An alternative to array-based diagnostics: a prospectively recruited cohort, comparing arrayCGH to next-generation...

Area of Science:

• Genomics
• Molecular Diagnostics
• Foetal Medicine

Background:

• Array comparative genomic hybridisation (aCGH) is routinely used for foetal abnormality investigations.
• Next-generation sequencing (NGS) is emerging as a contemporary method for copy number variation (CNV) detection.

Purpose of the Study:

• To compare an in-house NGS-based workflow (CNVseq) with aCGH for foetal samples.
• To evaluate CNVseq's robustness and sensitivity in prenatal diagnosis.

Main Methods:

• Screened DNA from 40 foetuses using 8x60K aCGH arrays and low-coverage whole genome sequencing (CNVseq).
• Utilized Illumina HiSeq2500 for sequencing multiplexed samples.
• Analyzed data for copy number imbalances and breakpoint precision.

Main Results:

• CNVseq achieved a mean resolution of 29kb, compared to 60kb for aCGH.
• Four clinically significant, concordant copy number imbalances were detected by both methods.
• CNVseq provided more precise genomic breakpoint definition.

Conclusions:

• CNVseq is a robust and sensitive alternative to aCGH for prenatal investigation of foetal structural abnormalities.
• NGS offers comparable turnaround time and sensitivity to aCGH.
• Low-coverage whole genome sequencing is poised to supersede aCGH in prenatal CNV detection.