Abstract
In this study, we show that the covariance between behavior and gene expression in the brain can help further unravel the determinants of neurobehavioral traits. Previously, a QTL for novelty induced motor activity levels was identified on murine chromosome 15 using consomic strains. With the goal of narrowing down the linked region and possibly identifying the gene underlying the quantitative trait, gene expression data from this F2-population was collected and used for expression QTL analysis. While genetic variation in these mice was limited to chromosome 15, eQTL analysis of gene expression showed strong cis-effects as well as trans-effects elsewhere in the genome. Using weighted gene co-expression network analysis, we were able to identify modules of co-expressed genes related to novelty induced motor activity levels. In eQTL analyses, the expression of Ly6a (a.k.a. Sca-1) was found to be cis-regulated by chromosome 15. Ly6a also surfaced in a group of genes resulting from the network analysis that was correlated with behavior. Behavioral analysis of Ly6a knock-out mice revealed reduced novelty induced motor activity levels when compared to wild type controls, confirming functional importance of Ly6a in this behavior, possibly through regulating other genes in a pathway. This study shows that gene expression profiling can be used to narrow down a previously identified behavioral QTL in mice, providing support for Ly6a as a candidate gene for functional involvement in novelty responsiveness.
Highlights
With a prevalence of 10–20% worldwide, mood disorders affect a substantial number of people and finding the genetic risk factors will aid in prevention and treatment [1]
To identify possible candidate genes for the behaviors of interest, we looked at overlap between Expression QTL (eQTL) and the region associated to behavior. 53 eQTLs overlap with both behavioral quantitative trait loci (QTL), while 27 more eQTLs only overlap with the broader peak of DM1
The aim of this study was to use gene expression data to narrow down a QTL found to be associated to exploration and noveltyinduced behavior
Summary
With a prevalence of 10–20% worldwide, mood disorders affect a substantial number of people and finding the genetic risk factors will aid in prevention and treatment [1]. The heritability estimates for mood disorders range from 43% for panic disorder to 28% for anxiety disorder, indicating a genetic component to these disorders [2]. Behavior and novelty responsiveness are considered to be an important endophenotype in anxiety research [3,4]. These behaviors are used to model different symptoms of mood disorders in mice, mainly fear, fatigue or loss of energy, and avoidance. These symptoms can be diminished when administering anxiolytic drugs [5,6,7]. Exploration behavior has been found to be significantly heritable in mice [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
