Chromosomal mutations translocation

Chromosomal mutations have also been described which produce a modified translocation factor protein with lowered affinity for fusidic acid. 

Mutational errors can extend to include more than just one base of a chromosome. Humans normally have 23 pairs of chromosomes. But mutations can produce a fetus that has an extra copy or copies of a chromosome. The unique physical appearance and retarded mental faculties associated with Down syndrome arise when three copies of chromosome 21 are present. Another type of chromosomal mutation occurs when portions of two adjacent chromosomes swap places with each other. Such a translocation mutation between chromosomes 9 and 22 lead to a certain type of leukemia. 

Lincomycin, which resembles erythromycin, in a dose of 500 mg t.i.d., is indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci, and staphylococci resistant to other antibiotics. Lincomycin inhibits protein synthesis by interfering with the formation of initiation complexes and with aminoacyl translocation reactions. The receptor for lincomycins on the 50S subunit of the bacterial ribosome is a 23S rRNA, perhaps identical to the receptor for erythromycins (see also Figure 88). Thus, these two drug classes may block each other s attachment and may interfere with each other. Resistance to lincomycin appears slowly, perhaps as a result of chromosomal mutation. Plasmid-mediated resistance has not been established with certainty. Resistance to lincomycin is not rare among streptococci, pneumococci, and staphylococci. C. difficile strains are regularly resistant. 

Mutations caused by substances with biogenetic effects may be divided into gene (point) mutations characterized by small changes of DNA (only one pair or at most several nucleotides are hit) and chromosomal mutations, visible under a conventional microscope (e.g. chromosome breaks, deletions, translocations, etc.). Depending on the mechanism of the effects of genotoxic substances, the mutation can result from (1) the substitution of analogues of bases, (2) the chemical conversion of DNA and of its nucleotides, (3) binding of chemical substances to DNA and (4) DNA depolymerization [3]. 

Anaviev and Gvozdev (1974 a) have studied the position effect of the mosaic type in D. melanogaster with the chromosomal mutation Dp (l f)R and the translocation of the euchromatic region 1A3-4-3A1-2 of the X chromosome to the centromere heterochromatin. According to their data, there is a delay of replication of the translocated euchromatin. RNA synthesis here was reduced to 60% of normal. These data show that the position effect is accompanied by alterations at the transcriptional level. The resistance of the eye mosaic peculiarities to inhibitors of cell division and RNA synthesis added at the end of the first larval stage does not contradict the above statements (Baker, 1967 Perez-Davila and Baker, 1967). 

Genetic Control. Manipulation of the mechanisms of inheritance of the insect pest populations has occurred most successhiUy through the mass release of steri1i2ed males, but a variety of other techniques have been studied, including the environmental use of chemostetilants and the mass introduction of deleterious mutations, eg, conditional lethals and chromosomal translocations (58 ndash 60) (see Genetic engineering). 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

Both AML and ALL are presumed to arise from clonal expansion of a single arrested cell. As these cells expand, they acquire one and often more chromosomal aberration, including translocations, inversions, deletions, point mutations, and... 

Figure 2. Genetic aberrations observed in HAT genes, (a) Schematic representation of a balanced chromosomal translocation. These translocations result in the formation two new fusion genes, which can give rise to one or two fusion proteins, (b) Examples of nonsense (RTS patient RT163.1), missense (RT209.1), deletion (followed by frame shift RT231.1) mutations, as well as sphee site acceptor (RT211.3) or splice site donor (RT39.1) mutations...

Despite the overall high incidence of RAS and KIT mutations in RUNXI/CBFp AML, secondary mutations in the majority of patients is not known. Similarly, the secondary mutations cooperating with t(I2 2I) preB-ALL have also remained elusive. Mutations in RTK occur rarely in t(I2 2I) ALL, and indeed deletion on chromosome I2p, including the non-translocated ETV6 allele, is the only consistent alteration in these patients observed to date (Armstrong and Look, 2005 Raynaud et al, 1996). 

Enl is a translocation partner for MLL that is a common target for chromosomal translocations in human acute leukemia. Truncating mutations of hSNF5/INH are associated with aggressive pediatric cancer... 

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

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