QTL Mapping of Impulsivity-related Traits Before and After a Stressful Life Chang

描述（由申请人提供）：冲动是大量精神疾病和社会心理问题的一个关键特征，包括双相情感障碍、注意缺陷多动障碍、行为障碍、酗酒和药物滥用。在确定数量性状位点（QTL）和候选基因方面进展缓慢，这些基因对冲动相关障碍的易感性有一致和显著的影响。为了在这一重要的研究领域取得进展，需要新的和更合适的动物模型来加强目前的人类研究。该研究将利用强大的Vervet research Colony （VRC）谱系和最近开发的Vervet遗传连锁图谱和基因组工具来鉴定数量性状位点（QTL），以可靠和有效地测量非人灵长类动物模型中冲动相关性状的行为。VRC谱系在一个复杂的大家庭中包含多达5代表型个体。利用vervet微卫星连锁图谱，对735名受试者的社会冲动性、攻击性、求新性、焦虑性、活动性和社交性等指标进行方差成分QTL分析。在发现目标性状的QTL之后，将使用SNP标记对连锁区域进行高密度定位。这将是首次在非人类灵长类动物模型中对冲动性障碍的客观测量、定量行为内表型进行全基因组研究。本研究还将通过比较生活压力改变前后两种不同环境下行为性状的QTL分析结果，为研究环境对易感位点检测的影响提供一个独特的机会。将对450只动物样本进行社会冲动性、攻击性、猎奇性、焦虑性、活动性和社交性的行为评估，这些评估将在VRC的越野运输和搬迁到一个更频繁的处理和干预的新设施后进行。这种转移将使我们能够比较基线和更有压力的环境条件下的QTL分析结果，以确定相同冲动相关性状的环境特异性QTL。这是一种评估基因-环境相互作用在测量遗传变异对行为特征影响中的作用的新方法

DESCRIPTION (provided by applicant): Impulsivity is a key feature of a large number of psychiatric disorders and psychosocial problems, including bipolar disorder, attention deficit hyperactivity disorder, conduct disorder, alcoholism, and substance abuse. Progress has been slow in identifying quantitative trait loci (QTL) and candidate genes that have consistent and significant effects on vulnerability for impulsivity-related disorders. New and more appropriate animal models are needed to augment current human studies to make progress in this important area of study. The proposed research will take advantage of the powerful Vervet Research Colony (VRC) pedigree and the recently developed vervet genetic linkage map and genomic tools to identify quantitative trait loci (QTL) for reliable and validated behavioral measures of impulsivity-related traits in a nonhuman primate model. The VRC pedigree contains up to 5 generations of phenotyped individuals in a single complex extended family. Variance components QTL analyses will be conducted on indices of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity, and Sociability for samples of up to 735 subjects using the vervet microsatellite linkage map. The discovery of putative QTL for the traits of interest will be followed up with high density mapping of the linkage region using SNP markers. This will be the first genome wide study of objectively measured, quantitative behavioral endophenotypes for impulsivity disorders in a nonhuman primate model. This study will also provide a unique opportunity to study the influence of the environment in the detection of susceptibility loci by comparing results from QTL analysis of behavioral traits in two different environments, before and after a stressful life change. Behavioral assessments of Social Impulsivity, Aggressiveness, Novelty Seeking, Anxiety, Activity and Sociability will be repeated for a sample of 450 animals following cross country transport and relocation of the VRC to a new facility with more frequent handling and interventions. The transfer will allow us to compare the results of QTL analyses under baseline and more stressful environmental conditions to identify environment-specific QTL for the same impulsivity-related traits. This is a novel way of assessing the role of the gene-environment interactions in measuring effects of genetic variation on behavior traits