Minisatellite
Encyclopedia
A minisatellite is a section of DNA
that consists of a short series of bases 10-60 bp. 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 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 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.
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.
. These variant repeats are tandemly intermingled, which makes minisatellites ideal for studying DNA
turnover mechanisms.
, 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 marker
s 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 frame
s.
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 hotspot
s in the human genome.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
that consists of a short series of bases 10-60 bp. These occur at more than 1,000 locations in the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
. 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
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
(G)) on one strand and pyrimidines (cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
(C) and thymine
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
(T)) 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 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.
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.
Structure
"Minisatellites" consist of repetitive, generally GC-rich, variant repeats that range in length from 10 to over 100 bpBase pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
. These variant repeats are tandemly intermingled, which makes minisatellites ideal for studying DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
turnover mechanisms.
Application
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 JeffreysAlec Jeffreys
Sir Alec John Jeffreys, FRS is a British geneticist, who developed techniques for DNA fingerprinting and DNA profiling which are now used all over the world in forensic science to assist police detective work, and also to resolve paternity and immigration disputes...
, 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
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
, minisatellites have been extensively used for DNA fingerprinting as well as for genetic marker
Genetic marker
A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify cells, individuals or species. It can be described as a variation that can be observed...
s in linkage analysis and population studies.
Minisatellites have also been implicated as regulators of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
(e.g., at levels of transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
, or imprint control) or as part of bona fide open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
s.
Pathology
Minisatellites have been associated with chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
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
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
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 hotspot
Recombination hotspot
Recombination hotspots are small regions in the genome of sexually reproducing organisms that exhibit highly elevated rates of meiotic recombination. The peak recombination rate within hotspots can be hundreds or thousands of times that of the surrounding region. The PRDM9 protein is suspected to...
s 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.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
- Fragile X
- Microsatellite
- Tandem repeatTandem repeatTandem repeats occur in DNA when a pattern of two or more nucleotides is repeated and the repetitions are directly adjacent to each other. -Example:An example would be:in which the sequence A-T-T-C-G is repeated three times.-Terminology:...
- TelomereTelomereA telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos "end" and merοs "part"...