American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn, text rev. (APA Publishing, Washington, DC, 2000).
Rojas, D. C. The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment. J. Neural Transm. (Vienna) 121, 891–905 (2014).
Guo, Y. P. & Commons, K. G. Serotonin neuron abnormalities in the BTBR mouse model of autism. Autism Res. 10, 66–77 (2017).
Ha, S., Sohn, I. J., Kim, N., Sim, H. J. & Cheon, K. A. Characteristics of brains in autism spectrum disorder: structure, function and connectivity across the lifespan. Exp. Neurobiol. 24, 273–284 (2015).
Nelson, S. B. & Valakh, V. Excitatory/inhibitory balance and circuit homeostasis in autism spectrum disorders. Neuron 87, 684–698 (2015).
Marchetto, M. C. et al. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Mol. Psychiatry 22, 820–835 (2017).
de la Torre-Ubieta, L., Won, H., Stein, J. L. & Geschwind, D. H. Advancing the understanding of autism disease mechanisms through genetics. Nat. Med. 22, 345–361 (2016).
Gupta, S. et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat. Commun. 5, 5748 (2014).
Parikshak, N. N. et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature 540, 423–427 (2016).
Irimia, M. et al. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 159, 1511–1523 (2014).
Wu, Y. E., Parikshak, N. N., Belgard, T. G. & Geschwind, D. H. Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder. Nat. Neurosci. 19, 1463–1476 (2016).
Nishikura, K. A-to-I editing of coding and non-coding RNAs by ADARs. Nat. Rev. Mol. Cell Biol. 17, 83–96 (2016).
Behm, M. & Öhman, M. RNA editing: a contributor to neuronal dynamics in the mammalian brain. Trends Genet. 32, 165–175 (2016).
Slotkin, W. & Nishikura, K. Adenosine-to-inosine RNA editing and human disease. Genome Med. 5, 105 (2013).
Khermesh, K. et al. Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer’s disease. RNA 22, 290–302 (2016).
Eran, A. et al. Comparative RNA editing in autistic and neurotypical cerebella. Mol. Psychiatry 18, 1041–1048 (2013).
Iossifov, I. et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74, 285–299 (2012).
Parikshak, N. N. et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008–1021 (2013).
Bahn, J. H. et al. Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Res. 22, 142–150 (2012).
Porath, H. T., Carmi, S. & Levanon, E. Y. A genome-wide map of hyper-edited RNA reveals numerous new sites. Nat. Commun. 5, 4726 (2014).
Picardi, E., D’Erchia, A. M., Lo Giudice, C. & Pesole, G. REDIportal: a comprehensive database of A-to-I RNA editing events in humans. Nucleic Acids Res. 45,(D1), D750–D757 (2017).
Levanon, E. Y. et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat. Biotechnol. 22, 1001–1005 (2004).
Oakes, E., Anderson, A., Cohen-Gadol, A. & Hundley, H. A. Adenosine deaminase that acts on RNA 3 (ADAR3) binding to glutamate receptor subunit B pre-mRNA inhibits RNA editing in glioblastoma. J. Biol. Chem. 292, 4326–4335 (2017).
Rakic, P. Evolution of the neocortex: a perspective from developmental biology. Nat. Rev. Neurosci. 10, 724–735 (2009).
Abrahams, B. S. et al. SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol. Autism 4, 36 (2013).
Hwang, T. et al. Dynamic regulation of RNA editing in human brain development and disease. Nat. Neurosci. 19, 1093–1099 (2016).
Liu, X. et al. Disruption of an evolutionarily novel synaptic expression pattern in autism. PLoS Biol. 14, e1002558 (2016).
Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008).
Davis, J. K. & Broadie, K. Multifarious functions of the Fragile X mental retardation protein. Trends Genet. 33, 703–714 (2017).
Darnell, J. C. et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 146, 247–261 (2011).
Zhang, Y. et al. The Fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J. 14, 5358–5366 (1995).
Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods 13, 508–514 (2016).
Ascano, M. et al. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature 492, 382–386 (2012).
Vasudevan, S. & Steitz, J. A. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 128, 1105–1118 (2007).
Van Nostrand, E. L. et al. A large-scale binding and functional map of human RNA binding proteins. Preprint at biorXiv https://www.biorxiv.org/content/early/2017/08/23/179648 (2017).
Hagerman, R., Hoem, G. & Hagerman, P. Fragile X and autism: intertwined at the molecular level leading to targeted treatments. Mol. Autism 1, 12 (2010).
Abbeduto, L., McDuffie, A. & Thurman, A. J. The fragile X syndrome-autism comorbidity: what do we really know? Front. Genet. 5, 355 (2014).
Pinto, Y., Cohen, H. Y. & Levanon, E. Y. Mammalian conserved ADAR targets comprise only a small fragment of the human editosome. Genome. Biol. 15, R5 (2014).
Irimia, M. et al. Evolutionarily conserved A-to-I editing increases protein stability of the alternative splicing factor Nova1. RNA Biol. 9, 12–21 (2012).
DiStefano, C. et al. Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome. J. Neurodev. Disord. 8, 19 (2016).
Battaglia, A. et al. The inv dup(15) syndrome: a clinically recognizable syndrome with altered behavior, mental retardation, and epilepsy. Neurology 48, 1081–1086 (1997).
Frith, C. & Dolan, R. The role of the prefrontal cortex in higher cognitive functions. Brain. Res. Cogn. Brain Res. 5, 175–181 (1996).
Jansen, A. et al. Gene-set analysis shows association between FMRP targets and autism spectrum disorder. Eur. J. Hum. Genet. 25, 863–868 (2017).
Pinto, D. et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet. 94, 677–694 (2014).
Fatemi, S. H. & Folsom, T. D. Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study. Mol. Autism 2, 6 (2011).
Patzlaff, N. E., Nemec, K. M., Malone, S. G., Li, Y. & Zhao, X. Fragile X related protein 1 (FXR1P) regulates proliferation of adult neural stem cells. Hum. Mol. Genet. 26, 1340–1352 (2017).
Charman, T. et al. IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP). Psychol. Med. 41, 619–627 (2011).
Finucane, B. M. et al. 15q duplication syndrome and related disorders. in GeneReviews (eds Adam, M. P. et al.) (University of Washington, Seattle, 2016).
Ahn, J. & Xiao, X. RASER: reads aligner for SNPs and editing sites of RNA. Bioinformatics 31, 3906–3913 (2015).
Lee, J. H., Ang, J. K. & Xiao, X. Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants. RNA 19, 725–732 (2013).
Feldmeyer, D. et al. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nat. Neurosci. 2, 57–64 (1999).
Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
Gu, Z., Gu, L., Eils, R., Schlesner, M. & Brors, B. circlize Implements and enhances circular visualization in R. Bioinformatics 30, 2811–2812 (2014).
Josse, J. & Husson, F. missMDA: a package for handling missing values in multivariate data analysis. J. Stat. Softw. 70, 31 (2016).
Langfelder, P., Zhang, B. & Horvath, S. Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R. Bioinformatics 24, 719–720 (2008).
Langfelder, P. & Horvath, S. Eigengene networks for studying the relationships between co-expression modules. BMC Syst. Biol. 1, 54 (2007).
Wheeler, E. C., Van Nostrand, E. L. & Yeo, G. W. Advances and challenges in the detection of transcriptome-wide protein-RNA interactions. Wiley Interdiscip. Rev. RNA https://doi.org/10.1002/wrna.1436 (2018).
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
Bailey, T. L., Johnson, J., Grant, C. E. & Noble, W. S. The MEME Suite. Nucleic Acids Res. 43(W1), W39–W49 (2015).
Aken, B. L. et al. The Ensembl gene annotation system. Database (Oxford) https://doi.org/10.1093/database/baw093 (2016).
Nojima, T., Gomes, T., Carmo-Fonseca, M. & Proudfoot, N. J. Mammalian NET-seq analysis defines nascent RNA profiles and associated RNA processing genome-wide. Nat. Protoc. 11, 413–428 (2016).
Sundararaman, B. et al. Resources for the comprehensive discovery of functional RNA elements. Mol. Cell 61, 903–913 (2016).
Bahn, J. H. et al. Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways. Nat. Commun. 6, 6355 (2015).