DISC1 in Schizophrenia: Genetic Mouse Models and Human Genomic Imaging
DISC1 in Schizophrenia: Genetic Mouse Models and Human Genomic Imaging
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DOI：
10.1093/schbul/sbq135
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发表时间：
2011-01-01
影响因子：
6.6
通讯作者：
Porteous, David J.
中科院分区：
文献类型：
--
作者：
Johnstone, Mandy;Thomson, Pippa A.;Porteous, David J.
精神分裂症和相关疾病有一个主要的遗传成分。几项大规模的研究已经发现了一些可能的候选基因，但这些基因尚未得到一致的复制，其潜在的生物学功能仍然难以捉摸。一个例外是“精神分裂症1型中断”（DISC 1），这是一个最初在苏格兰大家庭中发现的基因位点，显示出与平衡t（1;11）（q42.1;q14.3）染色体易位相关的重大精神疾病的沉重负担。DISC 1的大量遗传学和生物学研究在过去的10年中被报道：DISC 1现在被认为是一系列精神疾病的遗传风险因素，DISC 1影响中枢神经系统（CNS）功能的许多方面，包括神经发育，神经信号传导和突触功能。遗传学研究的证据表明DISC 1与数量性状之间存在关系，包括工作记忆、认知老化、前额叶皮质灰质体积以及海马结构和功能异常。DISC 1与许多蛋白质相互作用，这些蛋白质也参与神经元迁移、神经突生长、细胞骨架调节和信号转导，其中一些已被报道为精神病发病的独立遗传易感因素。在这里，我们专注于越来越多的文献有关DISC 1通路的遗传变异，在人类和小鼠大脑的功能和结构研究。
Schizophrenia and related disorders have a major genetic component. Several large-scale studies have uncovered a number of possible candidate genes, but these have yet to be consistently replicated and their underlying biological function remains elusive. One exception is 'Disrupted in schizophrenia 1' (DISC1), a gene locus originally identified in a large Scottish family, showing a heavy burden of major mental illnesses associated with a balanced t(1;11)(q42.1;q14.3) chromosome translocation. Substantial genetic and biological research on DISC1 has been reported in the intervening 10 years: DISC1 is now recognized as a genetic risk factor for a spectrum of psychiatric disorders and DISC1 impacts on many aspects of central nervous system (CNS) function, including neurodevelopment, neurosignaling, and synaptic functioning. Evidence has emerged from genetic studies showing a relationship between DISC1 and quantitative traits, including working memory, cognitive aging, gray matter volume in the prefrontal cortex, and abnormalities in hippocampal structures and function. DISC1 interacts with numerous proteins also involved in neuronal migration, neurite outgrowth, cytoskeletal modulation, and signal transduction, some of which have been reported as independent genetic susceptibility factors for psychiatric morbidity. Here, we focus on the growing literature relating genetic variation in the DISC1 pathway to functional and structural studies of the brain in humans and in the mouse.