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如何使用SNP_TATA_比较器,通过TATA结合蛋白对该启动子亲和力的变化,来发现由该基因启动子的调控性单核苷酸多态性(SNP)引起的基因表达显著变化。

How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene's Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter.

作者信息

Ponomarenko Mikhail, Rasskazov Dmitry, Arkova Olga, Ponomarenko Petr, Suslov Valentin, Savinkova Ludmila, Kolchanov Nikolay

机构信息

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia ; Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.

出版信息

Biomed Res Int. 2015;2015:359835. doi: 10.1155/2015/359835. Epub 2015 Oct 4.

Abstract

The use of biomedical SNP markers of diseases can improve effectiveness of treatment. Genotyping of patients with subsequent searching for SNPs more frequent than in norm is the only commonly accepted method for identification of SNP markers within the framework of translational research. The bioinformatics applications aimed at millions of unannotated SNPs of the "1000 Genomes" can make this search for SNP markers more focused and less expensive. We used our Web service involving Fisher's Z-score for candidate SNP markers to find a significant change in a gene's expression. Here we analyzed the change caused by SNPs in the gene's promoter via a change in affinity of the TATA-binding protein for this promoter. We provide examples and discuss how to use this bioinformatics application in the course of practical analysis of unannotated SNPs from the "1000 Genomes" project. Using known biomedical SNP markers, we identified 17 novel candidate SNP markers nearby: rs549858786 (rheumatoid arthritis); rs72661131 (cardiovascular events in rheumatoid arthritis); rs562962093 (stroke); rs563558831 (cyclophosphamide bioactivation); rs55878706 (malaria resistance, leukopenia), rs572527200 (asthma, systemic sclerosis, and psoriasis), rs371045754 (hemophilia B), rs587745372 (cardiovascular events); rs372329931, rs200209906, rs367732974, and rs549591993 (all four: cancer); rs17231520 and rs569033466 (both: atherosclerosis); rs63750953, rs281864525, and rs34166473 (all three: malaria resistance, thalassemia).

摘要

疾病生物医学单核苷酸多态性(SNP)标记的使用可以提高治疗效果。对患者进行基因分型,随后寻找比正常情况更频繁出现的SNP,这是转化研究框架内识别SNP标记的唯一普遍接受的方法。针对“千人基因组计划”中数百万未注释SNP的生物信息学应用,可以使这种SNP标记的搜索更具针对性且成本更低。我们使用了涉及费舍尔Z分数的网络服务来寻找候选SNP标记,以发现基因表达的显著变化。在这里,我们通过TATA结合蛋白对该启动子亲和力的变化,分析了SNP在基因启动子中引起的变化。我们提供了示例,并讨论了如何在对“千人基因组计划”中未注释SNP的实际分析过程中使用这种生物信息学应用。利用已知的生物医学SNP标记,我们在附近鉴定出17个新的候选SNP标记:rs549858786(类风湿性关节炎);rs72661131(类风湿性关节炎中的心血管事件);rs562962093(中风);rs563558831(环磷酰胺生物活化);rs55878706(疟疾抗性、白细胞减少症),rs572527200(哮喘、系统性硬化症和牛皮癣),rs371045754(乙型血友病),rs58774

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b70/4609514/6398360332c3/BMRI2015-359835.001.jpg

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