Long-read sequencing and de novo assembly of a Chinese genome

Lingling Shi; Yunfei Guo; Chengliang Dong; John Huddleston; Hui Yang; Xiaolu Han; Aisi Fu; Quan Li; Na Li; Siyi Gong; Katherine E Lintner; Qiong Ding; Zou Wang; Jiang Hu; Depeng Wang; Feng Wang; Lin Wang; Gholson J Lyon; Yongtao Guan; Yufeng Shen; Oleg V Evgrafov; James A Knowles; Francoise Thibaud-Nissen; Valerie Schneider; Chack-Yung Yu; Libing Zhou; Evan E Eichler; Kwok-Fai So; Kai Wang

doi:10.1038/ncomms12065

Long-read sequencing and de novo assembly of a Chinese genome

Nat Commun. 2016 Jun 30:7:12065. doi: 10.1038/ncomms12065.

Authors

Lingling Shi^{1

2

3}, Yunfei Guo⁴, Chengliang Dong⁴, John Huddleston⁵, Hui Yang⁴, Xiaolu Han⁶, Aisi Fu⁷, Quan Li⁴, Na Li¹, Siyi Gong¹, Katherine E Lintner⁸, Qiong Ding⁷, Zou Wang⁷, Jiang Hu⁹, Depeng Wang⁹, Feng Wang¹⁰, Lin Wang¹¹, Gholson J Lyon¹², Yongtao Guan¹³, Yufeng Shen¹⁴, Oleg V Evgrafov^{4

15}, James A Knowles^{4

15}, Francoise Thibaud-Nissen¹⁶, Valerie Schneider¹⁶, Chack-Yung Yu⁸, Libing Zhou^{1

2

3}, Evan E Eichler⁵, Kwok-Fai So^{1

2

3

17

18}, Kai Wang^{4

15}

Affiliations

¹ Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
² Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China.
³ Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
⁴ Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90089, USA.
⁵ Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
⁶ Genetic, Molecular, and Cellular Biology Program, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
⁷ Wuhan Institute of Biotechnology, Wuhan 430000, China.
⁸ Department of Pediatrics, The Ohio State University, and The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
⁹ Nextomics Biosciences, Wuhan 430000, China.
¹⁰ School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430000, China.
¹¹ Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
¹² Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, New York 11797, USA.
¹³ USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
¹⁴ Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, New York 10032, USA.
¹⁵ Department of Psychiatry &Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
¹⁶ National Center for Biotechnology Information, U.S. National Library of Medicine, Bethesda, Maryland 20894, USA.
¹⁷ Department of Ophthalmology, The University of Hong Kong, Hong Kong, China.
¹⁸ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.

Abstract

Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arrays and generate a de novo assembly of 2.93 Gb (contig N50: 8.3 Mb, scaffold N50: 22.0 Mb, including 39.3 Mb N-bases), together with 206 Mb of alternative haplotypes. The assembly fully or partially fills 274 (28.4%) N-gaps in the reference genome GRCh38. Comparison to GRCh38 reveals 12.8 Mb of HX1-specific sequences, including 4.1 Mb that are not present in previously reported Asian genomes. Furthermore, long-read sequencing of the transcriptome reveals novel spliced genes that are not annotated in GENCODE and are missed by short-read RNA-Seq. Our results imply that improved characterization of genome functional variation may require the use of a range of genomic technologies on diverse human populations.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Asian People / genetics*
Genome, Human*
Genomic Structural Variation
Humans
Male
Sequence Analysis, DNA
Sequence Analysis, RNA
Transcriptome

Abstract

Publication types

MeSH terms

Grants and funding