Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay
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 genera...
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| Veröffentlicht in: | Genome research 2005-02, Vol.15 (2), p.269-275 |
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| creator | Hardenbol, Paul Yu, Fuli Belmont, John Mackenzie, Jennifer Bruckner, Carsten Brundage, Tiffany Boudreau, Andrew Chow, Steve Eberle, Jim Erbilgin, Ayca Falkowski, Mat Fitzgerald, Ron Ghose, Sy Iartchouk, Oleg Jain, Maneesh Karlin-Neumann, George Lu, Xiuhua Miao, Xin Moore, Bridget Moorhead, Martin Namsaraev, Eugeni Pasternak, Shiran Prakash, Eunice Tran, Karen Wang, Zhiyong Jones, Hywel B Davis, Ronald W Willis, Thomas D Gibbs, Richard A |
| description | 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. |
| doi_str_mv | 10.1101/gr.3185605 |
| format | Article |
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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.</description><identifier>ISSN: 1088-9051</identifier><identifier>EISSN: 1549-5469</identifier><identifier>DOI: 10.1101/gr.3185605</identifier><identifier>PMID: 15687290</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Chromosome Inversion - genetics ; Chromosome Inversion - statistics & numerical data ; Cluster Analysis ; DNA Probes - genetics ; Gene Expression Profiling ; Genome, Human ; Genotype ; Humans ; Methods ; Molecular Probe Techniques - standards ; Molecular Probe Techniques - statistics & numerical data ; Molecular Probe Techniques - trends ; Molecular Probes - genetics ; Polymorphism, Single Nucleotide - genetics ; Research Design</subject><ispartof>Genome research, 2005-02, Vol.15 (2), p.269-275</ispartof><rights>Copyright © 2005, Cold Spring Harbor Laboratory Press 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-5a9f0c44fd0a1041648a461bab378898bfefe8ec18790506524d3a08c67117683</citedby><cites>FETCH-LOGICAL-c431t-5a9f0c44fd0a1041648a461bab378898bfefe8ec18790506524d3a08c67117683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC546528/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC546528/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15687290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hardenbol, Paul</creatorcontrib><creatorcontrib>Yu, Fuli</creatorcontrib><creatorcontrib>Belmont, John</creatorcontrib><creatorcontrib>Mackenzie, Jennifer</creatorcontrib><creatorcontrib>Bruckner, Carsten</creatorcontrib><creatorcontrib>Brundage, Tiffany</creatorcontrib><creatorcontrib>Boudreau, Andrew</creatorcontrib><creatorcontrib>Chow, Steve</creatorcontrib><creatorcontrib>Eberle, Jim</creatorcontrib><creatorcontrib>Erbilgin, Ayca</creatorcontrib><creatorcontrib>Falkowski, Mat</creatorcontrib><creatorcontrib>Fitzgerald, Ron</creatorcontrib><creatorcontrib>Ghose, Sy</creatorcontrib><creatorcontrib>Iartchouk, Oleg</creatorcontrib><creatorcontrib>Jain, Maneesh</creatorcontrib><creatorcontrib>Karlin-Neumann, George</creatorcontrib><creatorcontrib>Lu, Xiuhua</creatorcontrib><creatorcontrib>Miao, Xin</creatorcontrib><creatorcontrib>Moore, Bridget</creatorcontrib><creatorcontrib>Moorhead, Martin</creatorcontrib><creatorcontrib>Namsaraev, Eugeni</creatorcontrib><creatorcontrib>Pasternak, Shiran</creatorcontrib><creatorcontrib>Prakash, Eunice</creatorcontrib><creatorcontrib>Tran, Karen</creatorcontrib><creatorcontrib>Wang, Zhiyong</creatorcontrib><creatorcontrib>Jones, Hywel B</creatorcontrib><creatorcontrib>Davis, Ronald W</creatorcontrib><creatorcontrib>Willis, Thomas D</creatorcontrib><creatorcontrib>Gibbs, Richard A</creatorcontrib><title>Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay</title><title>Genome research</title><addtitle>Genome Res</addtitle><description>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. 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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. 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| subjects | Chromosome Inversion - genetics Chromosome Inversion - statistics & numerical data Cluster Analysis DNA Probes - genetics Gene Expression Profiling Genome, Human Genotype Humans Methods Molecular Probe Techniques - standards Molecular Probe Techniques - statistics & numerical data Molecular Probe Techniques - trends Molecular Probes - genetics Polymorphism, Single Nucleotide - genetics Research Design |
| title | Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay |
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