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      BAC-Based Sequencing of Behaviorally-Relevant Genes in the Prairie Vole

      research-article
      1 , * , 2 , 3 , NISC Comparative Sequencing Program 3 , 1 , 4 , 2
      PLoS ONE
      Public Library of Science

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          Abstract

          The prairie vole ( Microtus ochrogaster) is an important model organism for the study of social behavior, yet our ability to correlate genes and behavior in this species has been limited due to a lack of genetic and genomic resources. Here we report the BAC-based targeted sequencing of behaviorally-relevant genes and flanking regions in the prairie vole. A total of 6.4 Mb of non-redundant or haplotype-specific sequence assemblies were generated that span the partial or complete sequence of 21 behaviorally-relevant genes as well as an additional 55 flanking genes. Estimates of nucleotide diversity from 13 loci based on alignments of 1.7 Mb of haplotype-specific assemblies revealed an average pair-wise heterozygosity (8.4×10 −3). Comparative analyses of the prairie vole proteins encoded by the behaviorally-relevant genes identified >100 substitutions specific to the prairie vole lineage. Finally, our sequencing data indicate that a duplication of the prairie vole AVPR1A locus likely originated from a recent segmental duplication spanning a minimum of 105 kb. In summary, the results of our study provide the genomic resources necessary for the molecular and genetic characterization of a high-priority set of candidate genes for regulating social behavior in the prairie vole.

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          Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

          Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
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            Human-mouse alignments with BLASTZ.

            The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding genome evolution, a particularly sensitive method was needed to permit alignment of a large proportion of the neutrally evolving regions. We selected a program called BLASTZ, an independent implementation of the Gapped BLAST algorithm specifically designed for aligning two long genomic sequences. BLASTZ was subsequently modified, both to attain efficiency adequate for aligning entire mammalian genomes and to increase its sensitivity. This work describes BLASTZ, its modifications, the hardware environment on which we run it, and several empirical studies to validate its results.
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              Oxytocin, vasopressin, and the neurogenetics of sociality.

              There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                6 January 2012
                : 7
                : 1
                : e29345
                Affiliations
                [1 ]Center for Translational Social Neuroscience and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America
                [2 ]Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America
                [3 ]Genome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America
                [4 ]Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, United States of America
                Auburn University, United States of America
                Author notes

                Conceived and designed the experiments: LAM LJY JWT. Performed the experiments: JKD NISC. Analyzed the data: LAM PJT JWT. Wrote the paper: LAM JWT.

                [¤]

                Current address: Department of Biology, North Carolina State University, Raleigh, North Carolina, United States of America

                Article
                PONE-D-11-18761
                10.1371/journal.pone.0029345
                3253076
                22238603
                789ff2d2-c8e1-4c05-afe4-fce90f62355d
                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
                History
                : 22 September 2011
                : 25 November 2011
                Page count
                Pages: 6
                Categories
                Research Article
                Agriculture
                Animal Management
                Biology
                Computational Biology
                Genomics
                Evolutionary Biology
                Genetics
                Genomics
                Model Organisms
                Neuroscience
                Zoology
                Veterinary Science
                Animal Management

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                Uncategorized

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