Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex

Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex
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DOI:
10.1016/s0896-6273(00)00085-4
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发表时间:
2000-10-01
期刊:
影响因子:
16.2
通讯作者:
Levitt, P
Levitt, P
中科院分区:
医学1区
文献类型:
--
作者:
Mirnics, K;Middleton, FA;Levitt, P

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来自配对的精神分裂症患者和对照组的前额叶皮层微阵列表达谱和分层数据分析显示,所有精神分裂症患者编码突触前功能(PSYN)调节蛋白的转录本都减少。PSYN组的基因在不同的受试者中表现出不同的表达减少组合。超过250个其他基因组没有表现出表达改变。选定的PSYN微阵列观察结果通过原位杂交验证。在精神分裂症患者中,n -乙基马来酰亚胺敏感因子(n -乙基马来酰亚胺敏感因子)和突触素II (synapsin II)这两种功能基因组中变化最一致的转录本分别在10 / 10和9 / 10的受试者中减少。综合数据表明,精神分裂症患者在突触前功能上有共同的异常。我们提出了一个可预测的、可测试的模型。
Microarray expression profiling of prefrontal cortex from matched pairs of schizophrenic and control subjects and hierarchical data analysis revealed that transcripts encoding proteins involved in the regulation of presynaptic function (PSYN) were decreased in all subjects with schizophrenia. Genes of the PSYN group showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected PSYN microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the PSYN functional gene group, N-ethylmaleimide sensitive factor and synapsin II, were decreased in ten of ten and nine of ten subjects with schizophrenia, respectively. The combined data suggest that subjects with schizophrenia share a common abnormality in presynaptic function. We set forth a predictive, testable model.