空间定向及运动病易感性相关基因α_(2A)-AR启动子区域单核苷酸多态性位点生物信息学分析

Single nucleotide polymorphisms of spatial orientation and motion sickness susceptibility related α_(2A)-AR promoter region:a bioinformatic analysis

目的α2A-AR基因的精确表达对于运动病易感性、维持注意力分配、空间定向、学习和记忆功能非常重要,因此对该基因启动子区域单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点的功能意义及其保守性进行研究。方法采用生物信息学分析法对目前已报道的位于ADRA2A启动子区域的10个SNPs(S1～S10)进行分析。结果 S1、S3、S5和S8等位基因频率没有人种差异性。其余SNPs等位基因频率均有人种差异性;接近核心启动子SNPs的保守性高于远离核心启动子SNPs的保守性,提示位于核心启动子区域附近的SNPs影响α2A-AR基因表达的概率更大;大部分SNPs位点始祖等位基因是保守性的(S6除外),提示上述SNPs位点新生等位基因可能在人类进化过程起到作用;启动子软件分析得出,含S2、S5、S6、S7、S8、S9、S10等7个SNPs不同等位基因序列存在不同转录因子结合元件。含S1和S4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,而含S3序列没有预测到转录因子结合元件,提示不同等位基因转录结合位点存在差异性。结论上述差异可能是SNPs影响ADRA2A表达的重要原因之一,这些分析将为进一步研究ADRA2A启动子区域SNPs与运动病易感性、空间定向能力、注意力分配以及学习、记忆能力的关联性提供理论依据。

Objective To investigate the conservation and functions of the single nucleotide polymorphism （SNPs） on α2A-AR promoter region,for the accurate expression of α2A-AR gene is essential to the maintenance of motion sickness sus- ceptibility, attention allocation, spatial orientation, and learning and memory function. Methods Ten SNPs （S1-S10） re- ported from NCBI were analyzed with bioinformations methods. Results There were differences in the allele frequencies of the SNPs from different populations,except for S1, S3, S5 and S8. The conservation level of those SNPs near the core pro-moter was higher than that of SNPs far from the core promoter, pointing to the greater likelihood that the SNPs near the core promoter might affect α2A-AR expression. Most SNPs ancestral alleles, except S6, were conserved, suggesting they might play partial roles in human evolution. Sequences that included two SNPs alleles of $2, $4, S8, S9 and S10 were potential tran-scriptional elements like those including only one allele of S1 and S4. Conclusion These differences may be one of the sig-nificancet reasons that SNPs affect α2A-AR expression. Further studies should be performed to investigate the relationships between the SNPs on α2A-AR promoter region, motion sickness susceptibility, attention allocation, spatial orientation, and learning and memory function.