The USC PsychENCODE Project

描述（由申请人提供）：精神分裂症和双相情感障碍是神经精神性脑障碍，影响全球2%以上的人口，并造成巨大的人类痛苦。这两种疾病都是高度遗传的（>60-80%），但迄今为止已经鉴定的100多个基因座在总体疾病病因中并不占显著比例。更好地了解基因表达模式和环境因素在形成这些模式中的作用至关重要。使用来自50名精神分裂症患者和50名健康对照的嗅神经上皮（CRON）的培养神经元细胞，我们将确定具有足够统计能力的样本中的表观遗传染色质标记，以发现发育神经元中的mQTL和ChIP-QTL。可用的长RNA-seq（链特异性ncRNA和mRNA > 100 bp）、小RNA-seq（皮尔纳和miRNA）和> 30 x全基因组序列将与来自NOMe-seq（>18X）和H3 K4 me 1、H3 K4 me 3和H3 K27 Ac的ChIP-seq的数据组合。体外数据将由来自患有精神分裂症（SCZ; n=8）或双相情感障碍（BPD; n =8）的高加索男性和正常对照（CTL; n = 8）的高质量死后成人脑分析数据补充。分析将包括来自背外侧前额叶皮质（DLPFC）、海马（HIP）、杏仁核（AMY）、背尾状核（DC）和背侧前额叶核（NAc）的解剖切片中的H3 K4 me 1、H3 K4 me 3和H3 K27 Ac的长RNA-seq（链特异性ncRNA和mRNA > 100 bp）、小RNA-seq（皮尔纳和miRNA）、> 18倍的NOMe-seq和ChIP-seq。我们将绘制特定于大脑区域或疾病的基因组，转录组和表观基因组变化，并开发一个易于使用的，基于网络的信息学框架，用于将PsychENCODE项目的原始和计算数据传达给其他神经科学家。

DESCRIPTION (provided by applicant): Schizophrenia and bipolar disorder are neuropsychiatric brain disorders that affect more than 2% of the population worldwide and cause enormous human suffering. Both disorders are highly heritable (>60-80%), but the 100+ loci that have been identified to date collectively do not account for a significant percentage of overall disease causation. A better understanding of gene expression patterns and the role of environmental factors in forming these patterns is crucial. Using cultured neuronal cells derived from olfactory neuroepithelium (CNON) from 50 patients with schizophrenia and 50 healthy controls, we will determine epigenetic chromatin marks in a sample with sufficient statistical power to discover mQTL and ChIP-QTL in developing neurons. Available long RNA-seq (strand-specific ncRNA and mRNA >100bp), small RNA-seq (piRNA and miRNA), and >30x whole genome sequence will be combined with data from NOMe-seq at >18X and ChIP-seq of H3K4me1, H3K4me3, and H3K27Ac. The in- vitro data will be complemented by data from analyses of high-quality, post-mortem adult brains derived from Caucasian males with schizophrenia (SCZ; n=8) or bipolar disorder (BPD; n=8) and normal controls (CTL; n=8). Analyses will include long RNA-seq (strand-specific ncRNA and mRNA >100bp), small RNA-seq (piRNA and miRNA), NOMe-seq at >18X and ChIP-seq of H3K4me1, H3K4me3, and H3K27Ac in dissected sections from the dorsal lateral prefrontal cortex (DLPFC), hippocampus (HIP), amygdala (AMY), dorsal caudate (DC), and the nucleus accumbens (NAc). We will map genomic, transcriptomic and epigenomic changes specific to either brain region or disease and develop an easy-to-use, web-based informatics framework for communication of the raw and computed data of this PsychENCODE project to other neuroscientists.