scholarly journals In silico prediction of deleterious single nucleotide polymorphism in human AKR1C3 gene and identification of potent inhibitors using molecular docking approach

2021 ◽  
pp. 101514
Author(s):  
Saleh Abdullah Aloyuni
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Molecular Docking ◽  
In Silico ◽  
In Silico Prediction ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Docking Approach

Analysis in silico of the single nucleotide polymorphism G–152A in the promoter of the angiotensinogen gene of Indonesian patients with essential hypertension

2018 ◽  
Vol 12 (1) ◽  
pp. 15-25
Author(s):  
Akhiyan Hadi Susanto ◽  
Widodo ◽  
Mohammad Saifur Rohman ◽  
Didik Huswo Utomo ◽  
Mifetika Lukitasari
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Essential Hypertension ◽  
In Silico ◽  
Direct Sequencing ◽  
Hypoxia Inducible Factor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Hypoxia Inducible Factor 1 ◽  
Angiotensinogen Gene ◽  
Docking Approach

Abstract Background Single nucleotide polymorphism (SNP) G–152A (rs11568020) in the promoter of the angiotensinogen gene (AGT) may modulate its transcription. Translation of mRNA to angiotensinogen induces hypertension during hypoxia. The G allele at position –152 is located within the hypoxia-response element (HRE) transcription factor-binding site for the hypoxia-inducible factor 1 (HIF-1) heterodimer. However, the function of the –152 site in HIF-1 binding is not fully elucidated. Objectives To determine the frequency of SNP G–152A in Indonesian patients with hypertension and the function of this SNP. Methods We determined the frequency of the SNP in 100 patients by direct sequencing, and the influence of SNP G–152A on predicted binding of HIF-1 to the HRE using a docking approach in silico. Results The AGT promoter in our patients had genetic variants –152G and –152A (19:1). Predicted binding indicated that HIF-1 directly contacts the major groove of the G allele, but not the A allele. Scoring according to weighted sum High Ambiguity Driven biomolecular DOCKing showed that the score for the A allele–HIF-1 complex (–47.1 ± 6.9 kcal/mol) was higher than that for the G allele–HIF-1 complex (–94.6 ± 14.1 kcal/mol), indicating more favorable binding of HIF-1 to the G allele. Conclusions SNP G–152A reduces the favorability of binding of HIF-1 to the HRE. The occurrence of this SNP in the AGT promoter of Indonesian patients with essential hypertension suggests that the G allele is a genetic susceptibility factor in hypertension regulated by HIF-1.

In silico analysis of non-synonymous single nucleotide polymorphism in a human KLK-2 gene associated with prostate cancer

Meta Gene ◽  
2019 ◽  
Vol 21 ◽  
pp. 100578
Author(s):  
Tooba Yousefi ◽  
Seyed Mostafa Mir ◽  
Jahanbakhsh Asadi ◽  
Mehdi Tourani ◽  
Ansar Karimian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Nucleotide Polymorphism ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Silico Analysis

Molekulare Blutgruppenbestimmung

2017 ◽  
Vol 7 (02) ◽  
pp. 87-94
Author(s):  
Christoph Gassner
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Next Generation Sequencing ◽  
Blood Transfusion ◽  
International Society ◽  
In Silico ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Molekulare Analyse ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

ZusammenfassungDie erste molekulare Analyse einer menschlichen Blutgruppe erfolgte 1983 mittels eines Restriktions-Fragment-Längen-Polymorphismus (RFLP) am System Xg. Seither wurden in unzähligen Studien die molekularen Ursachen für Blutgruppen und deren Antigene erforscht,und das resultierende Wissen für eine ständige Verbesserung der entsprechenden Analysemethoden verwendet. Die Untersuchung kausaler Punktmutationen (Single Nucleotide Polymorphism, SNP) aller 36 von der International Society for Blood Transfusion (ISBT) anerkannten Blutgruppensysteme erlaubt heute eine der Serologie ebenbürtige, exakte Vorhersage der Blutgruppenantigene. In Patienten wird die molekulare Blutgruppenbestimmung bevorzugt in Form von Einzelprobenanalytik für die Diagnose von RhD-Varianten eingesetzt, um damit transfusionsrelevante Entscheidungen bezüglich RhD zu treffen und um die Rh-Prophylaxe noch zielsicherer zu steuern. An Spenderproben und im Hochdurchsatz ermöglicht die Blutgruppen-Genotypisierung die Schaffung einer ausreichenden Anzahl von Spender-Datensätzen, um immunisierte Patienten bestverträglich zu transfundieren oder deren Immunisierung bereits im Ansatz zu vermeiden. Gleichzeitig werden heutzutage an den gleichen Proben zusätzlich eine Vielzahl weiterer SNPs zur Identifikation von Spendern mit seltener Negativität für hochfrequente Antigene getestet. Derartig umfassende Spender-Datensätze werden bereits ideal genutzt für „In-silico-Kreuzproben“ eingesetzt. Next Generation Sequencing (NGS) ist auch in der Transfusionsmedizin der „neue Stern am Horizont“ und wird vermutlich innert weniger Jahre eine wichtige Rolle in der Analyse kompletter Blutgruppengenome (chronischer) Empfänger spielen. Blutgruppenbestimmung als frühestes Beispiel echter personalisierter Medizin wird in ihrer molekularen Version mit dazu beitragen, den gebührenden Platz der Transfusionsmedizin in der modernen Medizin zu behaupten.

scholarly journals Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse

PLoS Biology ◽  
2004 ◽  
Vol 2 (12) ◽  
pp. e393 ◽  
Author(s):  
Mathew T Pletcher ◽  
Philip McClurg ◽  
Serge Batalov ◽  
Andrew I Su ◽  
S. Whitney Barnes ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
In Silico ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
In Silico Mapping ◽  
Dense Single Nucleotide Polymorphism

scholarly journals Identification of Deleterious Single Nucleotide Polymorphism (SNP)s in the Human TBX5 Gene & Prediction of Their Structural & Functional Consequences: An In Silico approach

2020 ◽  
Author(s):  
A M U B Mahfuz ◽  
Md. Arif Khan
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Transcription Factor ◽  
In Silico ◽  
Developmental Process ◽  
Upper Limbs ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Functional Consequences ◽  
Tbx5 Gene

ABSTRACTT-box transcription factor 5 (TBX5) gene encodes the transcription factor TBX5 which plays a crucial role in the development of the heart and upper limbs. Alternative splicing resulting in several isoforms regulate the functions of this gene during the developmental process. Damaging single nucleotide variants in this gene alter the structure and disturb the functions of TBX5 and ultimately cause Holt-Oram Syndrome (HOS), an autosomal dominant disease where various congenital malformations of the heart (with or without conduction defects), upper limbs and shoulder girdles are observed. Besides HOS, TBX5 single nucleotide variants can also be associated with Dilated Cardiomyopathy, Atrial Fibrillation, and Tetralogy of Fallot without skeletal deformity.By exploiting available Single Nucleotide Polymorphism information in dbSNP, this study was designed to identify in silico the deleterious TBX5 SNPs, and predict their structural and functional consequences, and alteration of biochemical properties on the candidate protein. For this purpose, various reliable in silico analysis tools such as PROVEAN, SIFT, PolyPhen-2, MutPred2, PredictSNP1, PredictSNP2, MetaLR, MetaSVM, REVEL, ConSurf, NetsurfP-2.0, iStable 2.0, Missense3D, UTRdb, MirSNP, and Human Splicing Finder (HSF) have been used. 58 missense substitutions were found damaging by both sequence homology-based tools SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer), and structure homology-based tool PolyPhen-2 (Polymorphism Phenotyping-2). Among these 58 substitutions, 13 are already annotated as Pathogenic/Likely Pathogenic in ClinVar database, and so they were excluded. Then, the rest 45 high confidence substitutions were further scrutinized by various disease association predicting meta servers. Next, conservation profile of the native amino acid residues, their surface & solvent accessibility, and stability and structural integrity of the protein upon mutation were assessed. Analysis of 1 stop loss SNP, and 2 nonsense SNPs were done by PredictSNP2. Analysis of SNPs in the UTR region were done using UTRdb and MirSNP, and splice site SNPs were evaluated by Human Splicing Finder (HSF). This study provides a comprehensive list of most deleterious SNPs onTBX5 gene. The results from this study can help in early diagnosis of HOS and in relevant genetic counseling.

scholarly journals Analisis Bioinformatika Gen Cat (Homo sapiens): Penyandi Enzim Antioksidan Katalase dan Mutasi C330T pada Diabetes Melitus Tipe 1

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
Linda Weni
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Open Source ◽  
In Silico ◽  
Homo Sapiens ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Diabetes Melitus

Katalase (EC 1.11.16) adalah merupakan enzim antioksidan yang bertindak sebagai biokatalisator dengan mengubah H2O2 menjadi H2O dan O2. Enzim ini berperan penting dalam meregulasi metabolisme H2O2. Hidrogen peroksida adalah merupakan sebuah molekul kecil hasil samping dari metabolisme. Kelebihan H2O2 akibat defisiensi Katalase, menyebabkan kerusakan yang signifikan pada protein, DNA, RNA dan lipid sehingga hal ini juga berperan pada patogenesis berbagai penyakit, termasuk diabetes. Dalam studi in silico ini, perubahan yang terjadi pada mutasi SNP (single nucleotide polymorphism) C (330) T (rs 10011179) dari gen CAT akan diselidiki, termasuk hubungannya dengan risiko peningkatan resiko diabetes. Untuk itu dilakukan pencarian bioinformasi, diantaranya informasi tentang gen, protein dan penelusuran informasi penting lainnya yang dapat digunakan sebagai informasi pendukung penelitian. Analisis bioinformatika gen CAT dilakukan dengan menggunakan beberapa program open source dari situs web. Pada penelitian ini ternyata terjadi mutasi misssense SNP Ala110Val (C330T, rs1001179) yang ditemukan pada struktur 3D CAT pada urutan asam amino ke-110 (C330T) yang mengganggu fungsi amidasi protein CAT. Mutasi ini menyebabkan berkurangnya ekspresi gen CAT, yang berakibat pada berkurangnya aktivitas CAT sebagai biokatalis dan sebagai enzim antioksidan. Hal ini terkait dengan peningkatan risiko diabetes tipe 1.

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