Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays

Science. 2010 Jan 1;327(5961):78-81. doi: 10.1126/science.1181498. Epub 2009 Nov 5.


Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Computational Biology
  • Costs and Cost Analysis
  • DNA / chemistry*
  • DNA / genetics
  • Databases, Nucleic Acid
  • Genome, Human*
  • Genomic Library
  • Genotype
  • Haplotypes
  • Human Genome Project
  • Humans
  • Male
  • Microarray Analysis*
  • Nanostructures
  • Nanotechnology
  • Nucleic Acid Amplification Techniques
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA / economics
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, DNA / standards
  • Software


  • DNA