Gene networks associated with conditional fear in mice identified using a systems genetics approach

To uncover genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. We mapped 27 behavioral quantitative trait loci with a false discovery rate of 5%. We also identified two gene co-expression networks correlated with context-dependent immobility. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. We surveyed the architecture of brain transcript regulation and showed preservation of gene co-expression modules in hippocampus and striatum while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance associated strongly with fear phenotypes. Total mRNA islolated from hippocampus and striatum of strains from Hybrid Mouse Diversity Panel and gene expression quantified using Illumina MouseRef-8 v2.0 microarrays. Submission includes gene expression data from 100 strains of HMDP for hippocampus (n=1 for each strain) and 98 strains of HMDP for striatum (n=1 for each strain).为揭示调控条件性恐惧生物学过程的遗传网络，我们采用系统遗传学方法，对具有高定位分辨率的杂交小鼠多样性面板（Hybrid Mouse Diversity Panel，HMDP）展开分析。通过整合恐惧行为表型、海马体与纹状体的转录表达谱数据以及基因型信息，我们鉴定出两个与情境依赖性不动相关的基因共表达网络。我们借助模块内连通性分析与结构方程模型，对这些通路中的关键标记物与基因进行了优先级排序。我们共定位到27个行为数量性状基因座，错误发现率为5%。我们还鉴定出两个与情境依赖性不动相关的基因共表达网络。情境恐惧模块中连接度较高的基因包括Psmd6、Ube2a与Usp33，提示泛素化过程在学习记忆中发挥重要作用。我们对大脑转录调控的架构进行了调研，证实海马体与纹状体中存在基因共表达模块的保守性，同时也揭示了二者间的重要差异。Rps15a、Kif3a、Stard7、6330503K22RIK与Plvap等基因的转录本丰度与恐惧行为表型显著相关。我们从杂交小鼠多样性面板各品系的海马体与纹状体中分离总mRNA，并通过Illumina MouseRef-8 v2.0基因表达微阵列对基因表达水平进行定量检测。本数据集提交内容包含100个HMDP品系的海马体基因表达数据（每个品系n=1），以及98个HMDP品系的纹状体基因表达数据（每个品系n=1）。