title: Genetic influences on brain gene expression in rats selected for tameness and aggression.
abstract: Interindividual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior toward humans for >64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40, and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany Institute for Biochemistry, University of Leipzig, Medical Faculty, 04103 Leipzig, Germany henrikeheyne@hotmail.de falbert@mednet.ucla.edu.
authors.forename: Henrike O
authors.initials: HO
authors.lastname: Heyne
authors.affiliation: Institute for Biochemistry, University of Leipzig, Medical Faculty, 04103 Leipzig, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Lautenschläger
authors.affiliation: Swedish University of Agricultural Sciences, Department of Clinical Sciences, Division of Computational Genetics, Box 7078 SE-75007 Uppsala, Sweden.
authors.forename: Ronald
authors.initials: R
authors.lastname: Nelson
authors.affiliation: Swedish University of Agricultural Sciences, Department of Clinical Sciences, Division of Computational Genetics, Box 7078 SE-75007 Uppsala, Sweden Section of Population Genetics and Ecology, Institute of Marine Research, Havforskningsinstituttet, Nordnes 5817, Bergen, Norway.
authors.forename: François
authors.initials: F
authors.lastname: Besnier
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Maxime
authors.initials: M
authors.lastname: Rotival
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Cagan
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Rimma
authors.initials: R
authors.lastname: Kozhemyakina
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Irina Z
authors.initials: IZ
authors.lastname: Plyusnina
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Trut
authors.affiliation: Swedish University of Agricultural Sciences, Department of Clinical Sciences, Division of Computational Genetics, Box 7078 SE-75007 Uppsala, Sweden.
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Carlborg
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.affiliation: Department of Human Genetics, Gonda Center, University of California, Los Angeles, California 90095 Department of Biological Chemistry, Gonda Center, University of California, Los Angeles, California 90095 Howard Hughes Medical Institute, Gonda Center, University of California, Los Angeles, California 90095.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Institute for Biochemistry, University of Leipzig, Medical Faculty, 04103 Leipzig, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany Department of Human Genetics, Gonda Center, University of California, Los Angeles, California 90095 henrikeheyne@hotmail.de falbert@mednet.ucla.edu.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Albert
mesh_terms: D000374:Aggression; D000483:Alleles; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D008297:Male; D040641:Quantitative Trait Loci / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger
keywords: RNA sequencing; brain gene expression; genetics of tame and aggressive behavior; natural variation; quantitative trait locus (QTL) mapping in outbred rats