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 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).

scholarly journals Novel mutations within PRSS1 Gene that could potentially cause hereditary pancreatitis: Using Comprehensive in silico Approach

2019 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Abdelrahman H. Abdelmoneim ◽  
Nafisa M. Elfadol ◽  
Soada A. osman ◽  
Tebyan A. Abdelhameed ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Structure And Function ◽  
Incomplete Penetrance ◽  
Nucleotide Polymorphisms ◽  
Hereditary Pancreatitis ◽  
Novel Mutations ◽  
Autosomal Dominant Disorder ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundHereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. The comprehensive in silico analysis of coding SNPs, and their functional impacts on protein level, still remains unknown. In this study, we aimed to identify the pathogenic SNPs in PRSS1 gene by computational analysis approach.Materials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict Single-nucleotide polymorphisms influence on protein structure and function.ResultTwo novel mutations out of 339 nsSNPs that are found be deleterious effect on the PRSS1 structure and function.ConclusionThis is the first in silico analysis in PRSS1 gene, which will be a valuable resource for future targeted mechanistic and population-based studies.

scholarly journals In Silico Analysis of Huntingtin Homologs in Lower Eukaryotes

2021 ◽  
Vol 22 (6) ◽  
pp. 3214
Author(s):  
Valentina Brandi ◽  
Fabio Polticelli
Keyword(s):  
Autosomal Dominant ◽  
In Silico Analysis ◽  
Computational Approach ◽  
Autosomal Dominant Disorder ◽  
C Elegans ◽  
Functional Conservation ◽  
Lower Eukaryotes ◽  
Gene Coding ◽  
And Function ◽  
Silico Analysis

Huntington’s disease is a rare neurodegenerative and autosomal dominant disorder. HD is caused by a mutation in the gene coding for huntingtin (Htt). The result is the production of a mutant Htt with an abnormally long polyglutamine repeat that leads to pathological Htt aggregates. Although the structure of human Htt has been determined, albeit at low resolution, its functions and how they are performed are largely unknown. Moreover, there is little information on the structure and function of Htt in other organisms. The comparison of Htt homologs can help to understand if there is a functional conservation of domains in the evolution of Htt in eukaryotes. In this work, through a computational approach, Htt homologs from lower eukaryotes have been analysed, identifying ordered domains and modelling their structure. Based on the structural models, a putative function for most of the domains has been predicted. A putative C. elegans Htt-like protein has also been analysed following the same approach. The results obtained support the notion that this protein is a orthologue of human Htt.

scholarly journals Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension

2020 ◽  
Vol 33 (7) ◽  
pp. 670-675
Author(s):  
Peng Fan ◽  
Xiao-Cheng Pan ◽  
Di Zhang ◽  
Kun-Qi Yang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Early Onset ◽  
In Silico ◽  
Genetic Diagnosis ◽  
In Silico Analysis ◽  
Missense Variant ◽  
Chinese Family ◽  
Clinical Genetic ◽  
Autosomal Dominant Disorder ◽  
Liddle Syndrome ◽  
Silico Analysis

Abstract BACKGROUND Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.

scholarly journals Comprehensive in silico Analysis of IKBKAP gene that could potentially cause Familial dysautonomia

2018 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Enas A. Osman ◽  
Abdelrahman H. Abdelmoneiom ◽  
Dania M. Hassn ◽  
Hadeel M. Yousif ◽  
...  
Keyword(s):  
In Silico ◽  
Genetic Disorder ◽  
In Silico Analysis ◽  
Familial Dysautonomia ◽  
Structural Effect ◽  
Structure And Function ◽  
Genetic Studies ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundFamilial dysautonomia (FD) is a rare neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies. We aimed to identify the pathogenic SNPs in IKBKAP gene by computational analysis software’s, and to determine the structure, function and regulation of their respective proteins.Materials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict SNPs influence on protein structure and function.Result41 novel mutations out of 973 nsSNPs that are found be deleterious effect on the IKBKAP structure and function.ConclusionThis is the first in silico analysis in IKBKAP gene to prioritize SNPs for further genetic studies.

scholarly journals Unmasking of novel mutations within XK gene that could be used as Diagnostic Markers to Predict McLeod syndrome: Using in silico analysis

2019 ◽  
Author(s):  
Mujahed I. Mustafa ◽  
Mohamed A. Hassan
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Structural Effect ◽  
Novel Mutations ◽  
Multisystem Disorder ◽  
Functional Studies ◽  
Central Nervous Systems ◽  
The One ◽  
And Function ◽  
Silico Analysis

AbstractBackgroundMcLeod neuroacanthocytosis syndrome is a rare X-linked recessive multisystem disorder affecting the peripheral and central nervous systems, red blood cells, and internal organs.MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structural and functional level.Result2 novel mutations out of 104 nsSNPs that are found to be deleterious effect on the XK structure and function.ConclusionThe present study provided a novel insight into the understanding of McLeod syndrome, SNPs occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here; we prioritize SNPs for further genetic mapping studies. This will be a valuable resource for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.

scholarly journals The Association between SLC25A15 Gene Polymorphisms and Hyperornithinemia-hyperammonemia-homocitrullinuria Syndrome: Using In Silico Analysis

2019 ◽  
Author(s):  
Nuha A. Mahmoud ◽  
Dina T. Ahmed ◽  
Zainab O. Mohammed ◽  
Fatima A. Altyeb ◽  
Mujahed I. Mustafa ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Recessive ◽  
Urea Cycle ◽  
In Silico Analysis ◽  
Structure And Function ◽  
Medical Testing ◽  
Bioinformatics Tools ◽  
And Function ◽  
Silico Analysis ◽  
Selection Of

BackgroundHyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive inborn error of the urea cycle. It is caused by mutations in the SLC25A15 gene that codes the mitochondrial ornithine transporter. The aim of this study is to detect and identify the pathogenic SNPs in SLC25A15 gene through a combination set of bioinformatics tools and their effect on the structure and function of the protein.MethodsThe deleterious SNPs in SLC25A15 are detected by various bioinformatics tools, with addition to identifying their effects on the structure and function of this gene.Results20 deleterious SNPs out 287of were found to have their own damaging effects on the structure and function of the SLC25A15 gene.ConclusionThis study is the first in silico analysis of SLC25A15 using a selection of bioinformatics tools to detect functional and structural effects of deleterious SNPs. Finding the pathogenic SNPs is a promising start to innovate new, useful SNP diagnostic markers for medical testing and for safer novel therapies specifically targeting mutant SLC25A15.

In silico analysis of Nattokinase from Bacillus subtilis sp natto

2017 ◽  
Vol 9 (04) ◽  
Author(s):  
Cambyz Irajie ◽  
Milad Mohkam ◽  
Navid Nezafat ◽  
Fatemeh Mohammadi ◽  
Younes Ghasemi
Keyword(s):  
Bacillus Subtilis ◽  
Serine Protease ◽  
In Silico ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Dimensional Structure ◽  
Cardiovascular Therapy ◽  
And Function ◽  
Outlier Region ◽  
Silico Analysis

Nattokinase or subtilisin NAT (EC 3.4.21.62) is one of the most remarkable enzymes produced by Bacillus subtilis sp. Natto, which posses direct fibrinolytic activity. The aim of this study is in silico analysis of Nattokinase structure and function. The three-dimensional structure of serine protease Nattokinase from Bacillus subtilis sp. natto was determined using homology modeling performed by Geno3D2 Web Server and refined by ModRefiner. The obtained models were validated via programs such as RAMPAGE, ERRAT, 3D Match and verify 3D for consistency; moreover, functional analysis performed by PFP from Kihara Bioinformatics laboratory. RAMPAGE analysis showed that 96.7% of the residues are located in the favored region, 3.0% in allowed region and 0.4% in outlier region of the Ramachandran plot. The verify 3D value of 0.73 indicates that the environmental sketch of the model is fine. SOPMA and PSIPRED were exploited for computation of the secondary structural properties of serine protease Nattokinase. Active site determination via AADS suggested that this enzyme can be applied as a potent enzyme for cardiovascular therapy. However, these results should be more confirmed by wet lab researches for designing the more active enzyme for better functions on its fibrinolysis activity.

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.

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