Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization

Purpose: To determine the sensitivity of whole-genome oligonucleotide array comparative genomic hybridization for the detection of mosaic cytogenetic abnormalities. Methods: Mosaicism sensitivity was evaluated by testing artificially derived whole chromosome and segmental aneuploidies ranging from 0% to 100% abnormal and additional naturally occurring mosaic specimens. Results: Using combined dye-reversed replicates and an unfiltered analysis, oligonucleotide array comparative genomic hybridization detected as low as 10% and 20-30% mosaicism from whole chromosome and segmental aneuploidies, respectively. To investigate discrepancies between cultured and uncultured specimens, array comparative genomic hybridization was performed on DNA from additional direct product of conception specimens with abnormal karyotypes in culture. Interestingly, 5 of 10 product of conception specimens with double trisomies on cultured cell analysis had only a single trisomy by array comparative genomic hybridization and quantitative polymerase chain reaction on DNA from the uncultured direct specimen, and all harbored the more commonly observed trisomy. Thus, oligonucleotide array comparative genomic hybridization revealed previously unidentified placental mosaicism in half of the products of conception with double-aneuploid conventional karyotypes. Conclusion: Oligonucleotide array comparative genomic hybridization can detect low-level mosaicism for whole chromosome (similar to 10%) and segmental (similar to 20-30%) aneuploidies when using specific detection criteria. In addition, careful interpretation is required when performing array comparative genomic hybridization on DNA isolated from direct specimens as the results may differ from the cultured chromosome analysis. Genet Med 2010:12(2):85-92.