title: Structural alterations from multiple displacement amplification of a human genome revealed by mate-pair sequencing.
abstract: Comprehensive identification of the acquired mutations that cause common cancers will require genomic analyses of large sets of tumor samples. Typically, the tissue material available from tumor specimens is limited, which creates a demand for accurate template amplification. We therefore evaluated whether phi29-mediated whole genome amplification introduces false positive structural mutations by massive mate-pair sequencing of a normal human genome before and after such amplification. Multiple displacement amplification led to a decrease in clone coverage and an increase by two orders of magnitude in the prevalence of inversions, but did not increase the prevalence of translocations. While multiple strand displacement amplification may find uses in translocation analyses, it is likely that alternative amplification strategies need to be developed to meet the demands of cancer genomics.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Xiang
authors.initials: X
authors.lastname: Jiao
authors.forename: Magnus
authors.initials: M
authors.lastname: Rosenlund
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hooper
authors.forename: Christian
authors.initials: C
authors.lastname: Tellgren-Roth
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.forename: Yutao
authors.initials: Y
authors.lastname: Fu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mangion
authors.forename: Tobias
authors.initials: T
authors.lastname: Sjöblom
mesh_terms: D016477:Artifacts; D005189:False Positive Reactions; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D017422:Sequence Analysis, DNA