Abstract Ref Number = APCP153
Invited Speakers
Retno Sutomo Department of Pediatrics, School of Medicine, UniversitasGadjahMada, Yogyakarta, Indonesia
Child development istraditionally described as resultant of genetic and environmental factors. Recently, epigenetic mechanism has been increasingly considered as the third factor.It deals with change in gene expression without modifying DNA sequences. There are various epigenetic mechanisms, mainly DNA methylation, histone modification, and micro RNA. Epigenetic mechanisms play role within the earliest stages of cell differentiation and development, or even before fertilization. Egg and sperm cells undergo extensive and complex epigenetic remodeling, which may result in only one parental gene copy being expressed(genetic imprinting). During early embryonic stage, development and differentiation of cells into distinctive cell types involves epigenetic processes. Epigenetic events take place with key phases of normal brain developmentand neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Methylations of CpG site in the dopamine receptor D4 (DRD4)gene promoter inhibit gene transcription, implicating for ADHD development. Moreover,lower DNA methylation levels in the DRD4 and serotonin transporter genes result inmore severe ADHD. Epigenetic role in ASDhas been shown mainly in syndrome-related autism, e.g. Rett and fragile X syndromes (DNA methylation), Sotos and Kabuki syndromes (histone modification), and Prader-Willi and Angelmansyndroms (genetic imprinting). Epigenetic mechanisms also mediate long-term impacts of early life adversity (ELA), such as poverty and child abuse/neglect. Children experienced ELA shows more extensive epigenetic marking on the glucocorticoid receptorand serotonin transporter genes, which are related to child development, metabolism, and immune response. Epigenetic mechanisms provide explanations on how environment interact with genetic constitution in influencing child development. Couples of evidences show factors, such as nutrition, neonatal asphyxia, and smoking may induce or inhibit epigenetic mechanisms implicated in some developmental disorders. Interestingly, DNA methylation and histone modification seem to be reversible.Thus, epigenetic-related developmental disorders are potentially modifiable with targeted new treatment modalities.
Keywords: child development, epigenetic, DNA methylation, histone modification, micro RNA
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