Molecular Mechanisms of Social Behavior

项目描述（由申请人提供）：该项目的目标是全面了解银狐特定品系中某些遗传行为分离的遗传学。这些狐狸的行为范围与人类正常和无序的社交模式有显著的相似之处。拟议的研究将描述决定狐狸行为表型的基因位点，以深入了解社会行为的遗传学及其潜在的分子机制，不仅在狐狸中，而且在其他哺乳动物中，包括人类。在之前的研究中，俄罗斯细胞学和遗传学研究所（ICG）培育出了特定的银狐菌株（Vulpes Vulpes），它们对人类表现出极其友好的行为，与它们抵制人类接触的野生型祖先形成鲜明对比。目前的提案是康奈尔大学、ICG和犹他大学科学家的联合研究项目，旨在确定这些不同行为背后的分子遗传机制。狐狸的行为表型已经定义使用主成分分析。使用新开发的狐狸基因组减数分裂连锁图谱，在强大的狐狸回交谱系中绘制了这些行为表型的遗传位点。这些确定的数量性状位点将在大量信息丰富的实验谱系中得到验证。联合连锁和连锁不平衡定位将被应用于确定狐基因组中数量性状位点的关键区域，并确定潜在的候选基因。鉴定的基因座对行为的影响将在使用标记辅助选择的实验系谱中确定。对影响狐狸社会行为的基因和位点的鉴定有望为人类社会行为障碍的研究提供新的见解和候选基因。此外，这样一个建立良好的大型动物模型，在生物复杂性上介于啮齿动物和灵长类动物之间，将为研究自闭症、精神分裂症、焦虑、抑郁、人格障碍、恐慌症和其他特征等人类疾病的潜在疗法提供机会。

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.