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Wednesday, January 09, 2008

Frame Shit mutations Reading frame changes downstream to the mutant site

034. Base substitution mutations can have be following molecular consequences except:

1. Changes one codon for an amino acid into another codon for that same amino acid

2. Codon for one amino acid is changed into a codon of another amino acid

3. Reading frame changes downstream to the mutant site

4. Codon for one amino acid is changed into a translation termination codon

Answer

3. Reading frame changes downstream to the mutant site

Reference:

Harper 26th Edition Page 361

Lippincott 3rd Edition Page 431

Chaterjee 6th Edition Page 249

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Discussion

Changing a single nucleotide base on the mRNA chain (a point mutation) can lead to any one of the three results.

1. Silent mutation : The codon containing the changed base may code for the same amino acid. For example, if the series codon UCA is given a different third base-U- to become UCU, it still codes for serine. There fore this is termed a “silent” mutation

2. Missense mutation : The codon containing the changed base may code for a different amino acid. For example, if the serine codon UCA is given a different first base-C-to become CCA, it will code for a different amino acid, in this acse, praline. This substitution f an incorrect amino acid is called a “missense” mutation

3. Nonsense mutation : The codon containing the changed base may become a termination codon. For example, if the serine codon UCA is given a different second base-A-to become UAA, the new codon causes termination of translation at that point. The creation of a termination codon at an inappropriate place is called a “nonsense” mutation

Explanation

1. Silent mutation Changes one codon for an amino acid into another codon for that same amino acid

2. Codon for one amino acid is changed into a codon of another amino acid in Missense mutation

3. Reading frame changes downstream to the mutant site in Frameshift mutation

4. Codon for one amino acid is changed into a translation termination codon in terminal mutation

Comments

Frameshift mutations can be of two types

1. Deletion type :

2. Insertion type

Example of Frameshift mutation are

1. Hb Constant spring : elongation of alpha chain – extra 31 amino acids (Total 172)

2. HbWayne elongation of alpha chain total 147

Tips

The deletion (or insertion) of a single nucleotide from the coding strand of a gene results in an altered reading frame in the m-RNA (hence called as the frame shift mutation). The machinery translating the m-RNA does not recognize that a base is missing since there is no punctuation in the reading of codons. Thus a major alteration in the sequence of the amino acids in the protein molecule occur. Such an alteration in the reading frame results in a garbled translation of the m-RNA distal to the single nucleotide deletion.

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