Potential Value of Genomic Copy Number Variations in Schizophrenia.

Chuanjun Zhuo,Weihong Hou,Chongguang Lin,Jie Li,Lirong Hu

doi:10.3389/fnmol.2017.00204

Abstract

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.

Highlights

Schizophrenia is a complex neuropsychiatric disorder typically characterized by symptoms such as delusions and hallucinations, cognitive dysfunction, social deficit, and apathy (Owen et al, 2016)
Recent studies into the genetic causes underlying schizophrenia using comparative genomic hybridization, single nucleotide polymorphism (SNP) chips, and gene sequencing have identified different forms of genetic variants such as SNPs and copy number variations (CNVs) that have been shown to be associated with this disease (International Schizophrenia, 2008; St Clair, 2009; Levinson et al, 2011; Grayton et al, 2012; Kirov et al, 2012; Malhotra and Sebat, 2012; Hamshere et al, 2013; Ripke et al, 2013; Purcell et al, 2014)
We focus on the recent findings related to the important schizophrenia-associated CNVs and outline the potential values that the study of CNVs could bring to the areas of schizophrenia research, diagnosis, and therapy

Summary

Introduction

Schizophrenia is a complex neuropsychiatric disorder typically characterized by symptoms such as delusions and hallucinations, cognitive dysfunction, social deficit, and apathy (Owen et al, 2016).

Results

Conclusion