Abstract
Massively parallel sequencing technologies have identified a broad spectrum of human genome diversity. Here we deep sequenced and correlated 18 genomes and 17 transcriptomes of unrelated Korean individuals. This has allowed us to construct a genome-wide map of common and rare variants and also identify variants formed during DNA-RNA transcription. We identified 9.56 million genomic variants, 23.2% of which appear to be previously unidentified. From transcriptome sequencing, we discovered 4,414 transcripts not previously annotated. Finally, we revealed 1,809 sites of transcriptional base modification, where the transcriptional landscape is different from the corresponding genomic sequences, and 580 sites of allele-specific expression. Our findings suggest that a considerable number of unexplored genomic variants still remain to be identified in the human genome, and that the integrated analysis of genome and transcriptome sequencing is powerful for understanding the diversity and functional aspects of human genomic variants.
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Acknowledgements
We acknowledge the anonymous Korean individuals who participated in this study. We thank Y.J. Yoo and T. Bleazard at Seoul National University for their personal comments regarding this manuscript. We are indebted to the scientists who contributed to this work but were not included in the author list. This work has been supported in part by Green Cross Therapeutics (grant # 0411-20080023 to J.-S.S.), the Korean Ministry of Knowledge Economy (grant # 10037410 to J.-I.K.), the Korean Ministry of Education, Science and Technology (grant # M10305030000 to J.-S.S.; grant # 2010-0013662 to J.-I.K.) and the National Human Genome Research Institute of the US National Institutes of Health (grant # P41HG4221 to C.L.).
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Contributions
J.-S.S. and C.L. conceived of the project. J.-S.S. planned and managed the project. Y.S.J., J.-I.K., Sheehyun Kim, D.H., W.-C.L., Sujung Kim and S.-B.Y. analyzed sequencing data. D.H. and S.-S.P. developed the genome browser. J.-Y.S., S.-H.S., J.-Y.Y., H.C., K.-S.Y. and H.K. constructed libraries and executed sequencing. J.H.J. analyzed genotyping microarray experiments. H.P., S.L., H.-J.K., H.P.K. and O.G. assisted in the data analysis. Y.S.J., S.L., D.-S.L. and M.Y. performed validation analyses. J.-S.S., C.L., Y.S.J., J.-I.K., Sheehyun Kim, D.H., O.G. and D.R.G. wrote the manuscript.
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Supplementary information
Supplementary Text and Figures
Supplementary Note, Supplementary Figures 1–9 and Supplementary Tables 1, 2, 4, 5, 11, 13–15 and 18. (PDF 1862 kb)
Supplementary Table 3
Primers for validations (XLS 37 kb)
Supplementary Table 4
Indel list of 10 individuals extracted by whole genome sequencing (TXT 70434 kb)
Supplementary Table 6
Non-synonymous SNP list detected from 18 individuals (XLS 7569 kb)
Supplementary Table 7
Funtional assessment of nsSNP of 18 individuals (XLS 692 kb)
Supplementary Table 8
Super nsSNP gene list (XLS 44 kb)
Supplementary Table 9
List of Korean common novel nsSNP LD (XLS 212 kb)
Supplementary Table 10
Total 5,496 large deletion list of 8 individuals (XLS 1152 kb)
Supplementary Table 12
Breakpoints list of NA10851 (XLS 83 kb)
Supplementary Table 16
Expression map represented in RPKM value on all RefSeq genes (XLS 12011 kb)
Supplementary Table 17
List of Korean common novel transcripts (XLS 776 kb)
Supplementary Table 19
1,809 TBM sites (XLS 1606 kb)
Supplementary Table 20
580 Allele Specific Expression sites (XLS 448 kb)
Supplementary Table 21
Contig list generated by de novo assembly (XLS 4580 kb)
Supplementary Table 22
Alignment result of de novo assemble contigs (XLS 67 kb)
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Ju, Y., Kim, JI., Kim, S. et al. Extensive genomic and transcriptional diversity identified through massively parallel DNA and RNA sequencing of eighteen Korean individuals. Nat Genet 43, 745–752 (2011). https://doi.org/10.1038/ng.872
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DOI: https://doi.org/10.1038/ng.872
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