Zhuo Chuanjun, Hou Weihong, Lin Chongguang, Hu Lirong, Li Jie
Department of Psychological Medicine, Wenzhou Seventh People's HospitalWenzhou, China.
Department of Psychological Medicine, Tianjin Anding HospitalTianjin, China.
Front Mol Neurosci. 2017 Jun 21;10:204. doi: 10.3389/fnmol.2017.00204. eCollection 2017.
Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs) are one of the main forms of genomic variations, ubiquitously occurring in the human genome. An increasing number of studies have shown that CNVs account for population diversity and genetically related diseases, including schizophrenia. The last decade has witnessed rapid advances in the development of novel genomic technologies, which have led to the identification of schizophrenia-associated CNVs, insight into the roles of the affected genes in their intervals in schizophrenia, and successful manipulation of the target CNVs. In this review, we focus on the recent discoveries of important CNVs that are associated with schizophrenia and outline the potential values that the study of CNVs will bring to the areas of schizophrenia research, diagnosis, and therapy. Furthermore, with the help of the novel genetic tool known as the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) system, the pathogenic CNVs as genomic defects could be corrected. In conclusion, the recent novel findings of schizophrenia-associated CNVs offer an exciting opportunity for schizophrenia research to decipher the pathological mechanisms underlying the onset and development of schizophrenia as well as to provide potential clinical applications in genetic counseling, diagnosis, and therapy for this complex mental disease.
精神分裂症是一种极具破坏性的神经精神障碍,影响着全球约1%的人口,给家庭和社会带来了相当大的负担。尽管精神分裂症的确切病因尚不清楚,但多条科学证据表明,基因变异与该疾病的发生和早期发病密切相关。事实上,精神分裂症患者的遗传度高达80%。基因组拷贝数变异(CNV)是基因组变异的主要形式之一,普遍存在于人类基因组中。越来越多的研究表明,CNV与包括精神分裂症在内的群体多样性和遗传相关疾病有关。过去十年见证了新型基因组技术的快速发展,这些技术导致了与精神分裂症相关的CNV的识别、对受影响基因在精神分裂症间隔中的作用的深入了解,以及对目标CNV的成功操控。在本综述中,我们重点关注与精神分裂症相关的重要CNV的最新发现,并概述CNV研究将给精神分裂症研究、诊断和治疗领域带来的潜在价值。此外,借助一种名为成簇规律间隔短回文重复序列相关核酸酶9(CRISPR/Cas9)系统的新型基因工具,作为基因组缺陷的致病性CNV可以得到纠正。总之,精神分裂症相关CNV的最新新发现为精神分裂症研究提供了一个令人兴奋的机会,以破译精神分裂症发病和发展的病理机制,并为这种复杂精神疾病的遗传咨询、诊断和治疗提供潜在的临床应用。