This document outlines a presentation on interferon gamma (IFNG) structure, gene, function, and mutations/polymorphisms. It includes an introduction and outline, sections on interferon classification, IFNG structure and gene, function, and material/methods for analyzing single nucleotide polymorphisms (SNPs) in the IFNG gene. The results section screens SNPs using prediction tools and analyzes potentially deleterious SNPs, disease association, protein stability effects, molecular modeling, and docking. The conclusion discusses findings and their implications for interpreting mutation impacts and assisting with strategies like drug design.
Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed
across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and
palate.
AGBT 2013: Home Brewed Personalized Genomics - The Quest for Meaningful Analy...Golden Helix Inc
Personalized genomics may be moving into a new era with whole-exome and whole-genome sequencing becoming affordable and available to consumers. 23andMe recently piloted a more affordable 80x exome to their existing customers. But it remains to be seen whether this wealth of raw genomic data can be analyzed to provide meaningful results for both healthy and symptomatic individuals.
By acquiring 23andMe exomes on his family, Gabe puts himself in the position of a bioinformatically inclined consumer, but non-clinician, to approach this question with his own analysis. His trio consists of a healthy father and son, and a mother with clinically-diagnosed idiopathic rheumatoid arthritis.
The following goals were set for the analysis: 1) How accurate are variant calls from direct-to-consumer NGS services? 2) How useful and durable is the list of risk variants provided by 23andMe? 3) Can a healthy individual's exome provide additional risk information over standard genotype-array-based risk prediction? and 4) Can the state of our current understanding of the complex genomic architecture of autoimmune diseases be enough to to find potential driver variants and genes to explain the diagnosis of a single case?
Here Gabe presents his findings of this analysis and discuss how individualized genomics might change in the world of affordable sequencing.
NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in genes that encode receptor subunits are associated with several intractable neurodevelopmental disorders, including developmental and epileptic encephalopathy (DEE). To extend understanding of these intractable childhood diseases, we have begun to model these variants in laboratory mice.
Models studied so far are a constitutive knockin for GRIN2A variant p.Ser644Gly (S644G) based on one case, and a GRIN2D variant, p.Val667Ile (V667I), noted in at least three unrelated cases. Homozygous and heterozygous Grin2a S644G mice exhibit altered hippocampal morphology at 2 weeks, and homozygotes exhibit lethal tonic-clonic seizures in week 3. Heterozygotes have a normal lifespan without spontaneous seizures, but display a variety of distinct features including
resistance to electrically induced limbic seizures, as well as hyperactivity and repetitive and reduced anxiety behaviors. Multielectrode recordings of mutant neuronal networks reveal hyperexcitability and altered bursting and synchronicity of both mutant genotypes. When expressed in heterologous cells, mutant receptors exhibit enhanced NMDAR agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. Consistent with this, NMDAR-mediated synaptic currents in hippocampal slices from mutant mice show a prolonged deactivation time course. Standard antiepileptic drug monotherapy was ineffective in the patient, but combined treatment of NMDAR antagonists with antiepileptic drugs substantially reduced the seizure burden albeit without appreciable developmental improvement. Chronic treatment of homozygous mutant mouse pups with NMDAR antagonists delayed the onset of lethal seizures but did not prevent them.
Grin2d V667I knockin mice are at an earlier stage of study. In contrast to Grin2a S644G, V667I heterozygous mice are severely impaired and suffer from lethal tonic-clonic seizures with an onset from about 18 days to 3 months. The impairment precludes natural mating such that the line needs to be propagated by ovary transplantation. Young heterozygotes adults in video-EEG also exhibit very frequent interictal epileptiform spiking and spike-wave discharge activity, resembling absence seizures. Preliminary histology shows significant pyknotic nuclei appearing to evidence
cell death in the cerebral cortex. Pup developmental milestones, while not evidencing significant developmental delay, show unusual features including excessive maternal separation induced pup vocalization. Further studies are ongoing. Together these efforts illustrate the power of modelling severe neurodevelopmental seizure disorders using multiple experimental modalities and suggest their utility in identifying and evaluating new therapies.
An increasing number of de novo missense variants have been identified in the GRIN family of genes encoding glutamate receptors, which play multiple roles in the central nervous system including mediation of a slow, calcium permeable component of synaptic transmission. This presentation will introduce the NMDA receptor family and summarize broadly what is known about the GRIN variants across multiple genes. The rationale underlying functional analysis both in vitro and in vivo will be presented, along with a snapshot of the procedures utilized by the Center for Functional Evaluation of Rare Variants. The terms “gain-of-function” and “loss-of-function” will be considered in the context of functional data, and specific data provided illustrating how these properties can vary with gene, location of the variant, and altered function among multiple properties of NMDA receptors.
Development of a Multi-Variant Frequency Ladder™ for Next Generation Sequenci...Thermo Fisher Scientific
Increasing adoption of NGS has shed light on the need for more
standardized controls to evaluate and optimize system performance.
Samples containing mutations of interest are difficult to source and cell
line pooling experiments to determine limit of detection require significant
investments of time and money. To simultaneously evaluate variant
calling performance in >200 unique amplicons across 50 genes targeted
by NGS tests, AcroMetrix® has developed a proprietary
genomic/synthetic DNA material containing over 550 mutations as a
mixture of SNV’s indels and MNP’s. The limit of detection was then
determined for >400 variants using multiple platforms. Tumor samples
were diluted with matched normal samples to mimic a range of
frequencies. Linearity between the material and diluted tumor tissue
samples were compared. Overall, highly multiplex controls with tunable
frequencies allow for much more extensive, yet streamlined, assay
evaluation and facilitate implementation and impart confidence to NGS
testing.
Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed
across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and
palate.
AGBT 2013: Home Brewed Personalized Genomics - The Quest for Meaningful Analy...Golden Helix Inc
Personalized genomics may be moving into a new era with whole-exome and whole-genome sequencing becoming affordable and available to consumers. 23andMe recently piloted a more affordable 80x exome to their existing customers. But it remains to be seen whether this wealth of raw genomic data can be analyzed to provide meaningful results for both healthy and symptomatic individuals.
By acquiring 23andMe exomes on his family, Gabe puts himself in the position of a bioinformatically inclined consumer, but non-clinician, to approach this question with his own analysis. His trio consists of a healthy father and son, and a mother with clinically-diagnosed idiopathic rheumatoid arthritis.
The following goals were set for the analysis: 1) How accurate are variant calls from direct-to-consumer NGS services? 2) How useful and durable is the list of risk variants provided by 23andMe? 3) Can a healthy individual's exome provide additional risk information over standard genotype-array-based risk prediction? and 4) Can the state of our current understanding of the complex genomic architecture of autoimmune diseases be enough to to find potential driver variants and genes to explain the diagnosis of a single case?
Here Gabe presents his findings of this analysis and discuss how individualized genomics might change in the world of affordable sequencing.
NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in genes that encode receptor subunits are associated with several intractable neurodevelopmental disorders, including developmental and epileptic encephalopathy (DEE). To extend understanding of these intractable childhood diseases, we have begun to model these variants in laboratory mice.
Models studied so far are a constitutive knockin for GRIN2A variant p.Ser644Gly (S644G) based on one case, and a GRIN2D variant, p.Val667Ile (V667I), noted in at least three unrelated cases. Homozygous and heterozygous Grin2a S644G mice exhibit altered hippocampal morphology at 2 weeks, and homozygotes exhibit lethal tonic-clonic seizures in week 3. Heterozygotes have a normal lifespan without spontaneous seizures, but display a variety of distinct features including
resistance to electrically induced limbic seizures, as well as hyperactivity and repetitive and reduced anxiety behaviors. Multielectrode recordings of mutant neuronal networks reveal hyperexcitability and altered bursting and synchronicity of both mutant genotypes. When expressed in heterologous cells, mutant receptors exhibit enhanced NMDAR agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. Consistent with this, NMDAR-mediated synaptic currents in hippocampal slices from mutant mice show a prolonged deactivation time course. Standard antiepileptic drug monotherapy was ineffective in the patient, but combined treatment of NMDAR antagonists with antiepileptic drugs substantially reduced the seizure burden albeit without appreciable developmental improvement. Chronic treatment of homozygous mutant mouse pups with NMDAR antagonists delayed the onset of lethal seizures but did not prevent them.
Grin2d V667I knockin mice are at an earlier stage of study. In contrast to Grin2a S644G, V667I heterozygous mice are severely impaired and suffer from lethal tonic-clonic seizures with an onset from about 18 days to 3 months. The impairment precludes natural mating such that the line needs to be propagated by ovary transplantation. Young heterozygotes adults in video-EEG also exhibit very frequent interictal epileptiform spiking and spike-wave discharge activity, resembling absence seizures. Preliminary histology shows significant pyknotic nuclei appearing to evidence
cell death in the cerebral cortex. Pup developmental milestones, while not evidencing significant developmental delay, show unusual features including excessive maternal separation induced pup vocalization. Further studies are ongoing. Together these efforts illustrate the power of modelling severe neurodevelopmental seizure disorders using multiple experimental modalities and suggest their utility in identifying and evaluating new therapies.
An increasing number of de novo missense variants have been identified in the GRIN family of genes encoding glutamate receptors, which play multiple roles in the central nervous system including mediation of a slow, calcium permeable component of synaptic transmission. This presentation will introduce the NMDA receptor family and summarize broadly what is known about the GRIN variants across multiple genes. The rationale underlying functional analysis both in vitro and in vivo will be presented, along with a snapshot of the procedures utilized by the Center for Functional Evaluation of Rare Variants. The terms “gain-of-function” and “loss-of-function” will be considered in the context of functional data, and specific data provided illustrating how these properties can vary with gene, location of the variant, and altered function among multiple properties of NMDA receptors.
Development of a Multi-Variant Frequency Ladder™ for Next Generation Sequenci...Thermo Fisher Scientific
Increasing adoption of NGS has shed light on the need for more
standardized controls to evaluate and optimize system performance.
Samples containing mutations of interest are difficult to source and cell
line pooling experiments to determine limit of detection require significant
investments of time and money. To simultaneously evaluate variant
calling performance in >200 unique amplicons across 50 genes targeted
by NGS tests, AcroMetrix® has developed a proprietary
genomic/synthetic DNA material containing over 550 mutations as a
mixture of SNV’s indels and MNP’s. The limit of detection was then
determined for >400 variants using multiple platforms. Tumor samples
were diluted with matched normal samples to mimic a range of
frequencies. Linearity between the material and diluted tumor tissue
samples were compared. Overall, highly multiplex controls with tunable
frequencies allow for much more extensive, yet streamlined, assay
evaluation and facilitate implementation and impart confidence to NGS
testing.
Genetic variation in GRIN genes encoding N-methyl-D-aspartate receptor (NMDAR) subunits has been associated with a spectrum of neurological and neuropsychiatric disorders. This talk will focus on clinical phenotype, functional consequences, and potential rescue pharmacology of disease-associated GRIN2D missense variants. The GRIN2D variants are located in the pre-M1 helix, agonist-binding domain, transmembrane domain M3, and the intracellular CTD. Developmental and epileptic encephalopathy (DEE) is the unifying phenotype across all 13 patients. The seizure types ranged from focal seizures, atypical absence seizures, tonic or atonic seizures, to epileptic spasms. Eight patients showed certain degree of hypotonia and movement disorders, three patients have autistic behavior and one patient showed symptoms of ADHD. Functional analysis in vitro on six novel GRIN2D variants reveals that that all six variants decreased receptor surface expression, which may underline certain shared clinical symptoms. Three variants (Leu670Phe, Ala675Thr, Ala678Asp) showed significantly enhanced agonist potency, and/or increased channel open probability, while the other three (Ser573Phe, Ser1271Phe, Arg1313Trp) presented reduced
sensitivity to endogenous protons and decreased channel open probability. Three variants (Ser573Phe, Ala675Thr, Ala678Asp) significantly decrease current amplitude. GluN2D-Leu670Phe
prolongs synaptic-like response time course and increases charge transfer. GluN2D-Ala678Asp transfection significantly reduced cell viability of cultured cortical neurons. In addition, a set of FDA-approved NMDAR channel blockers were evaluated for their ability to rescue functional changes of mutant receptors. This work suggests the importance of functional and biochemical validation for each individual variant. Rescue pharmacology in vitro may provide potential benefit of precision
medicine for a subset of severe pediatric neurodevelopmental diseases.
Nicholas Young, Sphingosine 1-phosphate Receptor Subtype Influence over Gliob...Nicholas Young
My talk presenting my thesis work per invitation of Research and Development Division of Genzyme Corporation to the Lipid Storage Disorders Department. October 5, 2007. Boston, MA: "Sphingosine 1-phosphate Receptor Subtype Influence over Glioblastoma Multiforme Pathology". My PhD was earned through the Integrated Biomedical Sciences, September 2007, The Ohio State University, College of Medicine Columbus, OH. Area of focus for my PhD: Biochemical and Molecular Disease Mechanisms. Dissertation title: Sphingosine 1-phosphate Receptor Subtype Influence Over Glioblastoma Multiforme Malignant Behavior"
Hello everyone, I am Dr. Ujwalkumar Trivedi, Head of Biotechnology Department at Marwadi University Rajkot. I teach Molecular Biology to the students of M.Sc. Microbiology and Biotechnology.
The current presentation describes various co-transcriptional and post-transcriptional RNA modifications in eukaryotic cells. The following processes are described in detail:
1. 5' mRNA Capping
2. Splicing
3. Alternative Splicing
4. 3' Polyadenylation
5. RNA Editing
Enjoy Reading.
Los días 20 y 21 de octubre de 2016, la Fundacion Ramón Areces organizó un simposio internacional para analizar las 'Enfermedades raras de la piel: de la clínica al gen y viceversa'. El doctor Fernando Larcher Laguzzi, del CIEMAT-Universidad Carlos III de Madrid-IIS Fundación Jiménez Díaz, ejerció de coordinador.
Résistance de P. falciparum au Nigeria - Conférence du 5e édition du Cours international « Atelier Paludisme » - Christian HAPPI - University of Ibadan, Nigeria - chappi@hsph.harvard.edu
Widespread human T cell receptor beta variable gene polymorphism: implication...Thermo Fisher Scientific
Polymorphism within the TCRB variable gene (TRBV) has been linked to chronic autoimmune diseases such as Type 1 Diabetes, Rheumatoid Arthritis, Psoriatic Arthritis, Multiple Sclerosis and Asthma (1-8), and may also be mechanistically linked to immune mediated adverse events (IMAEs) during immunotherapy (9-11). Here we use the Ion-AmpliSeq™ Immune Repertoire Plus TCRB assay to evaluate TRBV gene polymorphism in a group of 85 Caucasians with melanoma. The assay provides coverage of all three CDR domains to enable detection of TRBV polymorphism. We find evidence of extensive genetic diversity within the TRBV gene, including 15 nonsynonymous variants that are absent from the IMGT database (12). TRBV gene allele typing may provide rich biomarker information for the prediction of IMAEs and chronic autoimmune disease.
The CFTR gene belongs to a family of genes that regulate the energy transfer that allows a cell to open and close its ion channels. It is located on human chromosome 7 and consists of twenty-seven sequences of DNA that encode 1,480 amino acids. The CFTR gene produces the CFTR protein, which regulates the chloride ion content of epithelial cells that line the nasal cavity, lungs, and stomach.
Carbohydrates in plant immunity By Kainat RamzanKainatRamzan3
The main classes of carbohydrates associated with plant immunity, their role, and mode of action. More precisely, the state of the art about the perception of “PAMP, MAMP, and DAMP
(Pathogen-, Microbe-, Damage-Associated Molecular Patterns) type” oligosaccharides is
presented and examples of induced defense events are provided.
Genetic variation in GRIN genes encoding N-methyl-D-aspartate receptor (NMDAR) subunits has been associated with a spectrum of neurological and neuropsychiatric disorders. This talk will focus on clinical phenotype, functional consequences, and potential rescue pharmacology of disease-associated GRIN2D missense variants. The GRIN2D variants are located in the pre-M1 helix, agonist-binding domain, transmembrane domain M3, and the intracellular CTD. Developmental and epileptic encephalopathy (DEE) is the unifying phenotype across all 13 patients. The seizure types ranged from focal seizures, atypical absence seizures, tonic or atonic seizures, to epileptic spasms. Eight patients showed certain degree of hypotonia and movement disorders, three patients have autistic behavior and one patient showed symptoms of ADHD. Functional analysis in vitro on six novel GRIN2D variants reveals that that all six variants decreased receptor surface expression, which may underline certain shared clinical symptoms. Three variants (Leu670Phe, Ala675Thr, Ala678Asp) showed significantly enhanced agonist potency, and/or increased channel open probability, while the other three (Ser573Phe, Ser1271Phe, Arg1313Trp) presented reduced
sensitivity to endogenous protons and decreased channel open probability. Three variants (Ser573Phe, Ala675Thr, Ala678Asp) significantly decrease current amplitude. GluN2D-Leu670Phe
prolongs synaptic-like response time course and increases charge transfer. GluN2D-Ala678Asp transfection significantly reduced cell viability of cultured cortical neurons. In addition, a set of FDA-approved NMDAR channel blockers were evaluated for their ability to rescue functional changes of mutant receptors. This work suggests the importance of functional and biochemical validation for each individual variant. Rescue pharmacology in vitro may provide potential benefit of precision
medicine for a subset of severe pediatric neurodevelopmental diseases.
Nicholas Young, Sphingosine 1-phosphate Receptor Subtype Influence over Gliob...Nicholas Young
My talk presenting my thesis work per invitation of Research and Development Division of Genzyme Corporation to the Lipid Storage Disorders Department. October 5, 2007. Boston, MA: "Sphingosine 1-phosphate Receptor Subtype Influence over Glioblastoma Multiforme Pathology". My PhD was earned through the Integrated Biomedical Sciences, September 2007, The Ohio State University, College of Medicine Columbus, OH. Area of focus for my PhD: Biochemical and Molecular Disease Mechanisms. Dissertation title: Sphingosine 1-phosphate Receptor Subtype Influence Over Glioblastoma Multiforme Malignant Behavior"
Hello everyone, I am Dr. Ujwalkumar Trivedi, Head of Biotechnology Department at Marwadi University Rajkot. I teach Molecular Biology to the students of M.Sc. Microbiology and Biotechnology.
The current presentation describes various co-transcriptional and post-transcriptional RNA modifications in eukaryotic cells. The following processes are described in detail:
1. 5' mRNA Capping
2. Splicing
3. Alternative Splicing
4. 3' Polyadenylation
5. RNA Editing
Enjoy Reading.
Los días 20 y 21 de octubre de 2016, la Fundacion Ramón Areces organizó un simposio internacional para analizar las 'Enfermedades raras de la piel: de la clínica al gen y viceversa'. El doctor Fernando Larcher Laguzzi, del CIEMAT-Universidad Carlos III de Madrid-IIS Fundación Jiménez Díaz, ejerció de coordinador.
Résistance de P. falciparum au Nigeria - Conférence du 5e édition du Cours international « Atelier Paludisme » - Christian HAPPI - University of Ibadan, Nigeria - chappi@hsph.harvard.edu
Widespread human T cell receptor beta variable gene polymorphism: implication...Thermo Fisher Scientific
Polymorphism within the TCRB variable gene (TRBV) has been linked to chronic autoimmune diseases such as Type 1 Diabetes, Rheumatoid Arthritis, Psoriatic Arthritis, Multiple Sclerosis and Asthma (1-8), and may also be mechanistically linked to immune mediated adverse events (IMAEs) during immunotherapy (9-11). Here we use the Ion-AmpliSeq™ Immune Repertoire Plus TCRB assay to evaluate TRBV gene polymorphism in a group of 85 Caucasians with melanoma. The assay provides coverage of all three CDR domains to enable detection of TRBV polymorphism. We find evidence of extensive genetic diversity within the TRBV gene, including 15 nonsynonymous variants that are absent from the IMGT database (12). TRBV gene allele typing may provide rich biomarker information for the prediction of IMAEs and chronic autoimmune disease.
The CFTR gene belongs to a family of genes that regulate the energy transfer that allows a cell to open and close its ion channels. It is located on human chromosome 7 and consists of twenty-seven sequences of DNA that encode 1,480 amino acids. The CFTR gene produces the CFTR protein, which regulates the chloride ion content of epithelial cells that line the nasal cavity, lungs, and stomach.
Carbohydrates in plant immunity By Kainat RamzanKainatRamzan3
The main classes of carbohydrates associated with plant immunity, their role, and mode of action. More precisely, the state of the art about the perception of “PAMP, MAMP, and DAMP
(Pathogen-, Microbe-, Damage-Associated Molecular Patterns) type” oligosaccharides is
presented and examples of induced defense events are provided.
Genome Editing Techniques by Kainat RamzanKainatRamzan3
Genome technology has revolutionized biological science through techniques of Gene Editing in order to edit any organism's genome.MegNs and zinc-finger nucleases are commonly understood to be used, as is the effector's transcriptional activator-like nucleases. In CRISPR/Cas9, genetic alterations, and gene functionality have become a well-known tool for understanding gene targeting.
Spectrophotometer techniques are mostly used to measure the concentration of solutes in solution by measuring the amount of light that is absorbed by the solution in a cuvette placed in the spectrophotometer.
Viruses are small obligate intracellular parasites, which by definition contain either a RNA or DNA genome surrounded by a protective, virus-coded protein coat. Viruses range from the
structurally simple and small parvoviruses and picornaviruses to the large and complex
poxviruses and herpesviruses. Viruses are classified on the basis of morphology, chemical
composition, and mode of replication. The viruses that infect humans are currently grouped into 21 families, reflecting only a small part of the spectrum of the multitude of different viruses whose host ranges extend from vertebrates to protozoa and from plants and fungi to bacteria.
Viruses are small obligate intracellular parasites, which by definition contain either an RNA or DNA genome surrounded by a protective, virus-coded protein coat. Viruses range from the structurally simple and small parvoviruses and picornaviruses to the large and complex poxviruses and herpesviruses. Viruses are classified on the basis of morphology, chemical composition, and mode of replication. The viruses that infect humans are currently grouped into 21 families, reflecting only a small part of the spectrum of the multitude of different viruses whose host ranges extend from vertebrates to protozoa and from plants and fungi to bacteria.
Classic problems and emerging areas of immune system by Kainat RamzanKainatRamzan3
The immune system can be simplistically viewed as having two “lines of defense” innate immunity and adaptive immunity. The immune system refers to a collection of cells and proteins that function to protect the skin, respiratory passages, intestinal tract, and other areas from foreign antigens, such as microbes, viruses, cancer cells, and toxins.
Transmembrane transport of ions and small molecules by Kainat RamzanKainatRamzan3
The plasma membrane is a selectively permeable barrier between the cell and the extracellular environment. Its permeability properties ensure that essential molecules such as ions, glucose, amino acids, and lipids readily enter the cell, and waste compounds leave the cell.
The term ‘virus’ derives from the Latin – poison or Venom.• Viruses are much smaller than bacteria, use their genome (DNA or RNA) to replicate themselves in the host cells and synthesize viral particle.The viral structure mainly having following parts: Viral genome, Capsid, Some are enclosed by an envelope while Some viruses have spikes.• Viruses are classified on basis of their morphology, structure, Genome, presence of envelope, type of host, mode of transmission, replication site and Baltimore classification.
Viral replication by Kainat Ramzan-SlideShareKainatRamzan3
Virus multiplication are in Following steps: attached, penetration, biosynthesis, maturation, assembly and release and also discribe the life of Bacteriophage by following two life cycle
Present By Kainat Ramzan
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
For more information, visit-www.vavaclasses.com
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
1. Kainat Ramzan – MPhil BioChemistry. Sem-IV 2022
Department of Biochemistry, University of Okara
A Presentation on
2. 1. Introduction
2. Interferon
3. Classification of IFN
4. IFNG Structure
5. IFNG Gene
6. IFN Function
7. IFNG Mutation and Polymorphism
8. Material and Methods
9. Results
10. Conclusion
11. References
OUTLINE
3. INTRODUCTION
3
⊳ Single nucleotide polymorphisms (SNPs) represents a single
nucleotide differences between at least two DNA sequences
⊳ SNPs are associated with various complex diseases
⊳ Mostly locate within a gene or in a regulatory region that can affect
the genes function
⊳SNPs are often used interchangeably with mutations, polymorphism
and substitution
⊳ Polymorphisms in genes related to cytokine expression could
affect the susceptibility to different diseases
4. INTERFERON
4
⊳ Interferons are protein family which produce antiviral and antiproliferative responses in cells
- No homology with type I IFNs
- Describe a factor with the ability to interfere
- With the growth of live influenza virus
⊳ IFN gamma, also known as IFNG, is a secreted protein that belongs to the type II interferon
family
⊳ All three major types differ in their;
• Primary protein sequences,
• Cognate receptors,
• Genetic loci,
• Cell types responsible for their production
First coined in 1957
5. CLASSIFICATION OF IFN
5
1. Type I IFNs
Encoded by 17 nonallelic genes
Lack introns
Located on chromosome 9 in humans
– Glycosylated proteins,160-200 amino acids
– Sharing 30% to 55% homology
2. Type II IFN
Encoded by 17 nonallelic genes
Lack introns
140 amino acids and shares no homology with type I IFNs
3. Type III IFNs
IFN molecules
– IL-28A, IL-28B, and IL-29
– Co-produced with IFN-β
– But act by binding to a different receptor from type I IFN receptors
IFNs are consisting of three major
types
Type I - IFN-α, -β,
-ε, -ω, Type II - IFN-γ,
Type III - IFN-λ1,
IFN-λ2 and IFN-λ3,
also called IL-29, IL-
28A and IL-28B
8. IFN-γ Structure
9
⊳ Dimeric in solution
⊳ Each subunit
- 6 α-helices, that comprise 62% of the structure
- No β-sheet
- Composed of 140 amino acids
- IFN-γ is a homo-dimer
- Composed of a four chain bundle
- IFN-γR1 and IFN-γR2 genes
10. IFN-γ Gene
⊳ X-ray crystallography and Nuclear Magnetic Resonance (NMR) methods shows;
⊳ Cytogenetic Location: 12q14
⊳ Base pairs 68,154,769 to 68,159,740
⊳ Composed of a four chain bundle of IFN-γR1 and IFN-γR2 genes
⊳ IFN-γR1 and IFN-γR2 receptors are located on chromosomes 6q23-q24 and 21q22.11 in
human and chromosomes 10 and 16 in mouse, respectively.
⊳ IFN-γ homo-dimer binds to the two IFN-γR1 chains but does not directly interact with
IFN-γR2
⊳ IFN-γR2 has been shown to be essential for downstream signaling events;
binding of the IFN-γ homo-dimer to the pre-assembled receptor triggers downstream JAK-
STAT events that activate IFN-γ regulated genes
1
0
11. IFN Function
⊳ Activating macrophages and enhancing their expression of
MHC class II molecules
- Resulting in enhanced antigen presentation to T cells
⊳ Regulates the expression of the major histocompatibility
complexes (MHC) I and II
- Involved in the antigen processing presentation pathways
⊳ Also mediates functions leukocyte attraction, maturation
and differentiation, natural killer (NK) cell
activity and immunoglobulin (Ig)
production and class switching in B cells
1
1
12. IFNG Mutations
Several SNPs in this gene have reportedly been associated with immunologic diseases
- Such as aplastic anemia, hepatitis infection, systemic lupus erythematosus, and asthma
The first intron of IFN-γ gene contains a polymorphic microsatellite that has been closely
correlated with disease susceptibility
Some of the disease-associated SNPs are functional
The SNPs in the 59 untranslated regions (UTR) are translation-level regulators
Some SNPs in the introns may function to modify mRNA expression
1
2
13. MaterialandMethods
14
1. Retrival of SNPs datasets
2. Predicting deleterious nature of SNPs
- SIFT, PolyPhen, PPH2,SNAP2, Provean, CADD, ConDEL
3. Predicting the association of SNPs
- P-Mutant, PhD-SNP, SNP & GO, Meta SNP
4. Effect of SNPs on Protein stability
- MU-Pro, I-mutant, iStable
5. Analysis of Sequence consequences
- ConSurf
6. PTM Modification
- Musite Deep
7. Protein Modeling & Visualization
- Alpafold, PyMol,SAVES
8. Analysis of Ligand binding/ Protein-ligand docking
- PyRx, Discovery Bovia
9. Molecular Dynamic Simulation
- VMD and NAMD
20. Molecular Modelingand Dockingof the IFNG
20
The modeled 3D structure and sequence of IFNG
generated by Alpha-Fold
The SDF file of ligand structures was converted to the
PDB format by using PyMol
PROCHECK produced a RAMACHANDRAN plot
for each of the generated IFNG PDB structures
AutoDock VINA, which was used in the PyRx tool,
produced 9 different conformational changes for each
ligand, which are classified according to binding
affinity (kcal/mol).
A.A ERRAT 3D verify Pro Check TM Align
CORE Allowed Generously Disallowed TM
Score
RMS
D
IFNG 95.2381 48.19% 95.50% 4.50% 0.00% 0.00%
R130C 97.9167 49.40% 96.10% 3.20% 0.60% 0.00% 0.99029 0.49
R152Q 95.2703 52.41% 94.80% 4.50% 0.60% 0.00% 0.99048 0.49
I72N 94.4444 45.18% 95.50% 4.50% 0.00% 0.00% 0.98851 0.53
I72T 96.6216 43.37% 97.40% 2.60% 0.00% 0.00% 0.99204 0.44
K78T 96.6216 51.81% 96.10% 3.20% 0.60% 0.00% 0.98802 0.55
V45E 94.7368 40.36% 95.50% 4.50% 0.00% 0.00% 0.99223 0.43
Y37C 98.6207 44.58% 95.50% 4.50% 0.00% 0.00% 0.98575 0.61
Y76F 97.9592 50.60% 94.20% 5.80% 0.00% 0.00% 0.98709 0.59
21. Conclusion
21
In the present study, we analyzed the novel nsSNPs associated with the IFNG
gene and serve as a platform data for exhibiting virtual screening of IFNG via in
silico analyses and also revealed the molecular approach to study fluctuations in
activity, durability, affinity, and other attributes.
The study findings and results can assist in interpreting the impact of these
mutations and other strategy such as drug design, and so on.
22. References
22
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