Molecular genetics of tame behavior

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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.