应用基于序列特征的单核苷酸短序列分析模型研究基因选择性剪接调控机制

项目名称： 应用基于序列特征的单核苷酸短序列分析模型研究基因选择性剪接调控机制

项目编号： No.61300057

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 自动化技术、计算机技术

项目作者： 马猛

作者单位： 安徽大学

项目金额： 23万元

中文摘要： 超过94%的人类基因都存在选择性剪接现象，基因选择性剪接是癌症、心脑血管疾病、糖尿病等发生的重要分子机制之一，不同剪接信号强度的变化可导致基因选择性剪接现象的发生。申请者拟通过基于序列特征的单核苷酸短序列分析模型，对剪接位点、分支位点、剪接调控元件三类基因选择性剪接信号分别进行强度量化和分类识别，依此探索基因选择性剪接调控机制。我们已经利用该模型对剪接调控元件的信号强度实现了量化，并依此分类识别了新的基因剪接调控元件，且计算和生物验证实验均已经证明了该模型的有效性。我们将利用该模型对剪接位点和分支位点进行信号强度的量化和分类识别，并进行相关的计算及生物验证；同时，观察糖尿病发病相关基因的单核苷酸多态性（SNP）对基因剪接信号强度的影响，并以此部分明确糖尿病相关基因SNP的致病机制，为糖尿病治疗的研究提供指导和依据。

中文关键词： 疾病突变；序列模式；剪接调控元件；剪接位点；启动子

英文摘要： Over 94% human genes show alternative splicing.Gene alternative splicing is one of the most important pathogenic molecular mechanisms for cancers, cardio-cerebral vascular diseases, diabetes and so on. The strength variation of different splicing signals leads to gene alternative splicing phenomena. The applicant will apply the mononucleotide short sequence analysis model based on sequential feature to quantitate the strength of three gene splicing signals including splicing sites,branch sites and splicing regulatory elements, and then classify and recognize these signals, which will be helpful to explore the gene alternative splicing regulatory mechanism. This model has been applied successfully to quantitate the strength of splicing regulatory elements and then classify and recognize the new gene splicing regulatory elements. Furthermoer the computational and biological validation experiments have proven the availability of such model. We plan to apply such model to the strength quantitation and classification and recognition of splice sites and branch sites, and then finish the corresponding computational and biological validation experiments. Moreover observe the effect of the SNPs from diabetes-related genes on gene splicing signals strength to partly clarify the pathogenic mechanism of the SNPs from the d

英文关键词： disease mutations；sequential pattern；splicing regulatory elements；splice sites；promoter