The Role of Repeat DNA Sequences in Human Evolution and Disease

Segmental chromosome duplications are an important evolutionary mechanism to produce new gene functions. Once an initial duplication takes place, the probability of a second event (structural change) increases. Segmental duplications (SDs) occur in many sizes and configurations. It has long been thought that SDs contribute to rapid evolution in primate genes. SDs tend to cluster around core duplicons, evolutionarily conserved sequences that are often shared between primate species. Many known SDs are associated with predisposition to human chromosome abnormalities and genetic diseases. Chromosome abnormalities in which SDs are implicated as the etiology include deletions, interstitial duplications, inversions, supernumerary marker chromosomes and translocations. Genomic abnormalities include DiGeorge and Velocardiofacial syndromes, Williams-Beuren syndrome, Prader-Willi and Angelman syndromes, cat eye syndrome, and many more. Segmental duplications also may play an important role in the etiology of some cancers. Most models for the likely mechanism of SD formation and expansion are based upon misalignment between juxtaposed non-allelic segmental duplications, followed by recombination.