Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites
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- dc.contributor.author Girirajan, Santhoshca
- dc.contributor.author Chen, Linca
- dc.contributor.author Graves, Tina A.ca
- dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
- dc.contributor.author Ventura, Marioca
- dc.contributor.author Fronick, Catrinaca
- dc.contributor.author Fulton, Lucindaca
- dc.contributor.author Rocchi, Marianoca
- dc.contributor.author Fulton, Robert S.ca
- dc.contributor.author Wilson, Richard K.ca
- dc.contributor.author Mardis, Elaine R.ca
- dc.contributor.author Eichler, Evan E.ca
- dc.date.accessioned 2013-04-03T09:17:55Z
- dc.date.available 2013-04-03T09:17:55Z
- dc.date.issued 2009ca
- dc.description.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), beta-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.
- dc.description.sponsorship This work is supported by a Marie Curie fellowship
- dc.format.mimetype application/pdfca
- dc.identifier.citation Girirajan S, Chen L, Graves T, Marques-Bonet T, Ventura M, Fronick C et al. Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites. Genome Res. 2009;19(2):178-90. DOI: 10.1101/gr.086041.108ca
- dc.identifier.doi http://dx.doi.org/10.1101/gr.086041.108
- dc.identifier.issn 1088-9051ca
- dc.identifier.uri http://hdl.handle.net/10230/20531
- dc.language.iso engca
- dc.publisher Cold Spring Harbor Laboratory Press-CSHL Pressca
- dc.relation.ispartof Genome Research. 2009;19(2):178-90
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/220278
- dc.rights © 2009, Genome Research by Cold Spring Harbor Laboratory Press, amb Llicència Creative Commons (Attribution-NonCommercial 3.0 Unported License)ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/3.0/
- dc.subject.other Genòmica
- dc.subject.other Gibons -- Genètica
- dc.subject.other Genètica humana
- dc.title Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sitesca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca