Molecular genetics of tame behavior

描述（由申请人提供）：焦虑症，自闭症，精神分裂症和类似的问题对家庭和社会有巨大的影响。尽管其强大的遗传成分，其复杂的异质遗传严重制约了努力，以确定其原因。提出了一种在犬科动物模型系统中识别行为性状相关基因的新方法。俄罗斯细胞学和遗传学研究所经过40多代的选择性繁殖，培育出两种银狐（Vulpesvulpes），它们表现出明显不同的遗传行为模式。我们项目的长期目标是确定导致这些狐狸行为差异的基因，以使它们能够在人类神经和行为综合征中进行评估。目前的建议基本上是一个试点研究，以建立我们的共同长期目标的主要依据的证据。目前建议的具体目标是：构建狐狸基因组的第一代减数分裂连锁图;开发三代实验回交狐狸谱系，为驯服/友好行为提供信息;在这些实验狐狸谱系中进行全基因组扫描以鉴定与行为表型相关的QTL;并评估与狐狸行为表型共分离的选定候选基因。为了实现这些目标，将利用犬分子遗传学和比较遗传学的最新进展。将通过用一组犬衍生的微卫星对狐狸家系进行基因分型来构建狐狸减数分裂图谱，并通过掺入对涉及人类和/或啮齿动物神经生理学和行为的基因特异性的标记物来优化。将通过杂交驯服/友好型和野生型狐狸，然后将F1子代回交到驯服/友好型亲本，开发实验性三代回交谱系。对于所有适度乐观的情况，模拟研究预测在所提出的全基因组扫描中QTL检测的功率水平> 0.8。将使用现有的和三代实验狐狸谱系，评价与人类和/或啮齿动物行为有关的一组候选基因与驯服和野生型行为表型的共分离。

DESCRIPTION (provided by applicant): Anxiety, autism, schizophrenia, and similar problems have enormous impact on families and society. Despite their strong genetic component, their complex heterogeneous inheritance seriously constrains efforts to identify their causes. A new approach to identify genes implicated in behavioral traits in a canid model system is proposed. Two strains of silver fox (Vulpes vulpes) developed over 40 generations of selective breeding at the Russian Institute of Cytology and Genetics exhibit remarkably different patterns of hereditary behavior. The long-term goal of our project is to identify genes contributing to behavioral differences in these foxes, to enable their evaluation in human neurological and behavioral syndromes. The current proposal is essentially a pilot study, to establish proof of the principal underlying our tong term goals. Specific aims for the current proposal are to: construct a first generation meiotic linkage map of the fox genome; develop three-generation experimental backcross fox pedigrees informative for tame/friendly behavior; perform a genome wide scan to identify QTLs associated with behavioral phenotypes in these experimental fox pedigrees; and evaluate selected candidate genes for co-segregation with fox behavioral phenotypes. To achieve these aims, advantage will be taken of recent progress in canine molecular and comparative genetics. The fox meiotic map will be built by genotyping fox pedigrees with a set of canine derived microsatellites and optimized by incorporation of markers specific for genes implicated in human and/or rodent neurophysiology and behavior. Experimental three-generation backcross pedigrees informative for tameness will be developed by crossbreeding tame/friendly and wild type foxes, then backcrossing the F1 progeny to tame/friendly parents. Simulation studies predict power levels > 0.8 for QTL detection in the proposed genome wide scan, for all modestly optimistic scenarios. A set of candidate genes implicated in human and/or rodent behavior will be evaluated for co segregation with tame and wild type behavioural phenotypes using existing and three-generation experimental fox pedigrees.