Gross Rearrangements Caused by Long Triplet and Other Repeat Sequences

This chapter focuses on gross rearrangements caused by long triplet and other repeat sequences. The most fascinating and unique feature of TRSs and other repeat sequences in DNA is their ability to adopt alternative conformations that differ dramatically from the commonly known, right-handed, antiparallel, double helix, generally referred to as B-DNA. The formation of non-B conformations in vivo is mostly based on the behavior of the DNA sequences in vitro, their relationships with DNA topology, and in certain cases antibody binding. Some of most relevant nonB-DNA are slipped (hairpin) structures, cruciforms, triplexes, tetraplexes and/-motifs, and left-handed Z-DNA are formed in chromosomes and elicit profound genetic consequences via recombination repair. On the other hand, repeating sequences, probably in their nonB conformations, cause gross genomic rearrangements such as deletions, insertions, inversions, translocations, and duplications. These rearrangements are the genetic basis for scores of human diseases, including polycystic kidney disease, adrenoleukodystrophy, follicular lymphomas, and spermatogenic failure.