Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression.

dc.contributor.author

Casanova, Emily L

dc.contributor.author

Sharp, Julia L

dc.contributor.author

Chakraborty, Hrishikesh

dc.contributor.author

Sumi, Nahid Sultana

dc.contributor.author

Casanova, Manuel F

dc.date.accessioned

2021-01-04T15:07:17Z

dc.date.available

2021-01-04T15:07:17Z

dc.date.issued

2016-01

dc.date.updated

2021-01-04T15:07:15Z

dc.description.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.

dc.identifier

82

dc.identifier.issn

2040-2392

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2040-2392

dc.identifier.uri

https://hdl.handle.net/10161/21984

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Molecular autism

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10.1186/s13229-016-0082-z

dc.subject

Cell Nucleus

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Humans

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Epilepsy

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Syndrome

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Nerve Tissue Proteins

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Nuclear Proteins

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Risk

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Autistic Disorder

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Comorbidity

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Chromatin Assembly and Disassembly

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Gene Expression Regulation

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Body Patterning

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Penetrance

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Databases, Genetic

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Neurogenesis

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Genetic Association Studies

dc.subject

Epigenomics

dc.subject

Intellectual Disability

dc.subject

Protein Interaction Maps

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Gene Ontology

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Autism Spectrum Disorder

dc.title

Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression.

dc.type

Journal article

duke.contributor.orcid

Chakraborty, Hrishikesh|0000-0001-9078-845X

pubs.begin-page

18

pubs.issue

1

pubs.organisational-group

School of Medicine

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Duke Clinical Research Institute

pubs.organisational-group

Biostatistics & Bioinformatics

pubs.organisational-group

Duke

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Basic Science Departments

pubs.publication-status

Published

pubs.volume

7

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