Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

• DOI: 10.1371/journal.pgen.1004402
• Publication Date: 2014-05-29T20:25:13Z
• Authors: Esther R. Berko; Masako Suzuki; Faygel Beren; Christophe Lemetre; Christine M. Alaimo; R. Brent Calder; Karen Ballaban-Gil; Batya Gounder; Kaylee Kampf; Jill Kirschen; Shahina B. Maqbool; Zeineen Momin; David M. Reynolds; Natalie Russo; Lisa Shulman; Edyta Stasiek; Jessica Tozour; Maria Valicenti-M...; Shenglong Wang; Brett S. Abrahams; Joseph Hargitai; Dov Inbar; Zhengdong Zhang; Joseph D. Buxbaum; Sophie Molholm; John J. Foxe; Robert W. Marion; Adam Auton; John M. Greally
• Keywords: Epigenome; Epigenomics; Neurodevelopmental disorder; Immune Dysregulation; Differentially methylated regions

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation epigenome pathogenesis condition remains unclear. The is interest as a possible mediator environmental effects during development, encoding cellular memory reflected by altered function progeny cells. Advanced maternal age (AMA) associated with an increased risk having child ASD for reasons that not understood. To explore whether AMA involves covert aneuploidy or epigenetic leading to offspring, we tested homogeneous ectodermal cell type from 47 individuals compared 48 typically developing (TD) controls born mothers ≥35 years, using quantitative genome-wide methylation assay. We show patterns dysregulated cells these individuals, accounted confounding due subject age, sex and ancestral haplotype. did find mosaic copy number variability occur at differentially-methylated regions subjects. Of note, loci distinctive were found genes expressed brain protein products significantly enriched interactions those produced known ASD-causing genes, representing perturbation epigenomic same networks compromised mechanisms. results indicate presence subpopulation epigenetically-dysregulated, ectodermally-derived subjects ASD. observed older may be aging parental gametes, influences embryogenesis could consequence mutations chromatin regulatory implicated dysregulatory mechanisms complement interact disorder.