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Title: Epigenetics and Mental Health; Implicating the role of DNA Methylation in Rett Syndrome

Mojgan Rastegar

University of Manitoba, Canada

Biography

Dr. Mojgan Rastegar has completed her PhD at the Université Catholique de Louvain (UCL) and postdoctoral training in US and Canada. In Canada, she conducted postdoctoral training at the McGill University (Montreal) and Hospital for Sick Children (Toronto). Dr. Rastegar is currently an Associate Professor of Biochemistry and Medical Genetics at the University of Manitoba (Canada). She has published more over 40 papers in reputed journals and has been serving as an editorial board member of several Journals including Frontiers in Genetics and Neural Plasticity, among others.

Abstract

In this presentation, I will mainly focus on an epigenetic neurological disorder that is caused by a genetic mutation, namely “Rett Syndrome (RTT)”. RTT is a neurodevelopmental disease that is caused by MECP2 gene mutations. The X-linked MECP2 gene encodes for MeCP2, an important epigenetic factor in the brain that binds to different types of DNA methylation. RTT patients appear normal at first, without showing any disease-associated symptoms during the first 6-18 months of their life, but by 1-2 years of age they start exhibiting developmental regression, mental disability, speech deficiencies, irregular breathing, seizers, anxiety, and autistic behaviours. Our lab has studied the expression and function of MeCP2 protein variants (E1 and E2) in the murine brain during development and in adult mouse. We have reported the regulation of E1 and E2 by DNA methylation, and their regulation by different types of DNA methylation. In this presentation, I will discuss how the epigenetic mechanisms might be interrupted in the human Rett Syndrome brains. By performing genome-wide DNA methylation on post-mortem human RTT brains in different brain regions that are associated with RTT phenotypes. The global DNA methylation patterns were analyzed by Illumina’s Infinium MethylationEPIC BeadChip, in parallel to different types of DNA methylation by dot blot. I will discuss the identified differences in the methylation patterns of gene promoters in different brain regions. Our data indicates the existence of an epigenetic signature for DNA methylation in brain cells and post-mortem brain of RTT patients, providing important insight into the pathobiology of disease in RTT patients.