Probabilistic Model for Fetal DNA Origin Determination
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Solution Overview
Problem
Current non-invasive prenatal testing (NIPT) methods face challenges in accurately determining the genetic origin of fetal cellular DNA, leading to potential misdiagnosis due to the persistence of fetal cells in maternal blood from previous pregnancies, and difficulties in distinguishing between homozygous and heterozygous scenarios when the mother is heterozygous for a recessive genetic disease.
Innovation Solution
A method involving a probabilistic model that determines the genetic origin of fetal cellular DNA by analyzing genotypes of the fetus and mother, identifying informative genetic markers, and calculating probabilities of the DNA originating from the current or historical pregnancy, using a computer system to process genetic data and determine the origin of fetal cellular DNA.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fetal cellular DNA is isolated from maternal blood for non-invasive prenatal testing, then the sensitivity of genetic diagnosis is improved, but the reliability of test results deteriorates due to potential contamination from historical pregnancies
Solution Approach 1:
The patent uses cell-free DNA as an intermediary substance to trace the origin of fetal cellular DNA. By analyzing the genetic composition of cfDNA in maternal plasma, the method determines whether fetal cellular DNA originates from current or historical pregnancy, thereby resolving the reliability issue while maintaining sensitivity
Solution Approach 2:
The patent implements a feedback mechanism where the genetic information from cfDNA is used to verify and validate the origin of fetal cellular DNA. This feedback loop allows the system to distinguish between current and historical pregnancy samples, ensuring reliable test results
2Ease of operation
If conventional non-invasive prenatal diagnosis methods are used when the mother is heterozygous for a recessive genetic disease, then the ease of operation is improved, but the measurement precision deteriorates due to inability to differentiate homozygous and heterozygous fetal scenarios
Solution Approach 1:
The patent adds another dimension of analysis by examining the genetic composition of cell-free DNA in maternal plasma alongside fetal cellular DNA. This additional dimensional information allows differentiation between homozygous and heterozygous fetal scenarios that cannot be distinguished by conventional methods alone
3Productivity
If fetal cells are assumed to originate from current pregnancy without verification, then the productivity of prenatal testing is improved, but the reliability deteriorates due to potential misdiagnosis from historical pregnancy cells
Solution Approach 1:
The patent performs preliminary verification by analyzing the genetic composition of cell-free DNA before proceeding with prenatal diagnosis using fetal cellular DNA. This preliminary action determines the origin of fetal cells, preventing misdiagnosis while maintaining testing efficiency
Data Source
AI summary
Disclosed are methods for determining a genetic origin of fetal cellular DNA obtained from a pregnant female who is carrying a fetus in a current pregnancy. Methods are also disclosed for using the fetal cellular DNA and fetal cell-free DNA (cfDNA) to determine fetal genetic conditions such as copy number variations. The methods disclosed uses a probabilistic model to determine fetal cellular DNA origin based on alleles observed at informative genetic marker of the fetal cellular DNA. Systems and computer program products for performing the methods are also disclosed.