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


METHODS
Prospective, randomized, and blinded study.


METHODS
Academic reproductive medicine center.


METHODS
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.


METHODS
Accuracy of copy number assignment and consistency of individual SNPs, whole chromosomes, and single cell aneuploidy status were determined.


METHODS
None.


RESULTS
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%.


CONCLUSIONS
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.
Treff
Nathan R
NR
Reproductive Medicine Associates of New Jersey, Morristown, New Jersey 07960, USA. ntreff@rmanj.com
Su
Jing
J
Tao
Xin
X
Levy
Brynn
B
Scott
Richard T
RT
D000782:Aneuploidy; D002460:Cell Line; D002877:Chromosomes, Human; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000378:metabolism; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D016678:Genome / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods; D015203:Reproducibility of Results