Whole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex.

Base Sequence / genetics Brain / embryology Computational Biology / methods Databases, Genetic Genetic Predisposition to Disease / genetics Genetic Variation / genetics Genome-Wide Association Study / methods Genomics / methods Humans Phenotype Polymorphism, Single Nucleotide / genetics Prefrontal Cortex / metabolism Quantitative Trait Loci / genetics Sequence Analysis, RNA / methods Transcriptome / genetics Exome Sequencing / methods Whole Genome Sequencing / methods
BrainVar DLPFC LOC101926933 RP11-298I3.1 AL132780.1 ENSG00000257285 PsychENCODE RHEBL1 dorsolateral prefrontal cortex fetal transition mTOR prenatal eQTL

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
07 04 2020
Historique:
received: 21 03 2019
revised: 06 11 2019
accepted: 16 03 2020
entrez: 9 4 2020
pubmed: 9 4 2020
medline: 28 4 2021
Statut: ppublish

Résumé

Gene expression levels vary across developmental stage, cell type, and region in the brain. Genomic variants also contribute to the variation in expression, and some neuropsychiatric disorder loci may exert their effects through this mechanism. To investigate these relationships, we present BrainVar, a unique resource of paired whole-genome and bulk tissue RNA sequencing from the dorsolateral prefrontal cortex of 176 individuals across prenatal and postnatal development. Here we identify common variants that alter gene expression (expression quantitative trait loci [eQTLs]) constantly across development or predominantly during prenatal or postnatal stages. Both "constant" and "temporal-predominant" eQTLs are enriched for loci associated with neuropsychiatric traits and disorders and colocalize with specific variants. Expression levels of more than 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell-type-specific genes and neuropsychiatric risk loci, underscoring the importance of cataloging developmental trajectories in understanding cortical physiology and pathology.

Identifiants

DOI: 10.1016/j.celrep.2020.03.053 PMID: 32268104 PMC: PMC7295160
pubmed: 32268104
pii: S2211-1247(20)30367-3
doi: 10.1016/j.celrep.2020.03.053
pmc: PMC7295160
mid: NIHMS1582939
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

107489

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH110928
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH094714
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH103877
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103365
Pays : United States
Organisme : NIDCR NIH HHS
ID : R03 DE025665
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG006399
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103392
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH057881
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103346
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105472
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103340
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103339
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109904
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH105881
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH106874
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110926
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH116488
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH106934
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115957
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH057881
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH105575
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227237
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109901
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD081256
Pays : United States
Organisme : NICHD NIH HHS
ID : R24 HD000836
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH111662
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH102791
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105898
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD096326
Pays : United States
Organisme : NHLBI NIH HHS
ID : K25 HL121295
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Donna M Werling (DM)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.

Sirisha Pochareddy (S)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Jinmyung Choi (J)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Joon-Yong An (JY)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea; School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea.

Brooke Sheppard (B)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Minshi Peng (M)

Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Zhen Li (Z)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA.

Claudia Dastmalchi (C)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Gabriel Santpere (G)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Neurogenomics Group, Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain.

André M M Sousa (AMM)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Andrew T N Tebbenkamp (ATN)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Navjot Kaur (N)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Forrest O Gulden (FO)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.

Michael S Breen (MS)

Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Lindsay Liang (L)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Michael C Gilson (MC)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Xuefang Zhao (X)

Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.

Shan Dong (S)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Lambertus Klei (L)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

A Ercument Cicek (AE)

Department of Computer Engineering, Bilkent University, Ankara 06800, Turkey; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Joseph D Buxbaum (JD)

Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Homa Adle-Biassette (H)

Department of Pathology, Lariboisière Hospital, APHP, Biobank BB-0033-00064, and Université de Paris, 75006 Paris, France.

Jean-Leon Thomas (JL)

Department of Neurology, Yale University School of Medicine, New Haven, CT 06511, USA; UMRS1127, Sorbonne Université, Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France.

Kimberly A Aldinger (KA)

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.

Diana R O'Day (DR)

Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.

Ian A Glass (IA)

Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.

Noah A Zaitlen (NA)

Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.

Michael E Talkowski (ME)

Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA.

Kathryn Roeder (K)

Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Matthew W State (MW)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA.

Bernie Devlin (B)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Stephan J Sanders (SJ)

Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: stephan.sanders@ucsf.edu.

Nenad Sestan (N)

Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06510, USA; Program in Cellular Neuroscience, Neurodegeneration, and Repair and Yale Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: nenad.sestan@yale.edu.

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence nucléotidique › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Sciences de l'information › Informatique › Biologie informatique › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Bases de données comme sujet › Bases de données factuelles › Bases de données génétiques › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Whole-Genome and RNA Sequencing Reveal...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Whole-Genome and RNA Sequencing Reveal...