Molecular Mechanisms of Social Behavior

描述（由申请人提供）：本项目的目标是充分了解特定品系银狐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混乱的社交模式有着显著的相似之处。拟议的研究将描述决定狐狸行为表型的遗传位点，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。在以前的研究中，俄罗斯细胞学和遗传学研究所（ICG）开发了特定的银狐（Vulpes vulpes）品系，它们对人类表现出极其友好的行为，与它们的野生型祖先相反，它们抵制人类接触。目前的提议是康奈尔大学、ICG和犹他州大学的科学家之间的联合研究项目，以确定这些不同行为背后的分子遗传机制。狐狸的行为表型已被定义使用主成分分析。这些行为表型的遗传位点已被映射在强大的狐狸回交家系使用新开发的狐狸基因组减数分裂连锁图谱。这些确定的数量性状基因座将在扩展的高信息量的实验家系中进行验证。联合连锁和连锁不平衡作图将被应用于确定狐狸基因组中数量性状位点已被鉴定的关键区域，并确定潜在的候选基因。将使用标记辅助选择在实验谱系中确定鉴定的基因座对行为的影响。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提供新的见解和候选基因。此外，这种在生物复杂性方面介于啮齿动物和灵长类动物之间的成熟的大型动物模型将为研究诸如自闭症、精神分裂症、焦虑症、抑郁症、人格障碍、恐慌症和其他特征的人类障碍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.