Functional genomics of human brain development and implications for autism spectrum disorders

Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic–epigenetic–environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics—non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.

• Publication year

  2015

• Venue

  Translational Psychiatry

• Publication date

  2015-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/tp.2015.153PMID 26506051PMCID 4930130
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Neuropathology of Autism

  2016cited by this paper
• Retraction Note: Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects

  2016cited by this paper
• A de novo convergence of autism genetics and molecular neuroscience.

  2014cited by this paper
• Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders

  2014cited by this paper
• A quantitative framework to evaluate modeling of cortical development by neural stem cells.

  2014cited by this paper
• A draft map of the human proteome

  2014cited by this paper
• The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing

  2014cited by this paper
• Human Accelerated Regions : plus rapide dans l ’ humain mais conservé ailleurs An RNA gene expressed during cortical development evolved rapidly in humans

  2014cited by this paper
• Role of radial glial cells in cerebral cortex folding.

  2014cited by this paper
• Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1

  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
• Microglia: new roles for the synaptic stripper.

  2013cited by this paper
• Review on intermediate filaments of the nervous system and their pathological alterations

  2013cited by this paper
• A Conserved Mammalian Protein Interaction Network

  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
• Microglial activation in young adults with autism spectrum disorder.

  2013cited by this paper
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  2013cited by this paper
• Expression of non-protein-coding antisense RNAs in genomic regions related to autism spectrum disorders

  2013cited by this paper
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  2013cited by this paper
• Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism.

  2013cited by this paper
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  2013cited by this paper
• Downregulation of the Expression of Mitochondrial Electron Transport Complex Genes in Autism Brains

  2013cited by this paper
• Sex differences in autism spectrum disorders.

  2013cited by this paper
• Power failure: why small sample size undermines the reliability of neuroscience

  2013cited by this paper
• Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism

  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
• Using the Student's "t"-Test with Extremely Small Sample Sizes.

  2013cited by this paper
• The genetic landscapes of autism spectrum disorders.

  2013cited by this paper
• Identification of Differentially Expressed MicroRNAs Across the Developing Human Brain

  2013cited by this paper
• Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia

  2013cited by this paper
• Cellular source and mechanisms of high transcriptome complexity in the mammalian testis.

  2013cited by this paper
• Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks

  2012cited by this paper
• Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome

  2012cited by this paper
• RNA Sequencing: Platform Selection, Experimental Design, and Data Interpretation

  2012cited by this paper
• β-Catenin signaling initiates the activation of astrocytes and its dysregulation contributes to the pathogenesis of astrocytomas

  2012cited by this paper
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  2012cited by this paper
• Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

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• Aberrant Expression of Long Noncoding RNAs in Autistic Brain

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• Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations

  2012cited by this paper
• Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages

  2012cited by this paper
• Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease

  2012cited by this paper
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  2012cited by this paper
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  2012cited by this paper
• The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost

  2012cited by this paper
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  2012cited by this paper
• Consensus Paper: Pathological Role of the Cerebellum in Autism

  2012cited by this paper
• Genome-wide expression studies in autism spectrum disorder, Rett syndrome, and Down syndrome.

  2012cited by this paper
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• Updated Energy Budgets for Neural Computation in the Neocortex and Cerebellum

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  2012cited by this paper
• The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression

  2012cited by this paper
• Genetic architecture in autism spectrum disorder.

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• Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders

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• Common genetic variants, acting additively, are a major source of risk for autism

  2012cited by this paper
• Gene expression studies in autism: moving from the genome to the transcriptome and beyond.

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• De novo gene disruptions in children on the autistic spectrum.

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• miRNA-132: a dynamic regulator of cognitive capacity

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• Phenotypic heterogeneity of genomic disorders and rare copy-number variants.

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• Brain region-specific altered expression and association of mitochondria-related genes in autism

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• Autism spectrum disorders—A genetics review

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• Integrating diverse genomic data using gene sets

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• The genetics of neurodevelopmental disease.

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• MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains

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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
• Epigenetic studies of schizophrenia: current status and future directions

  2019cites this paper
• Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders.

  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
• Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes.

  2018cites this paper
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  2018cites this paper
• Enduring neurobehavioural effects induced by early-life microbiota-gut-brain axis alterations

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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