Optical Genome Mapping and Single Nucleotide Polymorphism Microarray: An Integrated Approach for Investigating...

Area of Science:

• Genetics
• Genomic Medicine
• Reproductive Biology

Background:

• Conventional cytogenetic analysis of products of conception (POC) faces challenges like culture failure and contamination.
• Maternal cell contamination (MCC) significantly impedes accurate genetic diagnosis in POC specimens.
• Optical genome mapping (OGM) offers a culture-independent method for genetic analysis, potentially overcoming some limitations.

Purpose of the Study:

• To develop and evaluate an integrated workflow for improved genetic analysis of POC specimens.
• To address the challenges of microbial contamination and MCC in POC testing.
• To enhance the diagnostic yield compared to routine cytogenetic methods.

Main Methods:

• An integrated workflow combining MCC characterization, OGM, and SNP microarray (SNPM) with histological assessment was devised.
• POC tissues underwent MCC assessment.
• MCC-negative cases were analyzed using OGM, while MCC-positive cases utilized SNPM with histological evaluation.

Main Results:

• The proposed integrated workflow achieved a 93% success rate (29/31 cases) with a 45.1% diagnostic yield (14/31 cases).
• This significantly outperformed the routine workflow, which had a 9.6% success rate and a 6.4% diagnostic yield.
• The workflow effectively managed MCC, enabling definitive diagnoses in a higher proportion of cases.

Conclusions:

• The integrated workflow incorporating OGM and SNPM demonstrates significant clinical utility for POC specimen evaluation.
• This approach substantially increases the diagnostic yield for genetic analysis of POC.
• The strategy effectively overcomes limitations associated with conventional cytogenetics and contamination issues.