Efficient and Cost Effective Population Resequencing by Pooling and In-Solution Hybridization

被引：42

作者：

Bansal, Vikas ^{[1
]}

Tewhey, Ryan ^{[1
,2
]}

LeProust, Emily M. ^{[3
]}

Schork, Nicholas J. ^{[1
,4
]}

机构：

[1] Scripps Translat Sci Inst, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

[3] Agilent Technol LLSU, Genom, Santa Clara, CA USA

[4] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

来源：

PLOS ONE | 2011年 / 6卷 / 03期

关键词：

RARE VARIANTS; GENETIC-VARIATION; COMPLEX DISEASES; DNA; ASSOCIATION;

D O I：

10.1371/journal.pone.0018353

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 similar to 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).

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