title: Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder.
abstract: BACKGROUND
  Despite the profound clinical significance and strong heritability of alcohol use disorder (AUD), we do not yet have a comprehensive understanding of the naturally occurring genetic variance within the human genome that drives its development. This lack of understanding is likely to be due in part to the large phenotypic and genetic heterogeneities that underlie human AUD. As a complement to genetic studies in humans, many laboratories are using the invertebrate model organisms (iMOs) Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (nematode worm) to identify genetic mechanisms that influence the effects of alcohol (ethanol) on behavior. While these extremely powerful models have identified many genes that influence the behavioral responses to alcohol, in most cases it has remained unclear whether results from behavioral-genetic studies in iMOs are directly applicable to understanding the genetic basis of human AUD.
  
  
  METHODS
  In this review, we critically evaluate the utility of the fly and worm models for identifying genes that influence AUD in humans.
  
  
  RESULTS
  Based on results published through early 2015, studies in flies and worms have identified 91 and 50 genes, respectively, that influence 1 or more aspects of behavioral responses to alcohol. Collectively, these fly and worm genes correspond to 293 orthologous genes in humans. Intriguingly, 51 of these 293 human genes have been implicated in AUD by at least 1 study in human populations.
  
  
  CONCLUSIONS
  Our analyses strongly suggest that the Drosophila and C. elegans models have considerable utility for identifying orthologs of genes that influence human AUD.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.|Virginia Commonwealth University Alcohol Research Center, Richmond, Virginia.
authors.forename: Mike
authors.initials: M
authors.lastname: Grotewiel
authors.affiliation: Department of Pharmacology and Toxicology , Virginia Commonwealth University, Richmond, Virginia.|Virginia Commonwealth University Alcohol Research Center, Richmond, Virginia.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Bettinger
mesh_terms: D019973:Alcohol-Related Disorders / Q000175:diagnosis* / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods* / Q000639:trends; D006801:Humans
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins
keywords: Behavior; Genetics; Human; Sensitivity; Tolerance