High-throughput SNP genotyping by SBE/SBH

Despite much progress over the past decade, current single nucleotide polymorphism (SNP) genotyping technologies still offer an insufficient degree of multiplexing when required to handle user selected sets of SNPs. In this paper we propose a new genotyping assay architecture combining multiplexed solution-phase single-base extension (SBE) reactions with sequencing by hybridization (SBH) using universal DNA arrays such as all k-mer arrays. Simulation results on datasets both randomly generated and extracted from the NCBI dbSNP database suggest that the SBE/SBH architecture provides a flexible and cost-effective alternative to genotyping assays currently used in the industry, enabling genotyping of up to hundreds of thousands of SNPs per assay.