Fetal DNA Methylation Markers for Non-Invasive Prenatal Diagnosis
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Solution Overview
Problem
Current non-invasive prenatal diagnosis methods face challenges in distinguishing fetal DNA from maternal DNA in maternal plasma, limiting their applicability and accuracy, especially for pregnancies with female fetuses and conditions not associated with Y-chromosome sequences.
Innovation Solution
Identification of genomic sequences on chromosome 21 with different methylation profiles between fetal and maternal DNA, using bisulfite treatment and methylation-specific PCR to differentiate and quantify fetal DNA, allowing for accurate diagnosis of pregnancy-associated disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fetal DNA is detected in maternal plasma using PCR-based techniques, then non-invasive prenatal diagnosis is achieved, but the ability to distinguish fetal DNA from maternal DNA is limited
Solution Approach 1:
The patent applies parameter changes by utilizing the methylation status of DNA as a distinguishing parameter. Fetal DNA and maternal DNA are differentiated based on their different methylation patterns at specific genomic loci, allowing precise identification of fetal DNA in maternal plasma without invasive procedures
Solution Approach 2:
The patent uses an intermediary approach by employing methylation-specific markers as mediators between the detection system and the target DNA. These markers serve as intermediaries that enable the differentiation of fetal from maternal DNA through their distinct methylation characteristics
2Adaptability or versatility
If Y-chromosome sequences are used to distinguish fetal DNA, then male fetuses can be detected, but applicability is limited to male pregnancies
Solution Approach 1:
The patent achieves universality by developing a detection method that works for both male and female fetuses. Instead of relying on Y-chromosome sequences that only work for male pregnancies, the method uses methylation markers present in all fetal DNA, making the technique universally applicable to all pregnancies regardless of fetal sex
Solution Approach 2:
The patent inverts the approach by not searching for fetal-specific sequences in the traditional sense, but rather by exploiting the epigenetic differences (methylation patterns) between fetal and maternal DNA. This inversion of the detection strategy enables identification of fetal DNA through its unique methylation signature rather than through sequence-specific markers
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables reliable non-invasive detection and monitoring of fetal chromosomal abnormalities and pregnancy-related conditions by distinguishing fetal from maternal DNA, improving diagnostic accuracy and expanding applicability beyond male fetuses.
Implementation Method 1
treating a DNA sample with bisulfite or with a reagent that differentially modifies methylated and non-methylated DNA
Data Source
Figure 1A
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AI summary
This application provides the use of novel fetal markers for prenatal diagnosis and monitoring of certain pregnancy-related conditions. More specifically, the inventions resides in the discovery that certain CpG islands located on fetal chromosome 21 demonstrate a methylation profile that is distinct from that of corresponding CpG islands located on maternal chromosome 21. This application also provides kits for diagnosing or monitoring of the relevant conditions.