Large mosaic copy number variations confer autism risk.

Adult Autism Spectrum Disorder / epidemiology Autopsy Brain Chemistry / genetics Child Child Development Disorders, Pervasive / genetics Cohort Studies DNA Copy Number Variations Genetic Predisposition to Disease Genotype Germ-Line Mutation Humans Mosaicism Risk Assessment Tissue Banks

Journal

Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671

Informations de publication

Date de publication:
02 2021
Historique:
received: 09 01 2020
accepted: 21 11 2020
pubmed: 13 1 2021
medline: 20 3 2021
entrez: 12 1 2021
Statut: ppublish

Résumé

Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 probands with ASD and 5,500 unaffected siblings. We detected 46 mCNVs in probands and 19 mCNVs in siblings, affecting 2.8-73.8% of cells. Probands carried a significant burden of large (>4-Mb) mCNVs, which were detected in 25 probands but only one sibling (odds ratio = 11.4, 95% confidence interval = 1.5-84.2, P = 7.4 × 10

Identifiants

DOI: 10.1038/s41593-020-00766-5 PMID: 33432194 PMC: PMC7854495
pubmed: 33432194
doi: 10.1038/s41593-020-00766-5
pii: 10.1038/s41593-020-00766-5
pmc: PMC7854495
mid: NIHMS1648952
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

197-203

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH106883
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH104964
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : DP2ES030554
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : K25HL150334
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R01GM108348
Organisme : NIGMS NIH HHS
ID : R01 GM108348
Pays : United States
Organisme : NIMH NIH HHS
ID : F31 MH124393
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH104964
Organisme : NHLBI NIH HHS
ID : K25 HL150334
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : U01MH106883
Organisme : NINDS NIH HHS
ID : R01 NS032457
Pays : United States
Organisme : National Science Foundation (NSF)
ID : DMS-1939015
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : T32MH112510
Organisme : U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
ID : R01HG006855
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : T32GM007753
Organisme : NHGRI NIH HHS
ID : R01 HG006855
Pays : United States
Organisme : NIEHS NIH HHS
ID : DP2 ES030554
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH112510
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : F31MH124393

Commentaires et corrections

Type : CommentIn

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Auteurs

Maxwell A Sherman (MA)

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA. maxas@mit.edu.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. maxas@mit.edu.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. maxas@mit.edu.
ORCID: 0000-0002-5297-9252

Rachel E Rodin (RE)

Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.

Giulio Genovese (G)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-3066-5575

Caroline Dias (C)

Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
Division of Developmental Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Alison R Barton (AR)

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-0882-0196

Ronen E Mukamel (RE)

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Bonnie Berger (B)

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA.

Peter J Park (PJ)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. peter_park@hms.harvard.edu.
ORCID: 0000-0001-9378-960X

Christopher A Walsh (CA)

Broad Institute of MIT and Harvard, Cambridge, MA, USA. christopher.walsh@childrens.harvard.edu.
Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. christopher.walsh@childrens.harvard.edu.
ORCID: 0000-0002-0156-2238

Po-Ru Loh (PR)

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. poruloh@broadinstitute.org.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. poruloh@broadinstitute.org.
ORCID: 0000-0001-5542-9064

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Sciences sociales › Criminologie › Sciences légales › Médecine légale › Autopsie › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Métabolisme › Chimie du cerveau › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Phénomènes génétiques › Génotype › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation germinale › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Aberrations des chromosomes › Mosaïcisme › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Large mosaic copy number variations confer autism risk.
questionsmedicales.fr › Établissements, main d'oeuvre et services de soins de santé › Établissements de santé › Biobanques › Banques de tissus › Large mosaic copy number variations confer autism risk.