<P> Sanger sequencing and pyrosequencing are two methods that have been used to detect frameshift mutations, however, it is likely that data generated will not be of the highest quality . Even still, 1.96 million indel s have been identified through Sanger sequencing that do not overlap with other databases . When a frameshift mutation is observed it is compared against the Human Genome Mutation Database (HGMD) to determine if the mutation has a damaging effect . This is done by looking at four features . First, the ratio between the affected and conserved DNA, second the location of the mutation relative to the transcript, third the ratio of conserved and affected amino acids and finally the distance of the indel to the end of the exon . </P> <P> Massively Parallel Sequencing is a newer method that can be used to detect mutations . Using this method, up to 17 gigabases can be sequenced at once, as opposed to limited ranges for Sanger sequencing of only about 1 kilobase . Several technologies are available to perform this test and it is being looked at to be used in clinical applications . When testing for different carcinomas, current methods only allow for looking at one gene at a time . Massively Parallel Sequencing can test for a variety of cancer causing mutations at once as opposed to several specific tests . An experiment to determine the accuracy of this newer sequencing method tested for 21 genes and had no false positive calls for frameshift mutations . </P> <P> A US patent (5,958,684) in 1999 by Leeuwen, details the methods and reagents for diagnosis of diseases caused by or associated with a gene having a somatic mutation giving rise to a frameshift mutation . The methods include providing a tissue or fluid sample and conducting gene analysis for frameshift mutation or a protein from this type of mutation . The nucleotide sequence of the suspected gene is provided from published gene sequences or from cloning and sequencing of the suspect gene . The amino acid sequence encoded by the gene is then predicted . </P> <P> 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 . A frameshift mutation can drastically change the coding capacity (genetic information) of the message . Small insertions or deletions (those less than 20 base pairs) make up 24% of mutations that manifest in currently recognized genetic disease . </P>

Shift the reading frame of the genetic message