Genetics of Aggression in Drosophila

描述(由申请人提供)：了解攻击性的遗传和神经生物学基础对人类福利很重要，因为病理性的攻击性会导致社会破坏性的暴力行为。然而，我们对导致攻击性行为的遗传机制和环境触发因素的了解还远未完成。之所以出现这种困难，是因为攻击性是一种复杂的特征，受到多个基因相互作用的影响，这些基因的表达取决于环境，而且直到最近，还很难在适用于高通量基因分析的模型系统中对攻击性行为进行量化。我们已经开发了一种高通量、可重复性的方法来量化遗传模式生物--黑腹果蝇的攻击行为。这项研究计划的长期目标是确定影响果蝇攻击行为的基因网络，这些基因是导致自然发生的攻击变异的基因子集，是进化力量的底物；并确定遗传网络和环境因素之间的相互作用如何塑造果蝇攻击行为的表达。在本项目期间，我们将(1)筛选在同基因背景下产生的800个P-元件插入系，以确定影响攻击行为的新基因；(2)对影响攻击行为的P-元件插入系和攻击水平增加和降低的人工选择系进行全基因组表达研究，以确定影响攻击行为的共同调控遗传网络，并检验模型预测；以及(3)在选择的攻击行为水平增加和降低的品系之间定位影响攻击行为自然发生变异的数量性状基因座。 酗酒者、阿尔茨海默病患者和患有行为障碍(如边缘型人格障碍和间歇性爆发性障碍)的人的攻击性水平会增加。暴力行为和控制暴力行为的努力给我们的社会带来了巨大的社会和经济代价。确定哪些遗传因素影响人类的攻击性行为是具有挑战性的，但在模式生物中可以更容易地解决。鉴于攻击性等基本特征的功能在进化上的保守性，在模式生物中发现的基因和途径可以作为候选基因纳入人类连锁和关联研究中。

DESCRIPTION (provided by applicant): Understanding the genetic and neurobiological basis of aggression is important for human welfare, as pathological levels of aggression result in socially disruptive, violent behaviors. However, our understanding of the genetic mechanisms and the environmental triggers responsible for aggressive behavior is far from complete. The difficulty arises because aggression is a complex trait, affected by interacting ensembles of multiple genes whose expression depends on the environment, and because, until recently, it was difficult to quantify aggressive behavior in a model system amenable to high-throughput genetic analysis. We have developed a high-throughput, reproducible assay to quantify aggressive behavior in the genetic model organism, Drosophila melanogaster. The long-term goal of this research program is to identify networks of genes affecting Drosophila aggressive behavior, the subset of genes responsible for naturally occurring variation in aggression that are the substrate for evolutionary forces; and to determine how interactions between genetic networks and environmental factors shape the expression of aggressive behavior in Drosophila. In this project period, we will (1) screen a collection of 800 P-element insert lines that have been generated in a co-isogenic background to identify new genes affecting aggressive behavior, (2) conduct whole genome expression studies on P-element insert lines affecting aggressive behavior and artificial selection lines with increased and decreased levels of aggression, to identify co-regulated genetic networks affecting aggression, and test the model predictions; and (3) map quantitative trait loci affecting naturally occurring variation in aggressive behavior between lines selected for increased and decreased levels of aggressive behavior. Increased levels of aggression occur in alcoholics, Alzheimer's Disease patients, and individuals suffering from behavioral disorders, such as borderline personality disorder and intermittent explosive disorder. The social and economic costs to our society that result from violent behavior, and efforts to control it, are enormous. Determining what genetic factors affect aggressive behavior is challenging in humans, but can be addressed more readily in model organisms. Given the evolutionary conservation of function for fundamental traits, such as aggression, genes and pathways discovered in model organisms can be incorporated as candidate genes in human linkage and association studies.