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首页> 外文期刊>Journal of genetics >In silico analysis of nsSNPs in CYP19A1 gene affecting breast cancer associated aromatase enzyme
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In silico analysis of nsSNPs in CYP19A1 gene affecting breast cancer associated aromatase enzyme

机译：在影响乳腺癌相关芳香酶酶的CYP19A1基因中NSSNPS的硅分析

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The human aromatase protein encoded by CYP19A1 gene is the principle enzyme involved in the biogenesis of oestrogen in adipose tissues. An excessive exposure to endogenous oestrogen is regarded as an important determinant in the risk of breast cancer. Thus, in the present study we have used multiple computational methods to identify the most deleterious nonsynonymous SNPs in CYP19A1 gene that caused probable genotypic–phenotypic alterations susceptible to breast cancer malignancy. In this study, a total of 338 nsSNPs werescreened using 12 in silico tools including SIFT, PROVEAN, PolyPhene-2, SNAP2, I Mutant 3.0, MuPro, mCSM, PhD SNP, SNP&GO, P-Mut, Dr Cancer, and, CScape. Additionally the structural and functional consequences of missense mutations were validated using Consurf, ModPred, SOPMA, and, HOPE server tools. Of the 338 nsSNPs subjected to functional, protein stability, disease associated, and, cancer susceptible analysis, 14 variants were predicted to be highly deleterious mutants. Further, structural and molecular studies suggested10 variants (R435H, Y77C, Y81C, E302K, E210K; and L451P, G49D, G131D, L204W and D309) to have various deformities and caused structural disturbances of the protein. Through the combination of multiple computational tools and strategized analysis, we report seven novel high risk nsSNPs of human aromatase enzyme in association with the pathogenesis of human breast cancer.
机译：CYP19A1基因编码的人芳族酶蛋白是脂肪组织中雌激素生物发生的主要酶。过度暴露于内源性雌激素被认为是乳腺癌风险的重要决定因素。因此，在本研究中，我们使用了多种计算方法来鉴定CYP19A1基因中最有害的非型SNP，导致易患乳腺癌恶性肿瘤的可能基因型 - 表型改变。在本研究中，共使用338 NSSNPS在硅工具中使用12种，包括SIFT，促使，多骨-2，SNAP2，I突变3.0，MUPRO，MCSM，PHD SNP，SNP＆GO，P-MUT，癌症和，CSCAPT。此外，使用COARURF，MODPRED，SOPMA和Hope Server工具验证了致密突变的结构和功能后果。在经过功能性，蛋白质稳定性，疾病的338个NSSNP的中，癌症易感分析，预计14种变种是高度有害的突变体。此外，结构和分子研究表明了10个变体（R435H，Y77C，Y81C，E302K，E210K;和L451P，G49D，G131D，L204W和D309）具有各种畸形并引起蛋白质的结构干扰。通过多种计算工具和策略分析的组合，我们向人乳腺癌发病机制报告了七种新型高风险NSSNPS的人芳香酶酶。

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