A minisatellite, a class of variable number tandem repeat (VNTR), is a section of DNA that consists of a short series of nucleobases (10–60 base pairs). Minisatellites, which are often simply referred to as VNTRs, occur at more than 1,000 locations in the human genome. Minisatellites can sometimes be confused with the other family of VNTR, the microsatellites (also called "Short Tandem Repeats" or STRs), which are also sections of DNA but only consist of around 2–6 base pairs. Thus, minisatellites are longer in length than microsatellites.
"Minisatellites" consist of repetitive, generally GC-rich, variant repeats that range in length from 10 to over 100 base pairs. These variant repeats are tandemly intermingled, which makes minisatellites ideal for studying DNA turnover mechanisms. Some minisatellites contain a central (or "core") sequence of letters “GGGCAGGANG” (where N can be any base) or more generally a strand base with Purines (Adenine (A) and Guanine (G)) on one strand and Pyrimidines (Cytosine (C) and Thymine (T)) on the other. It has been proposed that this sequence encourages chromosomes to swap DNA. In alternative models, it is the presence of a neighbouring double-strand hotspots which is the primary cause of minisatellite repeat copy number variations. Somatic changes are suggested to result from replication difficulties (which might include replication slippage, among other phenomena). When such events occur, mistakes are made, thus causing minisatellites to have slightly different numbers of repeats, thereby making each individual unique.
Since the discovery of the first human minisatellite in 1980 by A.R. Wyman and R. White, this class of repeats has been an intense focus of study that has addressed the turnover mechanisms that provoke their instability. Due to their high level of polymorphism, minisatellites have been extensively used for DNA fingerprinting as well as for genetic markers in linkage analysis and population studies.
Minisatellites have been associated with chromosome fragile sites and are proximal to a number of recurrent translocation breakpoints.
Some human minisatellites (~1%) have been demonstrated to be hypermutable, with an average mutation rate in the germline higher than 0.5% up to over 20%, making them the most unstable region in the human genome known to date. While other genomes (mouse, rat and pig) contain minisatellite-like sequences, none was found to be hypermutable. Since all hypermutable minisatellites contain internal variants, they provide extremely informative systems for analyzing the complex turnover processes that occur at this class of tandem repeat. Minisatellite variant repeat mapping by PCR (MVR-PCR) has been extensively used to chart the interspersion patterns of variant repeats along the array, which provides details on the structure of the alleles before and after mutation.
Studies have revealed distinct mutation processes operating in somatic and germline cells. Somatic instability detected in blood DNA shows simple and rare intra-allelic events two to three orders of magnitude lower than in sperm. In contrast, complex inter-allelic conversion-like events occur in the germline.
Additional analyses of DNA sequences flanking human minisatellites have also revealed an intense and highly localized meiotic crossover hotspot that is centered upstream of the unstable side of minisatellite arrays. Repeat turnover therefore appears to be controlled by recombinational activity in DNA that flanks the repeat array and results in a polarity of mutation. These findings have suggested that minisatellites most probably evolved as bystanders of localized meiotic recombination hotspots in the human genome.
In humans, an expansion of triplet repeats such as CAG is associated with at least 14 disorders including Huntington`s disease.
Studies have shown that the evolutionary fate of minisatellites tends towards an equilibrium distribution in the size of alleles, until mutations in the flanking DNA affect the recombinational activity of a minisatellite by suppressing DNA instability. Such an event would ultimately lead to the extinction of a hypermutable minisatellite by meiotic drive.
In humans, 90% of minisatellites are found at the sub-telomeric region of chromosomes. The telomere sequence itself is a tandem repeat: TTAGGG TTAGGG TTAGGG …
- "minisatellite" at Dorland's Medical Dictionary[dead link]
- Minisatellite at the US National Library of Medicine Medical Subject Headings (MeSH)
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- Human Molecular Genetics By Tom Strachan, Andrew Read, pg. 289