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Introduction to Genomics
Published in Altuna Akalin, Computational Genomics with R, 2020
The mechanisms regulating gene expression are essential for all living organisms as they dictate where and how much of a gene product (it may be protein or ncRNA) should be manufactured. This regulation could occur at the pre- and co-transcriptional level by controlling how many transcripts should be produced and/or which version of the transcript should be produced by regulating splicing. The same gene could encode for different versions of the same protein via splicing regulation.This process defines which parts of the gene will go into the final mRNA that will code for the protein variant. In addition, gene products can be regulated post-transcriptionally where certain molecules bind to RNA and mark them for degradation even before they can be used in protein production.
Neuropathogenesis of viral infections
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Avindra Nath, Joseph R. Berger
In general, the host response to a viral infection is an effort to curtail the infection and consists of a variety of cellular and humoral immune responses. Recovery from the infection is due to the ability of the immune system to successfully clear the virus. Since viruses are an intracellular pathogen, it may involve killing the cells infected with the virus, although experimental systems suggest that under some circumstances, virus may be cleared from cells without killing them. Occasionally, the host responses may mount a fierce attack, where by the responses themselves may damage the uninfected cells. Much effort has been devoted in recent years to characterize these detrimental responses. It is possible that there are virus specific host responses, and these specific patterns may serve as signatures of each of the pathogens. Currently, efforts are underway to investigate these possibilities using microarrays and proteonomics based technologies which allow for the study of a large number of gene products simultaneously. However, mechanisms of viral clearance may also differ in various cell types. For example, in a sindibis virus model, it was shown that antibody responses were necessary for clearance of virus from cortical neurons while gamma interferon was necessary for elimination of virus from brain stem and spinal cord neurons [27].
RNA interference: a potential therapy for posterior pole diseases
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
The machinery to produce a protein is localized in each cell. Each human cell consists of a nucleus and cytoplasm. The nucleus contains chromosomes, composed of DNA. Segments of the long strands of DNA that make up the chromosomes are called genes. Genes consist of sequences of DNA that cells can translate into gene products. The cell accomplishes gene translation by producing messenger RNA (mRNA). The mRNA is then transcribed by ribosomes into an amino acid sequence that makes up peptides that are processed into proteins. mRNA provides the templates that the cell uses to manufacture proteins. One mRNA molecule can produce many protein molecules (Fig. 87.1). Selective destruction of mRNA producing disease-associated proteins is an ideal strategy for treating disease.
The role of proteomics in the multiplexed analysis of gene alterations in human cancer
Published in Expert Review of Proteomics, 2021
Niraj Babu, Mohd Younis Bhat, Arivusudar Everad John, Aditi Chatterjee
With the release of the human genome sequence in 2000, research community has realized the role of gene product proteins in regulating and controlling the phenotype. This led to the emergence of The Human Proteome Project (HPP) an international effort initiated by the Human Proteome Organization (HUPO). HPP directed its efforts to annotate all the proteins called chromosome-centric program (C-HPP) and to characterize role of these proteins in disease biology (B/D-HPP) with mass spectrometry as one of the main pillars of exploration. The aim of B/D-HPP is to create an in-depth repository of expressed protein isoforms/ post-translational modifications and apply this information to unravel molecular mechanisms that lead to cancer development and progression in addition to other disease conditions. The mandate of B/D-HPP is to bring transformation in biomedical research by making possible accurate and precise detection and quantification of all human proteins and their association with disease pathogenesis. This will further enable interrogation of genomics and proteomics data to improve clinical decision making and outcomes.
Case-only analysis of gene–gene interactions in inflammatory bowel disease
Published in Scandinavian Journal of Gastroenterology, 2020
Milda Aleknonytė-Resch, Sandra Freitag-Wolf, Stefan Schreiber, Michael Krawczak, Astrid Dempfle
Originally, the term ‘epistasis’ was used to refer to the ability of one or more genotypes of a gene, say A, to mask the phenotypic effects of another gene, B [5]. Over time, however, epistasis has become more or less synonymous of gene–gene interaction in general [6], where it is important to distinguish between biological and statistical interaction. The former is usually postulated when the gene products in question share some common role in the disease etiology, i.e., if they either interact physically with one another or if they impede upon one and the same, disease-relevant biological pathway. Statistical interaction, on the other hand, is defined as the lack of additivity of the genotype-associated disease risk difference, measured on a particular scale (usually linear, log or logit). Notably, absence of statistical interaction on one scale implies the presence of interaction on all other scales, i.e., there is no such thing as a lack of statistical gene–gene interaction. Statistical interaction can also be interpreted as ‘effect modification’ in that the risk difference associated with a given genotype of gene A, scaled correspondingly (i.e., risk difference, relative risk, or odds ratio), depends upon the genotype of gene B. While certain types of biological interaction result in statistical interaction on a certain scale, the presence of statistical interaction does not necessarily imply the concurrent presence of any meaningful biological interaction [7].
Approaching complexity: systems biology and ms-based techniques to address immune signaling
Published in Expert Review of Proteomics, 2020
Joseph Gillen, Caleb Bridgwater, Aleksandra Nita-Lazar
Reporter assays constitute the in vitro stimulation of a promoter and reporter gene pair to measure a response [2]. These assays can be extremely useful and are a robust method for high throughput screens of different drugs or compounds by the direct measurement of expressed gene products or the indirect changes in signal molecules regulated by genes. This is accomplished by transfecting a desired cell line to express a transcription factor activated promoter and a common reporter gene. The cells can then be stimulated to drive promoter activity. Ligand or agonist induction of the transcription factors leading to expression of the reporter gene. In the case of a luciferase reporter gene, luciferin, a luciferase substrate, can be added and the resulting luminescence measured as a corollary of stimulation. The unattractive variables of reporter assays tend to revolve around the limits in experimental design: reporter assays may take vast resources and long time periods to design and to target assays to transcription factors. Common reporter assays exploit the activity of reporter genes producing β-galactosidase, green fluorescent protein (GFP), and luciferase [2].