Quantification of rare allelic variants from pooled genomic DNA.

Druley, Todd E; Vallania, Francesco L M; Wegner, Daniel J; Varley, Katherine E; Knowles, Olivia L; Bonds, Jacqueline A; Robison, Sarah W; Doniger, Scott W et al. · Nat Methods · 2009

basic_science · Level V

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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.

Medical subject headings