scholarly journals Identification of High risk nsSNPs in Human TP53 Gene Associated with Li–Fraumeni Syndrome: An In Silico Analysis Approach

2020 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Naseem S. Murshed ◽  
Mazen A. Elbasher ◽  
Abdelrafie M. Makhawi
Keyword(s):  
High Risk ◽  
In Silico ◽  
3D Structure ◽  
In Silico Analysis ◽  
Tp53 Gene ◽  
Li Fraumeni Syndrome ◽  
Functional Inference ◽  
Li Fraumeni ◽  
The Impact ◽  
Silico Analysis

AbstractBackgroundLi–Fraumeni syndrome (LFS) is a cancer–prone conditions caused by a germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal dominant pattern of inheritance with high penetrance.PurposeThe aim of this study is to identify the high-risk pathogenic nsSNPs in PT53 gene that could be involved in the pathogenesis of Li–Fraumeni syndrome.MethodsThe nsSNPs in the human PT53 gene retrieved from NCBI, were analyzed for their functional and structural consequences using various in silico tools to predict the pathogenicity of each SNP. SIFT, Polyphen, PROVEAN, SNAP2, SNPs&Go, PHD-SNP, and P-Mut were chosen to study the functional inference while I-Mutant 3.0, and MUPro tools were used to test the impact of amino acid substitutions on protein stability by calculating ΔΔG value. The effects of the mutations on 3D structure of the PT53 protein were predicted using RaptorX and visualized by UCSF Chimera.ResultsA total of 845 PT53 nsSNPs were analyzed. Out of 7 nsSNPs of PT53 three of them (T118L, C242S, and I251N) were found high-risk pathogenic.ConclusionIn this study, out of 7 predicted high-risk pathogenic nsSNPs, three high-risk pathogenic nsSNPs of PT53 gene were identified, which could be used as diagnostic marker for this gene. The combination of sequence-based and structure-based approaches is highly effective for pointing pathogenic regions.

scholarly journals In silico analysis of CDC73 gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

2019 ◽  
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Alaa I. Mohammed ◽  
Esraa O. Gadim ◽  
Mayada A.Mohammed ◽  
Sara H. Hamza ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Dominant ◽  
In Silico Analysis ◽  
Autosomal Dominant Disorder ◽  
Variable Expression ◽  
Back Ground ◽  
And Function ◽  
Molecular Aberrations ◽  
The Impact ◽  
Silico Analysis

AbstractBack groundhyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs on CDC73 structure and function using different bioinformatics tools.MethodComputational analysis using eight different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function of CDC73 gene that might be causing jaw tumour.ResultsFrom (733) SNPs identified in the CDC73 gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.ConclusionEleven substantial genetic/molecular aberrations in CDC73 gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.

scholarly journals Identification of HPV16 in suspected cases of cervical lesions and docking Study of its L1 protein with some natural inhibitors.

2020 ◽  
Author(s):  
Yusuf Lukman ◽  
Doro Aliyu Bala ◽  
Kabir Imam Malik ◽  
Abdulkadir Saidu ◽  
Abdulhadi Sale Kumurya ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Prevalence Rate ◽  
In Silico ◽  
In Silico Analysis ◽  
Low Grade ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
L1 Protein ◽  
Silico Analysis

Abstract Background The Human papillomavirus (HPV) causes sexually transmitted diseases. Among several types of HPV variants, HPV 16 is listed as a high-risk group, the primary cervical cancer etiologic agent, which causes life-threatening disease among women worldwide. The presence of L1, E6 and E7 encoded oncoproteins are largely responsible for virulence and pathogenicity that leads to cervical lesions. This menace is required to be curbed by designing an anti-cancerous drugs. The protein receptor-inhibitor interaction adopted using in silico analysis is very important in drug designing. It was the objective of this study to identify HPV16 isolates from suspected cases of cervical cancer at SH Sokoto and SYMH Birnin Kebbi hospitals and also to identify potent HPV16’s L1 protein inhibitor using in silico analysis of Echinacoside, curcumin and Cichoric acid against the viral protein. Methods A total of 140 cervical smear samples consisting of 21 low grade squamous intraepithelial lesion, 6 high grade lesion and 117 negative pap smears were collected. The samples were subjected for molecular detection using PCR targeting E6 and L1 genes of the virus. Positive samples were sequenced using Sanger sequencing platform. All the sequencing data were analysed using bioedit software while data generated for the molecular prevalence was statistically analyzed using Chi-square. A comprehensive HPV L1 protein homology model was designed to predict the L1 protein interaction mechanism with natural inhibitory molecules using a structural drug design approach. AutoDock Vina was used to carry out the molecular docking. Results Out of the 140 samples, 24 samples were positive for the PCR representing 16.7% molecular prevalence rate. There is statistically significant association between cyto-diagnoses and presence of HPV16 ( P ˂0.05). The highest prevalence rate of 12(50% of positive sample) was recorded among women between 30-39 years old. Docking analysis showed that the Chicoric acid components of Echinacea purpurae have strong binding affinity to the L1 protein of the HPV. Conclusion This study provides data on HPV 16 epidemiology in northern Nigeria, High-risk type 16 HPV variant was identified and also provides novel evidence for consideration on certain interacting residues, when synthesizing Anti-HPV compounds in the wet lab.

scholarly journals A Novel Amino Acid Substitution, Fibrinogen Bβp.Pro234Leu, Associated with Hypofibrinogenemia Causing Impairment of Fibrinogen Assembly and Secretion

2020 ◽  
Vol 21 (24) ◽  
pp. 9422
Author(s):  
Takahiro Kaido ◽  
Masahiro Yoda ◽  
Tomu Kamijo ◽  
Shinpei Arai ◽  
Chiaki Taira ◽  
...  
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Contact Region ◽  
Chinese Hamster ◽  
In Silico Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Immunoblotting Analysis ◽  
Fibrin Polymerization ◽  
The Impact ◽  
Silico Analysis

We identified a novel heterozygous variant, Bβp.Pro234Leu (fibrinogen Tokorozawa), which was suspected to be associated with hypofibrinogenemia. Therefore, we analyzed the assembly and secretion of this fibrinogen using Chinese hamster ovary (CHO) cells. To determine the impact on the synthesis and secretion of fibrinogen of the Bβp.P234L and γp.G242E substitutions, we established recombinant variant fibrinogen-producing CHO cell lines. Synthesis and secretion analyses were performed using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis with the established cell lines. In addition, we performed fibrin polymerization using purified plasma fibrinogen and in-silico analysis. Both Bβp.P234L and γp.G242E impaired the secretion and synthesis of fibrinogen. Moreover, immunoblotting analysis elucidated the mobility migration of the Bβγ complex in Bβp.P234L. On the other hand, the fibrin polymerization of fibrinogen Tokorozawa was similar to that of normal fibrinogen. In-silico analysis revealed that the Bβp.P234 residue is located in the contact region between the Bβ and γ chains and contacts γp.G242 residue. The present study demonstrated that the Bβp.P234L substitution resulted in hypofibrinogenemia by decreasing the assembly and secretion of fibrinogen. Therefore, there is a possibility that substitutions in the contact region between the Bβ and γ chains impact the assembly and secretion of fibrinogen.

In Silico Analysis for Determination and Validation of Human CD20 Antigen 3D Structure

2017 ◽  
Vol 25 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Zahra Payandeh ◽  
Masoumeh Rajabibazl ◽  
Yousef Mortazavi ◽  
Azam Rahimpour
Keyword(s):  
In Silico ◽  
3D Structure ◽  
In Silico Analysis ◽  
Cd20 Antigen ◽  
Silico Analysis

scholarly journals Extensive In Silico Analysis of ATL1 Gene : Discovered Five Mutations That May Cause Hereditary Spastic Paraplegia Type 3A

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mujahed I. Mustafa ◽  
Naseem S. Murshed ◽  
Abdelrahman H. Abdelmoneim ◽  
Miyssa I. Abdelmageed ◽  
Nafisa M. Elfadol ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
In Silico ◽  
Computational Analysis ◽  
3D Structure ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Structural Level ◽  
Spastic Paraplegia ◽  
Analysis Tools ◽  
The Impact

Background. Hereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP which is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. SPG3A gene mutations and the phenotype-genotype correlations have not yet been recognized. The aim of this work was to categorize the most damaging SNPs in ATL1 gene and to predict their impact on the functional and structural levels by several computational analysis tools. Methods. The raw data of ATL1 gene were retrieved from dbSNP database and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0 and MUPro, respectively, to investigate their effect on the structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids. Results. Five nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, and rs1242753115). Conclusions. In this study, the impact of nsSNPs in the ATL1 gene was investigated by various in silico tools that revealed five nsSNPs (V67F, T120I, R217Q, R495W, and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein and, therefore, can be used as genomic biomarkers specifically before 4 years of age; also, it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.

In silico analysis of relative rareness, codon usage, and enzyme-substrate docking of Lampyroidea maculata luciferase

2020 ◽  
Vol 17 ◽  
Author(s):  
Mojtaba Mortazavi ◽  
Saman Hosseinkhani ◽  
Masoud Torkzadeh-Mahani ◽  
Safa Lotfi ◽  
Rahman Emamzadeh ◽  
...  
Keyword(s):  
Codon Usage ◽  
Binding Site ◽  
In Silico ◽  
Critical Role ◽  
3D Structure ◽  
In Silico Analysis ◽  
Living Organism ◽  
Industrial Biotechnology ◽  
Rare Codons ◽  
Silico Analysis

: Bioluminescence is the production and emission of light by the luciferase enzymes in a living organism. The luciferases were identified in different domains of life, but the Lampyridae luciferases are considered for biotechnological and clinical applications. Recently, the new Iranian luciferase gene from the Lampyroidea maculata has been cloned and characterized. In this study, in silico analysis of this enzyme as the codon usage bias parameters (CAI, CBI, ENC, and rare codons) were conducted. Furthermore, the 3D structure of this enzyme was modeled in the I-TASSER web server and the status of these rare codons in this model was studied using SPDBV and PyMOL software. In the following, the substrate-binding site was studied using the AutoDock Vina. By molecular modeling, some rare codons were identified that may have a critical role in the structure and function of this enzyme. The GC3% of the CDs was 17/304 and GC3 Skewness was 0.115. The molecular docking analysis recognizes some residues that yield closely related to the DLSA binding site. By these analyses, a new understanding of the sequence and structure of this enzyme was created, and our findings can be used in some fields of clinical and industrial biotechnology. This bioinformatics analysis plays an important role in the design of the new recombinant enzyme.

scholarly journals In silico analysis of CDC73 gene revealing 11 novel SNPs with possible association to Hyperparathyroidism-Jaw Tumor syndrome

2020 ◽  
Vol 4 (2) ◽  
pp. 67-81
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Alaa I. Mohammed ◽  
Esraa O. Gadim ◽  
Mayada Alhibir Mohammed ◽  
Sara H. Hamza ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Dominant ◽  
In Silico Analysis ◽  
Autosomal Dominant Disorder ◽  
Variable Expression ◽  
Project Hope ◽  
Molecular Aberrations ◽  
Structural Levels ◽  
The Impact ◽  
Silico Analysis

AbstractHyperparathyroidism-Jaw Tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the most deleterious SNPs mutations on CDC73 gene and to predict their influence on the functional and structural levels using different bioinformatics tools. Method: Computational analysis using twelve different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, P-Mut, I-Mutant ,Project Hope, Chimera, COSMIC and dbSNP Short Genetic Variations were used to identify the impact of mutations in CDC73 gene that might be causing jaw tumor. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven SNPs (G49C, L63P, L64P, D90H, R222G, W231R, P360S, R441C, R441H, R504S and R504H) has deleterious effect on the function and structure of protein and expected to cause the syndrome. Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene identified that could serve as diagnostic markers for hyperparathyroidism-jaw tumor (HPT-JT).

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