Gene networks associated with conditional fear in mice identified using a systems genetics approach.
Gene networks associated with conditional fear in mice identified using a systems genetics approach.
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DOI：
10.1186/1752-0509-5-43
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发表时间：
2011-03-16
影响因子：
--
通讯作者：
Smith DJ
中科院分区：
文献类型：
--
作者：
Park CC;Gale GD;de Jong S;Ghazalpour A;Bennett BJ;Farber CR;Langfelder P;Lin A;Khan AH;Eskin E;Horvath S;Lusis AJ;Ophoff RA;Smith DJ
我们对学习和记忆的遗传基础的理解仍然笼罩在神秘之中。为了探索控制条件性恐惧生物学的遗传网络，我们使用系统遗传学方法分析了具有高映射分辨率的杂交小鼠多样性面板（HMDP）。共定位了27个行为数量性状基因座，错误发现率为5%。通过整合恐惧表型、海马和纹状体的转录谱数据以及基因型信息，确定了与情境依赖性不动性相关的两个基因共表达网络。我们使用模块内连接测量和结构方程模型优先考虑这些通路中的关键标记和基因。在背景恐惧模块中高度连接的基因包括Psmd 6，Ube2a和Usp 33，这表明泛素化在学习和记忆中的重要作用。此外，我们调查了大脑转录调控的结构，并证明了海马和纹状体中基因共表达模块的保留，同时也强调了重要的差异。Rps15a、Kif3a、Stard7、6330503K22RIK和Plvap是其转录丰度与恐惧表型强烈相关的单个基因。我们的多方面映射策略的应用允许越来越详细的表征的遗传网络的行为。
Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the 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. A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also 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. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated 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 were strongly associated with fear phenotypes. Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.
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影响因子：
--
作者：
Aten JE;Fuller TF;Lusis AJ;Horvath S
通讯作者：
Horvath S
影响因子：
7
作者：
Huang, Guo-Jen;Shifman, Sagiv;Flint, Jonathan
通讯作者：
Flint, Jonathan
影响因子：
11
作者：
Camargo, L. M.;Collura, V.;Brandon, N. J.
通讯作者：
Brandon, N. J.
基因共表达网络分析的几何解释。
影响因子：
4.3
作者：
Horvath, Steve;Dong, Jun
通讯作者：
Dong, Jun
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y