Interfering effect of maternal cell contamination on invasive prenatal chromosome microarray analysis

Abstract

Objective To access the effect of maternal cell contamination (MCC) on the detection of copy number variation (CNV) by chromosome microarray analysis (CMA) in prenatal diagnostic samples. Methods Amniotic fluid DNA samples were collected from Department of Prenatal Diagnosis (Screening) Centre of Hangzhou Women′s Hospital from December 2016 to August 2018. Copy number variations (CNVs) were identified in these DNA samples by CMA and normal female genomic DNA was added to simulate different proportions of maternal cells contamination. The simulated samples were tested using an Agilent microarray chromosome chip 180K CGH (Agilent 180K CGH) and the results were analyzed by Agilent CytoGenomics software. Results The results showed that duplications of CNV could not be detected at>38.4% MCC. Deletions of CNV could not be detected at>41.3% of MCC. With the increase of MCC ratio, the detection rate of CNV decreased gradually. The array and software allowed detection of longer copy-number variations at higher levels of maternal cell contamination than shorter copy-number variations. For the same size CNV, the detection ability of the deleted CNV was slightly higher than that of duplication. In the male sample, the observable shift of the X/Y chromosome ratio at>10% MCC can be detected by the microarray. Conclusions When the MCC is higher than a particular ratio, it can affect the CMA detection of CNV. Based on the Agilent 180K CGH detection results for MCC mimics and the CNV detection specificity principle, the MCC threshold of the Agilent 180K CGH is set to 30% in view of conservative principles. Key words: Amniotic fluid; Prenatal diagnosis; Microarray analysis; DNA copy number variations