Exonizaton of Alu Insertion Polymorphisms

常见的基因变异可导致多种人类表型和罹患糖尿病的风险 罹患多种疾病。区分使役和非功能变体和 理解前者的分子机制共同构成了重要的挑战。 ALU散布重复序列是人类基因组中一种常见的结构变异类型。ALU插入 本质上能够影响mRNA序列并导致疾病--即使当 Repeat位于基因座内明显非编码的内含子序列中。 我们的假设是，一些遗传的Alu插入多态是导致 人类疾病风险的变种。我们建议通过确定那些Alu来缩小候选人名单 与疾病风险相关并影响相关信使核糖核酸转录本结构的插入。 我们将开发计算方法来识别RNA-SEQ数据中的Alu离解事件，以及 我们将通过实验评估Alu插入多态对mRNA剪接的影响 记者分析和基因组编辑策略。

Common genetic variants contribute to a wide spectrum of human phenotypes and risks of developing many types of diseases. Differentiating causative from non-functional variants and understanding molecular mechanisms of the former together represent important challenges. Alu interspersed repeats are a common type of structural variant in the human genome. Alu insertions are intrinsically capable of impacting mRNA sequence and resulting in disease - even when the repeat is positioned in apparently non-coding, intronic sequence within the gene locus. Our hypothesis is that some inherited Alu insertion polymorphisms are functioning as causative variants for human disease risk. We propose to narrow the list of candidates by identifying those Alu insertions that associate with disease risk and that impact the structure of a relevant mRNA transcript. We will develop computational approaches to identify Alu exonization events in RNA-seq data, and we will experimentally evaluate Alu insertion polymorphisms for effects on mRNA splicing using reporter assays and genome editing strategies.