Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects
Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects
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DOI：
10.1034/j.1601-183x.2003.00030.x
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发表时间：
2003-08-01
影响因子：
2.5
通讯作者：
Lu, L
中科院分区：
文献类型：
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作者：
Peirce, JL;Chesler, EJ;Lu, L
我们最近定位了两个对小鼠海马区结构有广泛影响的数量性状基因座：Hipp1a和Hipp5a。我们还注意到不同海马区的相对大小存在显著的应变差异。这些差异的估计遗传变异在海马体中为42%，在齿状回中为40%，在颗粒细胞层中为31%，在锥体细胞层中为18%。区域大小从最大到最小变化至少50%。在这里，我们利用这些差异来识别影响齿状回、颗粒细胞层、海马体本身和锥体细胞层的基因座。我们的样本由C57BL/6J、DBA/2J和32个BXD重组自交系组成。对体积数据进行了收缩和脑重量差异的校正。我们在染色体(Chr)6、13和15上发现了显著的基因座，在Chr11的近端发现了一个显著的相互作用基因座。HipV13a(Chr 13，42-78Mb)对齿状回体积的加性效应为0.56 mm(3)(12.1%)，GrV6a(Chr 6，29-65 Mb)对颗粒细胞层体积的加性效应为0.14 mm(3)(16.0%)。HipV13a还与DGVi11a相互作用，DGVi11a是位于近端Chr 11的一个基因座，它只通过对HipV13a的上位效应起作用，没有独立的主效应。HipV15a(Chr 15，0-51Mb)对海马体体积的加性效应为1.76 mm(3)(9.0%)。我们使用WebQTL，一个最近描述的基于网络的工具，来检查基因表达与海马体体积的遗传相关性。我们确定了一些在OTL间隔内映射的基因，并具有高度相关的表达模式。利用WebQTL已发表的BXD表型的广泛数据库，我们还发现了海马体体积和声学惊吓反应之间强烈的、具有潜在生物学意义的相关性。
We recently mapped two quantitative trait loci that have widespread effects on hippocampal architecture in mouse: Hipp1a and Hipp5a. We also noted remarkable strain differences in the relative sizes of different hippocampal regions. Estimated heritable variation for these differences was 42% in hippocampus proper, 40% in dentate gyrus, 31% in granule cell layer and 18% in pyramidal cell layer. Region size varied at least 50% from largest to smallest measurement. Here we have utilized these differences to identify loci with effects on the dentate gyrus, granule cell layer, hippocampus proper and pyramidal cell layer. Our sample consists of C57BL/6J and DBA/2J and 32 BXD recombinant inbred strains. Volumetric data were corrected for shrinkage and for differences in brain weight. We identified significant loci on chromosomes (Chr) 6, 13 and 15, and a significant interaction locus on proximal Chr 11. A suggestive distal Chr 1 locus overlaps with Hippla. HipV13a (Chr 13, 42-78Mb) has an additive effect of 0.56 mm(3) (12.1%) on dentate gyrus volume, while, GrV6a (Chr 6, 29-65 Mb) has additive effects of 0.14 mm(3) (16.0%) on the volume of the granule cell layer. HipV13a also interacts with DGVi11a, a locus on proximal Chr 11 that operates exclusively through its epistatic effect on HipV13a and has no independent main effect. HipV15a (Chr 15, 0-51 Mb) has an additive effect of 1.76 mm(3) (9.0%) on the volume of the hippocampus proper. We used WebQTL, a recently described web-based tool, to examine genetic correlation of gene expression with hippocampal volume. We identified a number of genes that map within the OTL intervals and have highly correlated expression patterns. Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response.