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Molecular refinement of gibbon genome rearrangements

¹ Department of Genetics and Microbiology, University of Bari, 70126 Bari, Italy; ² Washington University Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri 63108, USA; ³ Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; ⁴ Gibbon Conservation Center, Santa Clarita, California 91380, USA; ⁵ Howard Hughes Medical Institute, Seattle, Washington 98195, USA

The gibbon karyotype is known to be extensively rearranged when compared to the human and to the ancestral primate karyotype. By combining a bioinformatics (paired-end sequence analysis) approach and a molecular cytogenetics approach, we have refined the synteny block arrangement of the white-cheeked gibbon (Nomascus leucogenys, NLE) with respect to the human genome. We provide the first detailed clone framework map of the gibbon genome and refine the location of 86 evolutionary breakpoints to <1 Mb resolution. An additional 12 breakpoints, mapping primarily to centromeric and telomeric regions, were mapped to 5 Mb resolution. Our combined FISH and BES analysis indicates that we have effectively subcloned 49 of these breakpoints within NLE gibbon BAC clones, mapped to a median resolution of 79.7 kb. Interestingly, many of the intervals associated with translocations were gene-rich, including some genes associated with normal skeletal development. Comparisons of NLE breakpoints with those of other gibbon species reveal variability in the position, suggesting that chromosomal rearrangement has been a longstanding property of this particular ape lineage. Our data emphasize the synergistic effect of combining computational genomics and cytogenetics and provide a framework for ultimate sequence and assembly of the gibbon genome.

⁷ Corresponding authors.

E-mail rocchi{at}biologia.uniba.it; fax 39-080-544-3386.

E-mail eee{at}gs.washington.edu; fax (206) 221-5795.

[Supplemental material is available online at www.genome.org.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6052507

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