Mutations single base pair substitutions

Krawczak M. and Cooper D.N. (1996). Single base-pair substitutions in pathology and evolution two sides to the same coin. Hum. Mutat. 8 23-31. 

D.N. (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes causes and consequences. Hum. Genet., 90 (1-2), 41-54. 

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... 

Change in Base Sequence in DNA Causing Mutation A change in single base pair in DNA can cause substitution of Bio-organic Chemistry... 

Some strains of Mycobacterium tuberculosis, the causative agent of tuberculosis, are resistant to rifampicin. These strains become resistant through mutations that alter the rpoB gene, which encodes the /3 subunit of the RNA polymerase. Rifampicin cannot bind to the mutant RNA polymerase and so is unable to block the initiation of transcription. DNA sequences from a large number of rifampicin-resistant M. tuberculosis strains have been found to have mutations in a specific 69 bp region of rpoB. One well-characterized strain with rifampicin resistance has a single base pair alteration in rpoB that results in a single amino acid substitution in the J3 subunit a His residue is replaced by an Asp residue. 

The most extensively studied polymorphic alleles are those of 5,10-methylenetetrahydofolate reductase (MTHFR), the enzyme responsible for the irreversible reduction of 5,10-MTHF to 5-methyltetrahydrofoiate (5-MTHF), the methyl donor of homocysteine to methionine. A single point C to T mutation at base pair 677 (C677T), causing a substitution of valine for alanine, leads to a thermolabile protein with reduced enzymatic activity. The homozygous T/T enzyme has an incidence of around 12% in Asian and Caucasian populations, and a loss of enzyme activity of about 50%, and the heterozygous C/T variant can have an incidence of up to 50% in some populations, with a lesser degree of enzyme inactivity. ... 

Mutations can be categorized in several ways. One system is based on the nature of the change, specifically on the number of bases changed. Thus, we distinguish a point mutation, in which a single base pair is changed from a multiple mutation, in which two or more base pairs differ from the wild-type sequence. A point mutation may be a base substitution, a base insertion, or a base deletion, but the term most frequently refers to a base substitution. 

The platinum-DNA adduct that is the major source of mutation induction by cis-DDP is a matter of controversy. One study (17) found platinated d(GpNpG) sequences to be the most mutagenic loci for base pair substitution. Another (18) reported that d(ApG) and d(GpG) cross-links accounted for 90% of single base pair mutations, and that d(ApG) crosslinks were five times more mutagenic. This conflict may be due to the different systems used for these studies, and the range of mutations they detect. Site-specifically modified M13 genomes were constructed in part to answer the question of the mutability of individual platinum-DNA adducts... 

Alterations affecting single genes are termed point mutations. This category includes base pair substitutions and frame-shift mutations, in addition to other small deletions and insertions. For point mutations, the in vitro test systems are forward and reverse mutation assays in bacteria yeast ( ), fungi ( ), and mammalian cell cultures (b-1T),... 

Eighty distinct mutations in type I AT deficiency, ranging from single nucleotide substitutions, to deletion or insertion of a small number of nucleotides of 22 base pairs or less, to major deletions of either a part of or the entire AT gene, have been recognized (83). 

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