Microsatellite instability

Microsatellite instability (MSI) is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). The presence of MSI represents phenotypic evidence that MMR is not functioning normally.

MMR corrects errors that spontaneously occur during DNA replication, such as single base mismatches or short insertions and deletions. The proteins involved in MMR correct polymerase errors by forming a complex that binds to the mismatched section of DNA, excises the error, and inserts the correct sequence in its place. Cells with abnormally functioning MMR are unable to correct errors that occur during DNA replication and consequently accumulate errors. This causes the creation of novel microsatellite fragments. Polymerase chain reaction-based assays can reveal these novel microsatellites and provide evidence for the presence of MSI.

Microsatellites are repeated sequences of DNA. These sequences can be made of repeating units of one to six base pairs in length. Although the length of these microsatellites is highly variable from person to person and contributes to the individual DNA "fingerprint", each individual has microsatellites of a set length. The most common microsatellite in humans is a dinucleotide repeat of the nucleotides C and A, which occurs tens of thousands of times across the genome. Microsatellites are also known as simple sequence repeats (SSRs).

Microsatellite instability structure consists of repeated nucleotides, most often seen as GT/CA repeats.

Researchers have yet to confirm the precise definition of the MSI structure. While all researchers agree that microsatellites are repeat sequences, the lengths of the sequences remain in question. Some research suggest that MSIs are short tandem DNA repeat sequences of one to six base pairs throughout the genome, while other research suggests that the range may be two to five.

Although researchers do not agree on a specific threshold for the number of tandem repeats that constitute a microsatellite, there is a consensus around their relative size. Longer sequences are called minisatellite, and even longer sequences are called satellite DNA sites. Some scientists distinguish among the three categories by a minimum number of base pairs, and others use a minimum number of repeated units. The majority of repeats occur in untranslated regions, specifically introns. However, microsatellites that occur in coding regions often inhibit the expansion of most downstream events. Microsatellites make up approximately three percent of the human genome, or more than one million fragments of DNA. Microsatellite density increases with genome size and is seen twice as much at the ends of chromosome arms than in the chromosome bodies.

...
Wikipedia