Quantification of rare allelic variants from pooled genomic DNA

Todd E. Druley; Francesco L M Vallania; Daniel J. Wegner; Katherine E. Varley; Olivia L. Knowles; Jacqueline A. Bonds; Sarah W. Robison; Scott W. Doniger; Aaron Hamvas; F. Sessions Cole; Justin C. Fay; Robi D. Mitra

doi:10.1038/nmeth.1307

Quantification of rare allelic variants from pooled genomic DNA

Todd E. Druley, Francesco L M Vallania, Daniel J. Wegner, Katherine E. Varley, Olivia L. Knowles, Jacqueline A. Bonds, Sarah W. Robison, Scott W. Doniger, Aaron Hamvas, F. Sessions Cole, Justin C. Fay, Robi D. Mitra^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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.

Original language	English (US)
Pages (from-to)	263-265
Number of pages	3
Journal	Nature Methods
Volume	6
Issue number	4
DOIs	https://doi.org/10.1038/nmeth.1307
State	Published - 2009

Funding

This work was supported in part by the US National Institutes of Health under the Ruth L. Kirschstein National Research Service Award T32 HD 007499 from the National Institute of Child Health and Human Development (T.E.D.), the National Heart, Lung and Blood Institute (RO1HL065174, RO1HL082747, F.S.C.), the Children’s Discovery Institute Fellowship Award MC-F-2006-1 (T.E.D.), the Children’s Discovery Institute grant MC-II-2006-1 (R.D.M.) and the Saigh Foundation (F.S.C., R.D.M. and T.E.D).

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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10.1038/nmeth.1307

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title = "Quantification of rare allelic variants from pooled genomic DNA",

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.",

author = "Druley, {Todd E.} and Vallania, {Francesco L M} and Wegner, {Daniel J.} and Varley, {Katherine E.} and Knowles, {Olivia L.} and Bonds, {Jacqueline A.} and Robison, {Sarah W.} and Doniger, {Scott W.} and Aaron Hamvas and Cole, {F. Sessions} and Fay, {Justin C.} and Mitra, {Robi D.}",

note = "Funding Information: This work was supported in part by the US National Institutes of Health under the Ruth L. Kirschstein National Research Service Award T32 HD 007499 from the National Institute of Child Health and Human Development (T.E.D.), the National Heart, Lung and Blood Institute (RO1HL065174, RO1HL082747, F.S.C.), the Children{\textquoteright}s Discovery Institute Fellowship Award MC-F-2006-1 (T.E.D.), the Children{\textquoteright}s Discovery Institute grant MC-II-2006-1 (R.D.M.) and the Saigh Foundation (F.S.C., R.D.M. and T.E.D).",

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doi = "10.1038/nmeth.1307",

language = "English (US)",

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AU - Druley, Todd E.

AU - Vallania, Francesco L M

AU - Wegner, Daniel J.

AU - Varley, Katherine E.

AU - Knowles, Olivia L.

AU - Bonds, Jacqueline A.

AU - Robison, Sarah W.

AU - Doniger, Scott W.

AU - Hamvas, Aaron

AU - Cole, F. Sessions

AU - Fay, Justin C.

AU - Mitra, Robi D.

N1 - Funding Information: This work was supported in part by the US National Institutes of Health under the Ruth L. Kirschstein National Research Service Award T32 HD 007499 from the National Institute of Child Health and Human Development (T.E.D.), the National Heart, Lung and Blood Institute (RO1HL065174, RO1HL082747, F.S.C.), the Children’s Discovery Institute Fellowship Award MC-F-2006-1 (T.E.D.), the Children’s Discovery Institute grant MC-II-2006-1 (R.D.M.) and the Saigh Foundation (F.S.C., R.D.M. and T.E.D).

PY - 2009

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N2 - 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.

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Quantification of rare allelic variants from pooled genomic DNA

Abstract

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