Molecular Mechanisms of Social Behavior

描述(由申请者提供)：本项目的目标是全面了解在特定品系的银狐中分离的某些遗传行为的遗传学。这些狐狸的行为范围与人类正常和无序的社交模式有很大的相似之处。这项拟议的研究将表征决定狐狸行为表型的遗传基因，以深入了解社会行为的遗传学及其潜在的分子机制，不仅在狐狸身上，而且在包括人类在内的其他哺乳动物中。在之前的研究中，俄罗斯细胞学和遗传学研究所(ICG)培育出了特定品系的银狐，它们对人类表现出极其友好的行为，而它们的野生型祖先拒绝与人类接触。目前的提议是康奈尔大学、ICG和犹他大学的科学家们的联合研究项目，目的是定义这些不同行为背后的分子遗传机制。用主成分分析定义了狐狸的行为表型。利用新开发的狐狸基因组减数分裂连锁图谱，在强大的狐狸回交家系中定位了这些行为表型的遗传位点。这些已识别的数量性状基因座将在信息量很大的实验家系的扩展集合中得到验证。结合连锁和连锁不平衡作图将用于确定狐狸基因组中已识别出数量性状座位的关键区域，并确定潜在的候选基因。已识别的基因座对行为的影响将通过标记辅助选择在实验家系中确定。对影响狐狸社会行为的基因和基因座的识别有望为人类社会行为障碍提供新的见解和候选基因。此外，这样一个成熟的大型动物模型，在生物学复杂性上介于啮齿动物和灵长类动物之间，然后将提供机会，研究针对自闭症、精神分裂症、焦虑、抑郁、人格障碍、惊恐障碍和其他特征等人类疾病的潜在治疗方法。

DESCRIPTION (provided by applicant): The goal of this project to fully understand the genetics of certain inherited behaviors segregating in specific strains of silver foxes. The range of behaviors in these foxes has significant parallels to that of normal and disordered patterns of human sociability. The proposed research will characterize the genetic loci determining fox behavioral phenotypes to yield insights into the genetics of social behavior and its underlying molecular mechanisms, not only in foxes, but in other mammals, including humans. In previous studies, specific strains of silver fox (Vulpes vulpes) were developed, at the Russian Institute of Cytology and Genetics (ICG), that exhibit extremely friendly behavior towards humans, in contrast to their wild-type ancestors that resist human contact. The current proposal is a joint research project between scientists at Cornell University, ICG, and the University of Utah, to define the molecular genetic mechanisms underlying these different behaviors. Fox behavioral phenotypes have been defined using principal-components analysis. Genetic loci underlying these behavioral phenotypes have been mapped in powerful sets of fox backcross pedigrees using the newly developed meiotic linkage map of the fox genome. These identified quantitative trait loci will be validated in extended sets of highly informative experimental pedigrees. Combined linkage and linkage disequilibrium mapping will be applied to define the critical regions of the fox genome in which quantitative trait loci have been identified, and identify potential candidate genes. The effect of identified loci on behavior will be determined in experimental pedigrees using marker assisted selection. The identification of genes and loci influencing social behavior in foxes is anticipated to provide new insights into, and candidate genes for human disorders of social behavior. Furthermore, such a well- established large animal model, intermediate between rodents and primates in biological complexity, would then offer opportunities to investigate potential therapies for such human disorders as autism, schizophrenia, anxiety, depression, personality disorders, panic disorder and other traits.