Editing Frameshift mutation (section)

====Frequency====

Despite the rules that govern the genetic code and the various mechanisms present in a cell to ensure the correct transfer of genetic information during the process of DNA replication as well as during translation, mutations do occur; frameshift mutation is not the only type. There are at least two other types of recognized point mutations, specifically [[missense mutation]] and [[nonsense mutation]].<ref name=MBoG_6th_2008/> A frameshift mutation can drastically change the coding capacity (genetic information) of the message.<ref name=MBoG_6th_2008/> Small insertions or deletions (those less than 20 base pairs) make up 24% of mutations that manifest in currently recognized genetic disease.<ref name="predicting frameshifts">{{cite journal|last=Hu|first=J|author2=Ng, PC|title=Predicting the effects of frameshifting indels.|journal=Genome Biology|date=9 February 2012|volume=13|issue=2|pages=R9|pmid=22322200 |doi=10.1186/gb-2012-13-2-r9|pmc=3334572|doi-access=free}}</ref>

Frameshift mutations are found to be more common in repeat regions of DNA. A reason for this is because of slipping of the polymerase enzyme in repeat regions, allowing for mutations to enter the [[sequence]].<ref name="editing frameshift mutation">{{cite journal|last=Harfe|first=BD|author2=Jinks-Robertson, S|title=Removal of frameshift intermediates by mismatch repair proteins in Saccharomyces cerevisiae.|journal=Molecular and Cellular Biology|date=July 1999|volume=19|issue=7|pages=4766–73|pmid=10373526|pmc=84275|doi=10.1128/MCB.19.7.4766}}</ref> [[Experiment]]s can be run to determine the frequency of the frameshift mutation by adding or removing a pre-set number of nucleotides. Experiments have been run by adding four basepairs, called the +4 experiments, but a team from [[Emory University]] looked at the difference in frequency of the mutation by both adding and deleting a base pair. It was shown that there was no difference in the frequency between the addition and deletion of a base pair. There is however, a difference in the result of the protein.<ref name="editing frameshift mutation" />

[[Huntington's disease]] is one of the nine codon reiteration disorders caused by polyglutamine expansion mutations that include spino-cerebellar ataxia (SCA) 1, 2, 6, 7 and 3, spinobulbar muscular atrophy and dentatorubal-pallidoluysianatrophy. There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations, as frame shifting of the original SCA3 gene product encoding CAG/polyglutamines to GCA/polyalanines. Ribosomal slippage during translation of the SCA3 protein has been proposed as the mechanism resulting in shifting from the polyglutamine to the polyalanine-encoding frame. A dinucleotide deletion or single nucleotide insertion within the polyglutamine tract of huntingtin exon 1 would shift the CAG, polyglutamineen coding frame by +1 (+1 frame shift) to the GCA, polyalanine-encoding frame and introduce a novel epitope to the C terminus of Htt exon 1 (APAAAPAATRPGCG).<ref>{{cite journal|last=Davies|first=J E|author2=Rubinsztein, D C|title=Polyalanine and polyserine frameshift products in Huntington's disease|journal=Journal of Medical Genetics|volume=43|issue=11|pages=893–896|doi=10.1136/jmg.2006.044222 |pmid=16801344 |pmc=2563184 |year=2006}}</ref>