| DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution. | |
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MedLine Citation:
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PMID: 23042453 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up to 23 bp. Strikingly, Strand-seq of 62 single mES cells predicts that the mm 9 mouse reference genome assembly contains at least 17 incorrectly oriented segments totaling nearly 1% of the genome. These misoriented contigs and fragments have persisted through several iterations of the mouse reference genome and have been difficult to detect using conventional sequencing techniques. The ability to map SCE events at high resolution and fine-tune reference genomes by Strand-seq dramatically expands the scope of single-cell sequencing. |
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Authors:
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Ester Falconer; Mark Hills; Ulrike Naumann; Steven S S Poon; Elizabeth A Chavez; Ashley D Sanders; Yongjun Zhao; Martin Hirst; Peter M Lansdorp |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-07 |
Journal Detail:
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Title: Nature methods Volume: 9 ISSN: 1548-7105 ISO Abbreviation: Nat. Methods Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-07 Completed Date: 2013-01-14 Revised Date: 2013-05-03 |
Medline Journal Info:
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Nlm Unique ID: 101215604 Medline TA: Nat Methods Country: United States |
Other Details:
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Languages: eng Pagination: 1107-12 Citation Subset: IM |
Affiliation:
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Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Genomics Mice Sequence Analysis, DNA / methods* Sister Chromatid Exchange* Templates, Genetic* |
| Grant Support | |
ID/Acronym/Agency:
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105265//Canadian Institutes of Health Research; 294740//European Research Council; R01GM094146/GM/NIGMS NIH HHS; RMF-92093//Canadian Institutes of Health Research |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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