Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development.

Remarkable advances have been made in schizophrenia (SCZ) GWAS, but gleaning biological insight from these loci is challenging. Genetic influences on gene expression (e.g., eQTLs) are cell type-specific, but most studies that attempt to clarify GWAS loci's influence on gene expression have employed tissues with mixed cell compositions that can obscure cell-specific effects. Furthermore, enriched SCZ heritability in the fetal brain underscores the need to study the impact of SCZ risk loci in specific developing neurons. MGE-derived cortical interneurons (cINs) are consistently affected in SCZ brains and show enriched SCZ heritability in human fetal brains. We identified SCZ GWAS risk genes that are dysregulated in iPSC-derived homogeneous populations of developing SCZ cINs. These SCZ GWAS loci differential expression (DE) genes converge on the PKC pathway. Their disruption results in PKC hyperactivity in developing cINs, leading to arborization deficits. We show that the fine-mapped GWAS locus in the ATP2A2 gene of the PKC pathway harbors enhancer marks by ATACseq and ChIPseq, and regulates ATP2A2 expression. We also generated developing glutamatergic neurons (GNs), another population with enriched SCZ heritability, and confirmed their functionality after transplantation into the mouse brain. Then, we identified SCZ GWAS risk genes that are dysregulated in developing SCZ GNs. GN-specific SCZ GWAS loci DE genes converge on the ion transporter pathway, distinct from those for cINs. Disruption of the pathway gene CACNA1D resulted in deficits of Ca2+ currents in developing GNs, suggesting compromised neuronal function by GWAS loci pathway deficits during development. This study allows us to identify cell type-specific and developmental stage-specific mechanisms of SCZ risk gene function, and may aid in identifying mechanism-based novel therapeutic targets.

Isolation and Whole-Genome Sequencing of 12 Mushroom-Associated Bacterial Strains: an Inquiry-Based Laboratory Exercise in a Genomics Course at the Rochester Institute of Technology.

Here, we report the isolation, identification, and whole-genome sequences of 12 bacterial strains associated with four mushroom species. The study was done as an inquiry-based exercise in an undergraduate genomics course (BIOL 340) in the Thomas H. Gosnell School of Life Sciences at the Rochester Institute of Technology.

Data quality at the Singapore Cancer Registry: An overview of comparability, completeness, validity and timeliness.

AIM: To provide a comprehensive evaluation of the quality of the data at the Singapore Cancer Registry (SCR). METHODS: Quantitative and semi-quantitative methods were used to assess the comparability, completeness, accuracy and timeliness of data for the period of 1968-2013, with focus on the period 2008-2012. RESULTS: The SCR coding and classification systems follow international standards. The overall completeness was estimated at 98.1% using the flow method and 97.5% using the capture-recapture method, for the period of 2008-2012. For the same period, 91.9% of the cases were morphologically verified (site-specific range: 40.4-100%) with 1.1% DCO cases. The under-reporting in 2011 and 2012 due to timely publication was estimated at 0.03% and 0.51% respectively. CONCLUSION: This review shows that the processes in place at the SCR yields data which are internationally comparable, relatively complete, valid, and timely, allowing for greater confidence in the use of quality data in the areas of cancer prevention, treatment and control.