Copyright © 2003 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 72, Issue 5, 1101-1116, 1 May 2003
doi:10.1086/374385
Genome Architecture Catalyzes Nonrecurrent Chromosomal Rearrangements
Paweł Stankiewicz1, Christine J. Shaw1, Jason D. Dapper1, Keiko Wakui1, Lisa G. Shaffer1, *, Marjorie Withers1, Leah Elizondo3, Sung-Sup Park1, † and James R. Lupski1, 2, 3, 4, 
, 
1 Departments of Molecular and Human Genetics
2 Departments of Pediatrics
3 Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine,
4 Baylor College of Medicine Texas Children's Hospital, Houston
Address for correspondence and reprints: Dr. James R. Lupski, Department of Molecular and Human Genetics, Baylor College of Medicine, Room 604B, One Baylor Plaza, Houston, TX 77030.* Present affiliation: School of Molecular Biosciences, Washington State University–Spokane, Health Research and Education Center, Spokane, WA
† Present affiliation: Department of Clinical Pathology, Seoul National University Hospital, Seoul, South Korea.
Abstract
To investigate the potential involvement of genome architecture in nonrecurrent chromosome rearrangements, we analyzed the breakpoints of eight translocations and 18 unusual-sized deletions involving human proximal 17p. Surprisingly, we found that many deletion breakpoints occurred in low-copy repeats (LCRs); 13 were associated with novel large LCR17p structures, and 2 mapped within an LCR sequence (middle SMS-REP) within the Smith-Magenis syndrome (SMS) common deletion. Three translocation breakpoints involving 17p11 were found to be located within the centromeric α-satellite sequence D17Z1, three within a pericentromeric segment, and one at the distal SMS-REP. Remarkably, our analysis reveals that LCRs constitute >23% of the analyzed genome sequence in proximal 17p—an experimental observation two- to fourfold higher than predictions based on virtual analysis of the genome. Our data demonstrate that higher-order genomic architecture involving LCRs plays a significant role not only in recurrent chromosome rearrangements but also in translocations and unusual-sized deletions involving 17p.
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