title: Understanding complex transcriptome dynamics in schizophrenia and other neurological diseases using RNA sequencing.
abstract: How the human brain develops and adapts with its trillions of functionally integrated synapses remains one of the greatest mysteries of life. With tremendous advances in neuroscience, genetics, and molecular biology, we are beginning to appreciate the scope of this complexity and define some of the parameters of the systems that make it possible. These same tools are also leading to advances in our understanding of the pathophysiology of neurocognitive and neuropsychiatric disorders. Like the substrate for these problems, the etiology is usually complex-involving an array of genetic and environmental influences. To resolve these influences and derive better interventions, we need to reveal every aspect of this complexity and model their interactions and define the systems and their regulatory structure. This is particularly important at the tissue-specific molecular interface between the underlying genetic and environmental influence defined by the transcriptome. Recent advances in transcriptome analysis facilitated by RNA sequencing (RNA-Seq) can provide unprecedented insight into the functional genomics of neurological disorders. In this review, we outline the advantages of this approach and highlight some early application of this technology in the investigation of the neuropathology of schizophrenia. Recent progress of RNA-Seq studies in schizophrenia has shown that there is extraordinary transcriptome dynamics with significant levels of alternative splicing. These studies only scratch the surface of this complexity and therefore future studies with greater depth and samples size will be vital to fully explore transcriptional diversity and its underlying influences in schizophrenia and provide the basis for new biomarkers and improved treatments.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, New South Wales, Australia; The Schizophrenia Research Institute, Sydney, Australia. Electronic address: murray.cairns@newcastle.edu.au.
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Cairns
mesh_terms: D000818:Animals; D001483:Base Sequence / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
keywords: Neurological disease; RNA processing; RNA sequencing; Schizophrenia; Transcriptome