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Nat Neurosci. 2017 Apr;20(4):602-611. doi: 10.1038/nn.4524. Epub 2017 Mar 6.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.

Author information

1
The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
2
Deep Genomics Inc., Toronto, Canada.
3
Google, Mountain View, California, USA.
4
Verily Life Sciences, South San Francisco, California, USA.
5
Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
6
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
7
Autism Research Unit, The Hospital for Sick Children, Toronto, Canada.
8
Public Population Project in Genomics and Society, McGill University, Montreal, Canada.
9
BioTeam Inc., Middleton, Massachusetts, USA.
10
Dalla Lana School of Public Health and the Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
11
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
12
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada.
13
Department of Pediatrics, University of Alberta, Edmonton, Canada.
14
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
15
Bloorview Research Institute, University of Toronto, Toronto, Canada. .
16
Department of Psychiatry, McGill University, Montreal, Canada.
17
Departments of Pediatrics and of Psychology &Neuroscience, Dalhousie University and Autism Research Centre, IWK Health Centre, Halifax, Canada.
18
Department of Psychiatry, Queen's University, Kinston, Canada.
19
Children's Health Research Institute, London, Ontario, Canada.
20
Western University, London, Ontario, Canada.
21
Autism Speaks, New York, New York, USA.
22
Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
23
Department of Radiology, University of Washington, Seattle, Washington, USA.
24
Department of Speech and Hearing Sciences, University of Washington, Seattle, Washington, USA.
25
Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
26
Sleep Disorders Division, Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
27
Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
28
Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
29
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
30
Department of Electrical and Computer Engineering and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada.
31
Department of Medicine, University of California San Diego, La Jolla, California, USA.
32
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Canada.
33
Disciplines of Genetics and Medicine, Memorial University of Newfoundland and Provincial Medical Genetic Program, Eastern Health, St. John's, Canada.
34
Regional Genetics Program, The Children's Hospital of Eastern Ontario, Ottawa, Canada.
35
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
36
Centre of Genomics and Policy, McGill University, Montreal, Canada.
37
Child Youth and Family Services, Centre for Addiction and Mental Health, Toronto, Canada.
38
Department of Psychiatry, University of Toronto, Toronto, Canada.
39
Department of Psychiatry, The Hospital for Sick Children, Toronto, Canada.
40
Department of Pharmacology &Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
41
McLaughlin Centre, University of Toronto, Toronto, Canada.

Abstract

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.

PMID:
28263302
PMCID:
PMC5501701
DOI:
10.1038/nn.4524
[Indexed for MEDLINE]
Free PMC Article

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