brain transcriptional and epigenetic associations with autism自闭症大脑转录和表观遗传关联.pdfVIP

Brain Transcriptional and Epigenetic Associations with Autism 1 2 3 4 1,3,4,5 Matthew R. Ginsberg , Robert A. Rubin , Tatiana Falcone , Angela H. Ting , Marvin R. Natowicz * 1 Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, United States of America, 2 Department of Mathematics, Whittier College, Whittier, California, United States of America, 3 Neurological Institute, Cleveland Clinic, Cleveland, Ohio, United States of America, 4 Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, United States of America, 5 Pathology and Laboratory Medicine and Pediatrics Institutes, Cleveland Clinic, Cleveland, Ohio, United States of America Abstract Background: Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. Methodology/Principal Findings: To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. Conclusions/Significance: This work highlights two largely unrecognized molecular pathophysiological the