In vertebrate genome about 10 % of total DNA is formed of repeated fractions. These fractions are formed of a few hundred nucleotides in which a given sequence of nucleotides is repeated over again and again without interruption. These show tandem arrangement. The highly repeated sequences fall into three categories: satellite DNAs, minisatellites DNAs and microsatellites DNAs.
Minisatellites DNA or VNTRs: It is a section of DNA that consists of a short series of bases 10-60 bp. These occur at more than 1000 locations in the human genome. The Mini satellites consists of a short series of bases 10-60 bp. These occur at more than 1000 locations in the human genome. Mini satellites consists 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 mini satellites ideal for studying DNA turn over mechanisms. They are also called Variable Number of Tandem Repeats (VNTRs) because the number of repeats in a given mini satellite varies greatly among individuals.
Significance of Minisatellites: 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.
Microsatellites are repeating sequences of 1-6 base pairs of DNA. Microsatellites are typically neutral and co-dominance. They are used as molecular markers in genetics, for population and other studies. They can also be used to study gene duplication or deletion. One common example of microsatellite is a (CA)n repeat, where n is variable between alleles. These markers often present high levels of inter and intra specific polymorphism. CA nucleotide repeats are very frequent in human and other genomes., and are present every few thousand base pairs. As there are often many alleles present at a microsatellites locus, genotype within pedigrees are often many alleles present at a microsatellite locus, genotypes within pedigree are often fully informative, in that the progenitor of a particular allele can be often be identified. In this way, microsatelltes are ideal for determining paternity, population genetic studies and recombination mapping. It is also the only molecular marked to provide clues about which alleles are more closely related.
In human beings a gene FMR1 under normal conditions has 5 to 60 copies of a triplet CCG. If their repeat number rises above 200, the individual is mentally retarded. This condition is called fragile X syndrome because the microsatellite is present in the fragile site on X chromosome.
Microsatellites associated Human Diseases
- Fragile X syndrome (Gene: FMR1/FMR2)
- Myotonic dystrophy (Gene: DMPK)
- Friedreich ataxia (Gene: X25)
- Kennedy disease (Gene:AR)
- Huntington disease (Gene:HD)
- Haw River Syndrome (Gene:DRPLA)
- Spinocerebellar ataxia (Gene:SCA1)
Significance of Microsatellites
The role of micro and mini satellites in DNA structure or function is not known but their presence has helped in the construction of genetic maps, in the isolation of genes responsible for causing human diseases and in the development of technique of DNA finger printing. This is because the length of short tandem repeats varies from person to person.
Minisatellites vs Microsatellites
| a) Hypervriable family |
Total Size:1000-20,000 bp
b) Telomeric family:
Repeat size: 6 bp
Total size: 1000-20000 bp
| Repeat size: 1-4 bp|
Total sites: Less than 1000 bp
|Share a common core sequence (motif) GGGCAGGANG (where N is any base), dispersed, VNTRs usually TTAGGG and repeated about a thousand times protects chromosome ends.||Repeats A and CA are the most common Dispersed throughout genome.|
|Complexity of Array: Heterogeneous||Complexity of Array: Homogeneous|