癫痫相关基因SCN1A启动子区多态性位点的生物信息学分析

Bioinformatic Analysis of the Single Nucleotide Polymorphisms of the SCN1A Promoter Region

SCN1A是多种神经系统疾病的致病基因，该基因的精确表达对于维持神经系统正常功能非常重要．为了认识SCN1A启动子区多态性位点（single nucleotide polymorphisms．SNPs）的保守性及其功能意义，应用生物信息学方法分析了目前已发表位于SCN1A启动子区的11个SNPs，分别命名S1～S11．分析结果表明，S3、S5和S7等位基因频率没有人种差异性．其余SNP等位基因频率均有人种差异性；接近核心启动子的SNPs要比远离核心启动子SNPs的保守程度高．提示靠近核心启动子的SNPs影响SCN1A基因表达的概率可能越大；大部分SNPs祖传等位基因在哺乳动物中是保守的（S3除外）。暗示这些SNPs新生等位基因有可能在人类进化过程起到一定的作用：启动子分析软件预测发现。含S2、S4、S8及S9等4个SNPs不同等位基因的同一序列分别存在不同转录因子结合元件．而含S1和S11不同等位基因的同一序列都只能预测到含其中一个等位基因的序列存在转录因子结合元件．这些差异可能是SNPs影响SCN1A表达的重要原因之一．这些分析将为进一步研究．SCN1A启动子区SNPs与神经系统疾病的相互关系打下基础．

SCN1A is associated with several neurological disorders and its accurate expression is essential to normal biological function. To investigate the conservations and functions of the single nucleotide polymorphisms （SNPs） on SCN1A promoter region, 11 SNPs （named S1 - S11, respectively） were downloaded from the Internet and analyzed with bioinformatics methods. Results show that there are differences in the allele frequencies of the SNPs from different populations, except S3, S5 and S7. The conservation levels of those SNPs near the core promoter are higher than that of those SNPs far from the core promoter, implying the greater likelihood that the SNPs near the core promoter might affect SCNIA expression. Most SNP ancestral alleles, except S3, are conserved in mammals, suspecting they might play partial roles on human evolution. Those sequences including two SNP alleles of S2, S4, S8 and S9 are potential transcriptional elements and those sequences including only one allele of S1 and S11 are potential transcriptional elements, which may be one of the important reasons of SNPs affecting SCN1A expression.Further studies should be performed to investigate the relationships between the SNPs on SCN1A promoter region and neurological disorders.