The role of rare compound heterozygous events in autism spectrum disorder.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
22 06 2020
Historique:
received: 29 10 2019
accepted: 15 05 2020
revised: 05 05 2020
entrez: 24 6 2020
pubmed: 24 6 2020
medline: 22 6 2021
Statut: epublish

Résumé

The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X

Identifiants

pubmed: 32572023
doi: 10.1038/s41398-020-00866-7
pii: 10.1038/s41398-020-00866-7
pmc: PMC7308334
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

204

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Auteurs

Bochao Danae Lin (BD)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Fabrice Colas (F)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Isaac J Nijman (IJ)

Department of Medical Informatics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Jelena Medic (J)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

William Brands (W)

Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Jeremy R Parr (JR)

Institute of Neuroscience, Newcastle University, Newcastle, UK.

Kristel R van Eijk (KR)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Sabine M Klauck (SM)

Division of Molecular Genome Analysis and Division of Cancer Genome Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Andreas G Chiocchetti (AG)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, JW Goethe University Frankfurt, Frankfurt am Main, Germany.

Christine M Freitag (CM)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, JW Goethe University Frankfurt, Frankfurt am Main, Germany.

Elena Maestrini (E)

Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Elena Bacchelli (E)

Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Hilary Coon (H)

Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.

Astrid Vicente (A)

Instituto Nacional de Saúde Doutor Ricardo Jorge, Avenida Padre Cruz, Lisboa, Portugal.

Guiomar Oliveira (G)

Centro Hospitalar de Coimbra, Coimbra, Portugal.

Alistair T Pagnamenta (AT)

NIHR Oxford BRC, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Louise Gallagher (L)

Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland.

Sean Ennis (S)

Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.

Richard Anney (R)

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Thomas Bourgeron (T)

Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, Paris, France.

Jurjen J Luykx (JJ)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
GGNet Mental Health, Apeldoorn, The Netherlands.

Jacob Vorstman (J)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. jacob.vorstman@sickkids.ca.
Program in Genetics and Genome Biology, Research Institute, and Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada. jacob.vorstman@sickkids.ca.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada. jacob.vorstman@sickkids.ca.

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