Microsatellite - Introduction

Introduction

One common example of a microsatellite is a (CA)_n repeat, where n varies between alleles. These markers often present high levels of inter- and intra-specific polymorphism, particularly when the number of repetitions is 10 or greater. The repeated sequence is often simple, consisting of two, three or four nucleotides (di-, tri-, and tetranucleotide repeats respectively), and can be repeated 3 to 100 times, with the longer loci generally having more alleles due to the greater potential for slippage (see below). 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 microsatellite locus, genotypes within pedigrees are often fully informative, in that the progenitor of a particular allele can often be identified. In this way, microsatellites are ideal for determining paternity, population genetic studies and recombination mapping. It is also the only molecular marker to provide clues about which alleles are more closely related. Microsatellites are also predictors of SNP density as regions of thousands of nucleotides flanking microsatellites have an increased or decreased density of SNPs depending on the microsatellite sequence.

The variability of microsatellites is due to a higher rate of mutation compared to other neutral regions of DNA. These high rates of mutation can be explained most frequently by slipped strand mispairing (slippage) during DNA replication on a single DNA strand. Mutation may also occur during recombination during meiosis, although genomic microsatellite distributions are associated with sites of recombination most probably as a consequence of repetitive sequences being involved in recombination rather than being a consequence of it . Some errors in slippage are rectified by proofreading mechanisms within the nucleus, but some mutations can escape repair. The size of the repeat unit, the number of repeats and the presence of variant repeats are all factors, as well as the frequency of transcription in the area of the DNA repeat. Interruption of microsatellites, perhaps due to mutation, can result in reduced polymorphism. However, this same mechanism can occasionally lead to incorrect amplification of microsatellites; if slippage occurs early on during PCR, microsatellites of incorrect lengths can be amplified.