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Chunk #16 — GENETICS OF ALCOHOL BEHAVIOR IN INVERTEBRATE MODEL ORGANISM AND HUMAN AUD

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Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder.
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To assess the overlap between genetic findings in iMOs and humans at the level of individual genes, it was necessary to use common gene symbols for all orthologs, regardless of origin. We therefore identified human orthologs of fly and worm genes that influence alcohol-related behavior using DIOPT (Hu et al., 2011), FlyBase (Wilson et al., 2008), OrthoDB (Kriventseva et al., 2015), BLASTP (Altschul et al., 1997), and g:Profiler (Reimand et al., 2011) in addition to our recognition of well-established biochemical activities of gene products (e.g., the alcohol dehydrogenase [ADH]-encoding genes). Genes predicted to be conserved between iMOs and humans by these approaches were visually inspected and unconvincing orthologs (i.e., genes whose gene products were judged to be poorly conserved between humans and iMOs) were ignored. In practice, orthologs with fairly conservative scores (≥3) in DIOPT (which in turn uses several bioinformatic databases) were considered convincing.