Abstract
BackgroundSchizophrenia is a complex disorder with involvement of multiple genes.MethodsIn this study, genome-wide screening for DNA copy-number variations (CNVs) was conducted for ten pairs, a total of 20 cases, of affected siblings using oligonucleotide array-based CGH.ResultsWe found negative symptoms were significantly more severe (p < 0.05) in the subgroup that harbored more genetic imbalance (n ≧ 13, n = number of CNV-disrupted genes) as compared with the subgroup with fewer CNVs (n ≦ 6), indicating that the degree of genetic imbalance may influence the severity of the negative symptoms of schizophrenia. Four central nervous system (CNS) related genes including CCAAT/enhancer binding protein, delta (CEBPD, 8q11.21), retinoid × receptor, alpha (RXRA, 9q34.2), LIM homeobox protein 5 (LHX5, 12q24.13) and serine/threonine kinase 11 (STK11, 19p13.3) are recurrently (incidence ≧ 16.7%) disrupted by CNVs. Two genes, PVR (poliovirus receptor) and BU678720, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this BU678720 deletion and schizophrenia in a large case-control sample.ConclusionsWe conclude that the high genetic loading of CNVs may be the underlying cause of negative symptoms of schizophrenia, and the CNS-related genes revealed by this study warrant further investigation.
Highlights
Schizophrenia is a complex disorder with involvement of multiple genes
Classification of patients with schizophrenia A total of 379 loci disrupted by copy-number variations (CNVs) were found
In summary, our work further demonstrated that oligonucleotide array comparative genomic hybridization (CGH) is a useful platform for investigating the genomic aberrations of psychiatric disorders
Summary
Schizophrenia is a complex disorder with involvement of multiple genes. Schizophrenia is a devastating mental disorder, and its etiology has yet to be fully elucidated. Genetic epidemiological studies have shown that schizophrenia is predominantly genetically determined and has a high heritability, with a multi-locus inheritance model [1]. Chromosomal abnormalities occurring in patients with schizophrenia may provide useful information for locating and fine mapping the relevant gene loci. This has been demonstrated by the identification of the potential vulnerability genes of proline dehydrogenase (PRODH) [2] and Disrupted-in-Schizophrenia 1 (DISC1) [3,4] based on 22q11 micro-deletion syndrome and balance translocation (1;11) (q42.1;q14.3), respectively.
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