Wednesday, September 26, 2018
Time: 4:00 pm-5:00 pm, followed by reception
Speaker: Alika Maunakea, Ph.D.
Affiliation: Assistant Professor, Epigenomics Research Program, Department of Native Hawaiian Health, John A. Burns School of Medicine, University of Hawai’i, Mānoa
Host: Ravikiran Raju, M.D., Ph.D.
Talk title: Integrative epigenomic analyses support the early developmental origin of autism spectrum disorders.
Abstract: Autism spectrum disorders (ASD) are clinically heterogeneous neurobehavioral diseases suspected to originate in utero when brain cells undergo widespread epigenetic changes to the underlying chromatin landscape, including DNA methylation. Although the normal trajectory of DNA methylation is thought to be critical to transcriptional regulation in neurodevelopment, whether it is compromised in ASD is unknown. Using two complementary genome-wide approaches, we observed significant alterations to DNA methylation in a neural stem cell compartment of postmortem brain from individuals diagnosed with ASD. We found that many of these ASD-specific alterations reside within developmentally regulated chromatin domains, the methylation states of which remarkably resembled that of early fetal brain. Transcriptomic analyses independently demonstrated fetal stage-specific gene expression states in these affected individuals. Together, these findings suggest ASD may arise as a consequence of an “epigenetic delay” in shaping the chromatin landscape during neurodevelopment, providing molecular support of pathological observations implicating its early fetal origins.