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Published on: August 17, 2022
Integrated Single-Strand DNA Capture and Haplotype-Guided Variant Calling Platform for Non-Invasive Prenatal Testing
Jie Shen1,2,3, Wei Liu4, Li Lu2,3
1Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Diagnostics (Basel, Switzerland)
|August 13, 2026
Summary
This study developed a new non-invasive prenatal testing for monogenic disorders (NIPT-MD) platform. The robust NIPT-MD demonstrated high accuracy in detecting fetal genetic variants from maternal blood, offering a safe alternative to invasive testing.
Area of Science:
- Genetics
- Molecular Biology
- Bioinformatics
Background:
- Non-invasive prenatal testing for monogenic disorders (NIPT-MD) offers a safer alternative to invasive prenatal diagnosis.
- Clinical utility of NIPT-MD is often hindered by low fetal fraction (FF), technical artifacts, and distinguishing maternal from fetal DNA.
- Accurate fetal variant detection in cell-free DNA (cfDNA) is crucial for NIPT-MD.
Purpose of the Study:
- To develop and validate a robust NIPT-MD platform for common Mendelian inheritance patterns.
- To enhance the accuracy of fetal variant detection in cfDNA for NIPT-MD.
- To overcome challenges of low FF and maternal cfDNA background in NIPT-MD.
Main Methods:
- Developed a novel NIPT-MD platform using single-strand capture library preparation with unique molecular identifiers (UMIs).
- Quantified FF using a panel of high-minor-allele-frequency single-nucleotide polymorphisms (SNPs).
- Inferred fetal genotypes by resolving parental haplotypes using a statistical model integrating VAF and SNP counts.
Main Results:
- The UMI-enhanced single-strand capture protocol significantly reduced amplification biases.
- FF estimation algorithm showed strong concordance with established methods and spike-in samples.
- The platform accurately detected both paternally and maternally inherited pathogenic variants.
- Achieved high concordance with invasive testing in a retrospective cohort of 35 clinical cases.
Conclusions:
- An accurate and robust NIPT-MD platform for monogenic disorders has been developed and validated.
- The platform demonstrated high concordance with invasive testing in a clinical cohort.
- This NIPT-MD method shows significant promise for managing families at high risk for monogenic diseases.
