title: An evaluation of different target enrichment methods in pooled sequencing designs for complex disease association studies.
abstract: Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in-solution hybrid-capture performs best among the enrichment methods examined regardless of pool size.
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors: Aaron G
authors: AG
authors: Day-Williams
authors: Kirsten
authors: K
authors: McLay
authors: Eleanor
authors: E
authors: Drury
authors: Sarah
authors: S
authors: Edkins
authors: Alison J
authors: AJ
authors: Coffey
authors: Aarno
authors: A
authors: Palotie
authors: Eleftheria
authors: E
authors: Zeggini
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D004247:DNA / Q000032:analysis* / Q000235:genetics; D020869:Gene Expression Profiling; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; D004247:DNA