Genomic Alignment to Detect Conserved Regulatory Regions

描述（申请人摘要）：使用万维网服务器PipMaker比对和注释人和小鼠基因组序列。这种分析方法很容易鉴定直链淀粉基因的外显子。此外，保守的非编码区可以在PIP显示中被可视化为高评分片段对。因此，通过进化压力保守的调控元件也将在本研究中进行注释。具体而言，将计算人类和小鼠同线序列的比对，并将其放入数据库中供公众访问。比对区域内的调控元件将基于保守的非编码位点的密度进行分组。这些分组将被用作数据集，以评估使用定义的阈值来识别重要的调控元件是否比使用系统发育距离更能提供信息，系统发育距离可能会发现太多保守的非编码区，或者不够。除了从基因组序列数据中注释基因（便于阐明导致人类遗传疾病的基因）外，本研究的目的是绘制许多这些基因的调控元件。因此，将确定实验研究的关键目标。这些结果将与有兴趣研究对齐序列内基因表达调控的研究人员分享。本研究的另一个成果是为计算机科学家提供比对序列的数据集，这些科学家对改进识别基因组序列中转录因子结合位点的从头算方法感兴趣。

DESCRIPTION (Applicant's Abstract): Human and mouse genomic sequences will be aligned and annotated using the World Wide Web server PipMaker. This method of analysis easily identifies exons of orthologous genes. Furthermore, conserved noncoding regions can be visualized as high scoring segment pairs in a pip display. Thus, regulatory elements that are conserved via evolutionary pressure will also be annotated in this study. Specifically, alignments of syntenic human and mouse sequences will be computed and placed in a database for public access. Regulatory elements within aligned regions will be grouped based on the density of conserved noncoding sites. These groupings will be used as datasets to evaluate whether the use of defined thresholds for identifying important regulatory elements is more informative than the use of phylogenetic distance, which may find either too many conserved noncoding regions, or not enough. In addition to annotating genes from genomic sequence data (facilitating the elucidation of genes that contribute to human genetic disease) the purpose of this study is to map the regulatory elements for many of these genes. Thus, critical targets for experimental study will be identified. These results will be shared with researchers interested in studying regulated expression of genes within the aligned sequences. An additional outcome of this study is to provide datasets of aligned sequences to computer scientists interested in improving ab initio methods of identifying transcription factor binding sites in genomic sequences.