Frame-shift mutations

Patients with Duchenne muscular dystrophy are deficient not only in dystrophin but also in the dystro-glycan and sarcoglycan proteins. " " Evidently, dystrophin is needed for formation of the complex which plays an essential role in muscle. In both types of X-linked muscular dystrophy there are individuals with a wide range of point mutations, frame-shift mutations, and deletions in the dystrophin gene. ... 

Figure 2.18 Frame shift mutation caused by insertion of one base, G.

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...

Pai HV, Kommaddi RP, Chinta SJ, Mori T, Boyd MR, et al. 2004. A frame-shift mutation and alternate splicing in human brain generates a functional form of the pseudogene, cytochrome P4502D7 that demethylates codeine to morphine. J Biol Chem 279 27383-27389. 

A variety of AVPR2 nonsense mutations causes the most severely affected NDI phenotypes (121). Although truncation frequently occurs within TM domain 3, severe phenotypes have also been reported as a consequence of the Argl37His mutation. The Argl37His mutation is representative of variant receptors that are unable to activate stimulatory Gs proteins (122). The receptor fails to respond to agonist through stimulated adenylyl cyclase activity. Many other A VW 2 mutations, such as frame-shift and small in-frame deletions, also result in AVPR2s that fail to couple to G a (123). 

Karl M, Von Wichert G, Kempter E, et al. (1996) Nelson s syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. J Clin Endocrinol Metab. 81, 124-129. 

Nitrous acid causes point mutations (1). For example, C is converted to U, which in the next replication pairs with A instead of G. The alteration thus becomes permanent. Mutations in which a number of nucleotides not divisible by three are inserted or removed lead to reading errors in whole segments of DNA, as they move the reading frame (frame-shift mutations). This is shown in Fig. 2 using a simple example. From the inserted C onwards, the resulting mRNA is interpreted differently during translation, producing a completely new protein sequence. 

Frame-Shift Mutation A change in the structure of DNA such that the transcription of genetic information into RNA is completely altered because the start point for reading has been altered i.e. the reading frame has been altered. 

Funke H, Eckardstein A von, Pritchard PH, Karas M, Albers JJ, Assmann G (1991) A frame-shift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin cholesterol-acyltransferase deficiency, and corneal opacities. J Clin Invest 87 371-376... 

Frame-shift mutations If one or two nucleotides are either deleted from or added to the interior of a message sequence, a frame-shift mutation occurs and the reading frame is altered. The resulting amino acid sequence may become radically different from this point on (Figure 31.5). [Note If three nucleotides are added, a new amino acid is added to the peptide or, if three nucleotides are deleted, an amino acid is lost. In these instances, the reading frame is not affected.]... 

Frame-shift mutations as a result of addition or deletion of a base can cause an alteration in the reading frame of mRNA. 

Mutations involving deletion or insertion of one or a few nucleotides are called frame-shift mutations. 

Before the triplet nature of codons had been established, Crick and associates used frame-shift mutations in a clever way to demonstrate that the genetic code did consist of triplets of nucleotides.7 55/55a Consider what will happen if two strains of bacteria, each containing a frame-shift mutation (e.g., a -1 deletion), are mated. Genetic recombination can occur to yield mutants containing both of the frame-shift mutations. 

Chapters 11 and 31. Since cancers contain multiple mutations, they are complex diseases. However, many specific susceptibility loci are being located, including some for breast cancer (Box 11-D),392 prostate cancer,393 and familial adenomatous polyposis, a hereditary disease leading to colon cancer.388 394 Cancer has long been known to be associated with chromosome instability including deletion and insertion mutations at simple repeat sequences, frame-shift mutations,395 DNA breakage, translocation,396 and losses or gains of whole chromosomes 397... 

A suppressor of frame-shift mutations in Salmonella is a tRNA containing at the anticodon position the nucleotide quartet CCCC instead of the usual CCC triplet anticodon.442 443 It has eight unpaired bases in the anticodon loop instead of the usual seven. Other frame-shift repressor tRNAs have been identified in E. cob, 444 Salmonella, and yeast.445 Not all suppressor genes encode tRNAs. For example, a UGA suppressor from E. coli is a mutant 16S rRNA from which C1054 has been deleted.446 A general nonsense suppressor in yeast is homologous to yeast elongation factor EF-la as well as to E. coli EF-Tu.447... 

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