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Discovering Genes That Cause Disease
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
It is likely that the human transcript map will improve dramatically in the coming months. Partial cDNA sequences (expressed sequence tags, or ESTs) have been accumulating in public databases at an impressive rate, and a recent Merck-funded cDNA sequencing initiative at Washington University in St. Louis has produced 5' and 3' sequences for 140,000 cDNAs, and will reach 280,000 by the end of 1996. In a testimonial to international cooperation, an EST mapping consortium (with major genome center participants at Stanford, MIT, Oxford, Cambridge, and Paris) plans to map some 70,000 ESTs to 0.5 Mb intervals (perhaps 0.1 Mb intervals in the near future), utilizing the whole genome radiation hybrid and YAC panel approaches. Some 7000 have already been mapped. Recent announcements by the Institute for Genomic Research (TIGR) and Sandoz of their willingness to donate primers for this mapping effort are most welcome. With all of this activity, it seems likely that more than half of the human transcripts will be placed on the map in the next 12 months. The effect on the success rate of the positional candidate approach should be profound.
Disease Prediction and Drug Development
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
A microarray analysis placed expressed-genes in four categories: 1) significantly upregulated (gene-expression increases); 2) significantly downregulated; 3) insignificant gene-expression variations and 4) genes that are not expressed. A total of 165 genes (or ESTs) were upregulated, and 170 genes (or ESTs) were downregulated. EST (Expressed Sequence Tag) is a short subsequence of genes used to derive the gene-expressions of cloned DNA (cDNA). A total of 19 known genes and 21 ESTS had a separate gene-expression between HBV and HCV making them biomarkers for HBV and HCV. Additional genes were identified that were upregulated or downregulated in cancer improving the knowledge of genes involved in carcinogenesis. The techniques used to study and identify these genes were: 1) hierarchical clustering based upon edit-distance and 2) filtering the gene-expressions using a threshold value that separated significant upregulation or downregulation.
Functional Omics and Big Data Analysis in Microalgae
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Chetan Paliwal, Tonmoy Ghosh, Asha A. Nesamma, Pavan P. Jutur
Genomics is the study of the whole genome of an organism, including genes, recombinant cDNA, and expressed sequence tags (ESTs), to obtain a hypothesis of the cellular machinery (Rai et al. 2016). Initially, only information about sequencing and gene assembly can be deduced from the genomic data, but functional genomics can infer the function of a gene helping in understanding and regulation of the metabolic pathways (Jamers et al. 2009). The year 2005 marked the beginning of next-generation sequencing, which has led to an unprecedented rise in the amount of microalgal genome data (Lu et al. 2016). High throughput analysis and systematic sequencing methodology have enabled an understanding of the molecular machinery of microalgae. By the end of 2010, only 7 microalgal genomes existed, but as of now >30 microalgal genomes have been sequenced (Brodie et al. 2017; Rismani-Yazdi et al. 2011).
Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells
Published in Islets, 2022
Noriko Mizusawa, Nagakatsu Harada, Takeo Iwata, Izumi Ohigashi, Mitsuo Itakura, Katsuhiko Yoshimoto
Pancreatic islet β-cells (hereafter referred to as β-cells) are highly differentiated cells with cell-specific gene functions that contribute to physiological homeostasis in the body.1 Besides the genes encoding insulin, amylin, or PDX-1, several genes have been recently reported to be expressed predominantly or preferentially in pancreatic islets or β-cells.2–5 However, most genes responsible for the molecular basis of β-cell functions remain unidentified. We generated a complementary DNA (cDNA) library and determined the expression profile of MIN6 cells, one of the best-studied β-cell lines.6,7 In general, gene-expression differences have been determined using oligonucleotide microarrays to detect mRNA levels in cells8 or tissues,9 or under several pathological or physiological conditions, such as normal cells versus tumor cells,10 caloric restriction,11 or cells exposed to various glucose concentrations.12 Moreover, large-scale cDNA-sequencing analysis is advantageous for generating a catalog of expressed genes in target cells or tissues,13,14 and a pool of unknown expressed sequence tags (ESTs) obtained from such profiling would provide a source of novel genes.15,16
Prevention of ulcerative colitis by Huangqin decoction: reducing the intestinal epithelial cell apoptosis rate through the IFN-γ/JAK/ETS signalling pathway
Published in Pharmaceutical Biology, 2022
Xiaowei Mo, Kairui Tang, Lijing Deng, Xingyi Zhou, Xiaojuan Li, Yupei Zhang, Jing Wang
In this study, we found that the protein expression of related proteins in the JAK/STAT signalling pathway in the colon tissue of the UC group, such as JAN1, JAN2 and fragilis, was significantly upregulated compared to the NC group, indicating that the JAK/STAT signalling pathway in the UC group was activated. EST-1 is the prototypic member of a novel subset of the ETS transcription factor family, and its expression in the gastrointestinal tract is particularly high. The JAK/STAT signalling pathway regulates the functional activity of EST family proteins and participates in the process of cell apoptosis (Oikawa and Yamada 2003). Recently, experimental studies have shown that EST-1 promotes the progression of UC by accelerating the activation of NF-κB to promote intestinal epithelial apoptosis (Li et al. 2015).
Common light chain chickens produce human antibodies of high affinity and broad epitope coverage for the engineering of bispecifics
Published in mAbs, 2021
Kathryn H. Ching, Kimberley Berg, Kevin Reynolds, Darlene Pedersen, Alba Macias, Yasmina N. Abdiche, William D. Harriman, Philip A. Leighton
The common light chain construct (CmLC1, Figure 1) in OmniClic is inserted in the chicken light chain locus, as are all the human light chain transgenes in OmniChicken, thereby utilizing the endogenous transcriptional regulatory elements and non-translated regions for optimal lineage-specific expression. This location also ensures that gene conversion in the B cell lineage will be focused on the light chain transgene.40,41 The variable region is a pre-rearranged VK3-15/JK1 region made by joining the germline gene segments together, with no chewing back of the ends. This rearranged sequence is expressed in humans, as it is found in the National Center for Biotechnology Information’s Expressed Sequence Tags database. The V region splices to the chicken CL constant region, producing a chimeric light chain. In the OmniClic locus, the chicken VL pseudogenes remain upstream of the human pseudogenes (Figure 1).