Mutation frameshift

The conversion of a functional into a pseudogene most frequently results from mutations such as frameshift mutations or deletions. Even though pseudogenes might still have some retained functionality such as promoter-or enhancer-like features, they are usually classified as pseudogenes upon their lack of protein-coding ability. 

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

Frameshift Mutations Result From Deletion or Insertion of Nucleotides in DNA That Generates Altered mRNAs... 

P-Thalassemla (MIM 141900) A very wide variety of mutations in the p-globin gene, including deletions, nonsense and frameshift mutations, and others affecting every aspect of its structure (eg, splice sites, promoter mutants)... 

Resistance to certain antibiotics can arise as a consequence of mutations to chromosomal genes because of changes in the DNA sequence. Mutations can occin due to single base pair changes. Transitions involve the substitution of one purine (A or G) for another and therefore one pyrimidine (C or T) for another. Transversions involve a change from a pyrimidine to a purine and vice versa. Frameshift mutations occin when one or... 

Hereditary deficiency of LDH-B was first reported by Kitamura et al. in 1970 (K21). Since then, this enzyme deficiency has been discovered in at least five families in Japan. There were no clinical symptoms in these cases. On the other hand, LDH-A deficiency was associated with an exertional rhabdomyolysis and myoglobinuria after severe exercise (K15). One Japanese and one Italian with LDH-A deficiency showed the typical skin rash. To date, nine LDH-A variants have been analyzed at the molecular level, and four missense mutations, one nonsense mutation, one frameshift mutation due to a single base insertion, and three gene deletions have been elucidated (K16, M5). Missense mutations have also been identified in LDH-B deficiency (M6). 

Lamhonwah AM, Tein I. Carnitine uptake defect frameshift mutations in the human plasmalemmal carnitine transporter gene. Biochem Biophys Res Commun 1998 252(2) 396-401. 

We have not directly determined the relative frequencies of frameshift mutations and other mutational events in comparison to the base substitution mutations. However, based on the high frequency of nonsense mutations (11%) among all lacl mutants induced by BPDE and because nonsense mutations are monitorable at less than one-fifth of the lacl codons and, even then, only via certain base pair substitutions, we believe that base substitutions account for a major fraction of mutations induced by BPDE. 

For example, c-Fos is heavily phosphorylated on a series of serine residues in the C-terminal domain of the protein by several types of protein kinases. The likely functional importance of these phosphorylation sites is indicated by the fact that the difference between c-Fos (the normal cellular form of the protein) and v-Fos (the viral oncogene product) is a frameshift mutation in the v-Fos protein, which obliterates the phosphorylated serine residues. It is speculated that the loss of these phosphorylation sites removes one mechanism by which the cell can regulate the protein, thereby leading to cellular transformation. 

VOELKER, T.A., MORENO, J., CHRISPEELS, M.J., Expression analysis of a pseudogene in transgenic tobacco - a frameshift mutation prevents messenger-RNA accumulation, Plant Cell, 1990, 2,255-261. 

Two mutations were identified a splice variant that eliminated an exon and a frameshift mutation that truncated the protein. The linkage between the pseudogene polymorphism and these mutations was much stronger in Caucasians than African Americans. Thus a test for the pseudogene polymorphism in African Americans would have lower predictive values than in Caucasians. 

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. 

Frameshift Mutation A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH]... 

Frameshift mutations (choice A) are the result of the deletion or insertion of a series of nucleotides that are not a multiple of three (thus altering the reading frame). Although the insertion or deletion of a single nucleotide would produce a frameshift, it is highly unlikely that it would alter only a single amino acid. The shift in the reading frame typically alters a number of amino acids subsequent to the insertion or deletion site. 

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. 

VanWesenbeeck, L., Odgren, P.R., MacKay, C.A., D Angelo, M., Safadi, F.F., Popoff, S.N., VanHul, W., and Marks, S.C. Jr (2002) The Osteopetrotic Mntation Toothless (tl) is a Loss-of-Function Frameshift Mutation in the Rat Csfl Gene Evidence for Crucial Role for CSF-1 in Osteoclastogenesis and Endochondral Ossification. Proceedings of the National Academy of Sciences of the f/5A99, 14303-14308. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

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