Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites

Santhosh Girirajan, Lin Chen, Tina Graves, Tomas Marques-Bonet, Mario Ventura, Catrina Fronick, Lucinda Fulton, Mariano Rocchi, Robert S. Fulton, Richard K. Wilson, Elaine R. Mardis, Evan E. Eichler

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The gibbon genome exhibits extensive karyotypic diversity with an increased rate of chromosomal rearrangements during evolution. In an effort to understand the mechanistic origin and implications of these rearrangement events, we sequenced 24 synteny breakpoint regions in the white-cheeked gibbon (Nomascus leucogenys, NLE) in the form of high-quality BAC insert sequences (4.2 Mbp). While there is a significant deficit of breakpoints in genes, we identified seven human gene structures involved in signaling pathways (DEPDC4, GNG10), phospholipid metabolism (ENPP5, PLSCR2), β-oxidation (ECH1), cellular structure and transport (HEATR4), and transcription (ZNF461), that have been disrupted in the NLE gibbon lineage. Notably, only three of these genes show the expected evolutionary signatures of pseudogenization. Sequence analysis of the breakpoints suggested both nonclassical nonhomologous end-joining (NHEJ) and replication-based mechanisms of rearrangement. A substantial number (11/24) of human-NLE gibbon breakpoints showed new insertions of gibbon-specific repeats and mosaic structures formed from disparate sequences including segmental duplications, LINE, SINE, and LTR elements. Analysis of these sites provides a model for a replication-dependent repair mechanism for double-strand breaks (DSBs) at rearrangement sites and insights into the structure and formation of primate segmental duplications at sites of genomic rearrangements during evolution.

Original languageEnglish (US)
Pages (from-to)178-190
Number of pages13
JournalGenome research
Issue number2
StatePublished - Feb 2009

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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