title: Performance of high-throughput sequencing for the discovery of genetic variation across the complete size spectrum.
abstract: We observed that current high-throughput sequencing approaches only detected a fraction of the full size-spectrum of insertions, deletions, and copy number variants compared with a previously published, Sanger-sequenced human genome. The sensitivity for detection was the lowest in the 100- to 10,000-bp size range, and at DNA repeats, with copy number gains harder to delineate than losses. We discuss strategies for discovering the full spectrum of genetic variation necessary for disease association studies.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Andy Wing Chun
authors.initials: AW
authors.lastname: Pang
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Macdonald
authors.forename: Ryan K C
authors.initials: RK
authors.lastname: Yuen
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D056915:DNA Copy Number Variations; D017353:Gene Deletion; D014644:Genetic Variation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans
keywords: copy number variation; genome variation annotation; high-throughput sequencing; insertion/deletion