Non-Invasive Prenatal Paternity Testing via Cell-Free DNA Analysis
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Solution Overview
Problem
Current non-invasive prenatal paternity tests face challenges due to low levels and fragmentation of fetal DNA in cell-free samples from pregnant mothers, leading to concerns about accuracy.
Innovation Solution
A method using a panel of polymorphic nucleic acid targets that can be amplified and sequenced to determine fetus-specific alleles, allowing for the calculation of a paternity index by analyzing the genotypes of the mother, fetus, and alleged father, thereby determining paternity likelihood.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If non-invasive prenatal paternity tests are performed using cell-free samples from pregnant mothers, then the procedure is convenient and safe, but the accuracy remains a concern due to low levels and fragmentation of fetal DNA
Solution Approach 1:
The patent segments the fetal genome into multiple specific target regions (e.g., Y chromosome regions, paternal-specific autosomal regions) that can be independently amplified and analyzed. This segmentation allows the test to focus on informative regions where the alleged father and fetus have distinguishable genetic markers, thereby improving measurement precision despite the low overall concentration of fetal DNA in maternal cell-free DNA samples
Solution Approach 2:
The patent applies local quality by selecting and analyzing specific polymorphic regions (such as STR loci or SNP regions) that exhibit high variability between individuals. By concentrating analysis on these locally informative regions rather than attempting to analyze the entire genome, the method achieves high paternity determination accuracy even with limited fetal DNA material in the cell-free sample
2Measurement precision
If invasive procedures such as chorionic villus sampling or amniocentesis are used for prenatal paternity testing, then the accuracy is highly reliable, but the procedure becomes risky and complex
Solution Approach 1:
The patent extracts and analyzes only the necessary genetic information from cell-free DNA samples - specifically targeting polymorphic regions that can distinguish paternal from maternal origin. By extracting only the informative genetic markers needed for paternity determination rather than analyzing entire genomes or requiring cellular material, the method achieves high accuracy without the complexity and risks of invasive procedures
Solution Approach 2:
The patent uses cell-free DNA in maternal blood as an intermediary that contains fetal genetic material without requiring direct access to fetal cells. This intermediary approach allows paternal genetic information to be obtained indirectly through molecular amplification and analysis of circulating DNA fragments, eliminating the need for invasive sampling procedures while maintaining sufficient accuracy for paternity determination
3Measurement precision
If a panel of polymorphic nucleic acid targets is used with multiplexed amplification and sequencing, then the accuracy of fetal DNA quantification is improved, but the device and process complexity increases
Solution Approach 1:
The patent employs a universal multiplexed amplification system that can simultaneously target multiple polymorphic regions using a single reaction mixture containing multiple primer sets. This multi-functional approach allows the system to analyze numerous genetic markers in parallel, improving the precision of fetal DNA quantification and paternity determination while consolidating what would otherwise require multiple separate reactions into one unified process
Solution Approach 2:
The patent optimizes reaction parameters such as primer concentrations, annealing temperatures, and cycle conditions to enable efficient multiplexed amplification of multiple polymorphic targets simultaneously. By carefully adjusting these parameters, the method achieves high measurement precision for fetal DNA quantification while managing the complexity of the multiplexed system through standardized protocol optimization
Data Source
AI summary
This application provides methods and systems for paternity determination. In some embodiments, the method is a non-invasive prenatal paternity determination method, which comprises obtaining genotypes for one or more polymorphic nucleic acid targets in a genomic DNA sample obtained from an alleged father, isolating cell-free nucleic acids from a biological sample obtained from the pregnant mother comprising fetal nucleic acids. The amount of each allele of one or more polymorphic nucleic acid targets in cell-free nucleic acids are determined and informative polymorphic nucleic acid targets are identified. Next, the allele frequency of each allele of the selected informative polymorphic nucleic acid targets is measured and fetal genotypes for each selected informative polymorphic nucleic acid targets are determined based on the allele frequency. Finally, the paternity status of the fetus are determined based on the genotypes of the mother, alleged father and the fetus for the informative nucleic acid targets.