The USC PsychENCODE Project

南加州大学 PsychENCODE 项目

• 批准号: 8869039
• 负责人: PEGGY J Farnham
• 金额: $ 65万
• 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: 2014-06-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8869039
• 关键词: Accounting; Adult; Affect; Age; Amygdaloid structure; 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; Genes; Genetic; Genomics; Health; Hippocampus (Brain); Human; In Vitro; Indium; Individual; Informatics; Knowledge; Lateral; Maps; Mental disorders; Messenger RNA; MicroRNAs; Molecular; Neurons; Nucleus Accumbens; Online Systems; Patients; Pattern; Population; Prefrontal Cortex; Quantitative Trait Loci; Research; Role; Sampling; Schizophrenia; Small RNA; Structure; Susceptibility Gene; Tissues; caudate nucleus; cell type; epigenomics; genome sequencing; impaired brain development; male; neuroepithelium; neuropsychiatry; piRNA; transcriptome sequencing; transcriptomics

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）：精神分裂症和躁郁症是神经精神疾病，影响了全球超过2％的人口，并引起巨大的人类痛苦。这两种疾病都是高度遗传的（> 60-80％），但是迄今已确定的100多个基因座总体上没有占整体疾病因果关系的很大比例。更好地理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例精神分裂症患者和50个健康对照的嗅觉神经上皮层（CNON）的培养神经元细胞，我们将在具有足够统计能力的样品中确定表观遗传染色质标记，以发现MQTL和CHIP-QTL，以发现MQTL和CHIP-QTL。可用的长RNA-SEQ（链特异性ncRNA和mRNA> 100bp），小RNA-SEQ（PIRNA和miRNA）以及> 30x的全基因组序列将与Nome-Seq的数据> 18x和H3K4ME1，H3K4ME3的H3K4ME3和H3K4ME3，以及H3K27AC的H3K4ME1，H3K4ME1，H3K4ME1，H3K4ME1，以及H3K4ME3的数据结合使用。体外数据将得到来自具有精神分裂症（SCZ; n = 8）或双相情感障碍（BPD; n = 8）和正常控制（CTL; ctl; n = 8）的高质量成年大脑分析的数据。分析将包括长RNA-SEQ（链特异性ncRNA和mRNA> 100bp），小RNA-SEQ（PIRNA和miRNA），Nome-seq，> 18倍的Nome-Seq和H3K4ME1，H3K4ME3和H3K27AC的H3K4ME1，H3K4ME3和H3K27AC的chip-Seq在Dorsal Preecamp preecamp preecam frrontroncame cortriake cortriplate cortfrontfc（ （髋关节），杏仁核（Amy），背尾状（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的变化，并开发出易于使用的基于网络的信息学框架，以通信该Psychencode Project的原始数据和计算的数据，以与其他神经科学家联系。