Human Molecular Genetics Advance Access originally published online on January 9, 2008
Human Molecular Genetics 2008 17(8):1184-1191; doi:10.1093/hmg/ddn008
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Two different forms of palindrome resolution in the human genome: deletion or translocation
1 Division of Molecular Genetics, Institute for Comprehensive Medical Science and 2 Development Center for Targeted and Minimally Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Aichi 470-1192, Japan 3 Division of Human Genetics, The Children's Hospital of Philadelphia, PA 19104, USA 4 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
* To whom correspondence should be addressed at: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Tel: +81 562939391; Fax: +81 562938831; Email: kura{at}fujita-hu.ac.jp
Received November 14, 2007; Revised December 28, 2007; Accepted January 8, 2008
Regions containing palindromic sequence are known to be susceptible to genomic rearrangement in prokaryotes and eukaryotes. Palindromic AT-rich repeats (PATRR) are hypervariable in the human genome, manifesting size polymorphisms and a propensity to rearrange. Size variations are mainly the result of internal deletions, while two PATRRs on 11q23 and 22q11 (PATRR11 and 22) contribute to generation of the t(11;22), a recurrent constitutional translocation. In this study, we analyzed the PATRR11 sequence of numerous polymorphic alleles in detail. Various types of shorter variants are likely derived from the most frequent 
450 bp PATRR11 by deletion. Deletion variants possess a significant number of identical nucleotides at their two endpoints, indicating the possible involvement of direct repeats within the PATRR11. Rare variants with insertional alterations involve AT-rich sequences of unknown origin. This is in contrast to palindrome-mediated translocations between PATRRs that manifest smaller deletions and only a limited number of identical nucleotides at the breakpoints. Further, we identified a rare translocation product that has a non-AT-rich insertion of a transcribed gene segment at the translocation breakpoint. Our data suggest that the outcomes of palindrome-mediated re-arrangements reflect distinct molecular pathways; intra-palindrome re-arrangements are possibly dictated by a replication slippage or microhomology-directed repair pathway, and inter-palindrome translocations are likely driven by non-homologous end joining.
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]
|
|