Towards a reference genome that captures global genetic diversity
Journal
Nature Communications
Journal Volume
11
Journal Issue
1
Date Issued
2020
Author(s)
Wong, Karen H. Y.
Ma, Walfred
Wei, Chun-Yu
Yeh, Erh-Chan
Lin, Wan-Jia
Wang, Elin H. F.
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
Boffelli, Dario
Martin, David
Xiao, Ming
Kwok, Pui-Yan
Abstract
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.
SDGs
Type
journal article