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Mouse segmental duplication and copy number variation

Nature Genetics volume 40, pages 909–914 (2008)Cite this article

Abstract

Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. However, the architecture of mouse and human genomes differs markedly: most mouse duplications are organized into discrete clusters of tandem duplications that show depletion of genes and transcripts and enrichment of long interspersed nuclear element (LINE) and long terminal repeat (LTR) retroposons. We assessed copy number variation of the C57BL/6J duplicated regions within 15 mouse strains previously used for genetic association studies, sequencing and the Mouse Phenome Project. We determined that over 60% of these base pairs are polymorphic among the strains (on average, there was 20 Mb of copy-number-variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of interstrain copy number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, pheromone signaling and immune response.

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Figure 1: Mouse duplication patterns.
Figure 2: Distribution of mouse versus human duplication pairwise alignments.
Figure 3: LINE and LTR enrichment within mouse segmental duplications.
Figure 4: Copy-number variable mouse segmental duplications.

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Acknowledgements

We thank L. Rowe, C. Birkenmeier and G. Churchill for providing additional information regarding the relatedness of different inbred strains of mice used in this study. We thank A. Morrison for DNA sample preparation. We thank T. Brown, K. Augustyn and H. Mefford for assistance in preparation of this manuscript. This work was supported by US National Institutes of Health grant HG002385 to E.E.E. E.E.E. is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, 1705 NE Pacific Street, Seattle, 98195, Washington, USA

    Xinwei She, Ze Cheng & Evan E Eichler

  2. Department of Biostatistics and Department of Psychiatry, University of Michigan, 1420 Washington Heights, Ann Arbor, 48109, Michigan, USA

    Sebastian Zöllner

  3. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, 20894, Maryland, USA

    Deanna M Church

  4. Howard Hughes Medical Institute, Seattle, 98195, Washington, USA

    Evan E Eichler

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  1. Xinwei She
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  2. Ze Cheng
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  3. Sebastian Zöllner
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  4. Deanna M Church
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  5. Evan E Eichler
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Contributions

X.S., E.E.E. and Z.C. analyzed the duplication content and organization as well as the array comparative genomic hybridization data. D.M.C. provided access to the mouse genome assembly, annotated duplication/gene content and provided detailed quality control assessment regarding status of these regions and misassembly issues. S.Z. developed a novel HMM algorithm to identify significant transitions in log2 ratios corresponding to a likely copy number gain or loss. E.E.E. and X.S. conceived of the analyses and wrote the paper.

Corresponding author

Correspondence to Evan E Eichler.

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Supplementary Figures 1 and 2, Supplementary Tables 1–8, Supplementary Note (PDF 1082 kb)

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She, X., Cheng, Z., Zöllner, S. et al. Mouse segmental duplication and copy number variation. Nat Genet 40, 909–914 (2008). https://doi.org/10.1038/ng.172

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