The Genetics of Fetal Alcohol Spectrum Disorders

Abstract

Background The term Fetal Alcohol Spectrum Disorders (FASD) defines the full range of ethanol-induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic ethanol exposure. Among these variables, genetics appears to play an important role yet our understanding of the genetic predisposition to FASD is still in its infancy. Methods We review the current literature that relates to the genetics of FASD susceptibility and gene-ethanol interactions. Where possible, we comment on potential mechanisms of reported gene-ethanol interactions. Results Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in ethanol metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided additional insight into the genetics of FASD Conclusions Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic ethanol exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be done. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD.

Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis

“…Only a handful of gene-ethanol interactions have been identified to date. A detailed discussion of these interactions can be found elsewhere, 87,88 whereas here, we focus on findings in zebrafish. The many genetic tools available in zebrafish have proven successful in expanding our understanding of developmental biology.…”

Comparison of molecular marker expression in early zebrafish brain development following chronic ethanol or morpholino treatment

“…Many of the hallmark phenotypes of FASD are also produced with disruption of gene function in zebrafish (Eberhart et al, 2016). Relevant to these studies, our previous work showed agrin morphants displayed similar ocular defects to those induced by ethanol exposure, suggesting agrin as a target of prenatal ethanol exposure (Zhang et al, 2011).…”

Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder

“…Among the proposed models in this group are: alteration of the normal DNA methylation pattern and other epigenetic changes at the level of chromatin modifications, aberrant cell death (apoptosis), changes in growth and signaling factor expression (including IGF, EGF, and Shh), changes in cell adhesion, cytoskeleton and migration, abnormal inflammatory responses, changes in cholesterol homeostasis, deficient neurotransmitter signaling (choline), and changes in miRNA expression. The different models to explain FASD have been reviewed in a number of instances over the years (Caputo, Wood, & Jabbour, ; Chater‐Diehl, Laufer, & Singh, ; Eberhart & Parnell, ; Ehrhart et al, ; Gilbert‐Barness, ; Gupta, Gupta, & Shirasaka, ; Kalisch‐Smith & Moritz, ; Kane & Drew, ; Lunde et al, ; Lussier, Weinberg, & Kobor, ; Mandal, Halder, Jung, & Chai, ; Shabtai & Fainsod, ; Shenoda, ; Wells, Bhatia, Drake, & Miller‐Pinsler, ). In this review, we will focus on the reduction of retinoic acid signaling by alcohol exposure during early development and briefly summarize a few of the other related changes.…”