title: Genome architecture catalyzes nonrecurrent chromosomal rearrangements.
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 alpha-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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Shaw
authors.forename: Jason D
authors.initials: JD
authors.lastname: Dapper
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Marjorie
authors.initials: M
authors.lastname: Withers
authors.forename: Leah
authors.initials: L
authors.lastname: Elizondo
authors.forename: Sung-Sup
authors.initials: SS
authors.lastname: Park
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D002503:Centromere / Q000235:genetics; D019457:Chromosome Breakage / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D020161:Physical Chromosome Mapping; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*