Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour
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DOI：
10.1111/j.0953-816x.2004.03358.x
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Schalkwyk, LC
中科院分区：
文献类型：
--
作者：
Fernandes, C;Paya-Cano, JL;Schalkwyk, LC
小鼠近交系在表型的许多方面都有所不同，众所周知，基因表达也是如此。这使我们有机会分离表达变异的遗传方面，并将其与其他表型变量进行比较。我们在Affymetrix MGU74av2基因芯片上对一个明确定义的脑组织（海马体）进行了8个菌株的表达谱比较，每个菌株有4个重复。我们在海马基因表达中发现了大量的菌株特异性变异，超过200个基因通过非常保守的标准显示出菌株差异。许多基因驱动的基因表达差异可能导致包括行为差异在内的功能差异。大量的自交系可以用来鉴定与特定表型相关的基因，类似于遗传相关性。表达谱和功能之间的遗传相关性可能非常强大，特别是考虑到当前对多个菌株（小鼠表型计划）的大规模表型数据生成。例如，在我们的8个自交系中，200多个探针组之间的遗传相关性最强，并且根据这些菌株的攻击表型进行排名，发现Comt基因是已知参与攻击的基因。
Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.