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 ( = 0.995).