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Molecular Autism
Published in: Molecular Autism 1/2014

Open Access 01-12-2014 | Short report

Transcriptomic changes in the frontal cortex associated with paternal age

Authors: Rebecca G Smith, Cathy Fernandes, Rachel Kember, Leonard C Schalkwyk, Joseph Buxbaum, Abraham Reichenberg, Jonathan Mill

Published in: Molecular Autism | Issue 1/2014

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Abstract

Background

Advanced paternal age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the paternal age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced paternal age.

Findings

Transcriptomic profiling was undertaken for medial prefrontal cortex tissue dissected from the male offspring of young fathers (2 month old, 4 sires, n = 16 offspring) and old fathers (10 month old, 6 sires, n = 16 offspring) in a mouse model of advancing paternal age. We found a number of differentially expressed genes in the offspring of older fathers, many previously implicated in the aetiology of autism. Pathway analysis highlighted significant enrichment for changes in functional networks involved in inflammation and inflammatory disease, which are also implicated in autism.

Conclusions

We observed widespread alterations to the transcriptome associated with advanced paternal age with an enrichment of genes associated with inflammation, an interesting observation given previous evidence linking the immune system to several neuropsychiatric disorders including autism.
Appendix
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Metadata
Title
Transcriptomic changes in the frontal cortex associated with paternal age
Authors
Rebecca G Smith
Cathy Fernandes
Rachel Kember
Leonard C Schalkwyk
Joseph Buxbaum
Abraham Reichenberg
Jonathan Mill
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2014
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/2040-2392-5-24

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