Genetic copy number variants in sib pairs both affected with schizophrenia

Background. schizophrenia is a complex disorder with involvement of multiple genes. methods. 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. results. 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 (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. conclusions. 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. © 2010 lee et al; licensee biomed central ltd.