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用于识别功能性单核苷酸多态性的计算算法工具的应用。

Applications of computational algorithm tools to identify functional SNPs.

作者信息

George Priya Doss C, Sudandiradoss C, Rajasekaran R, Choudhury Parikshit, Sinha Priyanka, Hota Pragnya, Batra Udit Prakash, Rao Sethumadhavan

机构信息

School of Biotechnology, Chemical and Biomedical Engineering, Bioinformatics Division, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.

出版信息

Funct Integr Genomics. 2008 Nov;8(4):309-16. doi: 10.1007/s10142-008-0086-7. Epub 2008 Jun 19.

Abstract

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans. Understanding the functions of SNPs can greatly help to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, different computational algorithm tools like Sorting Intolerant from Tolerant, Polymorphism Phenotyping, UTRscan, FASTSNP, and PupaSuite were used for prioritization of high-risk SNPs in coding region (exonic nonsynonymous SNPs) and noncoding regions (intronic and exonic 5' and 3'-untranslated region (UTR) SNPs). In this work, we have analyzed the SNPs that can alter the expression and function of transcriptional factor TP53 as a pipeline and for providing a guide to experimental work. We identified the possible mutations and proposed modeled structure for the mutant proteins and compared them with the native protein. These nsSNPs play a critical role in cancer association studies aiming to explain the disparity in cancer treatment responses as well as to improve the effectiveness of the cancer treatments. Our results endorse the study with in vivo experimental protocols.

摘要

单核苷酸多态性(SNPs)是人类中最常见的遗传变异类型。了解SNPs的功能有助于深入理解人类表型变异的遗传学,特别是人类复杂疾病的遗传基础。通过实验方案从包含功能性和中性SNPs的集合中识别功能性SNPs的方法具有挑战性。为了探索基因突变与表型变异之间的可能关系,使用了不同的计算算法工具,如从耐受中筛选不耐受、多态性表型分析、UTRscan、FASTSNP和PupaSuite,对编码区(外显子非同义SNPs)和非编码区(内含子以及外显子5'和3'-非翻译区(UTR)SNPs)中的高风险SNPs进行优先级排序。在这项工作中,我们分析了可能改变转录因子TP53表达和功能的SNPs,以此作为一个流程,并为实验工作提供指导。我们确定了可能的突变,并提出了突变蛋白的模型结构,并将它们与天然蛋白进行比较。这些非同义SNPs在癌症关联研究中起着关键作用,旨在解释癌症治疗反应的差异,并提高癌症治疗的有效性。我们的结果支持了体内实验方案的研究。

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