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.
Laboratory of Clinical and Developmental Genomics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.|University of Cambridge, Robinson College, Cambridgeshire, UK.|Baylor College of Medicine MSTP, One Baylor Plaza, Houston, TX, USA.
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Ziats
Pediatrics and Developmental Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
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Grosvenor
Laboratory of Clinical and Developmental Genomics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
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Rennert
D000067877:Autism Spectrum Disorder / Q000235:genetics*; D001921:Brain / Q000254:growth & development*; D044127:Epigenesis, Genetic / Q000235:genetics*; D023281:Genomics; D006801:Humans; D059467:Transcriptome / Q000235:genetics