Codons genetic mutations

A base substitution can also result in the formation of a new inappropriate terminator (or non-sense) codon, and are thus known as non-sense mutations. The polypeptide formed from such mutated genes will be shorter than normal and is most likely to be inactive. Owing to the redundancy of the genetic code, about a quarter of all possible base substitutions will not result in an amino acid replacement and will be silent mutations. 

A 1-year-old toddler with cystic fibrosis (CF) is seen by his physician for an upper respiratory infection with Pseudomonas aeruginosa. He is started on oral norfloxacin and referred to a CF center as i potential candidate for gene therapy. Prior genetic testing of the patient identified the mutation causing cystic fibrosis as a 3-base-pair deletion in esan 10 of the CF gene. The nucleotide sequences f codons 506-511 in this region of the normal and mutant alleles are compared below. 

Although virologic failures have been uncommon in clinical trials of raltegravir to date, in vitro resistance requires only a single point mutation (eg, at codons 148 or 155). The low genetic barrier to resistance emphasizes the importance of combination therapies and of adherence. Integrase mutations are not expected to affect sensitivity to other classes of antiretroviral agents. 

Suppressor tRNAs constitute an experimentally induced variation in the genetic code to allow the reading of what are usually termination codons, much like the naturally occurring code variations described in Box 27-2. Nonsense suppression does not completely disrupt normal information transfer in a cell, because the cell usually has several copies of each tRNA gene some of these duplicate genes are weakly expressed and account for only a minor part of the cellular pool of a particular tRNA. Suppressor mutations usually involve a minor tRNA, leaving the major tRNA to read its codon normally. 

The mutation that leads to creation of a suppressor tRNA does not always occur in the anticodon. The suppression of UGA nonsense codons generally involves the tRNATlp that normally recognizes UGG. The alteration that allows it to read UGA (and insert Trp residues at these positions) is a G to A change at position 24 (in an arm of the tRNA somewhat removed from the anticodon) this tRNA can now recognize both UGG and UGA. A similar change is found in tRNAs involved in the most common naturally occurring variation in the genetic code (UGA = Trp see Box 27-2). 

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