Document Detail

Single-molecule sequencing of an individual human genome.
MedLine Citation:
PMID:  19668243     Owner:  NLM     Status:  MEDLINE    
Recent advances in high-throughput DNA sequencing technologies have enabled order-of-magnitude improvements in both cost and throughput. Here we report the use of single-molecule methods to sequence an individual human genome. We aligned billions of 24- to 70-bp reads (32 bp average) to approximately 90% of the National Center for Biotechnology Information (NCBI) reference genome, with 28x average coverage. Our results were obtained on one sequencing instrument by a single operator with four data collection runs. Single-molecule sequencing enabled analysis of human genomic information without the need for cloning, amplification or ligation. We determined approximately 2.8 million single nucleotide polymorphisms (SNPs) with a false-positive rate of less than 1% as validated by Sanger sequencing and 99.8% concordance with SNP genotyping arrays. We identified 752 regions of copy number variation by analyzing coverage depth alone and validated 27 of these using digital PCR. This milestone should allow widespread application of genome sequencing to many aspects of genetics and human health, including personal genomics.
Dmitry Pushkarev; Norma F Neff; Stephen R Quake
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-08-10
Journal Detail:
Title:  Nature biotechnology     Volume:  27     ISSN:  1546-1696     ISO Abbreviation:  Nat. Biotechnol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-10     Completed Date:  2009-12-29     Revised Date:  2014-08-28    
Medline Journal Info:
Nlm Unique ID:  9604648     Medline TA:  Nat Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-50     Citation Subset:  IM    
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MeSH Terms
Computer Simulation
Genome, Human*
Genomics / methods*
Polymorphism, Single Nucleotide
Reproducibility of Results
Sequence Analysis, DNA / methods*
Grant Support
Comment In:
Nat Biotechnol. 2009 Sep;27(9):777   [PMID:  19741610 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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