Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination-associated motifs

  • Abeysinghe S
  • Chuzhanova N
  • Krawczak M
 et al. 
  • 64


    Mendeley users who have this article in their library.
  • 186


    Citations of this article.


Translocations and gross deletions are important causes of both cancer and inherited disease. Such gene rearrangements are nonrandomly distributed in the human genome as a consequence of selection for growth advantage and/or the inherent potential of some DNA sequences to be frequently involved in breakage and recombination. Using the Gross Rearrangement Breakpoint Database [GRaBD;] (containing 397 germ-line and somatic DNA breakpoint junction sequences derived from 219 different rearrangements underlying human inherited disease and cancer), we have analyzed the sequence context of translocation and deletion breakpoints in a search for general characteristics that might have rendered these sequences prone to rearrangement. The oligonucleotide composition of breakpoint junctions and a set of reference sequences, matched for length and genomic location, were compared with respect to their nucleotide composition. Deletion breakpoints were found to be AT-rich whereas by comparison, translocation breakpoints were GC-rich. Alternating purine-pyrimidine sequences were found to be significantly over-represented in the vicinity of deletion breakpoints while polypyrimidine tracts were over-represented at translocation breakpoints. A number of recombination-associated motifs were found to be over-represented at translocation breakpoints (including DNA polymerase pause sites/frameshift hotspots, immunoglobulin heavy chain class switch sites, heptamer/nonamer V(D)J recombination signal sequences, translin binding sites, and the chi element) but, with the exception of the translin-binding site and immunoglobulin heavy chain class switch sites, none of these motifs were over-represented at deletion breakpoints. Alu sequences were found to span both breakpoints in seven cases of gross deletion that may thus be inferred to have arisen by homologous recombination. Our results are therefore consistent with a role for homologous unequal recombination in deletion mutagenesis and a role for nonhomologous recombination in the generation of translocations.

Author-supplied keywords

  • Breakpoint junction sequences
  • Cancer
  • Database
  • Deletion
  • Gene rearrangement
  • Inherited disease
  • Recombination, homologous
  • Recombination, nonhomologous
  • Translocation

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Nadia ChuzhanovaNottingham Trent University School of Science and Technology

  • Shaun S. Abeysinghe

  • Michael Krawczak

  • Edward V. Ball

  • David N. Cooper

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free