Abstract
Here we integrate the de novo assembly of an Asian and an African genome with the NCBI reference human genome, as a step toward constructing the human pan-genome. We identified ∼5 Mb of novel sequences not present in the reference genome in each of these assemblies. Most novel sequences are individual or population specific, as revealed by their comparison to all available human DNA sequence and by PCR validation using the human genome diversity cell line panel. We found novel sequences present in patterns consistent with known human migration paths. Cross-species conservation analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain ∼19–40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing to the genetic variation of the pan-genome indicates the importance of using complete genome sequencing and de novo assembly.
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Acknowledgements
This project is supported by the Chinese Academy of Science (GJHZ0701-6), the National Natural Science Foundation of China (30725008; 30890032), Shenzhen local government, the Danish Platform for Integrative Biology, the Ole Rømer grant from the Danish Natural Science Research Council. L. Goodman edited the manuscript. J. Sun, M. Zhao, Y. Liu, Y. Zheng and H. Wang helped on designing the primers. W. Jin helped on experimental validation. San A, J. Wang, Y. Huang, M. Jian, M. Chen, Y. Huang, Xiaoli Ren, H. Liang, H. Zheng, S. Lin helped on the data production.
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Ruiq. L., Y.L., Ha. Z. and Ruib. L. contributed equally to this work. H.Y., Ju. W. and Ji. W. managed the project. Ju. W., Ruiq. L., L.B. and Y.L. designed the analyses. Ju. W., Ruiq. L., Y.L., Ha. Z., Ruib. L., Ho. Z., Q.L., W.Q., G.Z., H.W., J.Q., X.J., D.L., Hon. C., S.L. and K.K. performed the data analyses. H.B. and How. C. contributed the DNA samples. Y.R., X.H. and Xu. Z. performed PCR validation. G.T., J. L., Xi. Z. performed sequencing. Ju. W., Ruiq. L., Y.L. and Ruib. L. wrote the paper.
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Supplementary Figs. 1–7, Supplementary Tables 1 and 2, and Supplementary Discussion (PDF 498 kb)
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Li, R., Li, Y., Zheng, H. et al. Building the sequence map of the human pan-genome. Nat Biotechnol 28, 57–63 (2010). https://doi.org/10.1038/nbt.1596
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DOI: https://doi.org/10.1038/nbt.1596
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