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Nat Biotechnol. 2015 Jun;33(6):617-22. doi: 10.1038/nbt.3200. Epub 2015 May 25.

De novo assembly of a haplotype-resolved human genome.

Author information

1
1] BGI-Shenzhen, Shenzhen, China. [2] BGI-Tianjin, Tianjin, China. [3] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
2
1] BGI-Shenzhen, Shenzhen, China. [2] BGI-Tianjin, Tianjin, China.
3
1] BGI-Shenzhen, Shenzhen, China. [2] HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory, Hong Kong, China.
4
1] BGI-Shenzhen, Shenzhen, China. [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
5
BGI-Shenzhen, Shenzhen, China.
6
1] BGI-Shenzhen, Shenzhen, China. [2] HKU-BGI Bioinformatics Algorithms and Core Technology Research Laboratory, Hong Kong, China. [3] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
7
1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
8
1] BGI-Shenzhen, Shenzhen, China. [2] Institute of Biomedicine, University of Aarhus, Aarhus, Denmark. [3] Danish Center for Translational Breast Cancer Research, Copenhagen, Denmark.
9
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
10
Complete Genomics Inc., Mountain View, California, USA.
11
1] BGI-Shenzhen, Shenzhen, China. [2] Department of Integrative Biology, University of California, Berkeley, California, USA. [3] Department of Statistics, University of California, Berkeley, California, USA.
12
1] BGI-Shenzhen, Shenzhen, China. [2] James D. Watson Institute of Genome Sciences, Hangzhou, China.
13
1] BGI-Shenzhen, Shenzhen, China. [2] James D. Watson Institute of Genome Sciences, Hangzhou, China. [3] Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
14
1] BGI-Shenzhen, Shenzhen, China. [2] Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
15
1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada. [3] Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
16
1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark. [3] Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. [4] Macau University of Science and Technology, Taipa, Macau, China. [5] Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.

Abstract

The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

PMID:
26006006
DOI:
10.1038/nbt.3200
[Indexed for MEDLINE]

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