Non-invasive Zygosity Determination via Maternal Plasma DNA Analysis
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Solution Overview
Problem
Current methods for determining zygosity in multiple-fetus pregnancies are invasive, inaccurate, or harmful, as they often require individual sampling of amniotic sacs or rely on ultrasound scanning, which can be limited or harmful to the fetus and mother.
Innovation Solution
A non-invasive method using a biological sample from the mother to analyze fetal and maternal DNA, measuring genetic differences and employing statistical methods to determine zygosity by analyzing normalized parameters and parental haplotype inheritance, allowing for the differentiation between monozygotic and dizygotic twins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ultrasound scanning is used to determine zygosity, then non-invasive assessment is provided, but accuracy is limited and it cannot differentiate when fetuses are of different sex
Solution Approach 1:
The patent replaces the mechanical/physical ultrasound scanning system with a molecular genetic analysis system. By using DNA analysis from maternal plasma to detect fetal genetic markers, the invention overcomes the physical limitations of ultrasound in visualizing and differentiating fetuses of different sexes, thereby improving both reliability and detectability of zygosity determination.
Solution Approach 2:
The patent introduces maternal plasma as an intermediary medium that contains fetal DNA. This intermediary allows indirect access to fetal genetic information without direct contact with the fetuses, enabling accurate zygosity determination while maintaining non-invasiveness and overcoming ultrasound limitations.
2Measurement precision
If invasive prenatal diagnosis such as amniocentesis is performed, then zygosity information can be obtained, but harm to the fetus and/or mother occurs
Solution Approach 1:
The patent extracts fetal DNA from maternal plasma, separating the diagnostic information (fetal DNA) from the invasive procedure. This extraction approach allows obtaining accurate zygosity information without performing invasive procedures like amniocentesis, thereby eliminating harm to the fetus and mother while maintaining measurement precision.
Solution Approach 2:
Maternal plasma serves as an intermediary that carries fetal DNA, allowing indirect sampling of fetal genetic material. This intermediary approach provides the same diagnostic information as direct fetal sampling but without the risks and harms associated with invasive procedures.
3Measurement precision
If individual sampling of each amniotic sac is performed for dizygotic twins, then accurate zygosity determination is achieved, but the procedure becomes more complex and time-consuming
Solution Approach 1:
The patent merges the sampling of multiple fetuses into a single maternal plasma sample. By analyzing fetal DNA present in the mother's circulation, the invention simultaneously obtains genetic information from all fetuses without requiring separate sampling procedures for each amniotic sac, thereby reducing procedural complexity while maintaining accuracy.
Solution Approach 2:
The maternal plasma sample serves as a universal source of fetal DNA that can provide genetic information for all fetuses simultaneously. This multi-functional approach allows determination of zygosity for any number of fetuses using the same sampling and analysis methodology, eliminating the need for procedure differentiation based on the number of fetuses.
Data Source
AI summary
Methods, systems, and apparatus are provided for determining zygosity of a multiple-fetus pregnancy using a biological sample taken from the mother. The fetal and maternal DNA in the sample (e.g. plasma) can be analyzed for a particular chromosomal region to identify genetic differences in the fetuses. For example, a normalized parameter for the measure of a primary or secondary allele can show variances for different chromosomal regions when fetuses are dizygotic. Such a variance can be determined relative to an expected value if the fetuses were genetically identical. Statistical methods are provided for analyzing the variation of the normalized parameters to determine fetal DNA concentration and the maternal-fetal mixed genotype at various loci. Parental genotype and haplotype information can also be used to identify inheritance of different parental haplotypes to indicate genetic differences among the fetuses.