Dr. Kwok, Pui-Yan 's publons link picture

Dr. Kwok, Pui-Yan

Emeritus Research Fellow
Academician, Academia Sinica
  • 02-2789-9143 (Lab) (Room No: N618)
  • 02-2652-3001 (Office)
  • 02-2789-9104
  • 02-2782-5573 (Fax)

  • Human genetics
  • Genomics
  • DNA sequence variation
  • Complex trait analysis,
  • Pharmacogenetics
  • Biotechnology

Education and Positions:
    • M.D. University of Chicago, Chicago, Pritzker School of Medicine, IL
    • Ph.D. University of Chicago, Chicago, IL

Highlight Detail

Towards a reference genome that captures global genetic diversity

Dr. Kwok, Pui-Yan
Nature Communications, Oct 30, 2020


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.