Abstract
Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome1, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome2,3. It is also enriched in segmental duplications, ranking third in density among the autosomes4. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution5,6, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.
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Acknowledgements
Special thanks are due to L. Gaffney for help with figures and tables. We thank T. Furey for help with lists of genetic markers and placement of RefSeqs, and K. Lindblad-Toh for sharing data on the opossum genome. We thank A. Kong for providing updated genetic map data, T. Hudson for technical advice, and the members of the Baylor College of Medicine Human Genome Sequencing Center, the J. Craig Venter Institute Joint Technology Center, and the Washington University Genome Sequencing Center for generation and early release of the genome assembly of the rhesus macaque. We also acknowledge the HUGO Gene Nomenclature Committee (S. Povey (chair), E. A. Bruford, R. C. Lovering, M. J. Lush, K. M. B. Sneddon, T. P. Sneddon, C. C. Talbot Jr and M. W. Wright) for assigning official gene symbols for human chromosome 17. We are grateful to all the members, present and past, of the Broad (and Whitehead) and Wellcome Trust Sanger sequencing platforms for their dedication and the consistent high quality of their data. The sequencing of human chromosome 17 was supported by a grant to the Whitehead Institute Center for Genome Research (now the Broad Institute) from the National Human Genome Research Institute (NHGRI). The sequencing of mouse chromosome 11 was supported by a grant to the Sanger Institute by the Wellcome Trust.
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Accession numbers for all clones contributing to the finished sequence of human chromosome 17 can be found in Supplementary Table S2, and for mouse chromosome 11 in Supplementary Table S5. The updated human chromosome 17 sequence can be accessed through GenBank accession number NC_000017. The updated mouse chromosome 11 sequence can be accessed through the accession numbers listed in Supplementary Table S5. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
Supplementary information
Supplementary Notes
This file contains the Supplementary Methods (including those for: mapping, sequencing, quality assessment and annotation of human chromosome 17; mapping, sequencing and quality assessment of mouse chromosome 11; duplication class clustering, syntenic mapping, ancestral reconstruction and assignment of breakpoints), Supplementary Results (including those for: gaps in the clone paths and extreme genes), Supplementary Discussion (including: Human-specific polymorphic inversion and class 3 duplicon fusion elements) and additional references. (DOC 67 kb)
Supplementary Tables 1–6
This file contains Supplementary Tables 1–6, covering gaps, clones, and contributing sequencing centers for human chromosome 17 and mouse chromosome 11; Human chromosome 17 gene content and tRNA genes on human chromosome 17. (DOC 3179 kb)
Supplementary Tables 7–11
This file contains Supplementary Tables 7–11, covering genetic markers and radiation hybrid markers for human chromosome 17 and mouse chromosome 11; Gene names and symbols for human chromosome 17. (DOC 3531 kb)
Supplementary Figures
Supplementary Figures nature04689-s4.pdf This file contains Supplementary Figures 1–5. (PDF 701 kb)
Supplementary Figure Legends
This file contains the legends for the Supplementary Figures. (DOC 24 kb)
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Zody, M., Garber, M., Adams, D. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature 440, 1045–1049 (2006). https://doi.org/10.1038/nature04689
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DOI: https://doi.org/10.1038/nature04689
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