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

PLoS One

Eleanor Drury¹  Sarah Edkins²  Aarno Palotie²  Aaron G. Day-Williams²  Kirsten McLay²  Alison J. Coffey²  Eleftheria Zeggini² 

[1] The Genome Analysis Centre, Norwich, United Kingdom;Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom

关键词: Alleles;    Gene pool;    Variant genotypes;    Polymerase chain reaction;    Genome analysis;    Sequence analysis;    Genome sequencing;    Genomic libraries;   

DOI  :  10.1371/journal.pone.0026279

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY