Structure of chromosomal duplicons and their role in mediating human genomic disorders

Chromosome-specific low-copy repeats, or duplicons, occur in multiple regio ns of the human genome. Homologous recombination between different duplicon copies leads to chromosomal rearrangements, such as deletions, duplication s, inversions, and inverted duplications, depending on the orientation of t he recombining duplicons. When such rearrangements cause dosage imbalance o f a developmentally important gene(s), genetic diseases now termed genomic disorders result, at a frequency of 0.7-1/1000 births. Duplicons can have s imple or very complex structures, with variation in copy number from 2 to > 10 repeats, and each varying in size from a Few kilobases in length to hund reds of kilobases. Analysis of the different duplicons involved in human ge nomic disorders identifies features that may predispose to recombination, i ncluding large size and high sequence identity between the recombining copi es, putative recombination promoting features, and the presence of multiple genes/pseudogenes that may include genes expressed in germ cells. Most of the chromosome rearrangements involve duplicons near pericentromeric region s, which may relate to the propensity of such regions to accumulate duplico ns. Detailed analyses of the structure, polymorphic variation, and mechanis ms of recombination in genomic disorders, as well as the evolutionary origi n of various duplicons will further our understanding of the structure, fun ction, and fluidity of the human genome.