Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism.
Flying Together: Drosophila as a Tool to Understand the Genetics of Human Alcoholism.
复制标题
DOI：
10.3390/ijms21186649
复制
发表时间：
2020-09-11
影响因子：
5.6
通讯作者：
Rothenfluh A
中科院分区：
文献类型：
--
作者：
Lathen DR;Merrill CB;Rothenfluh A
酒精使用障碍（AUD）对个人，家庭和社会造成了巨大的损失。遗传因素决定了高达60%的个人发展成问题的酒精习惯的风险。有效的AUD预防和治疗需要了解使人们易于酗酒的基因，在酒精反应中发挥作用，和/或有助于成瘾的发展。作为一种高度易处理和可翻译的遗传和行为模式生物，黑腹果蝇已被证明对发现重要基因和机制途径很有价值，这些基因和机制途径在人类中具有明显的直系同源物，有助于解释成瘾的复杂性。果蝇表现出非常强的面孔和机制的有效性作为一个模型的AUD，允许许多进步，在寻求了解人类基因参与这种疾病。这些进展通过基本上属于两类之一的方法发生：（1）通过人类全基因组关联研究（GWAS），AUD患者死后组织的转录组学或相关生理联系发现候选基因，然后在苍蝇中使用反向遗传学来验证候选基因的作用并研究其在酒精背景下的分子功能。(2)利用果蝇通过无偏筛选、GWAS、数量性状位点分析、转录组学或单基因研究发现候选基因，然后验证它们在人类遗传调查中的翻译作用。在这篇综述中，我们强调了果蝇作为酒精中毒模型的效用，通过调查我们对这些不同方法导致的人类AUDs的理解的最新进展。我们总结了人类和苍蝇之间在酒精相关功能中保守的基因。我们还提供了这些方法的一些优点和局限性的见解。总的来说，这篇综述展示了果蝇如何以及如何被用来回答关于酒精成瘾的重要遗传问题。
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, Drosophila melanogaster 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 Drosophila 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 Drosophila have and can be used to answer important genetic questions about alcohol addiction.
登录
查看更多内容
影响因子：
3.3
作者：
COHAN, FM;GRAF, JD
通讯作者：
GRAF, JD
影响因子：
5.3
作者：
Acevedo, Summer F.;de Portugal, Raniero L. Peru y Colon;Rothenfluh, Adrian
通讯作者：
Rothenfluh, Adrian
DOI：
10.1111/acer.13362
发表时间：
2017-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Adkins AE;Hack LM;Bigdeli TB;Williamson VS;McMichael GO;Mamdani M;Edwards AC;Aliev F;Chan RF;Bhandari P;Raabe RC;Alaimo JT;Blackwell GG;Moscati A;Poland RS;Rood B;Patterson DG;Walsh D;Collaborative Study of the Genetics of Alcoholism Consortium;Whitfield JB;Zhu G;Montgomery GW;Henders AK;Martin NG;Heath AC;Madden PAF;Frank J;Ridinger M;Wodarz N;Soyka M;Zill P;Ising M;Nöthen MM;Kiefer F;Rietschel M;German Study of the Genetics of Addiction Consortium;Gelernter J;Sherva R;Koesterer R;Almasy L;Zhao H;Kranzler HR;Farrer LA;Maher BS;Prescott CA;Dick DM;Bacanu SA;Mathies LD;Davies AG;Vladimirov VI;Grotewiel M;Bowers MS;Bettinger JC;Webb BT;Miles MF;Kendler KS;Riley BP
通讯作者：
Riley BP
影响因子：
3.4
作者：
Comasco E;Nordquist N;Göktürk C;Aslund C;Hallman J;Oreland L;Nilsson KW
通讯作者：
Nilsson KW
影响因子：
5.3
作者：
Butts, Andrew R.;Ojelade, Shamsideen;Rothenfluh, Adrian
通讯作者：
Rothenfluh, Adrian