Research Summary: Efficient and Cost Effective Population Resequencing by Pooling and In-Solution Hybridization

ABSTRACT

High-throughput sequencing of targeted genomic loci in large populations is an effective approach for evaluating the contribution of rare variants to disease risk. We evaluated the feasibility of using in-solution hybridization-based target capture on pooled DNA samples to enable cost-efficient population sequencing studies. For this, we performed pooled sequencing of 100 HapMap samples across ∼600 kb of DNA sequence using the Illumina GAIIx. Using our accurate variant calling method for pooled sequence data, we were able to not only identify single nucleotide variants with a low false discovery rate (<1%) but also accurately detect short insertion/deletion variants. In addition, with sufficient coverage per individual in each pool (30-fold) we detected 97.2% of the total variants and 93.6% of variants below 5% in frequency. Finally, allele frequencies for single nucleotide variants (SNVs) estimated from the pooled data and the HapMap genotype data were tightly correlated (correlation coefficient > =  0.995).

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Publisher: Public Library of Science

Date Published: 30-March-2011

Author(s): Bansal V., Tewhey R., LeProust E., Schork N.

Link: https://doi.org/10.1371/journal.pone.0018353

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