High-resolution mapping of DNaseI hypersensitive regulatory DNA in GTEx samples

在此输入文本，它是应用程序的新摘要信息。此部分不得超过30行 短信了 将遗传变异与基因表达和其他表型联系起来是基因组科学的主要目标。 基因表达模式在不同的细胞和组织类型之间变化很大，并且在一个区域内也存在区域性差异。 组织.因此，遗传变异对基因表达模式的影响预计会有很大的不同 组织之间的联系。基因型-组织表达（GTEx）正在建立资源数据库， 组织基因表达谱的综合分析及其与个体基因型的联系。 大多数与人类基因表达个体变异相关的变异位于基因组的非编码区， 基因组;其中，一部分预计将直接影响基因调控，通过扰动 调控DNA区域。系统地了解遗传变异对基因表达的影响， 因此，既需要全面描绘调控DNA，又需要了解 各个调节区域的致动在群体水平上变化。 在这个提案中，我们的目标是增强GTEx的中心目标-连接基因型与基因 表达模式-通过全面描绘非常高水平的调控DNA， 决议，并系统地确定遗传变异，影响其功能，通过废除 调节因子结合和局部染色质结构的扰动。我们将应用高分辨率 DNaseI超敏位点的基因组规模绘图，以全面描绘内部的调节DNA 来自GTEx项目积累的多种族人群的组织样本。我们还将应用基因组 以基因组规模和有针对性的方式绘制DNA酶I足迹图， 调节DNA的核苷酸分辨率。

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Connecting genetic variation with gene expression and other phenotypes is a major goal of genomic science. Gene expression patterns vary widely among different cell and tissue types, and also regionally within a tissue. The impact of genetic variation on gene expression patterns is thus expected to differ substantially between tissues. The Genotype-Tissue Expression (GTEx) is establishing resource databases to enable comprehensive analysis of tissue gene expression profiles and their connection with individual genotypes. Most variants linked to individual variation in human gene expression lie in non-coding regions of the genome; of these, a proportion is expected to directly impact gene regulation through perturbation of regulatory DNA regions. Systematic understanding of the impact of genetic variation on gene expression will thus require both comprehensive delineation of regulatory DNA, and an understanding of the degree to which actuation of individual regulatory regions varies at the population level. In this proposal we aim to empower the central goal of GTEx -- connecting genotype to gene expression patterns -- for diverse human tissues by comprehensively delineating regulatory DNA at very high resolution, and systematically identifying genetic variants that impact its function through abrogation of regulatory factor binding and perturbation of local chromatin architecture. We will apply high-resolution genome-scale mapping of DNaseI hypersensitive sites to comprehensively delineate regulatory DNA within tissue samples from a multi-ethnic population accrued by the GTEx project. We will also apply genomic DNaseI footprinting at genome-scale and in a targeted fashion to map transcription factor occupancy within regulatory DNA at nucleotide resolution.