Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays

Abstract

Objective: To develop and validate a whole genome amplification and single nucleotide polymorphism (SNP) microarray protocol for accurate single cell 24 chromosome aneuploidy screening.

Design: Prospective, randomized, and blinded study.

Setting: Academic reproductive medicine center.

Patient(s): Multiple euploid and aneuploid cell lines were obtained from a public repository and blastomeres were obtained after biopsy of cleavage stage embryos from 78 patients undergoing IVF.

Main outcome measure(s): Accuracy of copy number assignment and consistency of individual SNPs, whole chromosomes, and single cell aneuploidy status were determined.

Intervention(s): None.

Result(s): Single cells extracted from karyotypically defined cell lines provided 99.2% accuracy for individual SNPs, 99.8% accuracy for whole chromosomes, and 98.6% accuracy when applying a quality control threshold for the overall assignment of aneuploidy status. The concurrence for more than 80 million SNPs in 335 single blastomeres was 96.5%.

Conclusion(s): We have established and validated a SNP microarray-based single cell aneuploidy screening technology. Clinical validation studies are underway to determine the predictive value of this methodology.