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Roles of Nucleotide Sequence Analysis in Human Genetics and Genomics
Published in Hajiya Mairo Inuwa, Ifeoma Maureen Ezeonu, Charles Oluwaseun Adetunji, Emmanuel Olufemi Ekundayo, Abubakar Gidado, Abdulrazak B. Ibrahim, Benjamin Ewa Ubi, Medical Biotechnology, Biopharmaceutics, Forensic Science and Bioinformatics, 2022
S. S. D. Mohammed, I. Abraham, D. Enoma, L. E. Okoror
The sequence of chromosome 21 was a turning point for the understanding of Down syndrome. Persons that have Down syndrome might have a number of defects from birth. Approximately half of the children that are affected are given birth to with a defect of the heart. Other disorders such as digestive abnormalities (e.g., intestinal blockage) are less prominent (Antonarakis et al., 2004 and Stöppler, 2019). A child born with Down syndrome has a unique appearance, although all aspects of the child’s appearance need not be present as the phenotype. The combinations of genes might make the child look different from other patients. Popular symptoms of Down syndrome include: having a flat face and small head. Also having upward slanting eyes, short neck, and ears are flat and positioned lower than “normal.” There is tongue protrusion and it seems to be too big for the mouth, wide hands, muscles lacking tone, flexible joints, short fingers, and a single flexion crease in the palm. There are a lot of other abnormalities of the chromosome and they include: Klinefelter syndrome (47, XXY), Turner syndrome (45, X0), and Cri du chat syndrome. Some of these abnormalities might occur due to chromosomal translocation where in parts of two chromosomes are exchanged (Stöppler, 2019).
Resistance Mechanisms of Tumor Cells
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Almost all hematological tumors do not exhibit such a mutational landscape rather than display recurrent chromosomal translocations that result in “chimeric fusion genes” (see Fig. 17.1, upper right panel B). These fusions genes are highly specific and prototypic for leukemia disease subtypes (ALL, AML, CML, and CLL). The term “chromosomal translocation” describes an illegitimate exchange of chromosome material between two or more non-homologous chromosomes. In most cases, these illegitimate events are caused by a DNA damage situation where a subsequent DNA repair process results in wrongly fused “derivative chromosomes” (Reichel et al., 1998; Richardson et al., 1998). Chromosomal translocations can be subcategorized by the results of their illegitimate recombination event: (1) overexpression of proto-oncogenes by fusing them to strong enhancers, or (2) creation of chimeric fusion genes. Since these chromosomal changes occur recurrently at nearly precise points of our genomes, one might argue that these genes represent recombination hot spots. DNA damage situation may occur more frequently due to endogenous events (like, e.g., early apoptosis, torsional stress, DNase I hypersensitive sites, etc.) or exogenous xenobiotic stress conditions (Strick et al., 2000).
The roadmap towards cure of chronic hepatitis B virus infection
Published in Journal of the Royal Society of New Zealand, 2022
In contrast, HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. HBV X-inhibitors may be a potential approach to silence cccDNA without off-target effects. Direct gene editing approaches include cccDNA degradation through IFN-α/Lymphotoxin-β receptor agonist (via APOBEC3A/B), or cccDNA cleavage via nucleases including Zinc-finger nucleases (ZFNs), transcription-activator like effector nucleases (TALENS) and CRISPR/Cas9 approach. In in vitro experiments, combining Cas9 with guide RNAs which target conserved regions within HBV cccDNA, achieves profound reductions in cccDNA and all HBV proteins (Wang et al. 2017). In addition to destroying cccDNA, CRISPR/Cas9 will also remove HBV integrins from the host genome, thereby reducing any long-term risk of hepatocarcinogenesis. The important challenges facing the successful use of gene editing approaches in patients include how to measure efficacy (no standardised cccDNA quantification assay), how to deliver the drug efficiently to the nucleus of every infected hepatocyte and finally, how to mitigate the long-term risks of chromosomal translocation in otherwise healthy young people (Table 1).