In the 15q13 3 deletion region, the alpha 7 subunit of the nicoti

In the 15q13.3 deletion region, the alpha 7 subunit of the nicotinic receptor gene (CHRNA7) is present. This receptor is targeted to axons by NRG1, and has been implicated in schizophrenia and mental retardation.107 In the study from the International Schizophrenia Consortium,108 a genome -wide survey of 3391 patients with schizophrenia and in 3181 ancestrally matched controls using SNP arrays revealed 6753 rare CNVs. These rare CNVs, observed in less than 1% of the sample and more than 100Kb in length, were 1.15-fold increased in patients with schizophrenia in comparison with controls. They also observed deletions on 1q21.1

Inhibitors,research,lifescience,medical (0.29%, OR=6.6), 2p16.3 (0.12%, NRXN1), 7q35 (0.09%, CNTNAP2), 12p11.23 (0.12%), 15q13.3 (0.03%, APBA2), 15q13.3 (0.27%, CHRNA7, OR=17.9), 16p12.2-12.1, Inhibitors,research,lifescience,medical (0.12%) and 22q11.2 (VCFS region, 0.38%, OR=21.6). Further support for the role of rare CNVs in schizophrenia came from a recent study that analysed 471 patients with schizophrenia or schizoaffective disorder and 2792 controls.110 Kirov et al observed an excess of rare CNVs larger than 1Mb in cases (OR=2.26, P=0.00027) compared with controls. The associations were stronger with deletions

(OR=4.53, P=0.00013) than with duplications (OR=1.71, P=0.04). Similar to the abovementioned Inhibitors,research,lifescience,medical studies, these investigators also observed deletion at 22q11.2 in two schizophrenia patients. A deletion at 17p12 was also observed in two patients Inhibitors,research,lifescience,medical but not in controls. Unlike the ISC study,108 Kirov et al110 did not observe an overall excess burden of rare CNVs in their investigation. However, rare CNVs >500kb were also enriched in schizophrenia cases (OR=2.18). On combining their results with the ISC and the SGENE study,107 Kirov et al observed that the 17p12 deletion was more common in cases than controls (OR~10, 0.15% vs 0.015%) and also observed the deletion at 15q11.2 (OR=2.8, 0.62% vs 0.22). A duplication Inhibitors,research,lifescience,medical observed at 16p13.1, which includes the DISC1 interacting gene NDE1, was more common in cases than controls in the Kirov study as well as the ISC inhibitors purchase study108 Need et al100 in their GWAS investigation, analysed a subset of patients for presence of copy number variations, and they

identified large deletions (>2Mb) in eight cases but not in controls. Of these four CNVs, one was at 22q11.2, one at 16p13.11-p12.4 (includes the gene NDE1 a binding partner for DISC1), one at 8p22 and two CYTH4 at 1q21.1 (these are same as that reported by Stone et al108 and Stefansson et al107). Overall, similarly to Kirov et al,110 they did not observe an excess of rare CNVs (>100kb) in schizophrenia cases. Unlike Walsh et al111 they did not observe an excess of rare CNVs disrupting genes from the neurodevelopmental pathways. An important difference may have been that the primary investigation samples in the study by Walsh et al were child-onset schizophrenia patients. Similar observations have also been reported in Japanese schizophrenic patients.

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