An Evaluation of Different Target Enrichment Methods in Pooled Sequencing Designs for Complex Disease Association Studies

作者：Day Williams Aaron G^*; McLay Kirsten; Drury Eleanor; Edkins Sarah; Coffey Alison J; Palotie Aarno; Zeggini Eleftheria

来源：PLos One, 2011, 6(11): e26279.

DOI：10.1371/journal.pone.0026279

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.

• 出版日期2011-11-1