Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Highly Accessed Methodology article

High-throughput single nucleotide polymorphism genotyping using nanofluidic Dynamic Arrays

Jun Wang1, Min Lin1, Andrew Crenshaw23, Amy Hutchinson23, Belynda Hicks23, Meredith Yeager23, Sonja Berndt3, Wen-Yi Huang3, Richard B Hayes3, Stephen J Chanock3, Robert C Jones1 and Ramesh Ramakrishnan1*

Author Affiliations

1 Fluidigm Corporation, South San Francisco, CA, USA

2 Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc, Advanced Technology Program, NCI-FCRDC, Frederick, MD, USA

3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA

For all author emails, please log on.

BMC Genomics 2009, 10:561  doi:10.1186/1471-2164-10-561

Published: 28 November 2009

Abstract

Background

Single nucleotide polymorphisms (SNPs) have emerged as the genetic marker of choice for mapping disease loci and candidate gene association studies, because of their high density and relatively even distribution in the human genomes. There is a need for systems allowing medium multiplexing (ten to hundreds of SNPs) with high throughput, which can efficiently and cost-effectively generate genotypes for a very large sample set (thousands of individuals). Methods that are flexible, fast, accurate and cost-effective are urgently needed. This is also important for those who work on high throughput genotyping in non-model systems where off-the-shelf assays are not available and a flexible platform is needed.

Results

We demonstrate the use of a nanofluidic Integrated Fluidic Circuit (IFC) - based genotyping system for medium-throughput multiplexing known as the Dynamic Array, by genotyping 994 individual human DNA samples on 47 different SNP assays, using nanoliter volumes of reagents. Call rates of greater than 99.5% and call accuracies of greater than 99.8% were achieved from our study, which demonstrates that this is a formidable genotyping platform. The experimental set up is very simple, with a time-to-result for each sample of about 3 hours.

Conclusion

Our results demonstrate that the Dynamic Array is an excellent genotyping system for medium-throughput multiplexing (30-300 SNPs), which is simple to use and combines rapid throughput with excellent call rates, high concordance and low cost. The exceptional call rates and call accuracy obtained may be of particular interest to those working on validation and replication of genome- wide- association (GWA) studies.