Efficient and cost effective population resequencing by pooling and in-solution hybridization.
PLoS One
; 6(3): e18353, 2011 Mar 30.
Article
in En
| MEDLINE
| ID: mdl-21479135
ABSTRACT
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 â¼ 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 >â =â 0.995).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sequence Analysis, DNA
/
Genetics, Population
/
Nucleic Acid Hybridization
Type of study:
Health_economic_evaluation
Limits:
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2011
Document type:
Article
Affiliation country: