What are Missense Mutations?

A missense mutation is a type of genetic mutation in which a single base is replaced with another base, changing one “letter” in the coding sequence of DNA. Depending on where the mutation occurs and which base is changed, a missense mutation can lead to health problems or may result in no functional change. Several genetic conditions have been linked to missense mutations, and these mutations are also associated with a number of cancers.

This mutation is an example of a point mutation, in which a single nucleotide base in changed. In a transition, a purine is swapped for another purine, or a pyrimidine is swapped for another pyrimidine. In transversions, a purine and pyrimidine are swapped. Either changes the DNA sequence, which means that the DNA may code for a different protein than it is supposed to in healthy individuals. Depending on where on the gene the mutation occurs, this can cause a variety of consequences when the DNA codes a different protein.

In some cases, there is no functional change, or there is a change, but it is minimal. In others, the swap causes severe complications, because the body builds a totally different protein. Some examples of genetic conditions caused by missense mutations include some forms of cystic fibrosis, sickle cell anemia, and amyotrophic lateral sclerosis (ALS or Lou Gehrig's Disease). Missense mutations have also been linked with cancers which occur when cell division gets out of control. In order to confirm that a missense mutation has occurred, it is necessary to know which genes are involved in a patient's condition, and to identify the precise locations on the gene where abnormalities are occurring.

Many missense mutations are spontaneous, caused by errors in cell division which caused a transversion or a transition. Others may be caused by exposure to mutagens, such as hazardous gases. The first missense mutations were identified in the 1950s, and understanding of how such mutations work has greatly expanded since then, thanks to DNA sequencing and a greater understanding of the genome.

When a missense mutation does not cause a functional change, it is sometimes known as a conservative or silent mutation. People may be entirely unaware of the fact that they carry a mutation in these cases. Missense mutations which do result in changes are constantly being identified. Medical understanding of genetic diseases is also shifting in response to this new information, as researchers learn that the severity of genetic conditions can greatly vary, depending on the variations within an individual patient's genetic material.