminski</name><name sortKey="Mazzuferi, Manuela" sort="Mazzuferi, Manuela" uniqKey="Mazzuferi M" first="Manuela" last="Mazzuferi">Manuela Mazzuferi</name></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Grote, Alexander" sort="Grote, Alexander" uniqKey="Grote A" first="Alexander" last="Grote">Alexander Grote</name></region><name sortKey="Becker, Albert J" sort="Becker, Albert J" uniqKey="Becker A" first="Albert J" last="Becker">Albert J. Becker</name><name sortKey="Helmstaedter, Christoph" sort="Helmstaedter, Christoph" uniqKey="Helmstaedter C" first="Christoph" last="Helmstaedter">Christoph Helmstaedter</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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