Behavior Genetics Laboratory, Department of Cell Biology, Embryology and Genetics, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil.
Graduate Program of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil.
Curr Neuropharmacol. 2023;21(9):1840-1863. doi: 10.2174/1570159X20666220901154034.
Scientists have systematically investigated the hereditary bases of behaviors since the 19th century, moved by either evolutionary questions or clinically-motivated purposes. The pioneer studies on the genetic selection of laboratory animals had already indicated, one hundred years ago, the immense complexity of analyzing behaviors that were influenced by a large number of small-effect genes and an incalculable amount of environmental factors. Merging Mendelian, quantitative and molecular approaches in the 1990s made it possible to map specific rodent behaviors to known chromosome regions. From that point on, Quantitative Trait Locus (QTL) analyses coupled with behavioral and molecular techniques, which involved isolation of relevant blocks of genes, opened new avenues for gene mapping and characterization. This review examines the QTL strategy applied to the behavioral study of emotionality, with a focus on the laboratory rat. We discuss the challenges, advances and limitations of the search for Quantitative Trait Genes (QTG) playing a role in regulating emotionality. For the past 25 years, we have marched the long journey from emotionality-related behaviors to genes. In this context, our experiences are used to illustrate why and how one should move forward in the molecular understanding of complex psychiatric illnesses. The promise of exploring genetic links between immunological and emotional responses are also discussed. New strategies based on humans, rodents and other animals (such as zebrafish) are also acknowledged, as they are likely to allow substantial progress to be made in the near future.
自 19 世纪以来，科学家们一直出于进化问题或临床目的的动机，系统地研究行为的遗传基础。一个世纪前，对实验室动物遗传选择的先驱研究已经表明，分析受大量微效基因和难以计数的环境因素影响的行为具有巨大的复杂性。20 世纪 90 年代，孟德尔、定量和分子方法的融合使得将特定啮齿动物行为映射到已知染色体区域成为可能。从那时起，定量性状基因座（QTL）分析与行为和分子技术相结合，包括相关基因块的分离，为基因定位和特征提供了新的途径。这篇综述考察了 QTL 策略在情感性行为研究中的应用，重点是实验室大鼠。我们讨论了寻找在调节情感性方面发挥作用的数量性状基因（QTG）的挑战、进展和局限性。在过去的 25 年里，我们已经从与情感性相关的行为到基因走过了漫长的道路。在这种情况下，我们的经验被用来解释为什么以及如何在对复杂精神疾病的分子理解方面取得进展。还讨论了探索免疫和情绪反应之间遗传联系的前景。基于人类、啮齿动物和其他动物（如斑马鱼）的新策略也得到了承认，因为它们可能会在不久的将来取得实质性进展。
