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Definição e significado de Minisatellite

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minisatellite (n.)

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Minisatellite

                   

A minisatellite (also referred as VNTR) is a section of DNA that consists of a short series of bases 10-60 bp.[1][2] These occur at more than 1,000 locations in the human genome. Some minisatellites contain a central (or "core") sequence of letters “GGGCAGGANG” (where N can be any base) or more generally a strand bias with purines (adenosine (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 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 phenomena). When such events occur, mistakes are made, thus causing minisatellites at over 1000 locations in a person's genome to have slightly different numbers of repeats, thereby making each individual unique. The most highly mutable minisatellite locus described so far is CEB1 (D2S90) described by Vergnaud.[3]

Minisatellites have been confused with Microsatellites (also called as Short Tandem Repeats or STRs). STRs are also repeated sequences, but they are usually 2-13 nucleotides long. The term minisatellite has been interchangeably used with VNTRs at many places.

Contents

  Structure

"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.

  Application

Since the fortuitous discovery of the first human minisatellite in 1980 by A.R. Wyman and R. White[4] and especially the discovery that the extreme polymorphism of minisatellites made them superb for DNA fingerprinting by Alec Jeffreys,[5] 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.

  Pathology

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.[6]

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.

  Evolutionary aspects

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.

  Types

  Hypervariable minisatellites

These have core units 9–24 bp long and are found mainly at the centromeric regions.

  Telomeric minisatellites

These have core units 6 bp long, and have thousands of repeated sequences at the telomeres.

  Location

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 ...

  See also

  References

  1. ^ "minisatellite" at Dorland's Medical Dictionary
  2. ^ Minisatellite at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Buard J, Vergnaud G (July 1994). "Complex recombination events at the hypermutable minisatellite CEB1 (D2S90)". EMBO J. 13 (13): 3203–10. PMC 395212. PMID 8039512. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=395212. 
  4. ^ Wyman AR, White R (November 1980). "A highly polymorphic locus in human DNA". Proc. Natl. Acad. Sci. U.S.A. 77 (11): 6754–8. DOI:10.1073/pnas.77.11.6754. PMC 350367. PMID 6935681. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=350367. 
  5. ^ Jeffreys AJ (October 2005). "Genetic fingerprinting". Nat. Med. 11 (10): 1035–9. DOI:10.1038/nm1005-1035. PMID 16211029. 
  6. ^ Vergnaud G, Denoeud F (July 2000). "Minisatellites: mutability and genome architecture". Genome Res. 10 (7): 899–907. DOI:10.1101/gr.10.7.899. PMID 10899139. http://www.genome.org/cgi/pmidlookup?view=long&pmid=10899139. 
   
               

 

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