Differential Levels of Telomeric Oxidized Bases and TERRA Transcripts in Childhood Autism

Abstract

AbstractThe underlying molecular mechanisms responsible for the etiology of autism and its sex-biased prevalence remain largely elusive. Abnormally shortened telomeres have recently been associated with autism. We have previously shown that children with non-syndromic autism exhibit a sexually dimorphic pattern of relative telomere length (RTL). Only male children with autism have significantly shorter RTLs than the healthy controls and paired siblings. Autistic females have substantially longer RTLs than autistic males. Aberrantly high levels of oxidative stress plays a fundamental role in the pathophysiology of autism, and telomeres are thought to be susceptible to oxidative damage due to their high guanine-repeat content. Employing a quantitative PCR (qPCR)-based method, telomeric oxidized base lesions were measured using genomic DNA extracted from saliva samples, and levels of telomeric RNA transcripts know as TERRA were evaluated using reverse transcriptase qPCR technique. Our data show that the autistic children exhibit substantially higher levels of oxidative base lesions at their telomeres than the healthy controls and paired siblings. Intriguingly, despite having significantly longer RTLs, female children with autism have even higher levels of telomeric oxidized bases than their male counterparts. Furthermore, despite having significantly shorter RTLs, the male children with autism exhibit lower levels of TERRA expression from the short arms of chromosomes 17 and X/P compared to their individually-matched healthy controls. These findings open a fresh angle into autism. Abnormal TL and high levels of telomeric oxidized bases may serve as biomarkers for childhood autism.