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Identification of both copy number variation-type and constant-type core elements in a large segmental duplication region of the mouse genome

Juzoh Umemori127, Akihiro Mori3, Kenji Ichiyanagi4, Takeaki Uno5 and Tsuyoshi Koide16*

  • * Corresponding author: Tsuyoshi Koide

  • † Equal contributors

Author Affiliations

1 Mouse Genomics Resource Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan

2 Transdisciplinary Research Integration Center, Research Organization of Information and Systems, 4-3-13 Toranomon, Minato-ku, Tokyo 105-0001, Japan

3 Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA

4 Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

5 National Institute of Informatics, Hitotsubashi 2-1–2, Chiyoda-ku, Tokyo 101-8430, Japan

6 Department of Genetics, SOKENDAI, Mishima, Shizuoka 411-8540, Japan

7 Present address: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan

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BMC Genomics 2013, 14:455  doi:10.1186/1471-2164-14-455

Published: 8 July 2013



Copy number variation (CNV), an important source of diversity in genomic structure, is frequently found in clusters called CNV regions (CNVRs). CNVRs are strongly associated with segmental duplications (SDs), but the composition of these complex repetitive structures remains unclear.


We conducted self-comparative-plot analysis of all mouse chromosomes using the high-speed and large-scale-homology search algorithm SHEAP. For eight chromosomes, we identified various types of large SD as tartan-checked patterns within the self-comparative plots. A complex arrangement of diagonal split lines in the self-comparative-plots indicated the presence of large homologous repetitive sequences. We focused on one SD on chromosome 13 (SD13M), and developed SHEPHERD, a stepwise ab initio method, to extract longer repetitive elements and to characterize repetitive structures in this region. Analysis using SHEPHERD showed the existence of 60 core elements, which were expected to be the basic units that form SDs within the repetitive structure of SD13M. The demonstration that sequences homologous to the core elements (>70% homology) covered approximately 90% of the SD13M region indicated that our method can characterize the repetitive structure of SD13M effectively. Core elements were composed largely of fragmented repeats of a previously identified type, such as long interspersed nuclear elements (LINEs), together with partial genic regions. Comparative genome hybridization array analysis showed that whereas 42 core elements were components of CNVR that varied among mouse strains, 8 did not vary among strains (constant type), and the status of the others could not be determined. The CNV-type core elements contained significantly larger proportions of long terminal repeat (LTR) types of retrotransposon than the constant-type core elements, which had no CNV. The higher divergence rates observed in the CNV-type core elements than in the constant type indicate that the CNV-type core elements have a longer evolutionary history than constant-type core elements in SD13M.


Our methodology for the identification of repetitive core sequences simplifies characterization of the structures of large SDs and detailed analysis of CNV. The results of detailed structural and quantitative analyses in this study might help to elucidate the biological role of one of the SDs on chromosome 13.

Comparative genome hybridization array; Repetitive element; Retrotransposon; Mouse genome; Homology search