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精神分裂症中成纤维细胞和淋巴母细胞的基因表达谱:非神经细胞有参考价值吗?

Fibroblast and lymphoblast gene expression profiles in schizophrenia: are non-neural cells informative?

作者信息

Matigian Nicholas A, McCurdy Richard D, Féron François, Perry Christopher, Smith Heather, Filippich Cheryl, McLean Duncan, McGrath John, Mackay-Sim Alan, Mowry Bryan, Hayward Nicholas K

机构信息

Queensland Institute of Medical Research, Herston, Queensland, Australia.

出版信息

PLoS One. 2008 Jun 11;3(6):e2412. doi: 10.1371/journal.pone.0002412.

Abstract

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p < or = 0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed > or = 2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated.

摘要

淋巴母细胞样细胞系(LCLs)和成纤维细胞提供了方便获取的非神经元样本,可用于通过基因表达谱分析来研究精神分裂症(SZ)的病因。这假定与SZ风险相关的遗传机制具有全身效应,并导致所有组织中的基因表达发生变化。本研究及其他类似研究的广泛目标是,比较SZ患者和健康对照的非神经元组织转录组,可能会识别出与SZ相关的神经生物学缺陷背后的基因/通路失调。我们使用由18,664个探针组成的微阵列,比较了SZ病例和健康对照的LCLs的基因表达谱。为了识别与SZ的稳健关联,且这些关联不是患者或组织特异性的,我们还使用相同的微阵列检查了来自独立系列SZ病例和对照的成纤维细胞。在两种组织类型中,方差分析返回的差异表达基因数量大约是偶然预期的数量。在进行多重检验校正后,两种组织中均没有基因显著差异表达。即使使用宽松的参数(p≤0.05,不进行多重检验校正),在LCLs和成纤维细胞共有的SZ病例组和对照组之间,仍然没有差异表达基因同时显示出≥2倍的变化。我们得出结论,尽管之前评估非神经组织的微阵列研究数据令人鼓舞,但使用成纤维细胞和LCLs缺乏一组与SZ相关的趋同的差异表达基因,这表明非神经元组织用于检测与SZ相关的基因表达差异和/或通路的效用仍有待证明。

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