| 摘要: | 精神分裂症屬於complex disease之一，主要會造成病患無法區分虛實之間的差異，嚴重者將有危及生命的行為發生，但目前針對精神分裂症的相關研究，有許多假說相繼成立，包括：神經傳導素分泌失調、腦部發育不正常等，但仍無法明確地指出何種因素才是引發疾病的主要因子；故目前人類僅可藉由藥物阻斷特定神經傳導物質，以緩和病患發病的症狀。在此研究中我們採用不同於以往僅著重於研究基因序列的方式，反而以表觀基因體學研究方式為主。而分析數據主要來自精神分裂症病患與正常人兩組別，藉由微陣列偵測CpG island的甲基化程度，再將偵測到的數據，首先挑選出不含重複序列共7,843 個spots，接著選擇7,843 spots 當中甲基化程度差異大者前2,005個spots，此2,005 spots可作為分析觀察條件之一；另外，若僅以去除NA值為條件篩選7,843 spots，則可得到7,647 spots。所以在前述兩篩選條件中，分別可得2,005 spots與7,647 spots兩組基因，再利用計算partial correlation coefficient即可推測具甲基化程度相關性的基因對，以此為依據建立CpG island co-methylation network。接著再對各組網絡進行基本特性分析，而由我們分析結果得知，在病患所構成的網絡中不論在top 2,005 variable spots或是7,647 spots，其具關聯性的基因主要功能傾向以神經發育、訊號傳遞、DNA甲基化相關過程為主；但正常人所建立的網絡卻無此特徵。雖然藉由甲基化分析，仍無法確認甲基化程度的失常是否會影響腦中基因表現量，但我們分析結果可確定精神分裂症病患CpG islands甲基化程度的相關性比正常人還要密切，使得基因之間容易互相影響，導致基因在面對環境變化時缺少預防變異的機制，而增加基因失調的機率。 Schizophrenia is a complex disease. It affects the most basic human processes of perception, emotion, and judgment. However, progress in schizophrenia has been slow. Previous researches have shown many contentions about pathogenic factors, including deregulated neurotransmitter, development of the brain, and genetic risk factors. But these studies have not identified a key factor which directly induces people suffering from schizophrenia. Now, people use drugs to treat schizophrenia despite studies can not provide clear understanding of the pathogenesis of the disease. In this research, we investigate the difference of DNA methylation networks between schizophrenia and normal persons. First, we selected 2,005 spots and 7,647 spots from microarray, consisting a total of 13,056 spots. In order to establish the DNA methylation networks, we calculated partial correlation coefficients between methylation patterns of CpG islands. Our results found that major gene functions of the networks, from either 2005 spots or 7647 spots from patients , involved neural development, signal transduction, and the process of DNA methylation. By contrast, no specific functions in the networks of normal persons were observed. These results revealed the stronger correlation of gene methylation patterns in patients than in normal persons. We suggest that genes in patients with schizophrenia, having the above properties, hold defect in handling environmental changes, and might raise the possibility of alterations in gene regulation. |
