Combined array CGH plus SNP microarray analyses in a single assay for prenatal testing

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  Objective In prenatal diagnostics, both microarray comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of fetal structural anomalies.While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect small copy number variants (CNVs) due to the uneven distribution of SNPs across the genome.To provide comprehensive prenatal testing for both CNVs and copy neutral AOH.Methods We improved our target designed high-resolution oligonucleotide array that has targeted coverage of 1,650 genes with 15,000 SNP probes, referred to as Fetal DNA chip v2.0 (8x60K format).Results Of the 240 cases evaluated by this array, clinically significant CNVs were detected in 25 cases including 21 cases with pathogenic CNV events.In addition, 31 cases (13.0%) showed at least one AOH region >3 Mb, four of them with AOH >10 Mb demonstrated to be of clinical significant.Conclusion Our data demonstrate that even though this array has a lower density of SNP probes than commercially available SNP arrays, it reliably detected AOH events >3 Mb as well as Pathogenic CNVs.Thus, combining targeted array CGH with SNP probes into one platform provides clinically useful prenatal genetic screening in a more efficient manner.
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