Question

Examples of disorders caused by frameshift mutation.

Answer 1

Frameshift mutations are among the most deleterious changes to the coding sequence of a protein. They are extremely likely to lead to large-scale changes to polypeptide length and chemical composition, resulting in a non-functional protein that often disrupts the biochemical processes of a cell. Frameshift mutations can lead to a premature end to translation of the mRNA as well as the formation of an extended polypeptide.
The amino acid sequences downstream of the frameshift mutation are also likely to be chemically distinct from the original sequence. For instance, if a frameshift mutation occurs in an integral transmembrane protein, it could vastly alter the stretch of hydrophobic residues that span the lipid bilayer making it impossible for the protein to be present in its subcellular location. When such errors occur, the cell often perceives the lack of functional protein and tries to compensate by upregulating the expression of the mutated gene. This can even overwhelm the translation machinery of the cell, result in a large number of misfolded proteins that could eventually lead to large-scale impairment of all functions of even cell death.
Diseases caused by frameshift mutations in genes include Crohn’s disease, cystic fibrosis, and some forms of cancer. On the other hand, when some proteins become dysfunctional, they could have a protective effect, as seen in the resistance to HIV in people with a chemokine receptor gene (CCR5) containing a frameshift mutation.
Since frameshift mutations are usually changes to the genetic material in every cell, it is rare to find a cure. Most interventions are palliative.