Development of an Epigenetic Biomarker for Prediction of Fetal Alcohol Spectrum Disorders

PROJECT SUMMARY Prenatal alcohol exposure is the leading preventable cause of birth defects in the United Statesproducing an array of neurologicalbehavioral and physical abnormalities collectively known as fetal alcohol spectrum disordersFASDEarly intervention and treatment programs have been shown to reduce some of the long term adverse effectsbut this is dependent on identifying children at risk of fetal damage which is not detected in most casesMany children affected by FASD do not exhibit obvious physical indications of prenatal alcohol associated birth defectscreating challenges in making timely and accurate diagnosesThere is a critical need for development of biomarkers that can detect babies heavily exposed to alcohol throughout pregnancy to predict those at risk for developing the neurobehavioral and developmental disabilities associated with FASDPrenatal alcohol exposure has been shown to alter DNA methylation patterns of genes known to play important roles in development and contribute to abnormal embryonic developmentsuggesting that alcohol associated alterations in DNA methylation profilesidentified from neonatal blood spot samplescould be used as an alcohol biomarker in neonatesFindings from our Phase I study demonstrate that epigenetic profilesspecifically the differences in site specific CpG DNA methylationcan differentiate the incidence of prenatal alcohol exposure using neonatal blood spotsThe proposed SBIR Phase II project seeks to develop and validate the technology to generate quantitative DNA methylation screening assays using bisulfite pyrosequencing to analyze the differentially methylated sites that were found to be significantly associated with prenatal alcohol exposureThe technology that we will develop will use samples that are already routinely collected from newborns for comprehensive genetic screening assaysheel stick blood spotsand more recently for prenatal alcohol exposure screeningumbilical cord and heel stick blood spotstoextract and purify genomic DNA using an automated systemperform bisulfite PCR reactionsandscreen for epigenetic DNA methylation biomarkers of prenatal alcohol exposure using pyrosequencingThese assays will be used to screen genomic DNA collected from a large sampling of PEth positive and PEth negative neonatal blood spots to identify the epigenetic modifications that most significantly correlate with fetal alcohol exposureOur long term goal is to examine whether there is a correlation between these epigenetic biomarkers and an increased risk for the developmental disabilities associated with FASD