scholarly journals The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Katayoun Heshmatzad ◽  
Nejat Mahdieh ◽  
Ali Rabbani ◽  
Abdolah Didban ◽  
Bahareh Rabbani
Keyword(s):  
In Silico ◽  
Clinical Symptoms ◽  
Genetic Disorder ◽  
Pcr Amplification ◽  
In Silico Analysis ◽  
Genetic Studies ◽  
Novel Variants ◽  
Comprehensive Search ◽  
Glucocorticoid Deficiency ◽  
Pathogenic Analysis

Familial glucocorticoid deficiency is a rare autosomal recessive genetic disorder which belongs to a group of primary adrenal insufficiency (PAI) and is mainly caused by mutations in the MC2R and MRAP genes. A comprehensive search was conducted to find the reported variants of MC2R and MRAP genes. In silico pathogenic analysis was performed for the reported variants. PCR amplification and sequencing were performed for three patients. Structural analysis, modeling, and interactome analysis were applied to characterize novel MC2R variants and their proteins. About 80% of MC2R-related cases showed the clinical symptoms which were diagnosed at <2 years old. 107 patients had MC2R mutations (85 homozygotes, 21 compound heterozygotes, and 1 simple heterozygote). 59 variants were found in the MC2R gene. Four mutations were responsible for half of patients. 39 homozygous patients had MRAP mutations; 14 variants were determined in the MRAP gene. Nine proteins were predicted by STRING to associate with the studied proteins. Two novel MC2R variants, c.128T > G (p.Leu43Arg) and c.251T > A (p.Ile84Asn), were found in two patients at the age of above and below 2 years, respectively. Mutations in MC2R and MRAP genes are the main cause of FGD. Genetic studies and in silico analysis will help to confirm the diagnosis.

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 Two novel variants in DYRK1B causative of AOMS3: expanding the clinical spectrum

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elvia C. Mendoza-Caamal ◽  
Francisco Barajas-Olmos ◽  
Elaheh Mirzaeicheshmeh ◽  
Ian Ilizaliturri-Flores ◽  
Carlos A. Aguilar-Salinas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Protein Function ◽  
In Silico ◽  
Metabolic Diseases ◽  
In Silico Analysis ◽  
Diagnostic Strategies ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Silico Analysis

Abstract Background We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. Results After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. Conclusions Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

scholarly journals Metabolism of Daidzein and Genistein by Gut Bacteria of the Class Coriobacteriia

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2741
Author(s):  
Sebastian Tobias Soukup ◽  
Dominic Alexander Stoll ◽  
Nicolas Danylec ◽  
Alena Schoepf ◽  
Sabine Emma Kulling ◽  
...  
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Pcr Amplification ◽  
Protein Sequences ◽  
In Silico Analysis ◽  
Gut Bacteria ◽  
Strictly Anaerobic ◽  
Bacterial Strains ◽  
Related Family ◽  
Pure Bacterial Cultures

The intake of isoflavones is presumed to be associated with health benefits in humans, but also potential adverse effects of isoflavones are controversially discussed. Isoflavones can be metabolized by gut bacteria leading to modulation of the bioactivity, such as estrogenic effects. Especially bacterial strains of the Eggerthellaceae, a well-known bacterial family of the human gut microbiota, are able to convert the isoflavone daidzein into equol. In addition, metabolization of genistein is also described for strains of the Eggerthellaceae. The aim of this study was to identify and investigate gut bacterial strains of the family Eggerthellaceae as well as the narrowly related family Coriobacteriaceae which are able to metabolize daidzein and genistein. This study provides a comprehensive, polyphasic approach comprising in silico analysis of the equol gene cluster, detection of genes associated with the daidzein, and genistein metabolism via PCR and fermentation of these isoflavones. The in silico search for protein sequences that are associated with daidzein metabolism identified sequences with high similarity values in already well-known equol-producing strains. Furthermore, protein sequences that are presumed to be associated with daidzein and genistein metabolism were detected in the two type strains ‘Hugonella massiliensis’ and Senegalimassilia faecalis which were not yet described to metabolize these isoflavones. An alignment of these protein sequences showed that the equol gene cluster is highly conserved. In addition, PCR amplification supported the presence of genes associated with daidzein and genistein metabolism. Furthermore, the metabolism of daidzein and genistein was investigated in fermentations of pure bacterial cultures under strictly anaerobic conditions and proofed the metabolism of daidzein and genistein by the strains ‘Hugonella massiliensis’ DSM 101782T and Senegalimassilia faecalis KGMB04484T.

Abstract 489: Identification And In-silico Analysis Of Pathogenic Non-synonymous Snps Of Human Sos1 Protein In Noonan Syndrome

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Vinoth Sigamani ◽  
SHEEJA RAJASINGH ◽  
Narasimman Gurusamy ◽  
Shivaani Kirankumar ◽  
Jayavardini Vasanthan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Noonan Syndrome ◽  
In Silico ◽  
Genetic Disorder ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Post Translational Modification ◽  
Single Nucleotide ◽  
Skeletal Malformation ◽  
Structural And Functional Properties

Introduction: Noonan syndrome is a genetic disorder (autosomal dominant) characterized by short stature, congenital heart disease, bleeding problems, developmental delays, and skeletal malformation. It is mainly caused by a single nucleotide alteration in four genes PTPN11, SOS1, RAF1, and KRAS . In this study, we computationally analyzed the SOS1 gene to identify the pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs), which is known to cause Noonan syndrome. Hypothesis: We hypothesize that in-silico analysis of human SOS1 mutations in Noonan syndrome would be a promising predictor to study the post-translational modifications. Methods and Results: The variant information of SOS1 was collected from the dbSNP database and the literature review on Noonan syndrome. They were further analyzed by in-silico tools such as I-Mutant, iPTREE-STAB, and MutPred for their structural and functional properties. We found that 11 nsSNPs are more pathogenic for Noonan syndrome. The 3D comparative protein of 11 nsSNPs with its wild-type SOS1 was modeled by using I-Tasser and validated via ERRAT and RAMPAGE. The protein-protein interactions of SOS1, GATA4, TNNT2, and ACTN2 were analyzed using STRING, which showed that HRAS was intermediate between SOS1 and ACTN2 (Fig. 1) . Conclusion: This is the first in-silico study of the SOS1 variant with Noonan syndrome. We proposed that this 11 nsSNPs are the most pathogenic variant of SOS1 , which helps to screen the Noonan patient. Furthermore, our results are promising to study the gain/loss of post-translational modification (PTM) by mutation in cardiac genes and helps to explore the novel molecular pathways.$graphic_{DB5B0E7D-4DA6-4569-A16F-E05B2C9C4D2F}$$

HPV16 E6 variants: Frequency, association with HPV types and in silico analysis of the identified novel variants

2014 ◽  
Vol 86 (6) ◽  
pp. 968-974 ◽  
Author(s):  
Priyanka S. Gokhale ◽  
Archana Sonawani ◽  
Susan Idicula-Thomas ◽  
Shilpa Kerkar ◽  
Hemant Tongaonkar ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Hpv16 E6 ◽  
Novel Variants ◽  
Hpv Types ◽  
Silico Analysis

Geographical, Molecular, and Computational Analysis of Migraine-Causing Genes

2021 ◽  
Vol 20 (04) ◽  
pp. 391-403
Author(s):  
Muhammad Naveed ◽  
Bakhtawar Bukhari ◽  
Nadia Afzal ◽  
Haleema Sadia ◽  
Bisma Meer ◽  
...  
Keyword(s):  
In Silico ◽  
Computational Analysis ◽  
Pcr Amplification ◽  
In Silico Analysis ◽  
Bivariate Analysis ◽  
Headache Disorders ◽  
Gender And Age ◽  
Migraine Pathophysiology ◽  
Silico Analysis

Migraine is a re-occurring type of headache and causes moderate-to-severe pain that is troubling or pulsing. The pain occurs in half of the head, and common symptoms are photophobia, phonophobia, nausea, depression, anxiety, vomiting, etc. This study evaluates the prevalence of migraine and responsible genes through molecular modeling in the region of Bahawalpur, Pakistan. This research was aimed to determine the prevalence of migraine-causing genes in the population of Bahawalpur and also to do molecular and in-silico analysis of migraine-causing gene as no similar research was conducted before. The disease was characterized and diagnosed under the criteria of the Second Edition of the International Classification of Headache Disorders and molecular identification of migraine-causing genes, i.e. GRIA1, GRIA3, and ESR1, by PCR amplification. The total number of samples collected for migraine patients was 230, out of which 30 were positive for PCR amplification of the genes GRIA1, GRIA3, and ESR1. Therapeutic potentials of commercial drugs, namely Cyclobenzaprine, Divalproex, Ergotamine, and Sumatriptan, were analyzed in silico through molecular docking. Ergotamine demonstrated the highest binding affinity of [Formula: see text]8.4 kcal/mol for the target molecule and, hence, the highest potential. The bivariate analysis showed that the prevalence of migraine concerning gender and age was significantly correlated ([Formula: see text], [Formula: see text]). It was observed that almost 31.4% of women suffered from headaches daily, 70% weekly, 28.1% monthly, and 23.5% rarely. Comparatively, only 8.3% of males suffered from daily headaches, 34% weekly, 12.8% monthly, and 14.9% rarely. The study shows promising results and encourages future researchers to conduct such a comprehensive epidemiological study on an even larger population to justify a more precise association of risk factors involved in migraine pathophysiology.

scholarly journals Incomplete Segregation of MSH6 Frameshift Variants with Phenotype of Lynch Syndrome

2017 ◽  
Author(s):  
Raffaella Liccardo ◽  
Marina De Rosa ◽  
Giovanni Battista Rossi ◽  
Nicola Carlomagno ◽  
Paola Izzo ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
In Silico ◽  
Stop Codon ◽  
Direct Sequencing ◽  
Premature Stop Codon ◽  
In Silico Analysis ◽  
Frameshift Deletion ◽  
The Family ◽  
Novel Variants ◽  
Repair Genes

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma

2020 ◽  
Vol 47 (6) ◽  
pp. 398-408
Author(s):  
Sonam Tulsyan ◽  
Showket Hussain ◽  
Balraj Mittal ◽  
Sundeep Singh Saluja ◽  
Pranay Tanwar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gallbladder Carcinoma ◽  
In Silico ◽  
In Silico Analysis ◽  
Transcriptomic Profile ◽  
Silico Analysis
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