Understanding the basis of psychiatric disorders has been extremely challenging because there are many genetic variants that may increase risk but are insufficient to cause disease. Now investigators reporting in the July 3rd issue of the Cell Press journal Cell Stem Cell describe a strategy that may help reveal how such "subthreshold" genetic risks interact with other risk factors or environmental exposures to affect the development of the nervous system. Their research pinpoints a genetic variant that may predispose individuals to schizophrenia.
"We were able to use a set of cutting-edge tools to gain insight into a critical cellular process for normal brain development, the dysregulation of which may be a manifestation of a genetic predisposition for schizophrenia," says senior author Dr. Guo-li Ming, of Johns Hopkins University School of Medicine. The researchers' strategy -- generating disease-specific nerve cells, identifying a causative gene for developmental defects, validating the gene-specific defect in animal models, and then investigating interactions with other genes both in animal models and in humans -- represents a promising new approach for understanding the mechanisms underlying some of the most intractable psychiatric illnesses.
[Photo:Ā Yoon et al. use modeling in iPSCs and mice to examine the functional effects of 15q11.2 CNVs, a known risk factor for several neuropsychiatric disorders including schizophrenia. The cover image was created using images of neural rosettes derived from human iPSCs with and without a 15q11.2 microdeletion (round circles) and images of radial glial cells in the developing mouse cortex (thin filaments), and it is inspired by July 4th fireworks. Credit: Ki-Jun Yoon]
http://www.sciencedaily.com/releases/2014/07/140703125535.htm
Abstract available at Cell Stem Cell:Ā Modeling a Genetic Risk for Schizophrenia in iPSCs and Mice Reveals Neural Stem Cell Deficits Associated with Adherens Junctions and Polarity
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