预测与Rb1相关的nsSNPs的致病性——一种计算机模拟方法
Predicting Pathogenicity Of nsSNPs Associated With Rb1 -- An In Silico Approach
AI总结：
本文通过整合多种计算工具和数据库，系统筛选并预测了Rb1基因中425个错义nsSNPs的致病性，最终识别出17个对Rb1蛋白结构和功能具有破坏性影响的突变。
摘要：
单核苷酸多态性（SNPs）是DNA中特定位置上的变异。负责标记与疾病相关基因或在家族内追踪遗传性疾病的序列。Rb1基因中的这些变异可导致视网膜母细胞瘤以及单眼或双眼视网膜癌症、骨肉瘤、黑色素瘤、白血病、肺癌和乳腺癌。首先，使用NCBI维护的SNP数据库提取了一些主要数据。通过GeneMANIA分析了Rb1与其他基因的关联。使用十种不同的计算工具，即SIFT、Polyphen-2、I-Mutant 3.0、PROVEAN、SNAP2、PHD-SNP、PMut、SNPs&GO来筛选具有破坏性的SNP；使用ConSurf服务器估计氨基酸保守区域；使用Project Hope评估天然蛋白和突变蛋白的结构稳定性，并检查突变蛋白的结构效应。GeneMANIA预测RB1基因预计与20个其他基因（如CCND1和RBP2等）有强关联。根据从NCBI维护的dbSNP中检索到的数据，本研究中探查的Rb1基因共携带36,358个SNP。其中345个位于3'UTR，65个位于5'UTR，34,543个位于内含子区域。844个为编码区SNP，其中199个为同义突变，450个为非同义突变，包括425个错义突变、5个无义突变和20个移码突变，其余为其他类型的SNP。我们选取425个错义SNP进行研究。共预测出17个突变，即D332G、R445Q、E492V、P515T、W516G、V531G、E533K、E539K、M558R、W563G、L657Q、A658T、R661Q、D697H、D697E、P796L和R798W，对Rb1蛋白的结构和功能具有破坏性影响。
英文摘要：
Single nucleotide polymorphisms (SNPs) are variations at specific locations in DNA. Sequence responsible for marking genes associated with diseases or tracking inherited diseases within The family. These variations in the Rb1 gene can cause Retinoblastoma and cancer in the retina Of one eye or both, Osteosarcoma, Melanoma, Leukemias, Lungs, and Breast cancer. First of all,The SNP database hosted by NCBI was used to extract some principal data. The association of Rb1 to Other genes were analyzed by GeneMANIA. Ten different computational tools, i.eSIFT,Polyphen-2, I-Mutant 3.0,PROVEAN, SNAP2, PHD-SNP, PMut, SNPs&GO were used for the screening of damaging SNP for the estimation of conserved regions of amino acids Consurf Server was used for the evaluation of the structural stability of both native and mutant proteins, Project Hope was used to examine the structural effects of mutant protein.GeneMANIA predicted that RB1 Gene was expected to have a strong association with 20 other genes i.e. CCND1 and RBP2 etc. As per data retrieved from dbSNP hosted by NCBI,the Rb1 gene probed in this study carried a total of 36,358 SNPs. 345 were found in 3'UTR, 65 in 5'UTR, and 34,543 were found in the intron region. 844 were coding SNPs, and out of 844, 199 were synonymous And 450 were non-synonymous, including 425 missense, five nonsense, and 20 frameshift mutations. And remaining all are other types of SNPs. We took 425 missense SNPs for our investigation. A total of 17 mutations i.e. D332G, R445Q, E492V, P515T, W516G, V531G, E533K, E539K, M558R,W563G, L657Q, A658T, R661Q, D697H, D697E, P796L and R798W were predicted to have Damaging effects on structure and function of Rb1 protein..
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