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

166 Citations (Scopus)

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 2011
Externally publishedYes

Fingerprint

Haplotypes
Genes
Genome
High-Throughput Nucleotide Sequencing
Firearms
Human Genome
Diploidy
Cloning
Libraries
Single Nucleotide Polymorphism
Chromosomes
Organism Cloning
Nucleotides
Anchors
Polymorphism
Throughput

ASJC Scopus subject areas

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

Cite this

Kitzman, J. O., MacKenzie, A. P., Adey, A., Hiatt, J. B., Patwardhan, R. P., Sudmant, P. H., ... 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

Haplotype-resolved genome sequencing of a Gujarati Indian individual. / Kitzman, Jacob O.; MacKenzie, Alexandra P.; Adey, Andrew; Hiatt, Joseph B.; Patwardhan, Rupali P.; Sudmant, Peter H.; Ng, Sarah B.; Alkan, Can; Qiu, Ruolan; Eichler, Evan E.; Shendure, Jay.

In: Nature Biotechnology, Vol. 29, No. 1, 01.2011, p. 59-64.

Research output: Contribution to journalArticle

Kitzman, JO, MacKenzie, AP, Adey, A, Hiatt, JB, Patwardhan, RP, Sudmant, PH, Ng, SB, Alkan, C, Qiu, R, Eichler, EE & Shendure, J 2011, 'Haplotype-resolved genome sequencing of a Gujarati Indian individual', Nature Biotechnology, vol. 29, no. 1, pp. 59-64. https://doi.org/10.1038/nbt.1740
Kitzman JO, MacKenzie AP, Adey A, Hiatt JB, Patwardhan RP, Sudmant PH et al. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nature Biotechnology. 2011 Jan;29(1):59-64. https://doi.org/10.1038/nbt.1740
Kitzman, Jacob O. ; MacKenzie, Alexandra P. ; Adey, Andrew ; Hiatt, Joseph B. ; Patwardhan, Rupali P. ; Sudmant, Peter H. ; Ng, Sarah B. ; Alkan, Can ; Qiu, Ruolan ; Eichler, Evan E. ; Shendure, Jay. / Haplotype-resolved genome sequencing of a Gujarati Indian individual. In: Nature Biotechnology. 2011 ; Vol. 29, No. 1. pp. 59-64.
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