全基因组分析单核苷酸多态性对多聚腺苷化信号的影响

Genome Wide Analysis of the Influence on Polyadenylation Signal Caused by Single Nucleotide Polymorphism

单核苷酸多态性(single nucleotide polymorphism,SNP),主要是指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性,是人类可遗传的变异中最常见的一种。多聚腺苷化(polyadenylation,poly(A))是真核生物基因表达的一个重要步骤,对m RNA从细胞核输出及翻译过程起重要作用。Poly(A)位点的有效剪切、转录终止及翻译终止都跟poly(A)信号(poly(A)signal,PAS)密切相关。研究表明一些poly(A)信号上的碱基突变能够影响poly(A)位点的选择,即单核苷酸多态性能产生、改变或消除目前已被发现的PAS,从而导致poly(A)位点的差异性选择。本文对已发现的保守性排名前50的PAS进行分类,并从全基因组层面分析了SNP对于PAS的不同改变形式,筛选能改变PAS的SNP。为了分析SNP是否影响转录本长度,本文将SNP和EST比对到基因组上,筛选包含SNP的EST,最终筛选出能改变EST长度的SNP,说明了SNP可以通过改变PAS的形式来影响poly(A)位点的选择,进而影响转录本长度。

SNP（single nucleotide polymorphism） is one of the most common genetic variation of human, which mainly refers to DNA sequence polymorphism caused by the variation of single nucleotide at the genome level. Polyadenylation（poly（A）） is an important step of eukaryotic gene expression, which plays a significant role in the m RNA output step from the cell nucleus and in the translation process. The effective cleavage, transcription and translation terminate of poly（A） sites are closely related to poly（A） signals（PASs）. Studies have shown that bases mutation on some poly（A） signal can affect the choice of poly（A） sites. In other words, single nucleotide polymorphism can create, change, or eliminate the PAS, which can lead to the choice of alternative poly（A） sites. This paper classified the top 50 conserved PASs and analyzed the different change form of PASs influenced by SNPs from the genome-wide level to screen SNPs that can change PASs. In order to analyze whether SNPs can affect the length of transcripts, we mapped SNPs and ESTs to the genome to screen ESTs including SNPs, and eventually selected SNPs that can change the length of ESTs. The results illustrate that SNPs can influence the choice of poly（A） sites by changing the form of PASs to affect the length of transcripts.