| Identification of genetic variants using bar-coded multiplexed sequencing. | |
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MedLine Citation:
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PMID: 18794863 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We developed a generalized framework for multiplexed resequencing of targeted human genome regions on the Illumina Genome Analyzer using degenerate indexed DNA bar codes ligated to fragmented DNA before sequencing. Using this method, we simultaneously sequenced the DNA of multiple HapMap individuals at several Encyclopedia of DNA Elements (ENCODE) regions. We then evaluated the use of Bayes factors for discovering and genotyping polymorphisms. For polymorphisms that were either previously identified within the Single Nucleotide Polymorphism database (dbSNP) or visually evident upon re-inspection of archived ENCODE traces, we observed a false positive rate of 11.3% using strict thresholds for predicting variants and 69.6% for lax thresholds. Conversely, false negative rates were 10.8-90.8%, with false negatives at stricter cut-offs occurring at lower coverage (<10 aligned reads). These results suggest that >90% of genetic variants are discoverable using multiplexed sequencing provided sufficient coverage at the polymorphic base. |
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Authors:
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David W Craig; John V Pearson; Szabolcs Szelinger; Aswin Sekar; Margot Redman; Jason J Corneveaux; Traci L Pawlowski; Trisha Laub; Gary Nunn; Dietrich A Stephan; Nils Homer; Matthew J Huentelman |
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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: 2008-09-14 |
Journal Detail:
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Title: Nature methods Volume: 5 ISSN: 1548-7105 ISO Abbreviation: Nat. Methods Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-30 Completed Date: 2008-10-21 Revised Date: 2012-04-26 |
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: 887-93 Citation Subset: IM |
Affiliation:
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The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA. dcraig@tgen.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Automatic Data Processing* Genetic Variation* Genome, Human* Humans Polymorphism, Single Nucleotide Sequence Alignment |
| Grant Support | |
ID/Acronym/Agency:
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R01 N5059873//PHS HHS; U01 HL086528/HL/NHLBI NIH HHS; U01 HL086528-03/HL/NHLBI NIH HHS |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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