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.
At a glance
- Detection of large-scale variation in the human genome. Nat. Genet. 36, 949–951 (2004). et al.
- Origins and functional impact of copy number variation in the human genome. Nature advance online publication, doi:10.1038/nature08516 (7 October 2009). et al.
- The fine-scale and complex architecture of human copy-number variation. Am. J. Hum. Genet. 82, 685–695 (2008). et al.
- Global variation in copy number in the human genome. Nature 444, 444–454 (2006). et al.
- A highly annotated whole-genome sequence of a Korean individual. Nature 460, 1011–1015 (2009). et al.
- A high-resolution survey of deletion polymorphism in the human genome. Nat. Genet. 38, 75–81 (2006). , , , &
- Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations. Mol. Nutr. Food Res. 49, 972–976 (2005). et al.
- Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction. PLoS One 3, e2895 (2008). et al.
- Association of LY9 in UK and Canadian SLE families. Genes Immun. 9, 93–102 (2008). et al.
- Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes. BMC Med. Genet. 8 Suppl 1, S5 (2007). et al.
- High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554 (2004). et al.
- PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 24, 1477–1480 (2005). et al.
- Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood 78, 2747–2752 (1991). et al.
- Detection of RhD(el) in RhD-negative persons in clinical laboratory. J. Lab. Clin. Med. 146, 321–325 (2005). et al.
- Mapping and sequencing of structural variation from eight human genomes. Nature 453, 56–64 (2008). et al.
- Paired-end mapping reveals extensive structural variation in the human genome. Science 318, 420–426 (2007). et al.
- Proportionally more deleterious genetic variation in European than in African populations. Nature 451, 994–997 (2008). et al.
- Fine-scale structural variation of the human genome. Nat. Genet. 37, 727–732 (2005). et al.
- Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439, 851–855 (2006). et al.
- The importance of race and ethnic background in biomedical research and clinical practice. N. Engl. J. Med. 348, 1170–1175 (2003). et al.
- Gastric cancer in Japan. N. Engl. J. Med. 359, 2393–2394, author reply 2394–2395 (2008).
- Obesity and diabetes in the developing world—a growing challenge. N. Engl. J. Med. 356, 213–215 (2007). , &
- Body-mass index and mortality in Korean men and women. N. Engl. J. Med. 355, 779–787 (2006). et al.
- Supplementary Text and Figures (3M)
Supplementary Figures 1–11, Supplementary Tables 1–12 and Supplementary Note
- Supplementary Figure 3 (23M)
Read-depth information for 721 validated CNVs in AK1 using data for AK1 and NA10851
- Supplementary Table 3 (2M)
Absolute CNVs of 30 Asians
- Supplementary Table 5 (40K)
List of primers for qPCR and breakpoint sequencing experiments
- Supplementary Table 7 (1M)
List of 5,177 CNVE identified in the 30 Asians studied
- Supplementary Table 8 (348K)
List of OMIM genes in identified CNVs
- Supplementary Table 9 (40K)
List of microRNAs overlapping the personal CNVs identified in the study
- Supplementary Table 10 (52K)
List of fusion gene overlapping the personal CNVs identified in this study
- Supplementary Table 11 (116K)
Modified PANTHER ontology analysis