Human Molecular Genetics, 2003, Vol. 12, No. 15 1823-1837
DOI: 10.1093/hmg/ddg203
© 2003 Oxford University Press
Frequent translocations occur between low copy repeats on chromosome 22q11.2 (LCR22s) and telomeric bands of partner chromosomes
1Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA, 2Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA, 3Department of Obstetrics and Gynecology/Pediatrics, Montefiore Medical Center, 1635 Poplar Street, Bronx, NY 10461, USA and 4Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
Received April 8, 2003; Accepted May 21, 2003
The chromosome 22q11.2 region is susceptible to rearrangements, mediated by low copy repeats (LCR22s). Deletions and duplications are mediated by homologous recombination events between LCR22s. The recurrent balanced constitutional translocation t(11;22)(q23;q11) breakpoint occurs in an LCR22 and is mediated by double strand breaks in AT-rich palindromes on both chromosomes 11 and 22. Recently, two cases of a t(17;22)(q11;q11) were reported, mediated by a similar mechanism (21). Except for these constitutional translocations, the molecular basis for non-recurrent, reciprocal 22q11.2 translocations is not known. To determine whether there are specific mechanisms that could mediate translocations, we analyzed cell lines derived from 14 different individuals by genotyping and FISH mapping. Somatic cell hybrid analysis was carried out for four cell lines. In five cell lines, the translocation breakpoints occurred in the same LCR22 as for the t(11;22) translocation, suggesting that similar molecular mechanisms are responsible. An additional three occurred in other LCR22s, and six were in non-LCR22 regions, mostly in the proximal half of the 22q11.2 region. The translocation breakpoints on the partner chromosomes were all located in the telomeric bands, proximal to the most telomeric unique sequence probe, in eight cell lines and distal to those loci in six. Therefore, several of the breakpoints were found to occur in the vicinity of highly dynamic regions of the genome, 22q11.2 and telomeric bands. We hypothesize that these regions are more susceptible to breakage and repair, resulting in translocations.
* To whom correspondence should be addressed. Tel: +1 7184304274; Fax: +1 7184308778; Email: morrow{at}aecom.yu.edu
Present address: Washington State University Spokane, Health Research and Education Center, 310 N. Riverpoint Blvd, Spokane, WA 99210-1495, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Kurahashi, H. Inagaki, T. Kato, E. Hosoba, H. Kogo, T. Ohye, M. Tsutsumi, H. Bolor, M. Tong, and B. S. Emanuel Impaired DNA replication prompts deletions within palindromic sequences, but does not induce translocations in human cells Hum. Mol. Genet., September 15, 2009; 18(18): 3397 - 3406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kato, H. Inagaki, H. Kogo, T. Ohye, K. Yamada, B. S. Emanuel, and H. Kurahashi Two different forms of palindrome resolution in the human genome: deletion or translocation Hum. Mol. Genet., April 15, 2008; 17(8): 1184 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kurahashi, H. Inagaki, E. Hosoba, T. Kato, T. Ohye, H. Kogo, and B. S. Emanuel Molecular cloning of a translocation breakpoint hotspot in 22q11 Genome Res., April 1, 2007; 17(4): 461 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Babcock, S. Yatsenko, P. Stankiewicz, J. R. Lupski, and B. E. Morrow AT-rich repeats associated with chromosome 22q11.2 rearrangement disorders shape human genome architecture on Yq12 Genome Res., April 1, 2007; 17(4): 451 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kurahashi, H. Inagaki, K. Yamada, T. Ohye, M. Taniguchi, B. S. Emanuel, and T. Toda Cruciform DNA Structure Underlies the Etiology for Palindrome-mediated Human Chromosomal Translocations J. Biol. Chem., August 20, 2004; 279(34): 35377 - 35383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Shaw and J. R. Lupski Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease Hum. Mol. Genet., April 1, 2004; 13(90001): R57 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Gotter, T. H. Shaikh, M. L. Budarf, C. H. Rhodes, and B. S. Emanuel A palindrome-mediated mechanism distinguishes translocations involving LCR-B of chromosome 22q11.2 Hum. Mol. Genet., January 1, 2004; 13(1): 103 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Nimmakayalu, A. L. Gotter, T. H. Shaikh, and B. S. Emanuel A novel sequence-based approach to localize translocation breakpoints identifies the molecular basis of a t(4;22) Hum. Mol. Genet., November 1, 2003; 12(21): 2817 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. STANKIEWICZ, K. INOUE, W. BI, K. WALZ, S.-S. PARK, N. KUROTAKI, C.J. SHAW, P. FONSECA, J. YAN, J.A. LEE, et al. Genomic Disorders: Genome Architecture Results in Susceptibility to DNA Rearrangements Causing Common Human Traits Cold Spring Harb Symp Quant Biol, January 1, 2003; 68(0): 445 - 454. [Abstract] [PDF]
|
|