Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways

• Published in: PloS one 2011-09, Vol.6 (9), p.e24691-e24691
• Main Authors: Ziats, Mark N, Rennert, Owen M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autism; Biology; Brain; Brain - metabolism; Brain diseases; Child; Child Development Disorders, Pervasive - genetics; Child, Preschool; Childrens health; Databases, Genetic; Development and progression; Disease; Etiology; Female; Gene expression; Gene Expression Profiling - methods; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Genomes; Genomics; Humans; Infant; Infant, Newborn; JNK protein; Kinases; Laboratories; Ligands; MAP Kinase Signaling System - genetics; Medical research; Medicine; Mitogen-Activated Protein Kinases - genetics; Molecular biology; Molecular modelling; Mutation; Networks; Neural networks; Neuronal-glial interactions; Neurons; NF-kappa B - genetics; NF-κB protein; Pregnancy; Proto-Oncogene Proteins c-myc - genetics; Psychiatry; Schizophrenia; Signal transduction; Signal Transduction - genetics; Signal Transduction - physiology; Signaling; Studies; Tumor necrosis factor; Tumor Necrosis Factors - genetics; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024691

The Autism Spectrum Disorders (ASD) represent a clinically heterogeneous set of conditions with strong hereditary components. Despite substantial efforts to uncover the genetic basis of ASD, the genomic etiology appears complex and a clear understanding of the molecular mechanisms underlying Autism remains elusive. We hypothesized that focusing gene interaction networks on ASD-implicated genes that are highly expressed in the developing brain may reveal core mechanisms that are otherwise obscured by the genomic heterogeneity of the disorder. Here we report an in silico study of the gene expression profile from ASD-implicated genes in the unaffected developing human brain. By implementing a biologically relevant approach, we identified a subset of highly expressed ASD-candidate genes from which interactome networks were derived. Strikingly, immune signaling through NFκB, Tnf, and Jnk was central to ASD networks at multiple levels of our analysis, and cell-type specific expression suggested glia--in addition to neurons--deserve consideration. This work provides integrated genomic evidence that ASD-implicated genes may converge on central cytokine signaling pathways.