Abstract
BackgroundCopy 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Copy number variation (CNV), an important source of diversity in genomic structure, is frequently found in clusters called CNV regions (CNVRs)
Further magnification of these patches revealed a tartan-checked pattern with a complex arrangement of diagonal split lines, which indicated the presence of homologous repetitive sequences (Figure 1A)
After previously known repetitive elements had been masked using RepeatMasker [20], the number of diagonal lines obtained in the self-comparative plot described above was reduced in a large proportion of the Segmental duplication (SD) (Figure 1A, lower left)
Summary
Copy number variation (CNV), an important source of diversity in genomic structure, is frequently found in clusters called CNV regions (CNVRs). Comprehensive genomic analyses have shown that CNV sequences often overlap and form clusters of variable regions [3,6,7] These regions, known as CNV regions (CNVRs), are associated with variations in gene expression and phenotype [3,5,7,8,9,10,11,12,13,14,15]. Many of the large SDs contain repetitive sequences with ambiguous borders and copy numbers that vary among strains These sequences are called complex CNVRs [7]. We aimed to identify repetitive “core elements” as well as copy numbers of the elements and the detailed structure of large SDs in the mouse genome.
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