疾病相关基因单核苷酸多态性初筛的生物信息学策略及实验验证

目的 以筛选宫颈癌相关IL-18基因SNP位点为例,探讨筛选疾病相关SNP位点的生物信息学策略,并以实验验证.方法 使用SNPper软件从公共数据库dbSNP获得IL-18调控区和编码区的SNPs数据,使用PARSESNP软件进行筛选和分析编码区SNPs是否对基因表达产物产生影响;使用转录因子结合部位预测软件分析调控区SNPs是否对基因转录表达水平产生影响.然后通过病例-对照研究,使用直接测序法验证生物信息学方法结果的有效性.结果 生物信息学策略分析得到3个SNP位点(rs1946518、rs360719和rs187238),预测这些位点可能影响IL-18的转录表达水平,从而影响机体对肿瘤的抵抗作用.病例对照研究直接测序法分析,rs1946518和rs360719与宫颈癌相关;rs187238与宫颈癌无关联.结论 生物信息学策略分析疾病相关SNP位点,虽然存在假阳性等缺点,但仍然廉价可行,可以为疾病与基因关联性研究提供很有价值的信息.

Bioinformatical screening and laboratorial analysis of SNPs of the gene involved in susceptibility for disease

Objective] To establishe a bioinformatical method which can find the polymorphisms of the gene involved in susceptibility for a disease. Methods] We screened single nucleotide polymorphisms (SNPs) of IL-18 gene involved in susceptibility of cervical cancer by a bioinformatics approach, and analyzed their correlations to abnormal gene functions by sequences testing. Results] Three SNPs, rs1946518, rs360719 and rs187238, were screened by a bioinformatics approach. Two SNPs rs1946518 and rs360719, were proven to be involved in susceptibility for cervical neoplasm. Conclution] It is an inexpensive and effective method that we screen some important SNPs by a bioinformatics approach.