- Main
Towards a reference genome that captures global genetic diversity.
- Author(s): Wong, Karen HY
- Ma, Walfred
- Wei, Chun-Yu
- Yeh, Erh-Chan
- Lin, Wan-Jia
- Wang, Elin HF
- Su, Jen-Ping
- Hsieh, Feng-Jen
- Kao, Hsiao-Jung
- Chen, Hsiao-Huei
- Chow, Stephen K
- Young, Eleanor
- Chu, Catherine
- Poon, Annie
- Yang, Chi-Fan
- Lin, Dar-Shong
- Hu, Yu-Feng
- Wu, Jer-Yuarn
- Lee, Ni-Chung
- Hwu, Wuh-Liang
- Boffelli, Dario
- Martin, David
- Xiao, Ming
- Kwok, Pui-Yan
- et al.
Published Web Location
https://doi.org/10.1038/s41467-020-19311-wAbstract
The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.
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