What is it??

A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame (the grouping of the codons), resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein. A frameshift mutation is not the same as a single-nucleotide polymorphism in which a nucleotide is replaced, rather than inserted or deleted. A frameshift mutation will in general cause the reading of the codons after the mutation to code for different amino acids. The frameshift mutation will also alter the first stop codon ("UAA", "UGA" or "UAG") encountered in the sequence. The polypeptide being created could be abnormally short or abnormally long, and will most likely not be functional.

Association with Diseases

Frameshift is one of the three classes of recoding. Frame-shifts lead to waste of energy, resources and activity of the biosynthetic machinery. In addition, some peptides synthesized after frame-shifts are probably cytotoxic which serve as plausible cause for innumerable number of diseases and disorders such as muscular dystrophies, lysosomal storage disorders, and cancer. Hidden stop codons occur naturally in coding sequences among all organisms. These codons are associated with the early termination of translation for incorrect reading frame selection and help to reduce the metabolic cost related to the frameshift events.

Frameshift mutations are apparent in severe genetic diseases such as Tay-Sachs disease and Cystic Fibrosis; they increase susceptibility to certain cancers and classes of familial hypercholesterolaemia; in 1997,a frameshift mutation was linked to resistance to infection by the HIV retrovirus. Other diseases due to these mutations are Crohn's Disease, Tay-Sachs Disease, Smith-Magenis Syndrome, Hypertrophic Cardiomyopathy, and a lot more..

How to Tackle??

  • FrameOut Tool is a tool to predict the mutational events occuring in genomic sequences through frameshift events. Data is being framed by implementing HMM Algorithm.. Read More..
  • FrameOUT DB is a collection of all available frameshift events and their association with various diseases.. Read More..