Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development

Time-resolved transcriptome analysis of early pou5f1 mutant zebrafish embryos identified groups of developmental regulators, including SoxB1 genes, that depend on Pou5f1 activity, and a large cluster of differentiation genes which are prematurely expressed.Pou5f1 represses differentiation genes indirectly via activation of germlayer-specific transcriptional repressor genes, including her3, which may mediate in part Pou5f1-dependent repression of neural genes.A dynamic mathematical model is established for Pou5f1 and SoxB1 activity-dependent temporal behaviour of downstream transcriptional regulatory networks. The model predicts that Pou5f1-dependent increase in SoxB1 activity significantly contributes to developmental timing in the early gastrula.Comparison to mouse Pou5f1/Oct4 reveals evolutionary conserved targets. We show that Pou5f1 developmental function is also conserved by demonstrating rescue of Pou5f1 mutant zebrafish embryos by mouse POU5F1/OCT4

Copy Number Variants in German Patients with Schizophrenia

Large rare copy number variants (CNVs) have been recognized as significant genetic risk factors for the development of schizophrenia (SCZ). However, due to their low frequency (1∶150 to 1∶1000) among patients, large sample sizes are needed to detect an association between specific CNVs and SCZ. So far, the majority of genome-wide CNV analyses have focused on reporting only CNVs that reached a significant P-value within the study cohort and merely confirmed the frequency of already-established risk-carrying CNVs. As a result, CNVs with a very low frequency that might be relevant for SCZ susceptibility are lost for secondary analyses. In this study, we provide a concise collection of high-quality CNVs in a large German sample consisting of 1,637 patients with SCZ or schizoaffective disorder and 1,627 controls. All individuals were genotyped on Illumina's BeadChips and putative CNVs were identified using QuantiSNP and PennCNV. Only those CNVs that were detected by both programs and spanned ≥30 consecutive SNPs were included in the data collection and downstream analyses (2,366 CNVs, 0.73 CNVs per individual). The genome-wide analysis did not reveal a specific association between a previously unknown CNV and SCZ. However, the group of CNVs previously reported to be associated with SCZ was more frequent in our patients than in the controls. The publication of our dataset will serve as a unique, easily accessible, high-quality CNV data collection for other research groups. The dataset could be useful for the identification of new disease-relevant CNVs that are currently overlooked due to their very low frequency and lack of power for their detection in individual studies

Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder

A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia.status: publishe

Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder

A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophreni

CNVs in regions previously associated with SCZ.

<p>SCZ, schizophrenia; del, microdeletion; dup, microduplication; P, P-value; OR, odds ratio. Position according to NCBI built 36; all P-values and ORs were calculated using Fisher's exact test.</p><p>Two of the patients with a deletion in 1q21.1 and one patient with a deletion in 15q11.2 were already reported by Stefansson et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Stefansson1" target="_blank">[3]</a>, three patients with a deletion in Neurexin were included in Rujescu et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Rujescu1" target="_blank">[5]</a> and two patients with a deletion and one patient with a duplication in 16p13.11 were part of the study performed by Ingason et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Ingason1" target="_blank">[10]</a>.</p

Phenotypic information of patients with a CNV in regions previously associated with SCZ.

<p>Chr, chromosome; DEL, deletion; DUP, duplication; Diagnosis, DSM-IV diagnosis; f, female; m, male; AAO, age-at-onset; Family history SCZ, any fist degree relative with schizophrenia; ., missing data; Position according to NCBI built 36.</p