The 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.

中文翻译：

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儿童自闭症中端粒氧化碱基和TERRA转录本的差异水平

导致自闭症病因及其性别偏见患病率的潜在分子机制在很大程度上仍然难以捉摸。端粒异常缩短最近与自闭症有关。先前我们已经证明患有非综合症自闭症的儿童表现出相对端粒长度（RTL）的性二态模式。只有患有自闭症的男性儿童的RTL明显短于健康对照和配对的兄弟姐妹。自闭症女性比自闭症男性具有更长的RTL。异常高水平的氧化应激在自闭症的病理生理中起基本作用，端粒由于其鸟嘌呤重复含量高而被认为易受氧化损伤。采用基于定量PCR（qPCR）的方法，使用从唾液样品中提取的基因组DNA测量端粒氧化的基础病变，并使用逆转录酶qPCR技术评估称为TERRA的端粒RNA转录水平。我们的数据表明，自闭症儿童的端粒比健康对照和配对的兄弟姐妹表现出更高水平的氧化性基础病变。有趣的是，尽管自闭症儿童的RTL明显更长，但其端粒氧化碱基的含量甚至高于男性。此外，尽管自闭症男孩的RTL明显缩短，但与他们单独配对的健康对照组相比，自17号染色​​体的短臂和X / P的短臂表现出的TERRA表达水平较低。这些发现为自闭症开辟了新的角度。