A recurrent translocation is mediated by homologous recombination between HERV-H elements

Karen E. Hermetz, Urvashi Surti, Jannine D. Cody, M. Katharine Rudd

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability. Results: Array CGH resolved the breakpoints of the 6.97-Megabase (Mb) loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV) elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV. Conclusions: Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation. It is possible that normal sequence variation in substrates of non-allelic homologous recombination (NAHR) affects the alignment of recombining segments and influences the propensity to chromosome rearrangement.

Original languageEnglish (US)
Article number6
JournalMolecular Cytogenetics
Volume5
Issue number1
DOIs
StatePublished - 2012

Keywords

  • 18q
  • 18q22.3
  • 4q35.1
  • HERV
  • HERV-H
  • NAHR
  • recurrent translocation
  • t(4;18)
  • translocation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Biochemistry, medical

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