Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism.

Bibliographic Collection: 
APE
Publication Type: Journal Article
Authors: Willsey, A Jeremy; Sanders, Stephan J; Li, Mingfeng; Dong, Shan; Tebbenkamp, Andrew T; Muhle, Rebecca A; Reilly, Steven K; Lin, Leon; Fertuzinhos, Sofia; Miller, Jeremy A; Murtha, Michael T; Bichsel, Candace; Niu, Wei; Cotney, Justin; Ercan-Sencicek, A Gulhan; Gockley, Jake; Gupta, Abha R; Han, Wenqi; He, Xin; Hoffman, Ellen J; Klei, Lambertus; Lei, Jing; Liu, Wenzhong; Liu, Li; Lu, Cong; Xu, Xuming; Zhu, Ying; Mane, Shrikant M; Lein, Ed S; Wei, Liping; Noonan, James P; Roeder, Kathryn; Devlin, Bernie; Sestan, Nenad; State, Matthew W
Year of Publication: 2013
Journal: Cell
Volume: 155
Issue: 5
Pagination: 997-1007
Date Published: 2013 Nov 21
Publication Language: eng
ISSN: 1097-4172
Keywords: Animals, Brain, Child Development Disorders, Pervasive, Exome, Female, Fetus, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mice, Mutation, Neurons, Prefrontal Cortex, Sequence Analysis, DNA
Abstract:

Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to contribute to a common phenotype, we have attempted to identify time periods, brain regions, and cell types in which these genes converge. We have constructed coexpression networks based on the hcASD "seed" genes, leveraging a rich expression data set encompassing multiple human brain regions across human development and into adulthood. By assessing enrichment of an independent set of probable ASD (pASD) genes, derived from the same sequencing studies, we demonstrate a key point of convergence in midfetal layer 5/6 cortical projection neurons. This approach informs when, where, and in what cell types mutations in these specific genes may be productively studied to clarify ASD pathophysiology.

DOI: 10.1016/j.cell.2013.10.020
Alternate Journal: Cell