Haplotype-resolved genome sequencing of a gujarati indian individual

ABSTRACT Haplotype information is essential to the complete description and interpretation of genomes1, genetic diversity2 and genetic ancestry3. Although individual human genome sequencing

is increasingly routine4, nearly all such genomes are unresolved with respect to haplotype. Here we combine the throughput of massively parallel sequencing5 with the contiguity information

provided by large-insert cloning6 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 insertions7,8 to specific locations and haplotypes. Access through your institution

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OTHERS FULLY PHASED HUMAN GENOME ASSEMBLY WITHOUT PARENTAL DATA USING SINGLE-CELL STRAND SEQUENCING AND LONG READS Article Open access 07 December 2020 HAPLOTYPE-RESOLVED ASSEMBLY OF DIPLOID

GENOMES WITHOUT PARENTAL DATA Article 24 March 2022 HUMAN DE NOVO MUTATION RATES FROM A FOUR-GENERATION PEDIGREE REFERENCE Article Open access 23 April 2025 ACCESSION CODES ACCESSIONS

SEQUENCE READ ARCHIVE * 026360 CHANGE HISTORY * _ 12 APRIL 2011 In the version of this supplementary file originally posted online, Supplementary Figure 4a was not properly drawn. The error

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references ACKNOWLEDGEMENTS We thank C. Lee and M. Malig for technical assistance, J. Akey, T. O'Connor and P. Green for helpful discussions, D. Reich for ancestry information on

NA20847, the U.W. Genome Sciences Genomics Resource Center (GS-GRC) for sequencing and the 1000 Genomes Project for early data release. This work was supported by National Institutes of

Health grants AG039173 (J.B.H.) and HG002385 (E.E.E.), a National Science Foundation Graduate Research Fellowship (J.O.K.), a Natural Sciences and Engineering Research Council of Canada

Fellowship (P.H.S.) and a fellowship from the Achievement Rewards for College Scientists Foundation (J.B.H.). E.E.E. is an investigator of the Howard Hughes Medical Institute. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA 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 * Howard Hughes Medical Institute, Seattle, Washington, USA

Can Alkan & Evan E Eichler Authors * Jacob O Kitzman View author publications You can also search for this author inPubMed Google Scholar * Alexandra P MacKenzie View author publications

You can also search for this author inPubMed Google Scholar * Andrew Adey View author publications You can also search for this author inPubMed Google Scholar * Joseph B Hiatt View author

publications You can also search for this author inPubMed Google Scholar * Rupali P Patwardhan View author publications You can also search for this author inPubMed Google Scholar * Peter H

Sudmant View author publications You can also search for this author inPubMed Google Scholar * Sarah B Ng View author publications You can also search for this author inPubMed Google Scholar

* Can Alkan View author publications You can also search for this author inPubMed Google Scholar * Ruolan Qiu View author publications You can also search for this author inPubMed Google

Scholar * Evan E Eichler View author publications You can also search for this author inPubMed Google Scholar * Jay Shendure View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS The project was conceived and experiments planned by J.O.K., E.E.E. and J.S. J.O.K., A.P.M. and R.Q. carried out all experiments. J.O.K., A.A., J.B.H.,

R.P.P., P.H.S., S.B.N. and C.A. performed data analysis. J.O.K., A.P.M., A.A., J.B.H., R.P.P. and J.S. wrote the manuscript, and all authors reviewed it. All aspects of the study were

supervised by J.S. CORRESPONDING AUTHORS Correspondence to Jacob O Kitzman or Jay Shendure. ETHICS DECLARATIONS COMPETING INTERESTS J.S. is a member of the science advisory boards of Tandem

Technologies, Stratos Genomics, Good Start Genetics and Adaptive TCR. E.E.E. is on the scientific advisory board for Pacific Biosciences. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND

FIGURES Supplementary Tables 1–3,5, Supplementary Methods and Supplementary Figs. 1–7 (PDF 1756 kb) SUPPLEMENTARY TABLE 4 Pan-genome and novel sequence anchoring. (XLS 1322 kb) RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kitzman, J., MacKenzie, A., Adey, A. _et al._ Haplotype-resolved genome sequencing of a Gujarati Indian individual.

_Nat Biotechnol_ 29, 59–63 (2011). https://doi.org/10.1038/nbt.1740 Download citation * Received: 26 October 2010 * Accepted: 29 November 2010 * Published: 01 January 2011 * Issue Date:

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