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PMID: 19252504 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Quantification of rare allelic variants from pooled genomic DNA.

Nature methods ·Vol. 6 ·No. 4 ·2009-04-00 ·Pages 263-5

Druley TE, Vallania FL, Wegner DJ, Varley KE, Knowles OL, Bonds JA, Robison SW, Doniger SW, Hamvas A, Cole FS, Fay JC, Mitra RD

Abstract

We report a targeted, cost-effective method to quantify rare single-nucleotide polymorphisms from pooled human genomic DNA using second-generation sequencing. We pooled DNA from 1,111 individuals and targeted four genes to identify rare germline variants. Our base-calling algorithm, SNPSeeker, derived from large deviation theory, detected single-nucleotide polymorphisms present at frequencies below the raw error rate of the sequencing platform.

MeSH Terms
Algorithms Base Sequence Chromosome Mapping/methods DNA/genetics Gene Frequency/genetics Genetic Variation/genetics Molecular Sequence Data Polymorphism, Single Nucleotide/genetics Reproducibility of Results Sensitivity and Specificity Sequence Alignment/methods Sequence Analysis, DNA/methods Software
Chemicals
DNA
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Druley Todd E
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Vallania Francesco L M
Wegner Daniel J
Varley Katherine E
Knowles Olivia L
Bonds Jacqueline A
Robison Sarah W
Doniger Scott W
Hamvas Aaron
Cole F Sessions
Fay Justin C
Mitra Robi D
References (9)
9 references, click to expand
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Article Info
Journal
Nature methods
Abbr.
Nat Methods
ISSN
1548-7105
DOI
10.1038/nmeth.1307
Published
2009-04-00
Epub
2009-00-01
Pages
263-5
Language
English
Region
United States
NLM ID
101215604
PMCID
PMC2776647
Subset
IM
Grants
NHLBI NIH HHS · R01 HL082747-03 · United States
NHLBI NIH HHS · R01 HL065174-05 · United States
NHLBI NIH HHS · R01 HL065174 · United States
NHLBI NIH HHS · R01HL082747 · United States
NIGMS NIH HHS · R01 GM080669 · United States
NICHD NIH HHS · T32 HD 007499 · United States
NHLBI NIH HHS · R01 HL082747 · United States
NICHD NIH HHS · T32 HD007499 · United States
NHLBI NIH HHS · R01 HL065174-04 · United States
NHLBI NIH HHS · R01HL065174 · United States
External Links
PubMed source DOI: 10.1038/nmeth.1307 PMC Full Text View journal details
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