A frameshift mutation is a genetic defect that results in the production of abnormal, often non-functioning, proteins. An error in the sequence of genetic information causes the cell’s protein synthesis machinery to link amino acids together in the wrong order. Frameshift mutations are associated with a number of different human diseases, including Tay Sachs disease.
In order to understand why a frameshift mutation can cause disease, it helps to understand the basics of how proteins are made. The code for all proteins is in the deoxyribonucleic acid (DNA) stored in the nuclei of cells, and this DNA is made up of linked molecules known as nucleotides. To make a protein, the first step is for a molecule known as messenger ribonucleic acid (mRNA) to make a copy of the DNA. The mRNA then travels outside of the nucleus and is converted from a nucleotide sequence into a chain of amino acids with the help of structures known as ribosomes, in a process known as translation. Proteins are formed from these chains of amino acids.
During translation, a three-nucleotide sequence of mRNA called a codon specifies which amino acid should be linked up next. It is important to maintain the integrity of codons so the ribosome can link the correct amino acids together and form the correct protein. When a frameshift mutation occurs, there is an error in the mRNA sequence that results in the codons being read incorrectly.
For example, a possible mRNA sequence might be UUUAAAGGG, where each letter represents a nucleotide. The normal codons would thus be UUU, AAA, and GGG. If an error occurs in the mRNA, it may result in the sequence GUUUAAAGGG. The ribosome would read the codons as GUU, UAA, and AGG because the frame of reference was shifted by an extra nucleotide. As a result, either the incorrect amino acids would be linked together and the wrong protein would be made, or a codon might be read as a signal to stop, thus prematurely truncating the protein.
There are a number of different ways that a frameshift mutation can occur. It could occur by the insertion of one nucleotide, or it could also result from the deletion of a nucleotide. If three nucleotides are deleted, this would not be considered a frameshift mutation because the codons that come after the mutation are read normally, and they have not been shifted out of their normal frames.
Many different human diseases can result from a frameshift mutation. Tay Sachs disease, an inherited condition that typically results in death at a very young age, can be caused by a frameshift mutation. The genetic mutations can also be associated with the development of more common diseases, such as different types of cancers.