Expression Profiling of Autism Candidate Genes during Human Brain Development Implicates Central Immune Signaling Pathways
Open accessAbstract
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.
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The authors suggest that immune system genes may function as a fundamental convergence for autistic disorders.
“The authors suggest that immune system genes may function as a fundamental convergence for autistic disorders.”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Ziats and Rennert (2011)
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References 66 · Cited by 75
- Authors
- Ziats, M. N., & Rennert, O. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ziats, Mark N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-09-15
- Volume
- 6
- Issue
- 9
- Pages
- e24691
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3174192
- OpenAlex
- W2090898841
- Cited by
- 75
- References
- 66
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 9 · 2012: 11
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- autism spectrum disorder, autism candidate genes, human brain development, gene expression profiling, interactome networks, immune signaling pathways, NF-κB, TNF-α, JNK, cytokine signaling, glial cells, cell type-specific gene expression, neuroinflammation
- MeSH terms
- Adolescent, Adult, Brain, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Pregnancy, Signal Transduction, Proto-Oncogene Proteins c-myc, NF-kappa B, Genetic Predisposition to Disease, Gene Expression Profiling, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Databases, Genetic, Tumor Necrosis Factors, Young Adult
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