The goal of this work is to increase our understanding of the genetic predispositions underlying Fetal Alcohol Spectrum Disorders and to uncover novel pathogenic mechanisms in order to aid in prevention and intervention efforts. In our first approach, we will use RNA-Seq in mice and genetic screens in zebrafish to discover novel candidate genes that modify susceptibility to early gestational ethanol exposure. Subsequent experiments will use gene editing in zebrafish and MRI and behavioral phenotyping in mice to further confirm candidate genes that may have an interaction with ethanol. In a second approach, we will perform a forward genetic screen to identify loci that modulate gene-ethanol interactions, with follow up analyses in mouse and human.