Genetic copy number variants in sib pairs both affected with schizophrenia
Journal
Journal of Biomedical Science
Journal Volume
17
Journal Issue
1
Date Issued
2010
Author(s)
Abstract
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.
SDGs
Other Subjects
bu 678720; CCAAT enhancer binding protein delta; DNA; gene product; LIM homeobox protein 5; oligonucleotide; protein kinase LKB1; PVR protein; retinoid X receptor alpha; transcription factor; unclassified drug; virus protein; article; case control study; central nervous system; chromosome 12q; chromosome 19p; chromosome 8q; chromosome 9q; clinical article; comparative genomic hybridization; controlled study; disease severity; DNA microarray; female; gene deletion; gene disruption; gene expression; gene number; genetic analysis; genetic association; genetic disorder; genetic screening; genetic variability; genome wide screening; human; incidence; male; negative syndrome; nucleotide sequence; priority journal; schizophrenia; sibling; adult; copy number variation; genetics; human genome; methodology; pathology; pedigree; schizophrenia; sibling; single nucleotide polymorphism; Poliovirus; Adult; Comparative Genomic Hybridization; DNA Copy Number Variations; Genome, Human; Genome-Wide Association Study; Humans; Oligonucleotide Array Sequence Analysis; Pedigree; Polymorphism, Single Nucleotide; Schizophrenia; Siblings
Type
journal article