Microsatellites

Introduction to Microsatellites

Microsatellites are tandem repeats of short units of DNA that occur with high frequency throughout the genomes of many organisms. Microsatellite loci have a high degree of variability that is due to a high rate of mutations that alter microsatellite length. There are several major reasons for interest in microsatellite loci.

The abundance and high level of allelic variation at microsatellite loci in the genomes of many organisms has made them popular genetic markers.
Genetic distance measures based on microsatellites can be used to answer questions concerning population structure and divergence.
Expansion of one type of microsatellite (triplet repeats) leads to several human genetic disorders such as fragile X syndrome and myotonic dystrophy.

The primary mutational mechanism leading to changes in microsatellite length is polymerase template slippage. During replication of a repetitive region, DNA strands may dissociate, and reassociate incorrectly. Renewed replication in this misaligned state leads to insertion or deletion of repeat units, thus altering allele length.

$\begin{figure}\includegraphics {slip.eps}\end{figure}$

Since most of the observed changes in length are by plus or minus one repeat unit, the stepwise mutation model has often been used to model microsatellite evolution. In the stepwise mutation model, the length of a microsatellite varies at a fixed rate independent of length, according to a symmetric random walk on the positive integers. The problem with this model for the study of microsatellite length evolution is that a symmetric random walk does not converge to a stationary distribution, and it is expected to attain arbitrarily high values. Our model solves this problem by modifying the dynamics so that

slippage rate is proportional to length
point mutations cut the length of perfect repeats.

Details of the model
Results
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