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Chunk #21 — Discussion — Effect of alcohol on DNA methylation and phenotype

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Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation.
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We noted two trends in alcohol-induced, DNA methylation landscape changes. First, alcohol treatment was associated with a characteristic pattern of both increased and decreased DNA methylation: more genes showed a methylation increase in the HCP group, while a methylation decrease was noted for more genes in the LCP group. Second, this methylation pattern appeared to be associated with the severity of the neural tube abnormality phenotype (NTO vs. NTC): (a) in general, there were more methylation alterations (both increased- and decreased-methylation) in ALC-NTO than in ALC-NTC; (b) significantly, in the HCP, greater increased methylation occurred in ALC-NTO than in ALC-NTC, while in LCP, more decreased methylation occurred in ALC-NTO than ALC-NTC. As both of these trends were greater in ALC-NTO with severe neural tube defects than in ALC-NTC with an intact neural tube, this result demonstrates a correlation between methylation changes and alcohol-induced neural tube defects. This trend is more clearly demonstrated when the genes with methylation changes are plotted in each chromosome (discussed see below).