title: Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay.
abstract: Large-scale genetic studies are highly dependent on efficient and scalable multiplex SNP assays. In this study, we report the development of Molecular Inversion Probe technology with four-color, single array detection, applied to large-scale genotyping of up to 12,000 SNPs per reaction. While generating 38,429 SNP assays using this technology in a population of 30 trios from the Centre d'Etude Polymorphisme Humain family panel as part of the International HapMap project, we established SNP conversion rates of approximately 90% with concordance rates >99.6% and completeness levels >98% for assays multiplexed up to 12,000plex levels. Furthermore, these individual metrics can be "traded off" and, by sacrificing a small fraction of the conversion rate, the accuracy can be increased to very high levels. No loss of performance is seen when scaling from 6,000plex to 12,000plex assays, strongly validating the ability of the technology to suppress cross-reactivity at high multiplex levels. The results of this study demonstrate the suitability of this technology for comprehensive association studies that use targeted SNPs in indirect linkage disequilibrium studies or that directly screen for causative mutations.
authors.affiliation: ParAllele BioScience, Inc., South San Francisco, California 94080, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Hardenbol
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
authors.forename: John
authors.initials: J
authors.lastname: Belmont
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mackenzie
authors.forename: Carsten
authors.initials: C
authors.lastname: Bruckner
authors.forename: Tiffany
authors.initials: T
authors.lastname: Brundage
authors.forename: Andrew
authors.initials: A
authors.lastname: Boudreau
authors.forename: Steve
authors.initials: S
authors.lastname: Chow
authors.forename: Jim
authors.initials: J
authors.lastname: Eberle
authors.forename: Ayca
authors.initials: A
authors.lastname: Erbilgin
authors.forename: Mat
authors.initials: M
authors.lastname: Falkowski
authors.forename: Ron
authors.initials: R
authors.lastname: Fitzgerald
authors.forename: Sy
authors.initials: S
authors.lastname: Ghose
authors.forename: Oleg
authors.initials: O
authors.lastname: Iartchouk
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: George
authors.initials: G
authors.lastname: Karlin-Neumann
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lu
authors.forename: Xin
authors.initials: X
authors.lastname: Miao
authors.forename: Bridget
authors.initials: B
authors.lastname: Moore
authors.forename: Martin
authors.initials: M
authors.lastname: Moorhead
authors.forename: Eugeni
authors.initials: E
authors.lastname: Namsaraev
authors.forename: Shiran
authors.initials: S
authors.lastname: Pasternak
authors.forename: Eunice
authors.initials: E
authors.lastname: Prakash
authors.forename: Karen
authors.initials: K
authors.lastname: Tran
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Hywel B
authors.initials: HB
authors.lastname: Jones
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Willis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D007446:Chromosome Inversion / Q000235:genetics* / Q000706:statistics & numerical data; D016000:Cluster Analysis; D015342:DNA Probes / Q000235:genetics; D020869:Gene Expression Profiling; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015336:Molecular Probe Techniques / Q000592:standards / Q000706:statistics & numerical data / Q000639:trends*; D015335:Molecular Probes / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012107:Research Design
chemical_list: D015342:DNA Probes; D015335:Molecular Probes