Enrichment of sequencing targets from the human genome by solution hybridization

• Published in: Genome biology Vol. 10; no. 10; p. R116
• Main Authors: Tewhey, Ryan, Nakano, Masakazu, Wang, Xiaoyun, Pabón-Peña, Carlos, Novak, Barbara, Giuffre, Angelica, Lin, Eric, Happe, Scott, Roberts, Doug N, LeProust, Emily M, Topol, Eric J, Harismendy, Olivier, Frazer, Kelly A
• Format: Journal Article
• Language: English
• Published: London BioMed Central 16.10.2009
• Subjects: Animal Genetics and Genomics; Base Sequence; Bioinformatics; Biomedical and Life Sciences; Cell Line; DNA Probes - metabolism; Evolutionary Biology; Exons - genetics; Gene Library; genome; Genome, Human - genetics; Genotype; Human Genetics; Humans; Life Sciences; loci; Method; Microbial Genetics and Genomics; Mutation - genetics; nucleic acid hybridization; Nucleic Acid Hybridization - methods; Oligonucleotide Array Sequence Analysis; oligonucleotides; Plant Genetics and Genomics; Reproducibility of Results; Sequence Analysis, DNA - methods; single nucleotide polymorphism; Solutions; Additional Data File; Solution Hybridization; Fragment Library; Sequence Coverage; Capture Probe
• ISSN: 1474-760X; 1465-6906; 1474-760X; 1465-6914
• DOI: 10.1186/gb-2009-10-10-r116

To exploit fully the potential of current sequencing technologies for population-based studies, one must enrich for loci from the human genome. Here we evaluate the hybridization-based approach by using oligonucleotide capture probes in solution to enrich for approximately 3.9 Mb of sequence target. We demonstrate that the tiling probe frequency is important for generating sequence data with high uniform coverage of targets. We obtained 93% sensitivity to detect SNPs, with a calling accuracy greater than 99%.