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Brenndörfer, J.* ; Altmann, A.* ; Widner-Andrä, R.* ; Pütz, B.* ; Czamara, D.* ; Tilch, E. ; Kam-Thong, T.* ; Weber, P.* ; Rex-Haffner, M.* ; Bettecken, T.* ; Bültmann, A.* ; Müller-Myhsok, B.* ; Binder, E.E.* ; Landgraf, R.* ; Czibere, L.*

Connecting anxiety and genomic copy number variation: A genome-wide analysis in CD-1 mice.

PLoS ONE 10:e0128465 (2015)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Real-time Pcr; Gene-expression; Glyoxalase-i; Structural Variation; Bipolar Disorder; Candidate Genes; Microarray Data; Trait Anxiety; Animal-model; De-novo
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 10, Heft: 5, Seiten: , Artikelnummer: e0128465 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed