Genetic and epigenetic interactions underlying FASD

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Summary/Abstract Ethanol is the most common teratogen and the leading cause of mental retardation. Fetal alcohol exposure can cause numerous birth defects, most commonly effecting the craniofacial skeleton and nervous system. Fetal Alcohol Spectrum Disorder describes the full range of potential ethanol-induced birth defects and has been estimated to have a prevalence of 10 in 1000 births. The timing and concentration of fetal alcohol exposure are important determinants of FASD phenotypes. There also appears to be genetic and epigenetic factors underlying FASD, yet we know almost nothing about the interaction between these factors. The zebrafish embryo is particularly useful for these types of analyses. In Aim 1, we identify and characterize ethanol-sensitive gene modules and the ethanol-sensitive miRNAs that target them. In Aim 2, we develop tools to determine how miRNA activity alters cell behaviors. Because of the conservation of gene function between zebrafish and humans, the results from our studies will provide key insights into the interaction between genetic and epigenetic factors underlying FASD. !