Gene mutation

Gene mutations at the base pair level can affect gene expression or protein function in different ways. Sequence analysis is necessary for the detection of this mutation.

Gene mutations can be divided into point mutations in coding sequences and in non-coding sequences.

Point mutations in coding sequences include:

• Missense (not synonymous): mutations due to substitution of a base resulting in a change in amino acid sequence that may affect protein function.
• Nonsense mutations (stop mutation):base substitution results in the introduction of a stop codon, usually resulting in a truncated, nonfunctional protein.
• Silent(synonymous): In a silent mutation, an exchange of a base does occur. However, this exchange does not result in a change in amino acid sequence. The gene product is usually not affected. However, altered splicing behavior may occur if the consensus sequence of a splice site is affected, or a new splice site is created.
• Frameshift: In a frameshift mutation, insertions or deletions (in/dels) of bases lead to a shift in the reading frame and subsequently to the introduction of a premature stop codon. Either translation of a non-functional protein or premature degradation of the mRNA (Nonsense Mediated RNA Decay) occurs.
• InFrame: In an in-frame mutation, three (or a multiple of three) bases are deleted or inserted. Accordingly, additional or fewer amino acids are incorporated in the protein.

Mutations in noncoding sequences:

• Regulatory: Mutations that occur in regulatory sequences such as promtor and enhancer sequences, which regulate transcription, can affect transcription factor binding or result in a reduction or complete absence of transcription.
• Splice mutations: alterations in intronic sequences can lead to defective splicing behavior.

Trinucleotide repeat mutation: Amplification of a sequence of three repeating nucleotides. Although the number of triplet repeats in a given gene is generally variable, severe alteration of the gene product may occur depending on the number of repeats.

The error-free duplication of genetic information is the prerequisite for all life. Genetic information is based on a linear sequence of nucleotides within a DNA. DNA itself is a double-stranded chemical compound of sugar and phosphoric acid esters and 4 nitrogenous bases: adenine (A), thymine (T), guanine (G), cytosine (C) (see figure).