Rapid detection of aneuploidies on a benchtop sequencing platform.

Objective: To report a novel method of rapidly detecting fetal aneuploidies for spontaneous abortion using ultra-low whole genome sequencing data on a benchtop sequencing platform.

Method: Fetal chorionic villus samples were collected from 40 cases of spontaneous abortion with 22 different types of aneuploidy. Genomic DNA of each sample was extracted and sequenced on Illumina MiSeq platform. Unique reads of different read lengths were generated and analyzed using a z-score test.

Results: The entire test was finished in 48 hours. An average of 102 k unique reads was obtained for each sample, and all 40 different aneuploidy samples were correctly identified with a z-score of ≥3 or ≤ -3. No false positives or false negatives were observed. Further analysis demonstrated that read length and sequencing type (Paired-end or Single-end) significantly affects the efficiency of sex chromosomal aneuploidy detection. Paired-end 50 bp reads displayed the highest mapping rate and is recommended for future large-scale clinical settings.

Conclusion: Ultra-low whole genome sequencing can rapidly detect aneuploidy of chromosomes in spontaneous abortion samples in less than 48 hours and therefore can serve as an alternative option to current aneuploidy detection methods for aborted tissues.