GENE EXPRESSION PATTERNS IN SCHIZOPHRENIA

DNA微阵列技术的最新发展使得在一次实验中同时研究数千种不同基因的表达水平成为可能。 因此，DNA微阵列可能是研究复杂疾病的有力工具，这些疾病可能涉及许多基因表达水平的异常，并且可能继发于上游遗传或环境影响。 精神分裂症是一种病因不明的复杂疾病，目前还没有基因或生化测试可以诊断或预测其发作。 这个试验项目将检验这样一个假设，即精神分裂症患者白细胞基因表达水平的模式是保守的，与正常对照组相比有所改变。 选择血液样本进行这项先导性基因表达研究，因为它们很容易从我们机构的患者中获得，并且因为在以前的研究中获得的结果显示精神分裂症中免疫应答系统（IRS）介质浓度的改变提供了一些证据，表明该疾病中可能存在白细胞基因表达水平的改变。在本研究中，将从10名男性白人精神分裂症患者和10名年龄相似的男性白人对照受试者中获得血液样本。 这种性别和种族限制将使样品异质性最小化，并使试验样品大小的有用性最大化。将从每个受试者的血液白细胞中制备Cy 3或Cy 5荧光标记的cDNA，并将两个cDNA样品（一个Cy 3标记的和一个Cy 5标记的）与含有约9，000个已知人cDNA和EST的10个cDNA微阵列中的每一个杂交。 将扫描微阵列并测量每个点的荧光强度。 将通过双向聚类分析对所得基因表达水平模式进行分析和比较。 同样作为表达水平数据分析的一部分，将分析微阵列上代表的IRS标志物的表达水平。 如果项目数据表明精神分裂症受试者和对照受试者之间存在不同的基因表达水平，和/或精神分裂症的表达水平聚类特征，则将在更多受试者中进行进一步研究以确认该发现，并将包括其他种族群体和女性。这项研究有可能提供信息，使我们能够开发基于微阵列的测试，这可能有助于精神分裂症的诊断，也可能有助于识别有风险的个体。 这种测试将对公共卫生产生重大益处。

The recent development of DNA microarray technology has created the possibility of simultaneously studying the expression levels of thousands of different genes during a single experiment. DNA microarrays are therefore likely to be powerful tools for the study of complex diseases, which may involve abnormalities in the expression levels of many genes, and which may be secondary to upstream genetic or environmental effects. Schizophrenia is a complex disease of unknown cause and there are currently no genetic or biochemical tests that can diagnose or predict its onset. This pilot project will test the hypothesis that schizophrenia sufferers have conserved patterns of leukocyte gene expression levels, which are altered compared to normal control subjects. Blood samples were selected for this pilot gene expression study because they are readily obtainable from patients in our facilities, and because results obtained in previous studies showing altered concentrations of immune response system (IRS) mediators in schizophrenia provide some evidence to suggest there may be altered leukocyte gene expression levels in the disorder. In this study, blood samples will be obtained from ten male Caucasian schizophrenic patients and ten male Caucasian control subjects of similar age. This sex and ethnic restriction will minimize sample heterogeneity and maximize the usefulness of the pilot sample size Cy3 or Cy5 fluorescently labeled cDNA will be made from the blood leukocytes of each subject and two of the cDNA samples (one Cy3- and one Cy5-labeled) will be hybridized to each of ten cDNA microarrays containing approximately 9,000 known human cDNAs and ESTs. The microarrays will be scanned and the fluorescence intensities of each spot will be measured. The resulting gene expression level patterns will be analyzed and compared by 2-way clustering analyses. Also as part of the expression level data analysis, the expression levels of the IRS markers represented on the microarrays will be analyzed. If the project data indicate different gene expression levels between schizophrenic subjects and control subjects, and/or expression level clustering characteristic for schizophrenia, further studies to confirm the finding in larger numbers of subjects will be performed and will include other ethnic groups and women. This study has the potential of providing information that will allow us to develop microarray-based tests which may help in the diagnosis of schizophrenia, and may also help in the identification of individuals at risk. Such tests would have major public health benefits.