Genetics of Aggression in Drosophila

描述（由申请人提供）：了解攻击的遗传和神经生物学基础对人类福利很重要，因为病态的攻击会导致社会破坏和暴力行为。然而，我们对攻击性行为的遗传机制和环境触发因素的理解还远远不够。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，而这些基因的表达取决于环境，而且直到最近，在一个适合高通量遗传分析的模型系统中，很难量化攻击性行为。我们开发了一种高通量、可重复的测定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，这是负责自然发生的攻击变化的基因子集，是进化力量的基础；并确定遗传网络和环境因素之间的相互作用如何影响果蝇的攻击行为表达。在本项目期间，我们将(1)筛选800个共等基因背景下产生的p元素插入系，以确定影响攻击行为的新基因；(2)对影响攻击行为的p元素插入系和攻击水平增加和减少的人工选择系进行全基因组表达研究，以确定影响攻击的共调控遗传网络，并检验模型预测；(3)绘制影响自然发生的攻击行为变异的数量性状位点，这些变异是在选择攻击行为水平增加和减少的品系之间发生的。

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.