Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Girirajan et al Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites Santhosh Girirajan1*, Lin Chen1*, Tina Graves2, Tomas Marques-Bonet1, Mario Ventura3, Catrina Fronick2, Lucinda Fulton2, Mariano Rocchi3, Robert S. Fulton2, Richard K. Wilson2, Elaine R. Mardis2 and Evan E. Eichler1† 1. Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington, USA 2. Genome Sequencing Center, Washington University, St. Louis, Missouri, USA 3. Department of Genetics and Microbiology, University of Bari, 70126 Bari, Italy *These authors contributed equally to work †Corresponding author: Evan E. Eichler, PhD University of Washington School of Medicine Howard Hughes Medical Institute Box 355065 Foege S413C, 1705 NE Pacific St. Seattle, WA 98195 E-mail:
[email protected] 1 Downloaded from genome.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Girirajan et al ABSTRACT 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 (GIOT1), that have been disrupted in the NLE gibbon lineage.