## Slipped strand mispairing

**Slipped‑strand mispairing **leads first to local short-term denaturing of the double-helix DNA molecule and subsequently to *renaturation* of the segment of the strand, not with the original complementary part of the opposing strand, but with some other area containing the complementary base. If this event is followed by reparation and further replication of the given DNA segment, this is followed by either multiplication or, on the other hand, deletion of a certain sequential motif (Levinson & Gutman 1987)(Fig. VI.7).

*Slippage*can also occur during the replication itself by slippage of the template for the DNA-polymerase enzyme (Fig. VI.8). In the site where repetition occurs of a certain nucleotide or short oligonucleotide, the DNA-polymerase can “slip” backwards or forwards along the template at a certain moment and synthesize a new DNA strand twice in a row according to the same template section, or leave out a certain section of the template. The probability of this event is inversely proportional to the length of the oligonucleotide of which the given repetition consists and directly proportional to the number of oligonucleotides in the repetition. As a consequence, although *slippage* can be followed by insertion or deletion of the particular motif, there is clear asymmetry in the probability of the two events. Insertion of a new copy increases the probability of further *slippage*, while deletion reduces it. For example, it is known that the frequency of spontaneous insertion and deletion of A in pentanucleotide **AAAAA **is more than one order of magnitude greater than their frequency in tetranucleotide **AAAA**. This means that the familiar principle of *positive feedback* is important in multiplication of repetitive motifs and the entire process of multiplication of certain motifs has a marked accelerating, avalanche character.

Avalanche multiplication of motifs in the genome of the organism is responsible for a number of serious diseases. For example, multiplication of the (**CAG**)* _{n }*motif in the gene for androgen causes Kennedy’s disease, multiplication of the same motif on a different gene is responsible for Huntington’s disease, and multiplication of (

**CCG**)

*is observed in all cases of the fragile X chromosome syndrome (Lubjuhn, Schwaiger, & Epplen 1994).*

_{n}Multiplication and the general mutability of simple repetition segments form the basis for the **microsatellite analysis** technique (see XXIV.3.7).This technique, which is based on amplification and characterization of the individual loci containing simple repetitions, is broadly employed in various population studies. The mutability of these segments allows microsatellite analysis to monitor a large amount of genetic polymorphism even in mutually quite related individuals. This can be employed, for example, in determining paternity or in determining the internal structure of a population.