A comparison of array technologies and next generation sequencing technologies in preconception genetic diagnosis

OBJECTIVE: Genomic technologies significantly reduce cost and time for mutation screening. Classic Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) diagnostics are being replaced by Array and Next-Generation Sequencing (NGS) technologies. We compared both platforms’ ability to improve Preconception Genetic Diagnosis (PCGD). DESIGN: Our assay, built on Illumina’s Infinium iSelect HD genotyping platform, was compared to a major NGS technology. We looked at accuracy of genotype calls. We defined coverage as the number of specific mutations assay. We defined residual risk reduction as ability to detect de novo or other unknown mutations. We defined agility as ability to add/modify content on platform without impacting previously attempted loci. Finally, we looked at cost of each assay per-sample/perlocus basis. MATERIALS ANDMETHODS: Data from manufacturers, company representatives and laboratory findings were used to assemble results. RESULTS: Our platform, had accurate calls in excess of 99.7%. The NGS can achieve>99% accuracy with 50x depth. Both platforms include thousands of targets. Only array can detect large deletions. The NGS platform allows for greater reduction of residual risk. Looking at agility, the array platform retains 99.9999% of previously attempted loci with no reduction in performance upon addition of new content. This is not the case with NGS platform. The array technology is considerably more cost effective on a per-sample/per-locus basis.