Chromosomal Abnormalities and Gene Discovery in Schizophrenia

精神分裂症的細胞遺傳學研究

10.29478/TJP.200712.0002

方菊雄(Jye-Siung Fang)；陳嘉祥(Chia-Hsiang Chen)

精神分裂症 ； 染色體異常 ； 基因 ； 病理 ； schizophrenia ； chromosome ； gene ； pathogenesis

台灣精神醫學

21卷4期（2007 / 12 / 01）

242 - 253

英文

精神分裂症在臨床上是一種複雜的疾病，在遺傳學上也屬複雜的疾病，因此精神分裂症可說是複雜的遺傳性疾病。目前有幾種遺傳學上的方法來找精神分裂症的致病基因，像是聯 鎖分析，全基因組相關分析，染色體檢查，與基因體研究等。這些研究成果顯示精神分裂症可能和很多基因都有相關，這些基因雖不會直接致病，但會增加或減少罹病的機會，精神分裂症可能是這些基因的交互作用所導致。另外精神分裂症也可能是單一基因突變所導致的，這些突變比例可能不多，但嚴重到足以導致臨床症狀的出現，而且不同病人的致病基因可能 不同。精神分裂症合併出現染色體異常就是一個例子，其發生率低，因此臨床醫師很少安排精神分裂症病患做染色體檢查，但是隨著新技術的進步，新的分子細胞遺傳學變成一種很有用的研究工具。文獻上有一些精神分裂症病患合併出現染色體異常，透過這些染色體異常的 研究找出精神分裂症的致病基因。此外最近有一種新的技術，Array comparative genome hybridization (array CGH)，大大提升了偵測染色體異常的解析度。透過這個方法，研究人員 在發展遲緩病患與精神病患身上發現一些過去未被發現的染色體異常。因此結合傳統的細胞 遺傳學檢查與新的分子細胞遺傳學將使我們有機會找到精神分裂症的致病基因，對精神分裂症的致病機轉有新的了解，並且發展新的治療方法。

Background: Schizophrenia is a complex disease in its clinical aspect, it is also complex in genetic aspect. Hence, schizophrenia can be considered a complex genetic disease. Currently, there are several approaches to investigate the genetic underpinnings of schizophrenia, such as genetic linkage analysis, genome-wide association study, chromosome analysis, and genomic study. Lilerature Reviews: The results from these studies show that schizophrenia can be associated with common variants of many genes, and each gene contributes a small to modest risk to schizophrenia. In addition, schizophrenia can also be associated with rare mutations in a single gene that plays an essential role in brain function. Schizophrenia patients with chromosomal abnormalities belong to this category. The incidence of chromosomal abnormalities in the schizophrenic population is rare, and psychiatrists rarely refer schizophrenia patients for cytogenetic examinations. However, with the progress of molecular genetic technology, the new molecular cytogenetics becomes an important tool to discover genes-associated with schizophrenia. Chromosomal rearrangement is a common biological phenomenon in human genome, which can lead to inversion, translocation, deletion, and duplication of chromosome segments. Some rearrangements can cause diseases including psychiatric disorders. The accurate localization of these regions can help identify the disease-associated genes. Results: There are increasing reports of chromosomal aberrations associated with schizophrenia in the literature, and multiple schizophrenia genes have been identified through these chromosomal aberrations. Furthermore, the recent development of high density array comparative genome hybridization has greatly improved the resolution of conventional karyotype analysis, and studies have shown that this new technology is useful in detecting submicroscopic deletion and duplication in patients with developmental disorder and mental illness. Conclusion: The combination of conventional karyotype examination and new molecular cytogenetic analysis will offer an invaluable opportunity to discover genes associated with schizophrenia, leading to new insights into the pathogenesis of schizophrenia, and to better treatment of patients with schizophrenia in the future.

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