title: 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).
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute, La Jolla, California, United States of America. vbansal@scripps.edu
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
authors.forename: Ryan
authors.initials: R
authors.lastname: Tewhey
authors.forename: Emily M
authors.initials: EM
authors.lastname: Leproust
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
mesh_terms: D003362:Cost-Benefit Analysis; D005787:Gene Frequency / Q000235:genetics; D005828:Genetics, Population / Q000379:methods*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000191:economics* / Q000379:methods*; D012996:Solutions
chemical_list: D012996:Solutions