Genetic mutations frameshift mutation

Genetic Make up of Tester Strains. The most widely used strains are those developed by Bruce Ames and colleagues which are mutant derivatives of the organism Salmonella typhimurium. Each strain carries one of a number of mutations in the operon coding for histidine biosynthesis. In each case the mutation can be reverted either by base-change or by frameshift mutations. The genotype of the commonly used strains is shown in Table 6.6. 

Streisinger, G., Okada, T., Emrich, J., Newton J., Tougita, A., Terzaghi, E. and Inouye, M. (1966). Frameshift mutations and the genetic code. Cold Spring Harbor Symp. Quantum Biol. 31 77-84. 

Vaisse, C., Qement, K., Guy-Grand, B., and Eroguel, P. (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113-114. 

Frameshift mutations. Insertions or deletions of genetic material that lead to a shift in the translation of the reading frame. The mutation usually leads to nonfunctional proteins. 

Therefore, the genetic lesions caused by a mutagen can be detected in assays for many genetic end points, including base-pair substitution and frameshift mutation, deletion, mitotic recombination or gene conversion, unscheduled DNA synthesis, sister chromatid exchange, and chromosomal aberration.170... 

FRAMESHIFT MUTATION A gene mutation that occurs by the addition or deletion of one or a few base pairs and causes a shift in the reading frame of the genetic code, thereby altering the message encoded by all DNA base pairs that are read after the point of the mutation. 

Know the principles of the genetic code, the wobble hypothesis, and the concepts of nonsense, missense, and frameshift mutations and how they may be suppressed. 

Yeo GSH, Farooqi IS, Aminian S et al (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20 111-112... 

The complete removal or incorporation of a base-pair is more serious than the foregoing and may result in a frameshift mutation. Here the order of the genetic code is altered and hence the reading from that base code is shifted. 

Ripley, L.S. (1990) Frameshift mutation determinants of spedficity. Annu. Rev. Genet., 24, 189-213. 

In the history of drug metabolism, prominent were the discoveries of genetic variability of the metabolism of debrisoquine (14) and of sparteine (15). Subsequent studies indicated that both drugs are metabolized by the same enzyme (16), which turned out to be the P450 cytochrome CYP2D6 (17). The enzyme s variations were found to be complex (18) enzyme activity could be absent because of frameshift mutations, splicing defects, gene deletion, or the presence of a stop codon. The enzyme may function slowly because of various kinds of mutation, whereby some mutations affected only the interaction with specific substrates. Enzyme duplication or multiplication could lead to very fast action. 

Lawrence, C. W., O Brien, T., and Bond, J. (1984). UV-induced reversion of his4 frameshift mutations in rad6, revl, and rev3 mutants of yeast. Mol. Gen. Genet. 195, 487-490. 

Base pair substitution (A T to G C or G C to A T) and frameshift mutations (deletions) in S. typhimurium strains are represented to identify both types of mutation caused by a test compound. Therefore, differences in the activity of a test compound acting in these strains may yield some insight into how the compounds interact with the DNA of bacteria. Additionally, some genetic markers have been developed to make the strains more sensitive to certain types of mutagens. 

Fig. S. Frameshift mutations the two partial amino-acid sequences have been determined by Streisinger et a/. they are part of a protein produced by the bacterial virus T4. The base sequence has been deduced theoretically from the genetic code, the pair of frameshift mutations has removed one adenine and inserted another guanine, fifteen bases further on.

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