Missense mutations code for different amino acids, which may or may not alter the activity of a protein; and, nonsense mutations code for a stop codon, or premature termination codon (PTC+) which alters the code to that for a truncated protein. Nonsense mutations elicit nonsense-mediated mRNA decay (NMD).
Substitution mutations involve the replacement of one or more nucleotides with an equal number of different nucleotides – most substitutions involve a change in only one nucleotide (point mutations, single nucleotide polymorphisms). Because an equal number of nucleotides are substituted, frameshift is not a problem.
Deletions or insertions of short regions can occur by strand slippage, and deletions or insertions of longer regions can occur via homologous recombination. Deletion and insertion mutations often occur in repetitive sequences, such as deletion of "AT" from the sequence "ATAT" in the CFTR gene. Such mutations are most often caused by a "replication slippage", where the new strand mispairs with the template strand at repetitive sequences. Slippage can cause mispairing of several repeats. Forward slippage results in deletion mutations, while backward slippage results in insertions.
Replication slippage is mainly responsible for microsatellite polymorphisms, which are also called short tandem repeats (STR). In microsatellites, the repeat unit comprises only 1 to 6 bp and the whole repetitive region spans less than 150 bp, while minisatellites range from 1 to 20 kb, and satellites span from 100 kb to more than 1 Mb.
Mobile elements called insertion sequences exist in nature. These sequences encode only the information necessary for their insertion into DNA. Depending upon the particular insertion sequence, they can insert at specific regions or at random.
If the number of inserted bases is not a multiple of 3, insertion will cause frameshift, with serious consequences. A number of diseases are caused by insertions without frameshift - Huntington's chorea, Myotonic Dystrophy, Fragile X site A, Fragile X site E, Fragile X site F, Kennedy disease, SCA1, DRPLA.
External : Tandem repeats and morphological variation