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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Neurodevelopmental and neuropsychiatric disorders represent an interconnected molecular system

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Autor(es):
Cristino, A. S. [1] ; Williams, S. M. [1] ; Hawi, Z. [1, 2] ; An, J-Y [1] ; Bellgrove, M. A. [1, 2] ; Schwartz, C. E. [3] ; Costa, L. da F. [4] ; Claudianos, C. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072 - Australia
[2] Monash Univ, Sch Psychol & Psychiat, Melbourne, Vic 3004 - Australia
[3] Greenwood Genet Ctr, Greenwood, SC 29646 - USA
[4] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: MOLECULAR PSYCHIATRY; v. 19, n. 3, p. 294-301, MAR 2014.
Citações Web of Science: 89
Resumo

Many putative genetic factors that confer risk to neurodevelopmental disorders such as autism spectrum disorders (ASDs) and X-linked intellectual disability (XLID), and to neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and schizophrenia (SZ) have been identified in individuals from diverse human populations. Although there is significant aetiological heterogeneity within and between these conditions, recent data show that genetic factors contribute to their comorbidity. Many studies have identified candidate gene associations for these mental health disorders, albeit this is often done in a piecemeal fashion with little regard to the inherent molecular complexity. Here, we sought to abstract relationships from our knowledge of systems level biology to help understand the unique and common genetic drivers of these conditions. We undertook a global and systematic approach to build and integrate available data in gene networks associated with ASDs, XLID, ADHD and SZ. Complex network concepts and computational methods were used to investigate whether candidate genes associated with these conditions were related through mechanisms of gene regulation, functional protein-protein interactions, transcription factor (TF) and microRNA (miRNA) binding sites. Although our analyses show that genetic variations associated with the four disorders can occur in the same molecular pathways and functional domains, including synaptic transmission, there are patterns of variation that define significant differences between disorders. Of particular interest is DNA variations located in intergenic regions that comprise regulatory sites for TFs or miRNA. Our approach provides a hypothetical framework, which will help discovery and analysis of candidate genes associated with neurodevelopmental and neuropsychiatric disorders. (AU)

Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
Beneficiário:Roberto Marcondes Cesar Junior
Linha de fomento: Auxílio à Pesquisa - Temático