Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism
Alcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/18/6649 |
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| author | Daniel R. Lathen Collin B. Merrill Adrian Rothenfluh |
| author_facet | Daniel R. Lathen Collin B. Merrill Adrian Rothenfluh |
| author_sort | Daniel R. Lathen |
| collection | DOAJ |
| description | Alcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism, play a role in alcohol responses, and/or contribute to the development of addiction. As a highly tractable and translatable genetic and behavioral model organism, <i>Drosophila melanogaster</i> has proven valuable to uncover important genes and mechanistic pathways that have obvious orthologs in humans and that help explain the complexities of addiction. Vinegar flies exhibit remarkably strong face and mechanistic validity as a model for AUDs, permitting many advancements in the quest to understand human genetic involvement in this disease. These advancements occur via approaches that essentially fall into one of two categories: (1) discovering candidate genes via human genome-wide association studies (GWAS), transcriptomics on post-mortem tissue from AUD patients, or relevant physiological connections, then using reverse genetics in flies to validate candidate genes’ roles and investigate their molecular function in the context of alcohol. (2) Utilizing flies to discover candidate genes through unbiased screens, GWAS, quantitative trait locus analyses, transcriptomics, or single-gene studies, then validating their translational role in human genetic surveys. In this review, we highlight the utility of <i>Drosophila</i> as a model for alcoholism by surveying recent advances in our understanding of human AUDs that resulted from these various approaches. We summarize the genes that are conserved in alcohol-related function between humans and flies. We also provide insight into some advantages and limitations of these approaches. Overall, this review demonstrates how <i>Drosophila</i> have and can be used to answer important genetic questions about alcohol addiction. |
| first_indexed | 2024-03-10T16:24:27Z |
| format | Article |
| id | doaj.art-6919385be1294e2ba2f9a10bc4ac326e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:24:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6919385be1294e2ba2f9a10bc4ac326e2023-11-20T13:20:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118664910.3390/ijms21186649Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human AlcoholismDaniel R. Lathen0Collin B. Merrill1Adrian Rothenfluh2Department of Psychiatry and Neuroscience Ph.D. Program, University of Utah, Salt Lake City, UT 84108, USAMolecular Medicine Program, University of Utah, Salt Lake City, UT 84112, USADepartment of Psychiatry and Neuroscience Ph.D. Program, University of Utah, Salt Lake City, UT 84108, USAAlcohol use disorder (AUD) exacts an immense toll on individuals, families, and society. Genetic factors determine up to 60% of an individual’s risk of developing problematic alcohol habits. Effective AUD prevention and treatment requires knowledge of the genes that predispose people to alcoholism, play a role in alcohol responses, and/or contribute to the development of addiction. As a highly tractable and translatable genetic and behavioral model organism, <i>Drosophila melanogaster</i> has proven valuable to uncover important genes and mechanistic pathways that have obvious orthologs in humans and that help explain the complexities of addiction. Vinegar flies exhibit remarkably strong face and mechanistic validity as a model for AUDs, permitting many advancements in the quest to understand human genetic involvement in this disease. These advancements occur via approaches that essentially fall into one of two categories: (1) discovering candidate genes via human genome-wide association studies (GWAS), transcriptomics on post-mortem tissue from AUD patients, or relevant physiological connections, then using reverse genetics in flies to validate candidate genes’ roles and investigate their molecular function in the context of alcohol. (2) Utilizing flies to discover candidate genes through unbiased screens, GWAS, quantitative trait locus analyses, transcriptomics, or single-gene studies, then validating their translational role in human genetic surveys. In this review, we highlight the utility of <i>Drosophila</i> as a model for alcoholism by surveying recent advances in our understanding of human AUDs that resulted from these various approaches. We summarize the genes that are conserved in alcohol-related function between humans and flies. We also provide insight into some advantages and limitations of these approaches. Overall, this review demonstrates how <i>Drosophila</i> have and can be used to answer important genetic questions about alcohol addiction.https://www.mdpi.com/1422-0067/21/18/6649geneticsgene discoveryalcohol behavior<i>Drosophila</i>fruit flyAUD |
| spellingShingle | Daniel R. Lathen Collin B. Merrill Adrian Rothenfluh Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism International Journal of Molecular Sciences genetics gene discovery alcohol behavior <i>Drosophila</i> fruit fly AUD |
| title | Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism |
| title_full | Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism |
| title_fullStr | Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism |
| title_full_unstemmed | Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism |
| title_short | Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism |
| title_sort | flying together i drosophila i as a tool to understand the genetics of human alcoholism |
| topic | genetics gene discovery alcohol behavior <i>Drosophila</i> fruit fly AUD |
| url | https://www.mdpi.com/1422-0067/21/18/6649 |
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