Disrution of 3D Genome Organization Can Explain Alcohol Fetal Spectrum Disorder

Fetal Alcohol Spectrum Disorders (FASD) refers to a range of disorders caused by prenatal alcohol exposure and are characterized by neurodevelopmental impairment with or withoutspecific facial features, congenital anomalies, and poor growth. The spectrum is composed of four diagnostic categories: fetal alcohol spectrum (FAS), partial fetal alcohol spectrum (PFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). There is no specific diagnostic test or molecular biomarker for FASD, and without one, patients require evaluation through a multidisciplinary team approach. Epigenetics is the study of changes in gene activity that do not involve alterations to the DNA sequence. Alcohol exposure during pregnancy can lead to chromatin modifications like DNA methylation and histone modifications, indicative of an epigenetic mechanism for the FASD phenotype. Chromatin is an epigenetic componentwithin the 3D nuclear space, efficiently packaging the genome while allowing proper expression and replication of the genetic material. 3D Organization of the genome is a property of chromatin and its components, with CTCF acting as a major architectural protein, working jointly with cohesin to generate thousands of high-intensity chromatin loops. We hypothesize that disruption of these loops by prenatal alcohol exposure drives neurodevelopmental defects by altering the expression of genes critical for brain development and function. In this study, we used chromatin immunoprecipitation sequencing (ChIP-seq) and found that alcohol exposure increases the intensity of CTCF loops, and we hypothesize this is through the formation of adducts.