Upregulation of DGCR8, a Candidate Predisposing to Schizophrenia in Han Chinese, Contributes to Phenotypic Deficits and Neuronal Migration Delay

Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface. http://www.broad.mit.edu/mpg/haploview/ jcbarret@broad.mit.edu

Introduction The global burden of disease (GBD) studies have derived detailed and comparable epidemiological and burden of disease estimates for schizophrenia. We report GBD 2016 estimates of schizophrenia prevalence and burden of disease with disaggregation by age, sex, year, and for all countries. Method We conducted a systematic review to identify studies reporting the prevalence, incidence, remission, and/or excess mortality associated with schizophrenia. Reported estimates which met our inclusion criteria were entered into a Bayesian meta-regression tool used in GBD 2016 to derive prevalence for 20 age groups, 7 super-regions, 21 regions, and 195 countries and territories. Burden of disease estimates were derived for acute and residual states of schizophrenia by multiplying the age-, sex-, year-, and location-specific prevalence by 2 disability weights representative of the disability experienced during these states. Findings The systematic review found a total of 129 individual data sources. The global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28% (95% uncertainty interval [UI]: 0.24–0.31). No sex differences were observed in prevalence. Age-standardized point prevalence rates did not vary widely across countries or regions. Globally, prevalent cases rose from 13.1 (95% UI: 11.6–14.8) million in 1990 to 20.9 (95% UI: 18.5–23.4) million cases in 2016. Schizophrenia contributes 13.4 (95% UI: 9.9–16.7) million years of life lived with disability to burden of disease globally. Conclusion Although schizophrenia is a low prevalence disorder, the burden of disease is substantial. Our modeling suggests that significant population growth and aging has led to a large and increasing disease burden attributable to schizophrenia, particularly for middle income countries.

MicroRNAs (miRNAs) are a growing family of small non-protein-coding regulatory genes that regulate the expression of homologous target-gene transcripts. They have been implicated in the control of cell death and proliferation in flies, haematopoietic lineage differentiation in mammals, neuronal patterning in nematodes and leaf and flower development in plants. miRNAs are processed by the RNA-mediated interference machinery. Drosha is an RNase III enzyme that was recently implicated in miRNA processing. Here we show that human Drosha is a component of two multi-protein complexes. The larger complex contains multiple classes of RNA-associated proteins including RNA helicases, proteins that bind double-stranded RNA, novel heterogeneous nuclear ribonucleoproteins and the Ewing's sarcoma family of proteins. The smaller complex is composed of Drosha and the double-stranded-RNA-binding protein, DGCR8, the product of a gene deleted in DiGeorge syndrome. In vivo knock-down and in vitro reconstitution studies revealed that both components of this smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript.