A Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis.

This study compared the performance of 5-fold genome sequencing (GS) with single nucleotide polymorphism (SNP) array technology in detecting chromosomal abnormalities, particularly in the context of prenatal and postnatal diagnostics. A total of 42 samples, previously analyzed by SNP array, were re-examined using 5-fold GS to evaluate the detection of clinically significant copy number variations (CNVs), mosaicism, and absence of heterozygosity (AOH). The results revealed a 100% concordance between the two methods for the identification of clinically relevant CNVs, with both technologies detecting similar CNV size ranges. However, 5-fold GS demonstrated better precision in defining CNV breakpoints and exhibited a lower false-positive rate, as confirmed by quantitative PCR validation. Additionally, 5-fold GS detected mosaicism with comparable sensitivity to SNP array, capturing mosaic levels as low as 17%, whereas SNP array identified levels between 15% and 84%. For AOH detection, 5-fold GS identified all candidate AOH regions with a slightly better sensitivity, achieving a detection size limit of 4.8 Mb compared with SNP array's 5.08 Mb. Overall, 5-fold GS shows potential as a reliable method for chromosomal abnormality detection, offering high accuracy and clinical utility in both prenatal and postnatal genetic testing.