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Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing

Abstract

Copy number variants (CNVs) account for the majority of human genomic diversity in terms of base coverage. Here, we have developed and applied a new method to combine high-resolution array comparative genomic hybridization (CGH) data with whole-genome DNA sequencing data to obtain a comprehensive catalog of common CNVs in Asian individuals. The genomes of 30 individuals from three Asian populations (Korean, Chinese and Japanese) were interrogated with an ultra-high-resolution array CGH platform containing 24 million probes. Whole-genome sequencing data from a reference genome (NA10851, with 28.3× coverage) and two Asian genomes (AK1, with 27.8× coverage and AK2, with 32.0× coverage) were used to transform the relative copy number information obtained from array CGH experiments into absolute copy number values. We discovered 5,177 CNVs, of which 3,547 were putative Asian-specific CNVs. These common CNVs in Asian populations will be a useful resource for subsequent genetic studies in these populations, and the new method of calling absolute CNVs will be essential for applying CNV data to personalized medicine.

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Figure 1: Overview of the CNV discovery project for Asian populations.
Figure 2: Original approach for calling absolute copy number status.
Figure 3: Frequency of copy number gains and losses among 33 individuals.
Figure 4: Putative Asian population–specific copy number variants.
Figure 5: Effect of aCGH platforms in the CNV discovery.

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GenBank/EMBL/DDBJ

Gene Expression Omnibus

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Acknowledgements

We acknowledge R. Govindaraju for editing this manuscript. This work has been supported in part by Macrogen Inc. (MG2009009), Psoma Therapeutics Inc., the Korean Ministry of Education, Science and Technology (grant M10305030000), Green Cross Therapeutics (0411-20080023), the Department of Pathology at Brigham and Women's Hospital (to C.L.) and a US National Institutes of HealthGrant (HG004221 to C.L.).

Author information

Authors and Affiliations

Authors

Contributions

J.-S.S. and C.L. planned and managed the project. H.P., J.-I.K., Y.S.J., O.G., R.E.M., Y.J.Y., J.-Y.S., J.-S.H., W.C., G.-R.H. and K.D. executed and analyzed aCGH experiments. J.-I.K., Y.S.J., S.K., D.H., H.-J.K. and D.H. executed sequencing of the genome and analyzed sequence data. D.S., S.L., M.Y., Y.W.C., HyeRan Kim, S.J.Y., K.-S.Y. and Hyungtae Kim performed validation experiments; M.E.H., S.W.S., N.P.C. and C.T.-S. assisted in data analyses; J.-S.S., C.L., H.P., J.-I.K., Y.S.J. and H.P.K. wrote the manuscript.

Corresponding authors

Correspondence to Charles Lee or Jeong-Sun Seo.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–11, Supplementary Tables 1–12 and Supplementary Note (PDF 2730 kb)

Supplementary Figure 3

Read-depth information for 721 validated CNVs in AK1 using data for AK1 and NA10851 (PDF 23684 kb)

Supplementary Table 3

Absolute CNVs of 30 Asians (XLS 2289 kb)

Supplementary Table 5

List of primers for qPCR and breakpoint sequencing experiments (XLS 36 kb)

Supplementary Table 7

List of 5,177 CNVE identified in the 30 Asians studied (XLS 1468 kb)

Supplementary Table 8

List of OMIM genes in identified CNVs (XLS 348 kb)

Supplementary Table 9

List of microRNAs overlapping the personal CNVs identified in the study (XLS 36 kb)

Supplementary Table 10

List of fusion gene overlapping the personal CNVs identified in this study (XLS 50 kb)

Supplementary Table 11

Modified PANTHER ontology analysis (XLS 116 kb)

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Park, H., Kim, JI., Ju, Y. et al. Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing. Nat Genet 42, 400–405 (2010). https://doi.org/10.1038/ng.555

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