title: Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways.
abstract: 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.
authors.affiliation: Laboratory of Clinical and Developmental Genomics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America. ziatsm@mail.nih.gov
authors.forename: Mark N
authors.initials: MN
authors.lastname: Ziats
authors.forename: Owen M
authors.initials: OM
authors.lastname: Rennert
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020935:MAP Kinase Signaling System / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D048069:Tumor Necrosis Factors; D020928:Mitogen-Activated Protein Kinases