Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
PLoS One. 2011;6(11):e26279. doi: 10.1371/journal.pone.0026279. Epub 2011 Nov 1.
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.
pooled sequencing 可以是一种具有成本效益的疾病变异发现方法，但它在关联研究中的适用性仍不清楚。我们比较了序列富集方法与下一代测序在 1、2、10、20 和 50 个人的非索引池中结合使用，评估了它们发现变体和估计等位基因频率的能力。我们发现，由于无法以足够高的准确度估计等位基因频率，从而无法用于关联研究，因此 pooled resequencing 最适合用作变异发现工具，而无论池大小如何，在检查的富集方法中，solution hybrid-capture 的性能最佳。
