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. 2024 Apr;44(4):443-453.
doi: 10.1002/pd.6525. Epub 2024 Jan 27.

Validation of low-pass genome sequencing for prenatal diagnosis

Chloe Mighton  1   2 , Abdul Noor  1   3 , Nicholas Watkins  1   4 , Vanessa Di Gioacchino  1   4 , Jordan Lerner-Ellis  1   3 , Andrew Wong  1 , Elvira Mukharryamova  1   4 , Nina Anggala  1   4 , David Chitayat  4   5 , Elena Greenfeld  1   3
Affiliations

Validation of low-pass genome sequencing for prenatal diagnosis

Chloe Mighton et al. Prenat Diagn. 2024 Apr.

Abstract

Objective: Chromosomal microarray (CMA), while considered the gold standard for detecting copy number variants (CNVs) in prenatal diagnostics, has its limitations, including the necessity to replace aging microarray equipment, low throughput, a static design, and an inefficient multi-day workflow. This study evaluates the feasibility of low-pass genome sequencing (LP-GS) as a potential replacement for CMA in prenatal diagnostics.

Methods: We comprehensively compared LP-GS at 10x and 5x average depths with CMA in a prenatal laboratory. We examined parameters, including concordance, sensitivity, specificity, workflow efficiency, and cost-effectiveness.

Results: We found a high degree of agreement between LP-GS and CMA for detecting CNVs and absence of heterozygosity. Furthermore, compared to CMA, LP-GS increased workflow efficiency and proved to be cost-neutral at 10x and cost-effective at 5x.

Conclusion: Our study suggests that LP-GS is a promising alternative to CMA in prenatal diagnostics, offering advantages, including a more efficient workflow and scalability for larger testing volumes. Importantly, for clinical laboratories that have adopted next-generation sequencing in a separate capacity, LP-GS facilitates a unified NGS-centric approach, enabling workflow consolidation. By offering a single, streamlined platform for detecting a broad range of genetic variants, LP-GS may represent a critical step toward enhancing the diagnostic capabilities of prenatal laboratories.

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References

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