Molecular genetics of tame behavior

描述（由申请人提供）：焦虑、自闭症、精神分裂症以及类似的问题对家庭和社会有着巨大的影响。尽管它们具有很强的遗传成分，但它们复杂的异质遗传严重限制了确定其原因的努力。提出了一种识别犬科动物模型系统行为特征相关基因的新方法。俄罗斯细胞学和遗传学研究所的两种银狐（Vulpes Vulpes）经过40代的选择性育种，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，以便在人类神经和行为综合症中对它们进行评估。目前的建议基本上是一项试点研究，以确定我们长期目标的主要依据。目前的具体目标是：构建狐狸基因组的第一代减数分裂连锁图谱；开发三代实验性回交狐狸谱系，为驯服/友好行为提供信息；在这些实验狐狸家系中进行全基因组扫描，以确定与行为表型相关的qtl；并评估选择的候选基因与狐狸的行为表型共分离。为了实现这些目标，将利用犬类分子遗传学和比较遗传学的最新进展。狐狸减数分裂图谱将通过一组犬类衍生的微卫星对狐狸谱系进行基因分型，并通过纳入与人类和/或啮齿动物神经生理和行为相关的特定基因标记进行优化。将驯化型/友好型和野生型狐狸进行杂交，然后将F1后代与驯化型/友好型亲本进行回交，从而获得具有驯化性信息的实验性三代回交谱系。模拟研究预测，在所有适度乐观的情况下，在提议的全基因组扫描中，QTL检测的功率水平为>.8。一组与人类和/或啮齿动物行为相关的候选基因将利用现有的和三代实验狐狸谱系来评估与驯化型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.