Genetic copy number variants in sib pairs both affected with schizophrenia

Journal of Biomedical Science

Research

Chun-Chiang Wen¹  Chih-Min Liu¹  Hai-Gwo Hwu²  Chia-Huei Lee³  Shun-Min Chang³ 

[1] Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan;Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan;Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan;Department of Psychology, College of Science, National Taiwan University, Taipei, Taiwan;National Institute of Cancer Research, National Health Research Institutes, 350, Zhunan Town, Miaoli County, Taiwan;

关键词: Schizophrenia;    Negative Symptom;    Comparative Genomic Hybridization;    Homozygous Deletion;    Array Comparative Genomic Hybridization;   

DOI  :  10.1186/1423-0127-17-2

 received in 2009-07-31, accepted in 2010-01-11,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Lee et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.