Abstract—

Each neuron has 100–10000 connections (synapses) with other neural cells, therefore genome pathologies affecting a small proportion of brain cells are capable of causing dysfunction of the entire central nervous system (CNS). Recently, genome and chromosome instability has been uncovered in neurodegeneration (Alzheimer’s disease, ataxia telangiectasia). Somatic tissue-specific mosaicism was observed in the brain of individuals with neuropsychiatric diseases including schizophrenia, autism, intellectual disability, and epilepsy. The study of genetic processes in neurons allows determination of a certain number of genetic pathways and candidate processes, modifications of which can cause impaired genome stability. Brain-specific somatic mutations generally occur at the earliest stages of development. Accordingly, genome variability and somatic mosaicism are expected to be mediated by cell cycle regulation, DNA repair, DNA replication, and programmed cell death in the brain. Endomitosis, endoreduplication, and abortive entrance to the cell cycle are also commonly observed in neurodegeneration. Brain-specific genome instability may be a key element in the pathogenic cascade of neurodegeneration. Here we review the current state of knowledge concerning somatic genome variations in neurodegenerative and psychiatric diseases and analyze the causes and consequences of genomic instability in the CNS.

中文翻译：

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精神病和神经退行性疾病中基因组不稳定的原因和后果

摘要-

每个神经元与其他神经细胞有100-10000个连接（突触），因此影响小部分脑细胞的基因组病理学能够引起整个中枢神经系统（CNS）的功能障碍。最近，在神经变性（阿尔茨海默氏病，共济失调毛细血管扩张症）中发现了基因组和染色体的不稳定性。在患有精神分裂症，自闭症，智力障碍和癫痫症等神经精神疾病的人的大脑中观察到了特定的体细胞组织镶嵌症。对神经元遗传过程的研究可以确定一定数量的遗传途径和候选过程，对其进行修饰可能会导致基因组稳定性受损。脑特异性体细胞突变通常发生在发育的最早阶段。因此，预计基因组变异性和体细胞镶嵌性将通过细胞周期调节，DNA修复，DNA复制和大脑中程序性细胞死亡来介导。在神经变性中也常观察到内膜有丝分裂，核内复制和细胞周期的流产性进入。脑特异性基因组的不稳定性可能是神经退行性疾病的致病级联中的关键因素。在这里，我们回顾了有关神经退行性疾病和精神疾病中体细胞基因组变异的知识的现状，并分析了中枢神经系统基因组不稳定的原因和后果。脑特异性基因组的不稳定性可能是神经退行性疾病的致病级联中的关键因素。在这里，我们回顾了有关神经退行性疾病和精神疾病中体细胞基因组变异的知识的现状，并分析了中枢神经系统基因组不稳定的原因和后果。脑特异性基因组的不稳定性可能是神经退行性疾病的致病级联中的关键因素。在这里，我们回顾了有关神经退行性疾病和精神疾病中体细胞基因组变异的知识的现状，并分析了中枢神经系统基因组不稳定的原因和后果。