Detecting genomic aberration in patients with schizophrenia

• Main Authors: Nai-Wen Shih, 施乃文
• Other Authors: Yann-Jang Chen
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/61316479455880065899

碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 100 === Schizophrenia is a complex and severe mental illnesses. About 1% of the population is affected by schizophrenia. Schizophrenia patients have positive symptoms of the delusions, hallucinations and disorganized speech and negative symptoms such as reduced emotions, social withdrawal. The family and twins studies demonstrated a strong genetic component for the development of schizophrenia. Schizophrenia is a complex genetic disease that may involve many genes. However, the etiology of schizophrenia is so far unknown. And schizophrenia does not have clear disease markers. Recent studies have shown rare genomic aberrations play an important role in schizophrenia. Here, we based on chromosome structure analysis and copy number variants (CNVs) analysis to find the candidate gene with schizophrenia. Our study samples included patients (n=35) with DSM-IV diagnosis of schizophrenia, and patients’ family members (n=29) in 20 families from Taichung Veterans General Hospital. In this study, we used G-banding analysis to identify structural variants in 64 cases with schizophrenia, and all cases have normal karyotype only one patient(case ID Sczfam004004) carrying a chromosome balanced translocation, t(3;20)(q13.1;p13). We performed fluorescence in situ hybridization (FISH) with bacterial artificial chromosome clones to map the breakpoint site. We found two genes, ring finger protein 24 (RNF24) and spermine oxidase (SMOX), which are located around the breakpoint that may confer risk with schizophrenia. The CNVs were detected by using array-based comparative genome hybridization (arrayCGH), and analyzed by Nexus Copy NumberTM software. We found that there is no difference about the number of CN loss and CN gain between schizophrenia and non-schizophrenia. In family study, these overlap CNV regions in each family are we interested. We identified functions of these genes by DAVID software. The result showed that four genes: neuregulin 3(NRG3), nuclear receptor coactivator 7(NCOA7), transcription factor 4(TCF4), transferrin(TF) are significant correlation with schizophrenia (p-value=0.022). The genes analysis of tissue category of CNVs showed that 47 genes are significant correlation with brain tissue (p-value=0.00003), and 8 genes are significant correlation with hippocampus (p-value=0.0015). In trios study, de novo CNVs genes were analyzed by DAVID and IPA bioinformatics software. The results showed that these genes are significantly related to brain tissue and nervous system function. Although these gene function and canonical pathway still needs further study, the results in this study showed that the experimental approaches we have designed are useful. These specific genes we found are associated with schizophrenia. Our experimental approaches able find possible candidate genes with schizophrenia.