De novo assembly of a haplotype-resolved human genome

被引：51

作者：

Cao, Hongzhi ^{[1
,2
]}

Wu, Honglong ^{[1
,2
]}

Luo, Ruibang ^{[1
,4
]}

Huang, Shujia ^{[1
,5
]}

Sun, Yuhui ^{[1
,5
]}

Tong, Xin ^{[1
]}

Xie, Yinlong ^{[1
,4
]}

Liu, Binghang ^{[1
,4
]}

Yang, Hailong ^{[1
]}

Zheng, Hancheng ^{[1
,3
]}

Li, Jian ^{[1
,3
]}

Li, Bo ^{[1
]}

Wang, Yu ^{[1
,5
]}

Yang, Fang ^{[1
]}

Sun, Peng ^{[1
]}

Liu, Siyang ^{[1
,3
]}

Gao, Peng ^{[1
]}

Huang, Haodong ^{[1
,5
]}

Sun, Jing ^{[1
]}

Chen, Dan ^{[1
]}

He, Guangzhu ^{[1
]}

Huang, Weihua ^{[1
]}

Huang, Zheng ^{[1
]}

Li, Yue ^{[1
]}

Tellier, Laurent C. A. M. ^{[1
,3
]}

Liu, Xiao ^{[1
,3
]}

Feng, Qiang ^{[1
,3
]}

Xu, Xun ^{[1
]}

Zhang, Xiuqing ^{[1
]}

Bolund, Lars ^{[1
,6
,7
]}

Krogh, Anders ^{[1
,3
]}

Kristiansen, Karsten ^{[1
,3
]}

Drmanac, Radoje ^{[8
]}

Drmanac, Snezana ^{[8
]}

Nielsen, Rasmus ^{[1
,9
,10
]}

Li, Songgang ^{[1
]}

Wang, Jian ^{[1
,11
]}

Yang, Huanming ^{[1
,11
,12
]}

Li, Yingrui ^{[1
,13
]}

Wong, Gane Ka-Shu ^{[1
,14
,15
]}

Wang, Jun ^{[1
,12
,16
,17
,18
]}

机构：

[1] BGI Shenzhen, Shenzhen, Peoples R China

[2] BGI Tianjin, Tianjin, Peoples R China

[3] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[4] HKU BGI Bioinformat Algorithms & Core Technol Res, Hong Kong, Hong Kong, Peoples R China

[5] S China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510641, Guangdong, Peoples R China

[6] Univ Aarhus, Inst Biomed, Aarhus, Denmark

[7] Danish Ctr Translat Breast Canc Res, Copenhagen, Denmark

[8] Complete Genom Inc, Mountain View, CA USA

[9] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA

[10] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[11] James D Watson Inst Genome Sci, Hangzhou, Zhejiang, Peoples R China

[12] King Abdulaziz Univ, Princess AI Jawhara Albrahim Ctr Excellence Res H, Jeddah 21413, Saudi Arabia

[13] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[14] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada

[15] Univ Alberta, Dept Med, Edmonton, AB, Canada

[16] Macau Univ Sci & Technol, Taipa, Macau, Peoples R China

[17] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[18] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE BIOTECHNOLOGY | 2015年 / 33卷 / 06期

关键词：

SEQUENCE; SNP; CANCER;

D O I：

10.1038/nbt.3200

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：617 / +

页数：10

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