CFTR基因非单核苷酸多态性的计算和结构分析。

IF 3.5 Q1 EDUCATION & EDUCATIONAL RESEARCH
Genomic medicine Pub Date : 2008-01-01 Epub Date: 2008-05-14 DOI:10.1007/s11568-008-9019-8
C George Priya Doss, R Rajasekaran, C Sudandiradoss, K Ramanathan, R Purohit, R Sethumadhavan
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引用次数: 54

摘要

单核苷酸多态性(SNPs)正在深入研究,以了解复杂性状和疾病的生物学基础。通过了解snp的功能,可以了解人类表型变异的遗传学。在这项研究中,我们使用计算方法分析了可以改变导致囊性纤维化的CFTR基因候选基因的表达和功能的遗传变异。我们使用基于序列同源性的SIFT工具从进化角度筛选SNPs,发现17个(44%)nssnp是有害的。基于结构的方法PolyPhen server提示26个nsSNPS(66%)可能会破坏蛋白质的功能和结构。PupaSuite工具预测snp对受影响蛋白结构和功能的表型影响。进行结构分析,主要突变发生在CFTR基因编码的天然蛋白上,该蛋白位于id为rs1800093的nsSNP的氨基酸位置F508C。进一步分析了天然和突变模型蛋白的氨基酸残基的溶剂可及性、二级结构和稳定残基,以检查蛋白质的稳定性。我们进一步对这些snp进行了iHAP分析,以确定htsnp,并报告了未来CFTR突变研究的潜在候选基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel computational and structural analysis of nsSNPs in CFTR gene.

Single Nucleotide Polymorphisms (SNPs) are being intensively studied to understand the biological basis of complex traits and diseases. The Genetics of human phenotype variation could be understood by knowing the functions of SNPs. In this study using computational methods, we analyzed the genetic variations that can alter the expression and function of the CFTR gene responsible candidate for causing cystic fibrosis. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 17 nsSNPs (44%) were found to be deleterious. The structure-based approach PolyPhen server suggested that 26 nsSNPS (66%) may disrupt protein function and structure. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutation that occurred in the native protein coded by CFTR gene, and which is at amino acid position F508C for nsSNP with id (rs1800093). The amino acid residues in the native and mutant modeled protein were further analyzed for solvent accessibility, secondary structure and stabilizing residues to check the stability of the proteins. The SNPs were further subjected to iHAP analysis to identify htSNPs, and we report potential candidates for future studies on CFTR mutations.

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