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SNP GENOTYPING HIGH SAMPLE THROUGHPUT SNP GENOTYPING

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SNP GENOTYPING

HIGH SAMPLE THROUGHPUT SNP GENOTYPING

© 2011 Fluidigm Corporation. All rights reserved. Fluidigm, the Fluidigm logo, BioMark, Dynamic Array, EP1, FC1, and SNPtype are trademarks or registered trademarks of Fluidigm Corporation in the U.S. and/or other countries. All other trademarks are the property of their respective owners. Fluidigm recommends that you only purchase licensed PCR assay reagents from authorized sources.FOR RESEARCH USE ONLY. 100-4590 1/2012

Spitz, M.R., Gorlov, I.P., Amos, C.I., Dong, Q., Chen, W., Etzel, C.J., Gorlova, O.Y., Chang, D.W., Pu, X., Zhang, D., Wang, L., Cunningham, J.M., Yang, P., and Wu, X. August 25, 2011. Variants in Inflammation Genes Are Implicated in Risk of Lung Cancer in Never Smokers Exposed to Second-hand Smoke. Cancer Discovery

Chu, X. Song, H.D., et al. August 14, 2011. A genome-wide association study identifies two new risk loci for Graves’ disease. Nature Genetics

K. Shitara, S. Ito, K. Misawa, Y. Ito, H. Ito, S. Hosono, M. Watanabe, K. Tajima, H. Tanaka, K. Muro, and K. Matsuo. June 20, 2011. Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy. Annals of Oncology

Chan, M., Chan, M.W., Loh, T.W., Law, H.Y., Yoon, C.S., Than, S.S., Chua, J.M., Wong, C.Y., Yong, W.S., Yap, Y.S., Ho, G.H., Ang, P, and Lee, A.S.G. May 2011. Evaluation of Nanofluidics Technology for High-Throughput SNP Genotyping in a Clinical Setting. Journal of Molecular Diagnostics

P. J. Maughan, S. M. Smith, D. J. Fairbanks, and E. N. Jellen. March 16, 2011. Development, characterization and linkage mapping of single nucleotide polymorphisms in the gram Amaranths. The Plant Genome

Pharoah, P.D.P, Palmieri, R.T., Ramus, S.J. et al. March 8, 2011. The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer. Clinical Cancer Research/American Association of Cancer Research

Domingo, S., Cabeza, C.M., Pruvost, A., Torres, F., Salazar, J., del Mar Gutierrez, M., Mateo, M.G., Fontanet, A., Fernandez, I., Domingo, J.C., Villarroya, F., Vidal, F., and Baiget, M. January 31, 2011. Association of thymidylate synthase gene polymorphisms with stavudine triphosphate intracellular levels and lipodystrophy. American Society for Microbiology

Baak-Pablo, R., Dezentje, V., Guchelaar, H., & van der Straaten, T. September 16, 2010. Genotyping of DNA Samples Isolated from Formalin-Fixed Paraffin-Embedded Tissues Using Preamplification. Journal of Molecular Diagnostics

Pander, J., Wessels, J. A. M., Gelderblom, H., van der Straaten, T., Punt, C.J.A. & Guchelaar, H.-J. August 17, 2010. Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer. Annals of Oncology

PUBLICATIONS

Corporate Headquarters 7000 Shoreline Court, Suite 100 South San Francisco, CA 94080 USAToll-free: 1.866.FLUIDLINE | Fax: 650.871.7152 www.fluidigm.com

Sales North America | +1 650.266.6170 | [email protected] Europe/EMEA | +33 1 60 92 42 40 | [email protected] | +81 3 3555 2351 | [email protected] Asia | +1 650.266.6170 | [email protected]

Paez, D., Pare, L., Espinosa, I., Salazar, J., Del Rio, E., Barnadas, A., Marcuello, E. and Baiget, M. May 18, 2010. Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: Are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy? Cancer Science

Sagreiya, H., Berube, C., Wen, A., Ramakrishnan, R., Mir, A., Hamilton, A., Altman, R.B. May 3, 2010. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9. Pharmacogenetics and Genomics

Habicht, C., Seeb, L. W., Myers, K. W., Farley, E.V., Seeb, J. E. 2010. Summer-Fall Distribution of Stocks of Immature Sockeye Salmon in the Bering Sea as Revealed by Single-Nucleotide Polymorphisms. Transactions of the American Fisheries Society

Wang, J., Lin, M., Crenshaw, A., Hutchinson, A., Hicks, B., Yeager, M., Berndt, S., Huang, W.,Hayes, R.B., Chanock, S.J., Jones, R.C., and Ramakrishnan, R. 2009 Nov 28. High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays. BMC Genomics

Pushkarev, D., Neff, N.F., Quake, S.R. 2009 Aug 10. Single-molecule sequencing of an individual human genome. Nat Biotechnol

Lo, Y.M.D. 2009 Jan. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art. BJOG 116:152-157

Seeb, J.E., Pascal, C.E., Ramakrishnan, R., Seeb, L.W. 2009. SNP genotyping by the 5’-nuclease reaction: advances in high-throughput genotyping with nonmodel organisms. A. Komar, editor. Methods in molecular biology, single nucleotide polymorphisms, 2d edition. Humana Press P. 277-292

INCREASED PRODUCTIVITY WITH MICROFLUIDICS

The Fluidigm high sample throughput genotyping solution requires dramatically less manual manipulation and saves time and money over traditional 384-well plate applications. The microfluidics architecture does the work of automatically combining samples and primer-probe sets into 2,304 to 9,216 PCR reactions

The EP1™ System offers outstanding data quality—even from lower quality samples—and the most streamlined workflow in the industry.

Genotyping results can be obtained in a matter of hours with only minutes of hands-on time.

OUTSTANDING DATA QUALITY

Core strengths of the Fluidigm systems is their ability to obtain high call rates and accuracy using standard chemistries. Here, cattle sample data obtained from the USDA Agricultural Research Service (ARS) demonstrate the outstanding results achieved on the EP1 System. Typical cluster plots are displayed and call rates achieved on the Dynamic Array IFC are 99.9%.

EP1™ SYSTEM

The EP1 System, with the Dynamic Array IFCs, is uniquely suited for a range of applications that require very high sample throughput. These include validation studies in which many thousands of individuals, whether from a single seed lot or human population study, are tested against as many as 1,000 genetic markers. Validated markers can be integrated into an assortment of high-throughput applications such as the following:

Marker-assisted breeding and selection

Seed testing

Disease resistance

Population genetics

Parentage studies

EASY WORKFLOW WITH THE EP1 SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the FC1™ Cycler.

Read the IFC on the EP1 Reader in a matter of minutes.

1 2 3 4

The BioMark™ HD System significantly improves productivity by enabling the simultaneous performance of PCR reactions in nanoliter volumes, collects more data points per day at less cost than 384-well

systems, and enables the use of multiple reagents and different sample and assay configurations.

BIOMARK™ HD SYSTEM

The BioMark HD System sets a new standard for high-throughput real-time gene expression analysis and end-point genotyping with benefits that are impossible to reproduce using many other conventional PCR systems. The IFC technology both prepares and performs thousands of reactions in nanoliter volumes, saving both time and money, as well as reducing pipetting steps by 95%. The system streamlines workflows for applications demanding sensitivity and dynamic range at an extremely high throughput.

The system integrates thermal cycling and detection of PCR assays for all Dynamic Array IFCs, and acquires data for each reaction chamber on the IFC simultaneously and can operate in either real-time or end-point detection mode for genotyping experiments.

GENOTYPING ASSAYS

SNPtype™ Assays provide a high-throughput, low-cost SNP genotyping solution which enables rapid assay design and polymorphism screening. The assays are based on allele-specific PCR and combine the advantages of minimum experimental setup time and flexible assay choice with the reliability of Dynamic Array™ Integrated Fluidic Circuit (IFC) technology.

Designed to target species with available sequence information

Three- to four-week design and turnaround time with customer-provided sequences (minimum of 24 assays per order)

Access to loci-specific primer sequences assures reproducibility

Compatible with Specific Target Amplification (STA) protocol for improving results from samples of low quality and/or concentration, or from species with large genome sizes (>human); necessary STA primers provided

INDUSTRY CHALLENGES

Single nucleotide polymorphism (SNP) genotyping is a powerful tool in human genetics and agricultural biotechnology, with applications ranging from the discovery of human disease modifier regions to sample identification and tracking to marker-assisted breeding of livestock and crops. As SNP discovery accelerates through next-generation sequencing and genome-wide association studies, there is a critical need for high throughput, flexible, and cost-effective SNP genotyping solutions to validate and apply these polymorphisms.

AGBIO GENOTYPING

Agricultural biologists aim to accentuate valuable traits in plants and animals for disease resistance, robustness, and profitability. Wildlife managers work to attain ecological balance by maintaining the genetic fitness of wild migratory species. Both fields require low cost, high-throughput SNP genotyping. Our genotyping solution allows you to quickly and efficiently associate a SNP combination with a favorable trait for directed breeding of high yield dairy cows, validate seed populations, or manage the fitness of a wild salmon population.

THE FLUIDIGM SOLUTION FOR SNP GENOTYPING

384-well plate

96.96 Dynamic Array IFC

48.48 Dynamic Array IFC

192.24 Dynamic Array IFC

Master mix 46 mL 240 µL 480 µL 576 µL

Primer-probe (20X) 4.6 mL 240 µL 480 µL 72 µL

Plates 24 1 4 2

Time 8 days 4 hours 8 hours 2 hours

Pipette steps 18,432 192 384 432

Comparison of materials and pipetting steps between conventional microplates and Dynamic Array IFCs; 96 samples against 96 assays

Allele map with corresponding scatter plots

using 200-fold less master mix than traditional systems. Each microfluidic plate generates 24-fold more data than that produced by a 384-well plate. This radical advance in experiment density is fully leveraged through a hardware/software system that automates setup and data analysis.

HUMAN GENOTYPING

SNP combinations have been associated with human traits varying from longevity and obesity to metastatic and autoimmune disease, resulting in a better understanding of human metabolism, disease etiology, and population variation; driving new pharmaceutical development, and aiding in the advent of personalized medicine. Our genotyping solution enables you to quickly and efficiently identify these causal SNP combinations.

Call map view for 48 cattle samples and 48 SNPtype™ Assays (left); cluster plot for a typical SNPtype Assay (right).

EASY WORKFLOW WITH THE BIOMARK HD SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the BioMark HD Reader.

View and analyze results with the data analysis suite.

1 2 3 4

INCREASED PRODUCTIVITY WITH MICROFLUIDICS

The Fluidigm high sample throughput genotyping solution requires dramatically less manual manipulation and saves time and money over traditional 384-well plate applications. The microfluidics architecture does the work of automatically combining samples and primer-probe sets into 2,304 to 9,216 PCR reactions

The EP1™ System offers outstanding data quality—even from lower quality samples—and the most streamlined workflow in the industry.

Genotyping results can be obtained in a matter of hours with only minutes of hands-on time.

OUTSTANDING DATA QUALITY

Core strengths of the Fluidigm systems is their ability to obtain high call rates and accuracy using standard chemistries. Here, cattle sample data obtained from the USDA Agricultural Research Service (ARS) demonstrate the outstanding results achieved on the EP1 System. Typical cluster plots are displayed and call rates achieved on the Dynamic Array IFC are 99.9%.

EP1™ SYSTEM

The EP1 System, with the Dynamic Array IFCs, is uniquely suited for a range of applications that require very high sample throughput. These include validation studies in which many thousands of individuals, whether from a single seed lot or human population study, are tested against as many as 1,000 genetic markers. Validated markers can be integrated into an assortment of high-throughput applications such as the following:

Marker-assisted breeding and selection

Seed testing

Disease resistance

Population genetics

Parentage studies

EASY WORKFLOW WITH THE EP1 SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the FC1™ Cycler.

Read the IFC on the EP1 Reader in a matter of minutes.

1 2 3 4

The BioMark™ HD System significantly improves productivity by enabling the simultaneous performance of PCR reactions in nanoliter volumes, collects more data points per day at less cost than 384-well

systems, and enables the use of multiple reagents and different sample and assay configurations.

BIOMARK™ HD SYSTEM

The BioMark HD System sets a new standard for high-throughput real-time gene expression analysis and end-point genotyping with benefits that are impossible to reproduce using many other conventional PCR systems. The IFC technology both prepares and performs thousands of reactions in nanoliter volumes, saving both time and money, as well as reducing pipetting steps by 95%. The system streamlines workflows for applications demanding sensitivity and dynamic range at an extremely high throughput.

The system integrates thermal cycling and detection of PCR assays for all Dynamic Array IFCs, and acquires data for each reaction chamber on the IFC simultaneously and can operate in either real-time or end-point detection mode for genotyping experiments.

GENOTYPING ASSAYS

SNPtype™ Assays provide a high-throughput, low-cost SNP genotyping solution which enables rapid assay design and polymorphism screening. The assays are based on allele-specific PCR and combine the advantages of minimum experimental setup time and flexible assay choice with the reliability of Dynamic Array™ Integrated Fluidic Circuit (IFC) technology.

Designed to target species with available sequence information

Three- to four-week design and turnaround time with customer-provided sequences (minimum of 24 assays per order)

Access to loci-specific primer sequences assures reproducibility

Compatible with Specific Target Amplification (STA) protocol for improving results from samples of low quality and/or concentration, or from species with large genome sizes (>human); necessary STA primers provided

INDUSTRY CHALLENGES

Single nucleotide polymorphism (SNP) genotyping is a powerful tool in human genetics and agricultural biotechnology, with applications ranging from the discovery of human disease modifier regions to sample identification and tracking to marker-assisted breeding of livestock and crops. As SNP discovery accelerates through next-generation sequencing and genome-wide association studies, there is a critical need for high throughput, flexible, and cost-effective SNP genotyping solutions to validate and apply these polymorphisms.

AGBIO GENOTYPING

Agricultural biologists aim to accentuate valuable traits in plants and animals for disease resistance, robustness, and profitability. Wildlife managers work to attain ecological balance by maintaining the genetic fitness of wild migratory species. Both fields require low cost, high-throughput SNP genotyping. Our genotyping solution allows you to quickly and efficiently associate a SNP combination with a favorable trait for directed breeding of high yield dairy cows, validate seed populations, or manage the fitness of a wild salmon population.

THE FLUIDIGM SOLUTION FOR SNP GENOTYPING

384-well plate

96.96 Dynamic Array IFC

48.48 Dynamic Array IFC

192.24 Dynamic Array IFC

Master mix 46 mL 240 µL 480 µL 576 µL

Primer-probe (20X) 4.6 mL 240 µL 480 µL 72 µL

Plates 24 1 4 2

Time 8 days 4 hours 8 hours 2 hours

Pipette steps 18,432 192 384 432

Comparison of materials and pipetting steps between conventional microplates and Dynamic Array IFCs; 96 samples against 96 assays

Allele map with corresponding scatter plots

using 200-fold less master mix than traditional systems. Each microfluidic plate generates 24-fold more data than that produced by a 384-well plate. This radical advance in experiment density is fully leveraged through a hardware/software system that automates setup and data analysis.

HUMAN GENOTYPING

SNP combinations have been associated with human traits varying from longevity and obesity to metastatic and autoimmune disease, resulting in a better understanding of human metabolism, disease etiology, and population variation; driving new pharmaceutical development, and aiding in the advent of personalized medicine. Our genotyping solution enables you to quickly and efficiently identify these causal SNP combinations.

Call map view for 48 cattle samples and 48 SNPtype™ Assays (left); cluster plot for a typical SNPtype Assay (right).

EASY WORKFLOW WITH THE BIOMARK HD SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the BioMark HD Reader.

View and analyze results with the data analysis suite.

1 2 3 4

INCREASED PRODUCTIVITY WITH MICROFLUIDICS

The Fluidigm high sample throughput genotyping solution requires dramatically less manual manipulation and saves time and money over traditional 384-well plate applications. The microfluidics architecture does the work of automatically combining samples and primer-probe sets into 2,304 to 9,216 PCR reactions

The EP1™ System offers outstanding data quality—even from lower quality samples—and the most streamlined workflow in the industry.

Genotyping results can be obtained in a matter of hours with only minutes of hands-on time.

OUTSTANDING DATA QUALITY

Core strengths of the Fluidigm systems is their ability to obtain high call rates and accuracy using standard chemistries. Here, cattle sample data obtained from the USDA Agricultural Research Service (ARS) demonstrate the outstanding results achieved on the EP1 System. Typical cluster plots are displayed and call rates achieved on the Dynamic Array IFC are 99.9%.

EP1™ SYSTEM

The EP1 System, with the Dynamic Array IFCs, is uniquely suited for a range of applications that require very high sample throughput. These include validation studies in which many thousands of individuals, whether from a single seed lot or human population study, are tested against as many as 1,000 genetic markers. Validated markers can be integrated into an assortment of high-throughput applications such as the following:

Marker-assisted breeding and selection

Seed testing

Disease resistance

Population genetics

Parentage studies

EASY WORKFLOW WITH THE EP1 SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the FC1™ Cycler.

Read the IFC on the EP1 Reader in a matter of minutes.

1 2 3 4

The BioMark™ HD System significantly improves productivity by enabling the simultaneous performance of PCR reactions in nanoliter volumes, collects more data points per day at less cost than 384-well

systems, and enables the use of multiple reagents and different sample and assay configurations.

BIOMARK™ HD SYSTEM

The BioMark HD System sets a new standard for high-throughput real-time gene expression analysis and end-point genotyping with benefits that are impossible to reproduce using many other conventional PCR systems. The IFC technology both prepares and performs thousands of reactions in nanoliter volumes, saving both time and money, as well as reducing pipetting steps by 95%. The system streamlines workflows for applications demanding sensitivity and dynamic range at an extremely high throughput.

The system integrates thermal cycling and detection of PCR assays for all Dynamic Array IFCs, and acquires data for each reaction chamber on the IFC simultaneously and can operate in either real-time or end-point detection mode for genotyping experiments.

GENOTYPING ASSAYS

SNPtype™ Assays provide a high-throughput, low-cost SNP genotyping solution which enables rapid assay design and polymorphism screening. The assays are based on allele-specific PCR and combine the advantages of minimum experimental setup time and flexible assay choice with the reliability of Dynamic Array™ Integrated Fluidic Circuit (IFC) technology.

Designed to target species with available sequence information

Three- to four-week design and turnaround time with customer-provided sequences (minimum of 24 assays per order)

Access to loci-specific primer sequences assures reproducibility

Compatible with Specific Target Amplification (STA) protocol for improving results from samples of low quality and/or concentration, or from species with large genome sizes (>human); necessary STA primers provided

INDUSTRY CHALLENGES

Single nucleotide polymorphism (SNP) genotyping is a powerful tool in human genetics and agricultural biotechnology, with applications ranging from the discovery of human disease modifier regions to sample identification and tracking to marker-assisted breeding of livestock and crops. As SNP discovery accelerates through next-generation sequencing and genome-wide association studies, there is a critical need for high throughput, flexible, and cost-effective SNP genotyping solutions to validate and apply these polymorphisms.

AGBIO GENOTYPING

Agricultural biologists aim to accentuate valuable traits in plants and animals for disease resistance, robustness, and profitability. Wildlife managers work to attain ecological balance by maintaining the genetic fitness of wild migratory species. Both fields require low cost, high-throughput SNP genotyping. Our genotyping solution allows you to quickly and efficiently associate a SNP combination with a favorable trait for directed breeding of high yield dairy cows, validate seed populations, or manage the fitness of a wild salmon population.

THE FLUIDIGM SOLUTION FOR SNP GENOTYPING

384-well plate

96.96 Dynamic Array IFC

48.48 Dynamic Array IFC

192.24 Dynamic Array IFC

Master mix 46 mL 240 µL 480 µL 576 µL

Primer-probe (20X) 4.6 mL 240 µL 480 µL 72 µL

Plates 24 1 4 2

Time 8 days 4 hours 8 hours 2 hours

Pipette steps 18,432 192 384 432

Comparison of materials and pipetting steps between conventional microplates and Dynamic Array IFCs; 96 samples against 96 assays

Allele map with corresponding scatter plots

using 200-fold less master mix than traditional systems. Each microfluidic plate generates 24-fold more data than that produced by a 384-well plate. This radical advance in experiment density is fully leveraged through a hardware/software system that automates setup and data analysis.

HUMAN GENOTYPING

SNP combinations have been associated with human traits varying from longevity and obesity to metastatic and autoimmune disease, resulting in a better understanding of human metabolism, disease etiology, and population variation; driving new pharmaceutical development, and aiding in the advent of personalized medicine. Our genotyping solution enables you to quickly and efficiently identify these causal SNP combinations.

Call map view for 48 cattle samples and 48 SNPtype™ Assays (left); cluster plot for a typical SNPtype Assay (right).

EASY WORKFLOW WITH THE BIOMARK HD SYSTEM

Pipette samples and SNPtype Assays into the IFC.

Place the IFC onto the IFC Controller to automatically set up genotyping experiments.

Thermal cycle the IFC on the BioMark HD Reader.

View and analyze results with the data analysis suite.

1 2 3 4

SNP GENOTYPING

HIGH SAMPLE THROUGHPUT SNP GENOTYPING

© 2011 Fluidigm Corporation. All rights reserved. Fluidigm, the Fluidigm logo, BioMark, Dynamic Array, EP1, FC1, and SNPtype are trademarks or registered trademarks of Fluidigm Corporation in the U.S. and/or other countries. All other trademarks are the property of their respective owners. Fluidigm recommends that you only purchase licensed PCR assay reagents from authorized sources.FOR RESEARCH USE ONLY. 100-4590 1/2012

Spitz, M.R., Gorlov, I.P., Amos, C.I., Dong, Q., Chen, W., Etzel, C.J., Gorlova, O.Y., Chang, D.W., Pu, X., Zhang, D., Wang, L., Cunningham, J.M., Yang, P., and Wu, X. August 25, 2011. Variants in Inflammation Genes Are Implicated in Risk of Lung Cancer in Never Smokers Exposed to Second-hand Smoke. Cancer Discovery

Chu, X. Song, H.D., et al. August 14, 2011. A genome-wide association study identifies two new risk loci for Graves’ disease. Nature Genetics

K. Shitara, S. Ito, K. Misawa, Y. Ito, H. Ito, S. Hosono, M. Watanabe, K. Tajima, H. Tanaka, K. Muro, and K. Matsuo. June 20, 2011. Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy. Annals of Oncology

Chan, M., Chan, M.W., Loh, T.W., Law, H.Y., Yoon, C.S., Than, S.S., Chua, J.M., Wong, C.Y., Yong, W.S., Yap, Y.S., Ho, G.H., Ang, P, and Lee, A.S.G. May 2011. Evaluation of Nanofluidics Technology for High-Throughput SNP Genotyping in a Clinical Setting. Journal of Molecular Diagnostics

P. J. Maughan, S. M. Smith, D. J. Fairbanks, and E. N. Jellen. March 16, 2011. Development, characterization and linkage mapping of single nucleotide polymorphisms in the gram Amaranths. The Plant Genome

Pharoah, P.D.P, Palmieri, R.T., Ramus, S.J. et al. March 8, 2011. The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer. Clinical Cancer Research/American Association of Cancer Research

Domingo, S., Cabeza, C.M., Pruvost, A., Torres, F., Salazar, J., del Mar Gutierrez, M., Mateo, M.G., Fontanet, A., Fernandez, I., Domingo, J.C., Villarroya, F., Vidal, F., and Baiget, M. January 31, 2011. Association of thymidylate synthase gene polymorphisms with stavudine triphosphate intracellular levels and lipodystrophy. American Society for Microbiology

Baak-Pablo, R., Dezentje, V., Guchelaar, H., & van der Straaten, T. September 16, 2010. Genotyping of DNA Samples Isolated from Formalin-Fixed Paraffin-Embedded Tissues Using Preamplification. Journal of Molecular Diagnostics

Pander, J., Wessels, J. A. M., Gelderblom, H., van der Straaten, T., Punt, C.J.A. & Guchelaar, H.-J. August 17, 2010. Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer. Annals of Oncology

PUBLICATIONS

Corporate Headquarters 7000 Shoreline Court, Suite 100 South San Francisco, CA 94080 USAToll-free: 1.866.FLUIDLINE | Fax: 650.871.7152 www.fluidigm.com

Sales North America | +1 650.266.6170 | [email protected] Europe/EMEA | +33 1 60 92 42 40 | [email protected] | +81 3 3555 2351 | [email protected] Asia | +1 650.266.6170 | [email protected]

Paez, D., Pare, L., Espinosa, I., Salazar, J., Del Rio, E., Barnadas, A., Marcuello, E. and Baiget, M. May 18, 2010. Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: Are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy? Cancer Science

Sagreiya, H., Berube, C., Wen, A., Ramakrishnan, R., Mir, A., Hamilton, A., Altman, R.B. May 3, 2010. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9. Pharmacogenetics and Genomics

Habicht, C., Seeb, L. W., Myers, K. W., Farley, E.V., Seeb, J. E. 2010. Summer-Fall Distribution of Stocks of Immature Sockeye Salmon in the Bering Sea as Revealed by Single-Nucleotide Polymorphisms. Transactions of the American Fisheries Society

Wang, J., Lin, M., Crenshaw, A., Hutchinson, A., Hicks, B., Yeager, M., Berndt, S., Huang, W.,Hayes, R.B., Chanock, S.J., Jones, R.C., and Ramakrishnan, R. 2009 Nov 28. High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays. BMC Genomics

Pushkarev, D., Neff, N.F., Quake, S.R. 2009 Aug 10. Single-molecule sequencing of an individual human genome. Nat Biotechnol

Lo, Y.M.D. 2009 Jan. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art. BJOG 116:152-157

Seeb, J.E., Pascal, C.E., Ramakrishnan, R., Seeb, L.W. 2009. SNP genotyping by the 5’-nuclease reaction: advances in high-throughput genotyping with nonmodel organisms. A. Komar, editor. Methods in molecular biology, single nucleotide polymorphisms, 2d edition. Humana Press P. 277-292

SNP GENOTYPING

HIGH SAMPLE THROUGHPUT SNP GENOTYPING

© 2011 Fluidigm Corporation. All rights reserved. Fluidigm, the Fluidigm logo, BioMark, Dynamic Array, EP1, FC1, and SNPtype are trademarks or registered trademarks of Fluidigm Corporation in the U.S. and/or other countries. All other trademarks are the property of their respective owners. Fluidigm recommends that you only purchase licensed PCR assay reagents from authorized sources.FOR RESEARCH USE ONLY. 100-4590 1/2012

Spitz, M.R., Gorlov, I.P., Amos, C.I., Dong, Q., Chen, W., Etzel, C.J., Gorlova, O.Y., Chang, D.W., Pu, X., Zhang, D., Wang, L., Cunningham, J.M., Yang, P., and Wu, X. August 25, 2011. Variants in Inflammation Genes Are Implicated in Risk of Lung Cancer in Never Smokers Exposed to Second-hand Smoke. Cancer Discovery

Chu, X. Song, H.D., et al. August 14, 2011. A genome-wide association study identifies two new risk loci for Graves’ disease. Nature Genetics

K. Shitara, S. Ito, K. Misawa, Y. Ito, H. Ito, S. Hosono, M. Watanabe, K. Tajima, H. Tanaka, K. Muro, and K. Matsuo. June 20, 2011. Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy. Annals of Oncology

Chan, M., Chan, M.W., Loh, T.W., Law, H.Y., Yoon, C.S., Than, S.S., Chua, J.M., Wong, C.Y., Yong, W.S., Yap, Y.S., Ho, G.H., Ang, P, and Lee, A.S.G. May 2011. Evaluation of Nanofluidics Technology for High-Throughput SNP Genotyping in a Clinical Setting. Journal of Molecular Diagnostics

P. J. Maughan, S. M. Smith, D. J. Fairbanks, and E. N. Jellen. March 16, 2011. Development, characterization and linkage mapping of single nucleotide polymorphisms in the gram Amaranths. The Plant Genome

Pharoah, P.D.P, Palmieri, R.T., Ramus, S.J. et al. March 8, 2011. The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer. Clinical Cancer Research/American Association of Cancer Research

Domingo, S., Cabeza, C.M., Pruvost, A., Torres, F., Salazar, J., del Mar Gutierrez, M., Mateo, M.G., Fontanet, A., Fernandez, I., Domingo, J.C., Villarroya, F., Vidal, F., and Baiget, M. January 31, 2011. Association of thymidylate synthase gene polymorphisms with stavudine triphosphate intracellular levels and lipodystrophy. American Society for Microbiology

Baak-Pablo, R., Dezentje, V., Guchelaar, H., & van der Straaten, T. September 16, 2010. Genotyping of DNA Samples Isolated from Formalin-Fixed Paraffin-Embedded Tissues Using Preamplification. Journal of Molecular Diagnostics

Pander, J., Wessels, J. A. M., Gelderblom, H., van der Straaten, T., Punt, C.J.A. & Guchelaar, H.-J. August 17, 2010. Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer. Annals of Oncology

PUBLICATIONS

Corporate Headquarters 7000 Shoreline Court, Suite 100 South San Francisco, CA 94080 USAToll-free: 1.866.FLUIDLINE | Fax: 650.871.7152 www.fluidigm.com

Sales North America | +1 650.266.6170 | [email protected] Europe/EMEA | +33 1 60 92 42 40 | [email protected] | +81 3 3555 2351 | [email protected] Asia | +1 650.266.6170 | [email protected]

Paez, D., Pare, L., Espinosa, I., Salazar, J., Del Rio, E., Barnadas, A., Marcuello, E. and Baiget, M. May 18, 2010. Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: Are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy? Cancer Science

Sagreiya, H., Berube, C., Wen, A., Ramakrishnan, R., Mir, A., Hamilton, A., Altman, R.B. May 3, 2010. Extending and evaluating a warfarin dosing algorithm that includes CYP4F2 and pooled rare variants of CYP2C9. Pharmacogenetics and Genomics

Habicht, C., Seeb, L. W., Myers, K. W., Farley, E.V., Seeb, J. E. 2010. Summer-Fall Distribution of Stocks of Immature Sockeye Salmon in the Bering Sea as Revealed by Single-Nucleotide Polymorphisms. Transactions of the American Fisheries Society

Wang, J., Lin, M., Crenshaw, A., Hutchinson, A., Hicks, B., Yeager, M., Berndt, S., Huang, W.,Hayes, R.B., Chanock, S.J., Jones, R.C., and Ramakrishnan, R. 2009 Nov 28. High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays. BMC Genomics

Pushkarev, D., Neff, N.F., Quake, S.R. 2009 Aug 10. Single-molecule sequencing of an individual human genome. Nat Biotechnol

Lo, Y.M.D. 2009 Jan. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art. BJOG 116:152-157

Seeb, J.E., Pascal, C.E., Ramakrishnan, R., Seeb, L.W. 2009. SNP genotyping by the 5’-nuclease reaction: advances in high-throughput genotyping with nonmodel organisms. A. Komar, editor. Methods in molecular biology, single nucleotide polymorphisms, 2d edition. Humana Press P. 277-292