What mutation does not affect the length of a protein?

Learning Objectives

• Classify mutations in coding regions as silent, nonsense, missense, or frameshift.

The effect of a mutation will depend upon the function of the DNA sequence. Mutations in non-protein coding regions could occur in regulatory regions that affect genes or have no effect on a cell or organism.

When mutations occur in coding sequences, we can predict the effect on the primary structure of the protein using the codon table.

Both frameshift and nonsense mutations are likely to affect protein function by producing a shortened or extremely altered peptide that is unlikely to retain enough structure to perform the intended function. However, a frameshift or nonsense mutation that occurs near the 3' end of the gene might allow the protein to retain the ability to function. 

Silent mutations are least likely to affect protein function.

Missense mutations are often difficult to predict. If the change is to a similar amino acid or in a non-critical amino acid, the mutation protein may continue to function. However, if the amino acid is changed to a different type of amino acid or removes a critical amino acid (in terms of structure or activity), then the mutant protein may change in activity. 

Mutations that reduce the function of a gene product are called loss-of-function. If the gene product is completely non-functional, the allele is termed a null allele. Loss-of-function and null alleles are usually (but not always) recessive in diploid organisms, because one functional allele can usually supply enough protein product. 

Some mutations actually make proteins more active, for example, by altering an inhibitory domain; these mutations are called gain-of-function. Gain-of-function alleles are often dominant alleles because their new function or activity is produced independently of the other allele. 

A missense mutation is a DNA change that results in different amino acids being encoded at a particular position in the resulting protein. Some missense mutations alter the function of the resulting protein.

Missense Mutation. Missense mutations can also be benign and change an amino acid in a protein without altering its function.

Lawrence Brody, Ph.D.

Director

Division of Genomics and Society

A nonsense mutation occurs in DNA when a sequence change gives rise to a stop codon rather than a codon specifying an amino acid. The presence of the new stop codon results in the production of a shortened protein that is likely non-functional.

A nonsense mutation, or its synonym, a stop mutation, is a change in DNA that causes a protein to terminate or end its translation earlier than expected. This is a common form of mutation in humans and in other animals that causes a shortened or nonfunctional protein to be expressed.

The DNA sequence of a gene can be altered in a number of ways. Gene variants (also known as mutations) can have varying effects ­­on health, depending on where they occur and whether they alter the function of essential proteins. Variant types include the following:

Substitution

This type of variant replaces one DNA building block (nucleotide) with another. Substitution variants can be further classified by the effect they have on the production of protein from the altered gene.

• Missense: A missense variant
  
    is a type of substitution in which the nucleotide change results in the replacement of one protein building block (amino acid) with another in the protein made from the gene. The amino acid change may alter the function of the protein.

• Nonsense: A nonsense variant
  
    is another type of substitution. Instead of causing a change in one amino acid, however, the altered DNA sequence results in a stop signal that prematurely signals the cell to stop building a protein. This type of variant results in a shortened protein that may function improperly, be nonfunctional, or get broken down.

Insertion

An insertion

Deletion

A deletion

Deletion-Insertion

This variant occurs when a deletion and insertion happen at the same time in the same location in the gene. In a deletion-insertion variant, at least one nucleotide is removed and at least one nucleotide is inserted. However, the change must be complex enough to differ from a simple substitution. The resulting protein may not function properly. A deletion-insertion (delins) variant may also be known as an insertion-deletion (indel) variant.

Duplication

A duplication

Inversion

An inversion changes more than one nucleotide in a gene by replacing the original sequence with the same sequence in reverse order.

Frameshift

A reading frame consists of groups of three nucleotides that each code for one amino acid

Repeat expansion

Some regions of DNA contain short sequences of nucleotides that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of sequences of three nucleotides, and a tetranucleotide repeat is made up of sequences of four nucleotides. A repeat expansion