Molecular cloning of a translocation breakpoint hotspot in 22q11

Hiroki Kurahashi, Hidehito Inagaki, Eriko Hosoba, Takema Kato, Tamae Oe, Hiroshi Kogo, Beverly S. Emanuel

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

It has been well documented that 22q11 contains one of the most rearrangement-prone sites in the human genome, where the breakpoints of a number of constitutional translocations cluster. This breakage-sensitive region is located within one of the remaining unclonable gaps from the human genome project, suggestive of a specific sequence recalcitrant to cloning. In this study, we cloned a part of this gap and identified a novel 595-bp palindromic AT-rich repeat (PATRR). To date we have identified three translocation- associated PATRRs. They have common characteristics: (1) they are AT-rich nearly perfect palindromes, which are several hundred base pairs in length; (2) they possess non-AT-rich regions at both ends of the PATRR; (3) they display another nearby AT-rich region on one side of the PATRR. All of these features imply a potential for DNA secondary structure. Sequence analysis of unrelated individuals indicates no major size polymorphism, but shows minor nucleotide polymorphisms among individuals and cis-morphisms between the proximal and distal arms. Breakpoint analysis of various translocations indicates that double-strand-breakage (DSB) occurs at the center of the palindrome, often accompanied by a small symmetric deletion at the center. The breakpoints share only a small number of identical nucleotides between partner chromosomes. Taken together, these features imply that the DSBs are repaired through nonhomologous end joining or single-strand annealing rather than a homologous recombination pathway. All of these results support a previously proposed paradigm that unusual DNA secondary structure plays a role in the mechanism by which palindrome-mediated translocations occur.

Original languageEnglish
Pages (from-to)461-469
Number of pages9
JournalGenome Research
Volume17
Issue number4
DOIs
Publication statusPublished - 01-04-2007

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Molecular Cloning
Nucleotides
AT Rich Sequence
Human Genome Project
Homologous Recombination
DNA
Human Genome
Base Pairing
Sequence Analysis
Organism Cloning
Chromosomes
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Kurahashi, Hiroki ; Inagaki, Hidehito ; Hosoba, Eriko ; Kato, Takema ; Oe, Tamae ; Kogo, Hiroshi ; Emanuel, Beverly S. / Molecular cloning of a translocation breakpoint hotspot in 22q11. In: Genome Research. 2007 ; Vol. 17, No. 4. pp. 461-469.
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Molecular cloning of a translocation breakpoint hotspot in 22q11. / Kurahashi, Hiroki; Inagaki, Hidehito; Hosoba, Eriko; Kato, Takema; Oe, Tamae; Kogo, Hiroshi; Emanuel, Beverly S.

In: Genome Research, Vol. 17, No. 4, 01.04.2007, p. 461-469.

Research output: Contribution to journalArticle

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