Smith-Magenis Syndrome Deletion, Reciprocal Duplication dup(17)(p11.2p11.2), and Other Proximal 17p Rearrangements

摘要: 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 256 kb) distal 176 low-copy repeats (LCRs), termed SMS-REPs. These LCR copies mediate nonallelic homologous recombination (NAHR), resulting both SMS deletion reciprocal duplication dup(17)(p1 1.2p1 1.2). A third copy, middle SMS-REP 241 inverted located between them. Several additional large LCR17ps have been identified fomented breakpoint mapping deletions ascertained because an phenotype. LCRs 17p constitute more than 23% analyzed genome sequence, fourfold higher predictions based virtual analysis entire human genome. appear to play a significant role not only common recurrent duplications, but also other rearrangements including unusual sized (i.e., uncommon, nonrecurrent) chromosomal deletions, translocations, marker chromosomes. DNA sequence from 1.2) reveals ′recombination hotspots′ or remarkable positional preference for strand exchange NAHR events. Large palindromic LCRs, SMS-REPs, are responsible origin somatic isochromosome i(17q), one most structural abnormalities observed neoplasms, suggesting architecture may arole mitotic as well meiotic rearrangements. prominent features evolution this region whereby several serial segmental duplications played important accompanying primate speciation.