In-silico analysis of BCL2 gene using multiple bioinformatics tools to identify the most lethal mutations that are crucial for its structural and functional integrity

Abstract BCL2 was the first ever known gene for anti-apoptotic activity, that encodes for essential proteins of the external mitochondrial membrane. Regarding tumorigenesis, deregulated BCL2 expression and related proteins have been recognized as characteristic of several human cancers and there is concrete evidence that the deregulated expression of BCL2 like proteins plays a vital role in tumor development, persistence and therapeutic resistance. Therefore, it is important to identify the polymorphisms of BCL2 that are both structurally and functionally important for research to find their possible malfunctions and therapeutics. For this reason, in our research, we have used a variety of bioinformatics tools to recognize the most destructive nsSNPs that may be important for the structure and function of BCL2. In silico tools, PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 included a variety of other tools such as I Mutant, MutPred, and ConSurf, to study their conservation profiles to validate their stability, structural, and functional impacts. Post-transcriptional alteration sites were also predicted followed by application of 3-D mapping with I-TASSER and Phyre2 tools. Furthermore, the gene interactions were mapped via STRING and GeneMANIA. We also found that nsSNPs Q118R (rs759928495), G193R (rs1197820694), R129C (rs777784952), and Ll81V (rs752310933) are the most destructive nsSNPs in BCL2 genes that can have a vital part in BCL2 protein defects and possibly cause different cancers. Gene-gene interactions showed relation of BCL2 with other genes depicting its importance in several pathways and co-expressions. This research is the first of its kind and offers future prospects for the development of dedicated medicines as well. In the animal models, the effects of BCL2 can also be tested in diseases. Such should be the study of BCL2 proteins from cancer patients. The effects of BCL2 can also be tested on animal models.

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In-silico analysis of BCL2 gene using multiple bioinformatics tools to identify the most lethal mutations that are crucial for its structural and functional integrity

10.21203/rs.3.rs-310735/v3 ◽

2021 ◽

Author(s):

Usman Ghani ◽

Yasir Ali ◽

Karim Gul ◽

Abbas Khan ◽

Aamir sohail ◽

...

Keyword(s):

Animal Models ◽

In Silico ◽

Tumor Development ◽

In Silico Analysis ◽

Vital Role ◽

Gene Interactions ◽

Bioinformatics Tools ◽

Apoptotic Activity ◽

And Function ◽

Related Proteins

Abstract BCL2 was the first ever known gene for anti-apoptotic activity, that encodes for essential proteins of the external mitochondrial membrane. Regarding tumorigenesis, deregulated BCL2 expression and related proteins have been recognized as characteristic of several human cancers and there is concrete evidence that the deregulated expression of BCL2 like proteins plays a vital role in tumor development, persistence and therapeutic resistance. Therefore, it is important to identify the polymorphisms of BCL2 that are both structurally and functionally important for research to find their possible malfunctions and therapeutics. For this reason, in our research, we have used a variety of bioinformatics tools to recognize the most destructive nsSNPs that may be important for the structure and function of BCL2. In silico tools, PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 included a variety of other tools such as I Mutant, MutPred, and ConSurf, to study their conservation profiles to validate their stability, structural, and functional impacts. Post-transcriptional alteration sites were also predicted followed by application of 3-D mapping with I-TASSER and Phyre2 tools. Furthermore, the gene interactions were mapped via STRING and GeneMANIA. We also found that nsSNPs Q118R (rs759928495), G193R (rs1197820694), R129C (rs777784952), and Ll81V (rs752310933) are the most destructive nsSNPs in BCL2 genes that can have a vital part in BCL2 protein defects and possibly cause different cancers. Gene-gene interactions showed relation of BCL2 with other genes depicting its importance in several pathways and co-expressions. This research is the first of its kind and offers future prospects for the development of dedicated medicines as well. In the animal models, the effects of BCL2 can also be tested in diseases. Such should be the study of BCL2 proteins from cancer patients. The effects of BCL2 can also be tested on animal models.

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In-silico analysis of BCL2 gene using multiple bioinformatics tools to identify the most lethal mutations that are crucial for its structural and functional integrity

10.21203/rs.3.rs-310735/v1 ◽

2021 ◽

Author(s):

Usman Ghani ◽

Yasir Ali ◽

Karim Gul ◽

Rahmat Ullah ◽

Abbas Khan ◽

...

Keyword(s):

Animal Models ◽

In Silico ◽

Tumor Development ◽

In Silico Analysis ◽

Vital Role ◽

Gene Interactions ◽

Bioinformatics Tools ◽

Apoptotic Activity ◽

And Function ◽

Related Proteins

Abstract BCL2 was the first ever known gene for anti-apoptotic activity, that encodes for essential proteins of the external mitochondrial membrane. Regarding tumorigenesis, deregulated BCL2 expression and related proteins have been recognized as characteristic of several human cancers and there is concrete evidence that the deregulated expression of BCL2 like proteins plays a vital role in tumor development, persistence and therapeutic resistance. Therefore, it is important to identify the polymorphisms of BCL2 that are both structurally and functionally important for research to find their possible malfunctions and therapeutics. For this reason, in our research, we have used a variety of bioinformatics tools to recognize the most destructive nsSNPs that may be important for the structure and function of BCL2. In silico tools, PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 included a variety of other tools such as I Mutant, MutPred, and ConSurf, to study their conservation profiles to validate their stability, structural, and functional impacts. Post-transcriptional alteration sites were also predicted followed by application of 3-D mapping with I-TASSER and Phyre2 tools. Furthermore, the gene interactions were mapped via STRING and GeneMANIA. We also found that nsSNPs Q118R (rs759928495), G193R (rs1197820694), R129C (rs777784952), and Ll81V (rs752310933) are the most destructive nsSNPs in BCL2 genes that can have a vital part in BCL2 protein defects and possibly cause different cancers. Gene-gene interactions showed relation of BCL2 with other genes depicting its importance in several pathways and co-expressions. This research is the first of its kind and offers future prospects for the development of dedicated medicines as well. In the animal models, the effects of BCL2 can also be tested in diseases. Such should be the study of BCL2 proteins from cancer patients. The effects of BCL2 can also be tested on animal models.

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

10.1101/786301 ◽

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.

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In silico analysis ofIDH3Agene revealed Novel mutations associated with Retinitis Pigmentosa

10.1101/554196 ◽

2019 ◽

Author(s):

Thwayba A. Mahmoud ◽

Abdelrahman H. Abdelmoneim ◽

Naseem S. Murshed ◽

Zainab O. Mohammed ◽

Dina T. Ahmed ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

In Silico ◽

In Silico Analysis ◽

Photoreceptor Cells ◽

Structure And Function ◽

Novel Mutations ◽

Inherited Disorders ◽

Bioinformatics Tools ◽

And Function ◽

Silico Analysis

AbstractBackgroundRetinitis Pigmentosa (RP) refers to a group of inherited disorders characterized by the death of photoreceptor cells leading to blindness. The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein.Methodwe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein.Result20 deleterious SNPs out of 178 were found to have a damaging effect on the protein structure and function.Conclusionthis is the first in silico analysis of IDH3A gene and 20 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for Retinitis Pigmentosa.

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In Silico Analysis and Modeling of Novel Pathogenic Single Nucleotide Polymorphisms (SNPs) in Human CD40LG Gene

10.1101/552596 ◽

2019 ◽

Cited By ~ 1

Author(s):

Abdelrahman H. Abdelmoneim ◽

Mujahed I. Mustafa ◽

Thwayba A. Mahmoud ◽

Naseem S. Murshed ◽

Mohamed A. Hassan

Keyword(s):

In Silico ◽

Elevated Serum ◽

In Silico Analysis ◽

Structure And Function ◽

Immunoglobulin M ◽

Hyper Igm Syndrome ◽

Bioinformatics Tools ◽

Hyper Igm ◽

And Function ◽

Silico Analysis

Abstract:Background:The X-linked hyper-immunoglobulin M syndrome (XHIGM) is a rare, inherited immune deficiency disorder. It is more common in males. Characterized by elevated serum IgM levels and low to undetectable levels of serum IgG, IgA and IgE. Hyper-IgM syndrome is caused by mutations in the CD40LG gene. Located in human Xq26. CD40LG acts as an immune modulator in activated T cells.Method:We used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein.Result:8 novel SNPs out of 233 were found to have most deleterious effect on the protein structure and function. While modeling of nsSNPs was studied by Project HOPE software.Conclusion:Better understanding of Hyper-IgM syndrome caused by mutations in CD40LG gene was achieved using in silico analysis. This is the first in silico functional analysis of CD40LG gene and 8 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for hyper-IgM syndrome. These 8 novel SNPs may be important candidates for the cause of different types of human diseases by CD40LG gene.

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Novel deleterious nsSNPs within MEFV gene that could be used as Diagnostic Markers to Predict Hereditary Familial Mediterranean Fever: Using bioinformatics analysis

10.1101/424796 ◽

2018 ◽

Author(s):

Mujahed I. Mustafa ◽

Tebyan A Abdelhameed ◽

Fatima A. Abdelrhman ◽

Soada Ahmed Osman ◽

Mohamed A. Hassan

Keyword(s):

Familial Mediterranean Fever ◽

In Silico ◽

Mediterranean Basin ◽

Mefv Gene ◽

Structure And Function ◽

Diagnostic Markers ◽

Novel Mutations ◽

Bioinformatics Tools ◽

Mediterranean Fever ◽

And Function

AbstractBackgroundFamilial Mediterranean Fever (FMF) is the most common auto inflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin, we aimed to identify the pathogenic SNPs in MEFV by computational analysis software.MethodsWe carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function.Result23 novel mutations out of 857 nsSNPs that are found to be deleterious effect on the MEFV structure and function.ConclusionThis is the first in silico analysis in MEFV gene to prioritize SNPs for further genetic mapping studies. After using multiple bioinformatics tools to compare and rely on the results predicted, we found 23 novel mutations that may cause FMF disease and it could be used as diagnostic markers for Mediterranean basin populations.

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In silico analysis of squalene synthase in Fabaceae family using bioinformatics tools

Journal of Genetic Engineering and Biotechnology ◽

10.1016/j.jgeb.2018.06.001 ◽

2018 ◽

Vol 16 (2) ◽

pp. 739-747 ◽

Cited By ~ 3

Author(s):

Zahra Aminfar ◽

Masoud Tohidfar

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Squalene Synthase ◽

Bioinformatics Tools ◽

Silico Analysis

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

10.1101/729764 ◽

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.

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

10.1101/436071 ◽

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.

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