Specific chromosomal rearrangements

In ebook "Genome instability in cancer development" studies on animal tumour viruses and chromosome rearrangements in human tumours have concurred to identify so-called ‘proto-oncogenes’ and ‘tumour suppressor genes’, whose deregulation promotes carcinogenesis. These important findings not only explain the occurrence of certain hereditary tumours, but they also set the stage for the development of anti-cancer drugs that specifically target activated oncogenes.

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Ebook "Genome instability: Methods and protocols" presents forty-two methods and protocols to analyze diverse aspects of genome instability. Chapters detail mutagenesis and repair, methods to quantify and analyze the properties of DNA double-strand breaks, profile replication, replication proteins strand-specifically, genome instability, fluorescence microscopic techniques, and genomic and proteomic approaches.

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Aedes aegypti is the primary vector of arthropod-borne viruses and one of the most widespread and invasive mosquito species. Due to the lack of efficient specific drugs or vaccination strategies, vector population control methods, such as the sterile insect technique, are receiving renewed interest.

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Somatic evolution of malignant cells produces tumors composed of multiple clonal populations, distinguished in part by rearrangements and copy number changes affecting chromosomal segments. Whole genome sequencing mixes the signals of sampled populations, diluting the signals of clone-specific aberrations, and complicating estimation of clone-specific genotypes.

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It is known that all tumors studied in sufficient number to draw conclusions show characteristic/ specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient.

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Chromosomal rearrangements are the typical phenomena in cancer genomes causing gene disruptions and fusions, corruption of regulatory elements, damage to chromosome integrity.

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Chromosomal rearrangements apparently account for the presence of a pri-mate-specific gene (protease serine 3) in chromosome 9. This gene encodes, as the result of alternative splicing, both mesotrypsinogen and trypsino-gen 4. Whereas mesotrypsinogen is known to be a pancreatic protease, neither the chemical nature nor biological function of trypsinogen 4 has been explored previously.

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Uncovering Recurrent Submicroscopic Rearrangements As a Cause of Disease For five decades since Fred Sanger's (1) seminal discovery that proteins have a specific structure, since Linus Pauling's (2) discovery that hemoglobin from patients with sickle cell anemia is molecularly distinct, and since Watson and Crick's (3) elucidation of the chemical basis of heredity, the molecular basis of disease has been addressed in the context of how mutations affect the structure, function, or regulation of a gene or its protein product.

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Applications of FISH The majority of FISH applications involve hybridization of one or two probes of interest as an adjunctive procedure to conventional chromosomal banding techniques. In this regard, FISH can be utilized to identify specific chromosomes, characterize de novo duplications or deletions, and clarify subtle chromosomal rearrangements. Its greatest utilization, however, is in the detection of microdeletions (see below). Though conventional cytogenetic studies can detect some microdeletions, initial detection and/or confirmation with FISH is essential.

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