Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China.
Stress. 2009 Nov;12(6):499-506. doi: 10.3109/10253890802666112.
Previous studies have revealed that the subunit alpha 2 (Gabra2) of the gamma-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.
先前的研究表明，γ-氨基丁酸受体的亚基 alpha 2（Gabra2）在应激反应中起着关键作用。然而，关于 Gabra2 和应激反应的遗传调控网络知之甚少。我们结合基因表达微阵列分析和数量性状位点（QTL）作图，以表征 BXD 重组近交系（RI）小鼠海马体中 Gabra2 表达的遗传调控网络。我们的分析发现，在 BXD RI 株系以及亲本株系 C57BL/6J 和 DBA/2J 之间，海马体中 Gabra2 的表达水平存在很大差异。表达 QTL（eQTL）作图显示，Gabra2 的三个微阵列探针集具有非常显著的连锁可能性比统计（LRS）分数。基因共调控网络分析表明，包括 Gria3、Chka、Drd3、Homer1、Grik2、Odz4、Prkag2、Grm5、Gabrb1 和 Nlgn1 在内的 10 个基因与应激反应直接或间接相关。通过联合调控映射，有 11 个基因被认为是 Gabra2 的下游基因。遗传基因组学方法表明，eQTL 研究在确定与应激反应等复杂特征相关的遗传调控网络方面具有重要性和潜在的力量。
