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PMID: 24387789 Published · ppublish English Journal Article Review

A de novo convergence of autism genetics and molecular neuroscience.

Trends in neurosciences ·Vol. 37 ·No. 2 ·2014-02-00 ·Pages 95-105

Krumm N, O'Roak BJ, Shendure J, Eichler EE

Abstract

Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental disorders with large genetic components, but identification of pathogenic genes has proceeded slowly because hundreds of loci are involved. New exome sequencing technology has identified novel rare variants and has found that sporadic cases of ASD/ID are enriched for disruptive de novo mutations. Targeted large-scale resequencing studies have confirmed the significance of specific loci, including chromodomain helicase DNA binding protein 8 (CHD8), sodium channel, voltage-gated, type II, alpha subunit (SCN2A), dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), and catenin (cadherin-associated protein), beta 1, 88 kDa (CTNNB1, beta-catenin). We review recent studies and suggest that they have led to a convergence on three functional pathways: (i) chromatin remodeling; (ii) wnt signaling during development; and (iii) synaptic function. These pathways and genes significantly expand the neurobiological targets for study, and suggest a path for future genetic and functional studies.

Keywords
autism genetics autism spectrum disorder copy number variant exome sequencing intellectual disability single nucleotide variant
MeSH Terms
Autistic Disorder/genetics Exome/genetics Genetic Predisposition to Disease Humans Neurosciences/trends
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Krumm Niklas
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
O'Roak Brian J
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Shendure Jay
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Eichler Evan E
Department of Genome Sciences, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: [email protected].
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Article Info
Journal
Trends in neurosciences
Abbr.
Trends Neurosci
ISSN
1878-108X
DOI
10.1016/j.tins.2013.11.005
Email
[email protected]
Published
2014-02-00
Epub
2013-00-30
Pages
95-105
Language
English
Region
England
NLM ID
7808616
PMCID
PMC4077788
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · T32 GM007266 · United States
External Links
PubMed source DOI: 10.1016/j.tins.2013.11.005 PMC Full Text View journal details
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