Mirnics Károly, Levitt Pat, Lewis David A
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. karoly+@pitt.edu
Biol Psychiatry. 2006 Jul 15;60(2):163-76. doi: 10.1016/j.biopsych.2006.02.003. Epub 2006 Apr 17.
Transcriptome profiling using DNA microarrays are data-driven approaches with the potential to uncover unanticipated relationships between gene expression alterations and psychiatric disorders. Studies to date have yielded both convergent and divergent findings. Differences may be explained, at least in part, by the use of a variety of microarray platforms and analytical approaches. Consistent findings across studies suggest, however, that important relationships may exist between altered gene expression and genetic susceptibility to psychiatric disorders. For example, GAD67, RGS4, DTNBP1, NRG1, and GABRAB2 show expression alterations in the postmortem brain of subjects with schizophrenia, and these genes have been also implicated as putative, heritable schizophrenia susceptibility genes. Thus, we propose that for some genes, altered expression in the postmortem human brain may have a dual origin: polymorphisms in the candidate genes themselves or upstream genetic-environmental factors that converge to alter their expression level. We hypothesize that certain gene products, which function as "molecular hubs," commonly show altered expression in psychiatric disorders and confer genetic susceptibility for one or more diseases. Microarray gene expression studies are ideally suited to reveal these putative disease-associated molecular hubs and to identify promising candidates for genetic association studies.
使用DNA微阵列进行转录组分析是一种数据驱动的方法,有潜力揭示基因表达改变与精神疾病之间意想不到的关系。迄今为止的研究得出了一些一致和不一致的结果。这些差异至少部分可以通过使用各种微阵列平台和分析方法来解释。然而,各研究中的一致发现表明,基因表达改变与精神疾病的遗传易感性之间可能存在重要关系。例如,GAD67、RGS4、DTNBP1、NRG1和GABRAB2在精神分裂症患者的死后大脑中显示出表达改变,并且这些基因也被认为是假定的遗传性精神分裂症易感基因。因此,我们提出,对于某些基因,死后人类大脑中的表达改变可能有双重起源:候选基因本身的多态性或上游遗传环境因素共同作用以改变其表达水平。我们假设某些作为“分子枢纽”发挥作用的基因产物,在精神疾病中通常会显示表达改变,并赋予一种或多种疾病的遗传易感性。微阵列基因表达研究非常适合揭示这些假定的疾病相关分子枢纽,并为遗传关联研究确定有前景的候选基因。