The USC PsychENCODE Project

描述(申请人提供)：精神分裂症和双相情感障碍是一种神经精神性大脑疾病，影响全球超过2%的人口，并造成巨大的人类痛苦。这两种疾病都是高度可遗传的(&gt；60-80%)，但到目前为止已经确定的100+个基因座加在一起并不能占总疾病病因的很大比例。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。利用来自50名精神分裂症患者和50名健康对照的嗅神经上皮(CNON)培养的神经细胞，我们将在一个具有足够统计能力的样本中确定表观遗传学染色质标记，以发现发育中的神经元中的mQTL和ChIP-QTL。可用的长RNA-seq(链特异性ncRNA和mRNA；100bp)、小RNA-seq(piRNA和miRNA)和&gt；30x全基因组序列将与来自H3K4me1、H3K4me3和H3K27Ac的Nome-seq at&gt；18X和Chip-seq的数据相结合。体外数据将得到来自高加索男性精神分裂症(SCZ；n=8)或双相情感障碍(BPD；n=8)和正常对照组(CTL；n=8)的高质量死后成人大脑的分析数据的补充。分析将包括来自背侧前额叶皮质(DLPFC)、海马体(HIP)、杏仁核(AMY)、背侧尾状核(DC)和伏核(NAC)的长RNA-序列(链特异性ncRNA和mRNA；100bp)、小RNA-序列(piRNA和miRNA)、Nome-seq at&gt；18X和H3K4me1、H3K4me3和H3K27Ac的ChIP-seq。我们将绘制特定于大脑区域或疾病的基因组、转录和表观基因组变化图，并开发一个易于使用的、基于网络的信息学框架，用于将这一心理编码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.