Haplotype-resolved genome sequencing of a Gujarati Indian individual

Jacob O. Kitzman, Alexandra P. MacKenzie, Andrew Adey, Joseph B. Hiatt, Rupali P. Patwardhan, Peter H. Sudmant, Sarah B. Ng, Can Alkan, Ruolan Qiu, Evan E. Eichler, Jay Shendure

Research output: Contribution to journalArticle

170 Scopus citations

Abstract

Haplotype information is essential to the complete description and interpretation of genomes, genetic diversity and genetic ancestry. Although individual human genome sequencing is increasingly routine, nearly all such genomes are unresolved with respect to haplotype. Here we combine the throughput of massively parallel sequencing with the contiguity information provided by large-insert cloning to experimentally determine the haplotype-resolved genome of a South Asian individual. A single fosmid library was split into a modest number of pools, each providing ∼3% physical coverage of the diploid genome. Sequencing of each pool yielded reads overwhelmingly derived from only one homologous chromosome at any given location. These data were combined with whole-genome shotgun sequence to directly phase 94% of ascertained heterozygous single nucleotide polymorphisms (SNPs) into long haplotype blocks (N50 of 386 kilobases (kbp)). This method also facilitates the analysis of structural variation, for example, to anchor novel insertions to specific locations and haplotypes.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalNature biotechnology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Haplotype-resolved genome sequencing of a Gujarati Indian individual'. Together they form a unique fingerprint.

  • Cite this

    Kitzman, J. O., MacKenzie, A. P., Adey, A., Hiatt, J. B., Patwardhan, R. P., Sudmant, P. H., Ng, S. B., Alkan, C., Qiu, R., Eichler, E. E., & Shendure, J. (2011). Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nature biotechnology, 29(1), 59-64. https://doi.org/10.1038/nbt.1740