GENETIC ANALYSIS OF ANXIETY RELATED BEHAVIORS

焦虑是普遍的，致残的，代价高昂的。 的识别 使个体易患焦虑症的基因应该会大大改善我们的 预防、诊断和治疗各种精神疾病的能力。 我在NRSA奖学金期间提出的工作目标是使用 数量性状基因座分析以鉴定基因座（并且，如果可能， 基因座内的基因），特别影响相关行为 近交系小鼠 两个近交系小鼠品系， 焦虑相关行为（在高架十字迷宫中测量） 和暗光箱[DLB]测定）。 第一代 将杂交（F1）动物（通过两种品系杂交产生） 与亲本菌株之一回交以产生 250 - 400只第二代（N2）动物。 每只N2代动物 将接受焦虑的DLB和DLB测试。那些N2动物， 表现出极端（高或低）水平的焦虑相关行为将 使用微卫星标记进行基因分型。 数量性状 基因座（QTL）将通过寻找水平之间的相关性来定位， 行为和特定微卫星标记的存在。 的 然后将在表达的序列标签数据库中搜索基因， 区域的QTL，可能是焦虑相关性状的候选人。 如果没有位于QTL内的候选基因证明 与焦虑相关行为、高级交叉 将产生用于QTL的精细遗传作图的品系。 我的希望 这项工作将最终导致识别 使人易患严重焦虑症的同源人类基因。

Anxiety is prevalent, disabling, and costly. The identification of genes that predispose individuals to anxiety should greatly improve our ability to prevent, diagnose, and treat various psychiatric disorders. The goal of my proposed work during the NRSA Fellowship is to use quantitative trait locus analysis to identify loci (and, if possible, the genes within the loci) that affect-related behaviors in particular inbred mouse strains. Two inbred mouse strains that differ greatly in anxiety-related behaviors (as measured in the elevated plus-maze [EPM] and dark-light box [DLB] assays) will be identified. First- generation hybrid (F1) animals (produced by crossbreeding the two strains) will be backcrossed to one of the parental strains to produce a population of 250 to 400 second-generation (N2) animals. Each N2 generation animal will undergo the EPM and DLB assays of anxiety. Those N2 animals that show extreme (high or low) levels of anxiety-related behaviors will undergo genotyping using microsatellite markers. Quantitative trait loci (QTLs) will be localized by finding correlations between levels of behavior and the presence of particular microsatellite markers. The expressed sequence tag database will then be searched for genes in the region of the QTLs that might be candidates for anxiety-related traits. If there are no candidate genes located within the QTLs that prove to be associated with the anxiety-related behaviors, advanced intercross lines will be produced for fine genetic mapping of the QTLs. My hope is that this work will ultimately lead to the identification of homologous human genes that predispose people to severe anxiety.