This study provided a valuable contribution by carefully classifying a major developmental phenotype (neural tube closure or failure to close) and comparing with sub-categorized promoter regions based on CpG content. It is clear that the effects of fetal alcohol exposure may have been hidden if all promoters were considered as a single group. Furthermore, comparing and contrasting methylation status, averaged over an entire promoter region versus the status identified with a more sophisticated model, allowed for local changes in methylation (using consecutive probe modeling), obtaining more general and more promoter-specific results. The study combined the mapping of differentially-methylated CpG islands and promoter regions with RNA expression analysis to link hypothesized effects of methylation or demethylation on gene expression. Furthermore, by classifying probed regions by CpG density, the authors were able to more precisely parse out biological effects linked with patterns of regulation.
