De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations

Nat Commun. 2018 Aug 2;9(1):3040. doi: 10.1038/s41467-018-05513-w.


The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) "Linked-Read" technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA Transposable Elements / genetics
  • Genetic Variation*
  • Genetics, Population
  • Genome, Human*
  • Haplotypes / genetics*
  • Humans
  • Primates / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Reproducibility of Results
  • Sequence Analysis, DNA / methods*
  • Transcription, Genetic
  • Transcriptome / genetics


  • DNA Transposable Elements