China
Africa
Explore chapters and articles related to this topic
Genetics and genomics of exposure to high altitude
Published in Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson, Ward, Milledge and West's High Altitude Medicine and Physiology, 2021
Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson
The human genome, comprising more than 3.2 billion nucleotides of deoxyribonucleic acid (DNA) in the form of adenine (A), thymine (T), guanine (G), and cytosine (C), is organized in double-stranded bases within 23 pairs of chromosomes in the nucleus and ≈16,569 nucleotides in the circular mitochondrial genome. Only a small portion (∼2%) of the human genome encodes genes that are transcribed and translated into a sequence of amino acids that make up proteins to carry out various functions within the cell. The cellular roles of regulatory sequence outside coding portions of the genome (ENCODE Consortium 2012) and nonprotein-coding ribonucleic acids (RNAs) that are transcribed from DNA (Bartoszewski and Sikorski 2018) are active areas of research.
Transcriptionally Regulatory Sequences of Phylogenetic Significance
Published in S. K. Dutta, DNA Systematics, 2019
The innate differences between organisms predict a varied complexity in transcriptional regulation for prokaryotes and eukaryotes. In bacteria and bacteriophages regulation is achieved largely by interaction between proteins, such as polymerase and repressors, with specific DNA sequences, such as promoters and operators. In eukaryotic cells transcriptional control involves many different regulatory sequences such as enhancers, long terminal repeats, internal as well as distal and proximal regulators, Z-DNA, etc., in addition to the classical promoters. While the plethora of macromolecular elements participating in the recognition of and interaction with these sequences are yet to be fully identified, it is clear that as in prokaryotes, eukaryotic chromatin requires interaction among and between proteins and nucleic acids. The presence of more complex transcriptional regulation in more highly evolved systems, such as methylation of specific sequences and temporal and tissue-specific expression of different members in a gene family during development, is only beginning to be understood at the phylogenetic level.
The Role of Human Genetics in HIV-1 Infection
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Maureen P. Martin, Mary Carrington
The CCR5 promoter region has been characterized by several groups (95–99), and it appears that transcription is initiated from two distinct promoters, one of which lies upstream of exon 1 (PU), and another that lies downstream within the region that includes intron 1, exon 2, and part of exon 3 (PD) (97) (Figure 1). The downstream promoter is the stronger of the two when tested in a variety of cells, including monocytic and lymphocytic cell lines, and CD4+ T cells (97). Sequence motifs similar to consensus sequences for a variety of transcription factors have been identified in the PD promoter region (98). Polymorphisms in cis-regulatory sequences can affect the strength of the promoter by altering the affinity of regulatory proteins for these elements. Such polymorphisms could account for some of the heterogeneity in both CCR5 expression and the rate of HIV disease progression that has been observed among individuals.
Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mateusz Kciuk, Adrianna Gielecińska, Somdutt Mujwar, Mariusz Mojzych, Beata Marciniak, Rafał Drozda, Renata Kontek
The increased production and storage of acidic metabolites, mainly lactate, carbon dioxide (CO2), and protons (H+), that occurs as a result of cancer cells' metabolic rewiring in hypoxia force changes in the expression of enzymes and transporters that act in concert to provide effective pH regulation to offset the potentially damaging repercussions of an increasingly hypoxic and acidic tumor microenvironment47. HIF-mediated expression of CAIX is one of the major adaptations to hypoxic conditions48,49, while CAXII is not induced by the protein50. Moreover, CAIX can be induced by processes that are not dependent on hypoxia, such as lactate and the redox-mediated stabilization of HIF-151,52. Not only does HIF contribute to the expression of CAs. Enzyme expression may be regulated by other transcription factors such as transcription factor AP-1/AP-2 (AP-1/AP-2), protein C-ets-1 (ETS-1), transcription factor SP1/SP3 (SP1/SP3), and epigenetically controlled via regulation of methylation status of the regulatory sequences of CAS9 gene or by posttranscriptional mechanisms through splicing and mRNA stabilization8,53. It is worth mentioning that in renal cell malignancies, inactivation of the pVHL tumor suppressor protein, which negatively regulates HIF stability, results in a constitutive increase in the expression of the CA9 gene54.
The molecular mechanisms and targeting strategies of transcription factors in cholangiocarcinoma
Published in Expert Opinion on Therapeutic Targets, 2022
Jiao Wang, Fujing Ge, Tao Yuan, Meijia Qian, Fangjie Yan, Bo Yang, Qiaojun He, Hong Zhu
A transcription factor binds a DNA helices to specific regulatory sequences, subsequently activating or inhibiting gene transcription via a trans-activation or trans-repression domain, respectively [26]. TFs account for about 8% of the total human genes and 20% of all oncogenes discovered so far, and their mutations are the basis of many diseases, and about one-third of human developmental disorders are attributed to the dysfunction of TFs, which explains why the coding sites of TFs in the genome are so rich in ultra-conserved elements [27,28]. Considering that TFs are indispensable in CCA, we present an overview of the recent studies examining the various roles of TFs in regulating the progression and development of CCA. We also highlight possible therapeutic pathways and the latest treatment strategies for CCA by targeting TFs.
β-Thalassemia Intermedia Caused by the β-Globin Gene 3′ Untranslated Region: Another Case Report
Published in Hemoglobin, 2022
Fan Jiang, Gui-Lan Chen, Jian Li, Xue-Wei Tang, Dong-Zhi Li
The term codon +32 (A>C) mutation has also been reported in an Indian family and a Japanese family. Heterozygotes for this mutation presented with a typical β-thal phenotype in both families [6,7]. The 3′UTR plays an important role in the posttranscriptional regulation of gene expression by affecting mRNA processing, including interactions between mRNA structural components (cis-regulatory sequences) and specific trans-acting factors [8,9]. Therefore, alterations that modify the 3′UTR sequence could lead to errors in the processes of mRNA sub-cellular localization, stability, and efficiency of translation. Using bioinformatics analysis, Sen et al. [7] found that by its binding of two miRNAs, hsa-miR-451a and hsa-miR-3914, at the mutation position, the term codon +32 possibly influences the mRNA stability through recruiting RNA binding proteins. Other mutations in the 3′UTR of the β-globin gene have also been described, and all of them are associated with β+-thal [10,11]. The severity of the disease in β-thal is predominantly determined by the type of the mutation(s) on the β-globin gene. However, the low incidence of rare mutations and the variability of accompanying mutations, make it difficult to predict the clinical severity of compound heterozygotes. Our report, combined with others, provides useful information related to genetic counseling and prenatal diagnosis for the families involved.