Genetic Copy Number Variants in Sib Pairs Both Affected with Schizophrenia

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2010 Jan 13

PMID 20064257

Citations 14

Authors

Chia-Huei Lee

Chih-Min Liu

Chun-Chiang Wen

Shun-Min Chang

Hai-Gwo Hwu

Affiliations

Soon will be listed here.

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 x 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.

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