Genetic copy number variants in sib pairs both affected with schizophrenia

• Main Authors: Chang Shun-Min, Wen Chun-Chiang, Liu Chih-Min, Lee Chia-Huei, Hwu Hai-Gwo
• Format: Article
• Language: English
• Published: BMC 2010-01-01
• Series: Journal of Biomedical Science
• Online Access: http://www.jbiomedsci.com/content/17/1/2
• ISSN: 1021-7770; 1423-0127

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex disorder with involvement of multiple genes.</p> <p>Methods</p> <p>In 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.</p> <p>Results</p> <p>We 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 (<it>CEBPD</it>, 8q11.21), retinoid × receptor, alpha (<it>RXRA</it>, 9q34.2), LIM homeobox protein 5 (<it>LHX5</it>, 12q24.13) and serine/threonine kinase 11 (<it>STK11</it>, 19p13.3) are recurrently (incidence ≧ 16.7%) disrupted by CNVs. Two genes, <it>PVR </it>(poliovirus receptor) and <it>BU678720</it>, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this <it>BU678720 </it>deletion and schizophrenia in a large case-control sample.</p> <p>Conclusions</p> <p>We 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.</p>