The USC PsychENCODE Project

南加州大学 PsychENCODE 项目

• 批准号: 9505455
• 负责人: PEGGY J Farnham
• 金额: $ 12.89万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-16 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9505455
• 关键词: Adult; Affect; Age; Amygdaloid structure; Anatomy; Autopsy; Bipolar Disorder; Brain; Brain Diseases; Brain region; Caucasians; Cell Line; Cells; ChIP-seq; Chromatin; Collection; Communication; Complement; Data; Data Analyses; Disease; Dorsal; Elements; Environmental Risk Factor; Epigenetic Process; Etiology; Gene Expression; Gene Expression Profile; Genetic; Genomics; Heritability; Hippocampus (Brain); Human; In Vitro; Individual; Knowledge; Lateral; Maps; Mental disorders; Messenger RNA; MicroRNAs; Molecular; Neurons; Nucleus Accumbens; Patients; Pattern; Population; Prefrontal Cortex; Quantitative Trait Loci; Research; Role; Sampling; Schizophrenia; Susceptibility Gene; Tissues; caudate nucleus; cell type; epigenomics; genomic data; impaired brain development; male; neuroepithelium; neuropsychiatric disorder; neuropsychiatry; piRNA; public health relevance; transcriptome sequencing; transcriptomics; web-based informatics; whole genome

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.

描述（由申请人提供）：精神分裂症和双向情感障碍是神经精神性脑部疾病，影响全球 2% 以上的人口，给人类带来巨大痛苦。这两种疾病都具有高度遗传性 (>60-80%)，但迄今为止已确定的 100 多个位点在总体疾病因果关系中所占的比例并不大。更好地了解基因表达模式以及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 名健康对照者的嗅神经上皮 (CNON) 的培养神经元细胞，我们将确定样本中的表观遗传染色质标记，具有足够的统计能力来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 >100bp）、小 RNA-seq（piRNA 和 miRNA）和 >30x 全基因组序列将与来自 >18X 的 NOMe-seq 和 H3K4me1 ChIP-seq 的数据相结合、H3K4me3 和 H3K27Ac。体外数据将得到来自患有精神分裂症 (SCZ; n=8) 或双相情感障碍 (BPD; n=8) 和正常对照 (CTL) 的白人男性的高质量死后大脑分析数据的补充。 ；n=8)。分析将包括长 RNA-seq（链特异性 ncRNA 和 mRNA >100bp）、小 RNA-seq（piRNA 和 miRNA）、>18X 的 NOMe-seq 以及 H3K4me1、H3K4me3 和 H3K27Ac 解剖切片中的 ChIP-seq背外侧前额叶皮层 (DLPFC)、海马体 (HIP)、杏仁核(AMY)、背侧尾状核 (DC) 和伏隔核 (NAc)。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图，并开发一个易于使用的、基于网络的信息学框架，用于将该 PsychENCODE 项目的原始数据和计算数据传达给其他神经科学家。