Abstract
An approx 4-Mb genomic segment on chromosome 17p1 1.2 commonly deleted in 70-80% of patients with the Smith-Magenis syndrome (SMS) is flanked by large, complex, highly identical (approx 98.7%), and directly oriented, proximal (approx 256 kb) and distal (approx 176 kb) low-copy repeats (LCRs), termed SMS-REPs. These LCR copies mediate nonallelic homologous recombination (NAHR), resulting in both SMS deletion and the reciprocal duplication dup(17)(p1 1.2p1 1.2). A third copy, the middle SMS-REP (approx 241 kb) is inverted and located between them. Several additional large LCR17ps have been identified fomented by breakpoint mapping in patients with deletions ascertained because of an SMS phenotype. LCRs in proximal 17p constitute more than 23% of the analyzed genome sequence, approx fourfold higher than predictions based on virtual analysis of the entire human genome. LCRs appear to play a significant role not only in common recurrent deletions and duplications, but also in other rearrangements including unusual sized (i.e., uncommon, recurrent and nonrecurrent) chromosomal deletions, reciprocal translocations, and marker chromosomes. DNA sequence analysis from both common and unusual sized recurrent SMS deletions and common dup(17)(p1 1.2p1 1.2) reveals ′recombination hotspots′ or a remarkable positional preference for strand exchange in NAHR events. Large palindromic LCRs, mapping between proximal and middle SMS-REPs, are responsible for the origin of a recurrent somatic isochromosome i(17q), one of the most common recurrent structural abnormalities observed in human neoplasms, suggesting genome architecture may play arole in mitotic as well as meiotic rearrangements. LCRs in proximal 17p are also prominent features in the genome evolution of this region whereby several serial segmental duplications have played an important role in chromosome evolution accompanying primate speciation.
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Stankiewicz, P., Bi, W., Lupski, J.R. (2006). Smith-Magenis Syndrome Deletion, Reciprocal Duplication dup(17)(p11.2p11.2), and Other Proximal 17p Rearrangements. In: Lupski, J.R., Stankiewicz, P. (eds) Genomic Disorders. Humana Press. https://doi.org/10.1007/978-1-59745-039-3_12
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DOI: https://doi.org/10.1007/978-1-59745-039-3_12
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