Instability of the DNA repeats mutation in humans hereditary disorders

摘要

Nearly 40 hereditary disorders in humans result from an increase in the number of copies of simple DNA repeats in genomic DNA. DNA repeats expansion mutations are dynamic and ongoing within tissues and across generations, leading to disease. These DNA repeats seem to be predisposed to expansion because they have unusual structural features, such as hairpins, slipped-strand DNA, DNA unwinding elements, tetraplexes, triplexes and sticky DNA,which disrupt the DNA replication, repair and recombination machineries. In general, repeats instability disorders fall into four mechanistic classes of pathogenesis including: loss-of-protein function, gain-of-protein function, gain-of-RNA function, or epigenetic-dysregulation. Here we review and compare the unusual DNA structures, molecular mechanisms of repeat expansions and modes of disease pathogenesis in the processes of DNA repeats instability.