Minisatellite
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- This article is about the DNA sequence. See also miniaturized satellite for the size class of orbiting spacecraft
A minisatellite is a section of DNA that consists of a short series of bases 10-100bp, these occur at more than 1000 locations in the human genome. Some minisatellites contain a central (or "core") sequence of letters “GGGCAGGAXG” (where X can be any letter) or more generally a strand bias with purines on one strand and pyrimidines on the other. It has been proposed that this sequence per se encourages chromosomes to swap DNA. In alternative models, it is the presence of a neighbouring cis-acting meiotic double-strand break hotspot 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 phenomenons). When such events occur, mistakes are made, this causes minisatellites at over 1000 locations in a persons genome to have slightly different numbers of repeats, thereby making them unique. The most highly mutable minisatellite locus described so far is CEB1 (D2S90) described by Vergnaud.
"Minisatellites" consist of repetitive, generally GC-rich, variant repeats that range in length from 10 to over 100 bp. These variant repeats are tandemly intermingled, which makes minisatellites ideal for studying DNA turnover mechanisms.
Since the fortuitous discovery of the first human minisatellite in 1980 by A.R. Wyman and R. White and especially the discovery that the extreme polymorphism of minisatellites made them superb for DNA fingerprinting by Alec Jeffreys, this class of repeats has been an intense focus of studies that have 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 also been implicated as regulators of gene expression (e.g., at levels of transcription, alternative splicing, or imprint control) or as part of bona fide open reading frames.
Finally, 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 that 0.5% up to over 20%, making them the most unstable region in the human genome known to date. It is interesting to note that 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 (reviewed by Vergnaud and Denoeud, Genome Research 2000).
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.
Finally, 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 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 ...
