Structural Annotation of the Human Genome

产品说明：基因组学方法旨在鉴定人类基因组中的所有功能元件并了解其功能。这种大规模的方法被认为大大增加了对人类生物学和疾病的了解。在这里，它建议进一步开发和验证一种新的和独特的方法来确定人类基因组中的功能元件。 该方法是基于这样的假设，即序列元素之间的直接物理相互作用将指向它们之间的功能关系。 例如，调控元件已经显示出与其靶基因物理相互作用以控制转录。 基因组元件之间类似的长程相互作用被认为涉及其他基因组过程，如DNA复制、修复、减数分裂重组和染色体凝聚。 因此，染色体相互作用和染色体结构特征的鉴定通常可以导致发现功能元件。这一建议需要进一步开发和验证一种方法，这种方法依赖于确定和计算分析染色体相互作用作为识别功能元件的手段。 将使用我们开发的分子方法学“染色体构象捕获”或“3C”测量染色体相互作用。 本提案的主要目标是评估使用这种结构方法来寻找功能要素的情况。 具体目标1：开发基于3C的强大策略，以识别人类基因组中的功能元件。 具体目标2：为ENCODE项目选定的区域生成两个重点相互作用频率数据集。 具体目标3：通过构建结构模型来解释3C相互作用频率数据集。 分析所获得的数据，并将这些数据与来自其他ENCODE项目的结果相结合，预计将提供有关这种染色体结构方法是否适合寻找功能元件的信息。

DESCRIPTION: (provided by applicant) Genomics approaches aim to identify all functional elements in the human genome and to understand their functions. Such large-scale approaches are thought to greatly increase insights in human biology and disease. Here it is proposed to further develop and validate a new and unique methodology to identify functional elements in the human genome. The approach is based on the hypothesis that direct physical interactions between sequence elements will point to functional relationships between them. For example, regulatory elements have been shown to physically interact with their target genes to control transcription. Similar long-range interactions between genomic elements are thought to be involved in other genomic processes such as DNA replication, repair, meiotic recombination and chromosome condensation. Therefore, identification of chromosomal interactions, and chromosome structural features in general may result in finding functional elements. This proposal entails the further development and validation of an approach that relies on determination and computational analysis of chromosomal interactions as a means to identify functional elements. Chromosomal interactions will be measured using a molecular methodology, "Chromosome Conformation Capture" or "3C" that we have developed. The main goal of this proposal is to assess the use of this structural approach to find functional elements. Specific Aim 1: Development of robust 3C-based strategies to identify functional elements in the human genome. Specific Aim 2: To generate two focused interaction frequency datasets for regions selected by the ENCODE project. Specific Aim 3: To interpret 3C interaction frequency datasets by building structural models. Analysis of the data obtained and integration of these data with results derived from other ENCODE projects is expected to provide information regarding the suitability of this chromosome structural approach to find functional elements.