Variable number tandem repeat

A variable number tandem repeat (or VNTR) is a location in a genome where a short nucleotide sequence is organized as a tandem repeat. These can be found on many chromosomes, and often show variations in length between individuals. Each variant acts as an inherited allele, allowing them to be used for personal or parental identification. Their analysis is useful in genetics and biology research, forensics, and DNA fingerprinting.

File:VNTRDemo.gif

Schematic of a Variable Number of Tandem Repeats in 4 alleles.

Variations of VNTR (D1S80) allele lengths in 6 individuals.

VNTR 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 the repeats are segments of non-repetitive sequence (shown here as thin lines), allowing the VNTR blocks to be extracted with restriction enzymes and analyzed by RFLP, or amplified by the polymerase chain reaction (PCR) technique and their size determined by gel electrophoresis.

Use of VNTRs in genetic analysis

VNTRs were an important source of RFLP genetic markers used in linkage analysis (mapping) of diploid genomes. Now that many genomes have been sequenced, VNTRs have become essential to forensic crime investigations, via DNA fingerprinting and the CODIS database. When removed from surrounding DNA by the PCR or RFLP methods, and their size determined by gel electrophoresis or Southern blotting, 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 and breeding patterns in populations 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.

Chromosomal locations of the 13 VNTR loci in the CODIS panel.

VNTR 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, 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 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 of VNTRs

There are two principal families of VNTRs: microsatellites and minisatellites. The former are repeats of sequences less than about 5 base pairs in length (an arbitrary cutoff), while the latter involve longer blocks. Confusing this distinction is the recent use of the terms Short Tandem Repeat (STR) by forensic geneticists and Simple Sequence Repeat (SSR) by plant scientists, which are more descriptive, but whose definitions are similar to that of microsatellites. VNTRs with very short repeat blocks may be unstable - dinucleotide repeats may vary from one tissue to another within an individual, while trinucleotide repeats have been found to vary from one generation to another (see Huntington's disease). The 13 assays used in the CODIS database are usually referred to as STRs, and most analyze VNTRs that involve repeats of 4 base pairs.

See also

• Tandem repeat
• Short tandem repeat
• Microsatellite
• Minisatellite
• MLVA
• AFLP

Software for MLVA typing

• BioNumerics (using the BioNumerics MIRU-VNTR plugin specifically developed for running a popular MLVA assay genotyping Mycobacterium tuberculosis strains)

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
  • Tandem Repeats Finder
  • Mreps
  • STAR
  • TRED
  • TandemSWAN
  • Microsatellite repeats finder
  • JSTRING - Java Search for Tandem Repeats in genomes
  • Phobos - a tandem repeat search tool for perfect and imperfect repeats - the maximum pattern size depends only on computational power
• Variable Number of Tandem Repeats at the US National Library of Medicine Medical Subject Headings (MeSH)