Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression.
Abstract
BACKGROUND:Intellectual disability (ID), autism, and epilepsy share frequent yet variable
comorbidities with one another. In order to better understand potential genetic divergence
underlying this variable risk, we studied genes responsible for monogenic IDs, grouped
according to their autism and epilepsy comorbidities. METHODS:Utilizing 465 different
forms of ID with known molecular origins, we accessed available genetic databases
in conjunction with gene ontology (GO) to determine whether the genetics underlying
ID diverge according to its comorbidities with autism and epilepsy and if genes highly
penetrant for autism or epilepsy share distinctive features that set them apart from
genes that confer comparatively variable or no apparent risk. RESULTS:The genetics
of ID with autism are relatively enriched in terms associated with nervous system-specific
processes and structural morphogenesis. In contrast, we find that ID with highly comorbid
epilepsy (HCE) is modestly associated with lipid metabolic processes while ID without
autism or epilepsy comorbidity (ID only) is enriched at the Golgi membrane. Highly
comorbid autism (HCA) genes, on the other hand, are strongly enriched within the nucleus,
are typically involved in regulation of gene expression, and, along with IDs with
more variable autism, share strong ties with a core protein-protein interaction (PPI)
network integral to basic patterning of the CNS. CONCLUSIONS:According to GO terminology,
autism-related gene products are integral to neural development. While it is difficult
to draw firm conclusions regarding IDs unassociated with autism, it is clear that
the majority of HCA genes are tightly linked with general dysregulation of gene expression,
suggesting that disturbances to the chronology of neural maturation and patterning
may be key in conferring susceptibility to autism spectrum conditions.
Type
Journal articleSubject
Cell NucleusHumans
Epilepsy
Syndrome
Nerve Tissue Proteins
Nuclear Proteins
Risk
Autistic Disorder
Comorbidity
Chromatin Assembly and Disassembly
Gene Expression Regulation
Body Patterning
Penetrance
Databases, Genetic
Neurogenesis
Genetic Association Studies
Epigenomics
Intellectual Disability
Protein Interaction Maps
Gene Ontology
Autism Spectrum Disorder
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https://hdl.handle.net/10161/21984Published Version (Please cite this version)
10.1186/s13229-016-0082-zPublication Info
Casanova, Emily L; Sharp, Julia L; Chakraborty, Hrishikesh; Sumi, Nahid Sultana; &
Casanova, Manuel F (2016). Genes with high penetrance for syndromic and non-syndromic autism typically function
within the nucleus and regulate gene expression. Molecular autism, 7(1). pp. 18. 10.1186/s13229-016-0082-z. Retrieved from https://hdl.handle.net/10161/21984.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Hrishikesh Chakraborty
Professor of Biostatistics & Bioinformatics

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