| Autor: |
Brenndörfer J; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany., Altmann A; Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany., Widner-Andrä R; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany., Pütz B; Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany., Czamara D; Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany., Tilch E; Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany., Kam-Thong T; Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany., Weber P; Department of Molecular Genetics of Affective Disorders, Max Planck Institute of Psychiatry, Munich, Germany., Rex-Haffner M; Department of Molecular Genetics of Affective Disorders, Max Planck Institute of Psychiatry, Munich, Germany., Bettecken T; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany., Bultmann A; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany., Müller-Myhsok B; Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany., Binder EE; Department of Molecular Genetics of Affective Disorders, Max Planck Institute of Psychiatry, Munich, Germany., Landgraf R; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany., Czibere L; Department of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany. |
| Abstrakt: |
Genomic copy number variants (CNVs) have been implicated in multiple psychiatric disorders, but not much is known about their influence on anxiety disorders specifically. Using next-generation sequencing (NGS) and two additional array-based genotyping approaches, we detected CNVs in a mouse model consisting of two inbred mouse lines showing high (HAB) and low (LAB) anxiety-related behavior, respectively. An influence of CNVs on gene expression in the central (CeA) and basolateral (BLA) amygdala, paraventricular nucleus (PVN), and cingulate cortex (Cg) was shown by a two-proportion Z-test (p = 1.6 x 10-31), with a positive correlation in the CeA (p = 0.0062), PVN (p = 0.0046) and Cg (p = 0.0114), indicating a contribution of CNVs to the genetic predisposition to trait anxiety in the specific context of HAB/LAB mice. In order to confirm anxiety-relevant CNVs and corresponding genes in a second mouse model, we further examined CD-1 outbred mice. We revealed the distribution of CNVs by genotyping 64 CD 1 individuals using a high-density genotyping array (Jackson Laboratory). 78 genes within those CNVs were identified to show nominally significant association (48 genes), or a statistical trend in their association (30 genes) with the time animals spent on the open arms of the elevated plus-maze (EPM). Fifteen of them were considered promising candidate genes of anxiety-related behavior as we could show a significant overlap (permutation test, p = 0.0051) with genes within HAB/LAB CNVs. Thus, here we provide what is to our knowledge the first extensive catalogue of CNVs in CD-1 mice and potential corresponding candidate genes linked to anxiety-related behavior in mice. |
