Thirty five novel nsSNPs may effect on ADAMTS13 protein leading to Thrombotic thrombocytopenic purpura (TTP) using bioinformatics approach

ABSTRACTBackgroundGenetic polymorphisms in the ADAMTS13 gene are associated with thrombotic thrombocytopenic purpura or TTP, a life-threatening microangiopathic disorder. This study aims to predict the possible pathogenic SNPs of this gene and their impact on the protein structure and function using insilico methods.MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms applied collectively to predictthe effect of single nucleotide substitution on both structure and function of the ADAMTS13 protein.ResultsFifty one mutations were found to be highly damaging to the structure and function of the protein. Of those, thirty five were novel nsSNPs not previously reported in the literature.ConclusionAccording to our analysis we found thirty five nsSNPs effects on ADAMTS13 protein leading to thrombotic thrombocytopenic purpura using computational approach. Bioinformatics tools are vital in prediction analysis, making use of increasingly voluminous biomedical data thereby providing markers for screening or for genetic mapping studies.

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Thirty two novel nsSNPs May effect on HEXA protein Leading to Tay-Sachs disease (TSD) Using a Computational Approach

10.1101/762518 ◽

2019 ◽

Author(s):

Tebyan A. Abdelhameed ◽

Mohamed Mustafa Osman Fadul ◽

Dina Nasereldin Abdelrahman Mohamed ◽

Amal Mohamed Mudawi ◽

Sayaf Kamal Khalifa Fadul Allah ◽

...

Keyword(s):

Nucleotide Substitution ◽

Neurodegenerative Disorder ◽

Structure And Function ◽

Single Nucleotide Substitution ◽

Single Nucleotide ◽

Bioinformatics Tools ◽

Tay Sachs Disease ◽

Hexosaminidase A ◽

And Function

ABSTRACTBackgroundGenetic polymorphisms in the HEXA gene are associated with a neurodegenerative disorder called Tay-Sachs disease (TSD) (GM2 gangliosidosis type 1). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools.MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of the hexosaminidase A protein.ResultsFifty nine mutations were found to be highly damaging to the structure and function of the HEXA gene protein.ConclusionAccording to this study, thirty two novel nsSNP in HEXA are predicted to have possible role in Tay-Saches Disease using different bioinformatics tools. Our findings could help in genetic study and diagnosis of Tay-Saches Disease.

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Insilico Analysis Reveal Three novel nsSNPs May effect on GM2A protein Leading to AB variant of GM2 gangliosidosis

10.1101/853085 ◽

2019 ◽

Author(s):

Tebyan A. Abdelhameed ◽

Mujahed I. Mustafa ◽

Dina N. Abdelrahman ◽

Fatima A. Abdelrhman ◽

Mohamed A. Hassan

Keyword(s):

Binding Sites ◽

Nucleotide Substitution ◽

Neurodegenerative Disorder ◽

Structure And Function ◽

Gm2 Gangliosidosis ◽

Novel Mutations ◽

Single Nucleotide ◽

Bioinformatics Tools ◽

Gm2 Activator ◽

And Function

ABSTRACTBackgroundAB variant of GM2 gangliosidosis caused as a result of mutations in GM2 activator gene (GM2A) which is regarded as neurodegenerative disorder. This study aimed to predict the possible damaging SNPs of this gene and their impact on the protein using different bioinformatics tools.MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different tools collectively predicted the effect of single nucleotide substitution on both structure and function of GM2 activator.ResultsThree novel mutations were found to be highly damaging to the structure and function of the GM2A gene.ConclusionFour SNPs were found to be highly damaging SNPs that affect function, structure and stability of GM2A protein, which they are: C99Y, C112F, C138S and C138R, three of them are novel SNPs (C99Y, C112F and C138S). Also 46 SNPs were predicted to affect miRNAs binding sites on 3’UTR leading to abnormal expression of the resulting protein. These SNPs should be considered as important candidates in causing AB variant of GM2 gangliosidosis and may help in diagnosis and genetic screening of the disease.

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Comprehensive Analysis of HEXB Protein Reveal Forty Two Novel nsSNPs That May Lead to Sandhoff disease (SD) Using Bioinformatics

10.1101/853077 ◽

2019 ◽

Author(s):

Tebyan A. Abdelhameed ◽

Mosab M. Gasmelseed ◽

Mujahed I. Mustafa ◽

Dina N. Abdelrahman ◽

Fatima A. Abdelrhman ◽

...

Keyword(s):

Neurodegenerative Disorder ◽

Sandhoff Disease ◽

Structure And Function ◽

Beta Subunit ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Bioinformatics Tools ◽

Hexosaminidase A ◽

And Function ◽

Hexb Gene

ABSTRACTBackgroundSingle Nucleotide Polymorphisms (SNPs) in the HEXB gene are associated with a neurodegenerative disorder called Sandhoff disease (SD) (GM2 gangliosidosis-O variant). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools.MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of beta subunit beta subunit of both hexosaminidase A and hexosaminidase B proteins.ResultsForty nine mutations were found to be extremely damaging to the structure and function of the HEXB gene protein.ConclusionAccording to this study, forty two novel nsSNP in HEXB are predicted to have possible role in Sandhoff disease using different bioinformatics tools, beside two SNPs found to have effect on miRNAs binding site affecting expression of HEXB gene. Our findings may assist in genetic study and diagnosis of Sandhoff disease.

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A single nucleotide substitution in the coding region of Ogura male sterile gene, orf138, determines effectiveness of a fertility restorer gene, Rfo, in radish

Molecular Genetics and Genomics ◽

10.1007/s00438-021-01777-y ◽

2021 ◽

Author(s):

Hiroshi Yamagishi ◽

Megumi Jikuya ◽

Kanako Okushiro ◽

Ayako Hashimoto ◽

Asumi Fukunaga ◽

...

Keyword(s):

Male Sterility ◽

Nucleotide Substitution ◽

Fertility Restoration ◽

Type A ◽

Restorer Gene ◽

Single Nucleotide Substitution ◽

Coding Region ◽

Fertility Restorer ◽

Single Nucleotide ◽

Fertility Restorer Gene

AbstractCytoplasmic male sterility (CMS) observed in many plants leads defect in the production of functional pollen, while the expression of CMS is suppressed by a fertility restorer gene in the nuclear genome. Ogura CMS of radish is induced by a mitochondrial orf138, and a fertility restorer gene, Rfo, encodes a P-type PPR protein, ORF687, acting at the translational level. But, the exact function of ORF687 is still unclear. We found a Japanese variety showing male sterility even in the presence of Rfo. We examined the pollen fertility, Rfo expression, and orf138 mRNA in progenies of this variety. The progeny with Type H orf138 and Rfo showed male sterility when their orf138 mRNA was unprocessed within the coding region. By contrast, all progeny with Type A orf138 were fertile though orf138 mRNA remained unprocessed in the coding region, demonstrating that ORF687 functions on Type A but not on Type H. In silico analysis suggested a specific binding site of ORF687 in the coding region, not the 5′ untranslated region estimated previously, of Type A. A single nucleotide substitution in the putative binding site diminishes affinity of ORF687 in Type H and is most likely the cause of the ineffectiveness of ORF687. Furthermore, fertility restoration by RNA processing at a novel site in some progeny plants indicated a new and the third fertility restorer gene, Rfs, for orf138. This study clarified that direct ORF687 binding to the coding region of orf138 is essential for fertility restoration by Rfo.

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