A frameshift is a [[Genetic_mutation}genetic mutation]] caused by one or more nucleotides being inserted or deleted in a DNA sequence. As nucleotides are translated by the ribosomes in triplet codons, if the number of nucleotides being inserted or deleted is not divisible by three, then the sequence of amino acids downstream from the mutation is completely changed and the end product polypeptide will be changed. These kinds of mutations are called frameshifts as they cause the reading frames of the mRNA to 'shift' in a certain direction and give a different result to the original.
One or more nucleotides are added to the DNA sequence. This results in a longer triplet codon sequence, which when translated produces a different protein. This most commonnly happens in microsatillite regions due to the DNa polymerase slippage.
One or more nucleotides are removed from the DNA sequence
What are the consequences of frameshifts?
As the entire nucleotide after the point of mutation is altered, a different sequences of amino acids is coded for and subsequently the protein made will be different to intended. The shifted reading frame changes the point at which the stop codon will occur, therefore the protein could be terminated before it is fully sequenced or the nucleotide sequence will just continue to be translated until a stop codon is reached, which could lead to the protein being longer than intended. These changes to the gene sequence and consequently the proteins being made can have very serious effects on the organism;
- Cancer - Frameshifts are known to be a factor in colorectal cancer and in the case of prostate cancer; prevent apoptosis from occuring, leading to tumour formation.
- Cystic Fibrosis - The mutation that causes cystic fibrosis deletes an entire amino acid, causing a frameshift.
- Tay-Sachs Disease - Starts in the womb and is caused by several frameshift mutations.
- ↑ Hartl et al. (2009) Genetics: Analysis of genes and genomes, 7th Edition - Chapter 10: Pages 368 - 369 and Chapter 14: Pages 515 - 516