Resolution of trisomic mosaicism in prenatal diagnosis: estimated performance of a 50K SNP microarray

Objective To evaluate the ability of a DNA single nucleotide polymorphism (SNP) microarray to detect chromosome mosaicism for trisomy in prenatal samples in order to compare this with conventional cytogenetics. Method We created a dilution series of mock mosaic samples, by mixing measured amounts of fibroblast cells containing trisomy 8 from a male with aliquots of cells with a normal female karyotype. DNAs were extracted from these mosaic mixtures, then analysed on the Affymetrix 50K Xba SNP chip. Duplicate aliquots of each mosaic sample were probed using interphase FISH, with centromeric probes for chromosomes X, Y and 8, to estimate independently the proportion of male trisomy 8 in each sample. Data from the arrays were analysed using publicly available analysis tools. Statistical calculations were then performed using a Student's t-test to determine if there was a significant difference between the copy numbers of each chromosome. Results These experiments using the Affymetrix 50K Xba SNP microarray showed mosaicism to be obvious at 20% and with additional statistical calculations, the lower limit for detection is about 10%. Conclusion The SNP microarray platform tested can detect mosaicism for trisomy in prenatal samples at levels comparable with conventional cytogenetic techniques in routine use. Copyright (c) 2007 John Wiley & Sons, Ltd.