Variable number tandem repeat
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A variable number tandem repeat (or VNTR) is a location in a
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
where a short nucleotide sequence is organized as a tandem repeat. These can be found on many
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
s, and often show
variations Variation or Variations may refer to: Science and mathematics * Variation (astronomy), any perturbation of the mean motion or orbit of a planet or satellite, particularly of the moon * Genetic variation, the difference in DNA among individua ...
in length (number of repeats) among individuals. Each variant acts as an inherited
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...
, allowing them to be used for personal or parental identification. Their analysis is useful in
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar work ...
and
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary ...
research,
forensics Forensic science, also known as criminalistics, is the application of science to criminal and civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standards of admissible evidence and crimin ...
, and
DNA fingerprinting DNA profiling (also called DNA fingerprinting) is the process of determining an individual's DNA characteristics. DNA analysis intended to identify a species, rather than an individual, is called DNA barcoding. DNA profiling is a forensic t ...
.


Structure and allelic variation

In the schematic above, the rectangular blocks represent each of the repeated DNA sequences at a particular VNTR location. The repeats are in tandem – i.e. they are clustered together and oriented in the same direction. Individual repeats can be removed from (or added to) the VNTR via recombination or replication errors, leading to alleles with different numbers of repeats. Flanking regions are segments of non-repetitive sequence (shown here as thin lines), allowing the VNTR blocks to be extracted with
restriction enzyme A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class ...
s and analyzed by RFLP, or amplified by the
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR) technique and their size determined by
gel electrophoresis Gel electrophoresis is a method for separation and analysis of biomacromolecules ( DNA, RNA, proteins, etc.) and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size (IEF ...
.


Use in genetic analysis

VNTRs were an important source of RFLP
genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...
s used in
linkage analysis Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be sepa ...
(mapping) of diploid genomes. Now that many genomes have been sequenced, VNTRs have become essential to
forensic Forensic science, also known as criminalistics, is the application of science to criminal and civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standards of admissible evidence and criminal p ...
crime investigations, via
DNA fingerprint DNA profiling (also called DNA fingerprinting) is the process of determining an individual's DNA characteristics. DNA analysis intended to identify a species, rather than an individual, is called DNA barcoding. DNA profiling is a forensic tec ...
ing and the
CODIS The Combined DNA Index System (CODIS) is the United States national DNA database created and maintained by the Federal Bureau of Investigation. CODIS consists of three levels of information; Local DNA Index Systems (LDIS) where DNA profiles ori ...
database. When removed from surrounding DNA by the PCR or RFLP methods, and their size determined by gel electrophoresis or
Southern blot A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detecti ...
ting, they produce a pattern of bands unique to each individual. When tested with a group of independent VNTR markers, the likelihood of two unrelated individuals' having the same allelic pattern is extremely low. VNTR analysis is also being used to study
genetic diversity Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is dis ...
and breeding patterns in
populations Population typically refers to the number of people in a single area, whether it be a city or town, region, country, continent, or the world. Governments typically quantify the size of the resident population within their jurisdiction using a ...
of wild or domesticated animals. As such, VNTRs can be used to distinguish strains of bacterial pathogens. In this microbial forensics context, such assays are usually called Multiple Loci VNTR Analysis or
MLVA Multiple loci VNTR analysis (MLVA) is a method employed for the genetic analysis of particular microorganisms, such as pathogenic bacteria, that takes advantage of the polymorphism of tandemly repeated DNA sequences. A " VNTR" is a "variable-numbe ...
.


Inheritance

In analyzing VNTR data, two basic genetic principles can be used: * Identity Matching – both VNTR alleles from a specific location must match. If two samples are from the same individual, they must show the same allele pattern. * Inheritance Matching – the VNTR alleles must follow the rules of inheritance. In matching an individual with his parents or children, a person must have an allele that matches one from each parent. If the relationship is more distant, such as a grandparent or sibling, then matches must be consistent with the degree of relatedness.


Relationship to other types of repetitive DNA

Repetitive DNA, representing over 40% of the human genome, is arranged in a bewildering array of patterns. Repeats were first identified by the extraction of
Satellite DNA Satellite DNA consists of very large arrays of tandemly repeating, non-coding DNA. Satellite DNA is the main component of functional centromeres, and form the main structural constituent of heterochromatin. The name "satellite DNA" refers to the ...
, which does not reveal how they are organized. The use of restriction enzymes showed that some repeat blocks were interspersed throughout the genome.
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. T ...
later showed that other repeats are clustered at specific locations, with tandem repeats being more common than inverted repeats (which may interfere with DNA replication). VNTRs are the class of clustered tandem repeats that exhibit allelic variation in their lengths.


Classes

VNTRs are a type of minisatellite in which the size of the repeat sequence is generally ten to one hundred base pairs. Minisatellites are a type of DNA tandem repeat sequence, meaning that the sequences repeat one after another without other sequences or nucleotides in between them. Minisatellites are characterized by a repeat sequence of about ten to one hundred nucleotides, and the number of times the sequence repeats varies from about five to fifty times. The sequences of minisatellites are larger than those of
microsatellite A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
s, in which the repeat sequence is generally 1 to 6 nucleotides. The two types of repeat sequences are both tandem but are specified by the length of the repeat sequence. VNTRs, therefore, because they have repeat sequences of ten to one hundred nucleotides in which every repeat is exactly the same, are considered minisatellites. However, while all VNTRs are minisatellites, not all minisatellites are VNTRs. VNTRs can vary in number of repeats from individual to individual, as where some non-VNTR minisatellites have repeat sequences that repeat the same number of times in all individuals containing the tandem repeats in their genomes.https://www2.le.ac.uk/departments/mathematics/redundant-content/event-microsites/bio/Dubrova.pdf


See also

* AFLP *
MLVA Multiple loci VNTR analysis (MLVA) is a method employed for the genetic analysis of particular microorganisms, such as pathogenic bacteria, that takes advantage of the polymorphism of tandemly repeated DNA sequences. A " VNTR" is a "variable-numbe ...
*
Short tandem repeat A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
* Tandem repeat


Software for MLVA typing

* BioNumerics (using th
BioNumerics MIRU-VNTR plugin
specifically developed for running a popular MLVA assay genotyping ''
Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on it ...
'' strains)


References


External links

*Examples : *
VNTRs
– info and animated example *Databases : *
The Microorganisms Tandem Repeats Database
*
The MLVAbank
*
Short Tandem Repeats Database
*
Tandem Repeats Database (TRDB)
*Search tools :
TAPO: A combined method for the identification of tandem repeats in protein structures
*

*
Mreps
*
STAR
*
TRED
*

*
Microsatellite repeats finder
*
JSTRING – Java Search for Tandem Repeats in genomes
*

* {{Repeated sequence Repetitive DNA sequences