Beyond Genes: Germline Disruption in the Etiology of Autism Spectrum Disorders

• Type of Material: Article
• Authors: Jill Escher, Escher Fund Autism; Wei Yan, Harbor-UCLA Medical Center; Emilie F Rissman, North Carolina State University; Hsiao-Lin V Wang, Emory University; Arturo Hernandez, Maine Medical Center Research Institute; Victor Corces, Emory University
• Language: English
• Date: 2021-10-01
• Publisher: SPRINGER/PLENUM PUBLISHERS
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10803-021-05304-1
• Title of Journal or Parent Work: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
• Volume: 52
• Issue: 10
• Start Page: 4608
• End Page: 4624
• Grant/Funding Information: The authors have no funding to declare.
• Keywords: Germ cells; AFFECTS LEARNING-FUNCTION; Non-genetic inheritance; HERITABILITY; DEVELOPMENTAL-DISABILITIES; Epigenetics; SPERM; SEVOFLURANE EXPOSURE; Psychology; Gene expression; DNA METHYLATION; Autism spectrum disorder; BISPHENOL-A; Psychology, Developmental; EPIGENETIC MECHANISMS; INHALATION ANESTHETICS; CHILDREN; Social Sciences; Genetic toxicology
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Investigations into the etiology of autism spectrum disorders have been largely confined to two realms: variations in DNA sequence and somatic developmental exposures. Here we suggest a third route—disruption of the germline epigenome induced by exogenous toxicants during a parent’s gamete development. Similar to cases of germline mutation, these molecular perturbations may produce dysregulated transcription of brain-related genes during fetal and early development, resulting in abnormal neurobehavioral phenotypes in offspring. Many types of exposures may have these impacts, and here we discuss examples of anesthetic gases, tobacco components, synthetic steroids, and valproic acid. Alterations in parental germline could help explain some unsolved phenomena of autism, including increased prevalence, missing heritability, skewed sex ratio, and heterogeneity of neurobiology and behavior.