Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

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.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View