Transcriptome-wide analysis of DNA-RNA hybrids reveals how non-coding RNAs contribute to ASDs

Autism spectrum disorders (ASDs) are a class of neurodevelopmental disorders with a strong genetic basis. Inaddition to genetic factors, the role of epigenetic and environmental factors has also been reported in ASDs. Still, thepathogenesis of ASDs is not well understood. DNA-RNA hybrids are epigenetic factors whose abnormal accumulationon the genome can lead to genomic instability and DNA damage. Their various roles in neurological disordersmake them promising candidates for investigating the pathogenesis of ASDs. In this study, we investigated thedistribution of DNA-RNA hybrids in the blood samples of ASD patients compared to control samples using RNA Seq data analysis. Furthermore, transcriptome assembly methods were used to discover novel non-coding transcriptsinvolved in ASDs. The overall distribution of DNA-RNA hybrids showed that in contrast to previous studies, mostof these hybrids were accumulated in exonic regions. Moreover, we found ۳۰۱ genes with significant accumulationof DNA-RNA hybrids in ASD samples. Interestingly, we observed ASD risk genes like SMARCC۲ and GIGYF۱among these genes. This can point to a novel mechanism that can disrupt the normal function of these genesand lead to the pathogenesis of ASDs. Furthermore, there were numerous mitochondrial genes among the geneswith significant DNA-RNA hybrid accumulation, which can put an emphasis on the previously reported role ofmitochondrial dysfunction in the pathogenesis of ASDs. Finally, we found a gene module containing ۴۵ novel lncRNAgenes that showed DNA-RNA hybrid accumulation in ASD samples and can be used to classify ASD and controlsamples. In summary, our study showed that DNA-RNA hybrids demonstrate a distinct pattern of transcriptomicprofiles in ASD and control samples, thus a potential role for DNA-RNA hybrids in the pathogenesis of ASDs canbe inferred. In addition, the genes introduced in this study can be potential biomarker candidates in future studies.

کلیدواژه ها:

DNA-RNA hybrids ، ASDs ، RNA-Seq ، transcriptome assembly ، lncRNA