Non-invasive Prenatal Screening via Allele Frequency Analysis
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Solution Overview
Problem
Current non-invasive prenatal screening methods using circulating cell-free fetal DNA (ccffDNA) are limited in diagnosing genetic disorders, particularly those with small mutations, such as recessive disorders, where both parents are carriers, making it difficult to detect conditions like sickle cell anemia without invasive procedures.
Innovation Solution
A method involving amplifying DNA regions encompassing mutation sites in maternal and fetal DNA samples, followed by sequencing to determine the mutant allele frequency, using specific primers and a two-step PCR process to identify fetal contributions to the allelic ratio, enabling non-invasive prenatal diagnosis of recessive disorders like sickle cell anemia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive methods such as amniocentesis and chorionic villus sampling are used for prenatal diagnosis, then diagnostic accuracy is improved, but fetal risk increases
Solution Approach 1:
The invention extracts and analyzes cell-free fetal DNA (cfDNA) from maternal plasma, separating the diagnostic function from invasive fetal sampling. By isolating fetal genetic material that naturally circulates in maternal blood, the method achieves diagnostic accuracy without exposing the fetus to procedural risks associated with amniocentesis or chorionic villus sampling.
Solution Approach 2:
The invention uses maternal plasma as an intermediary medium to access fetal genetic information. Instead of directly sampling fetal tissue or fluid, the method analyzes cfDNA that has been released by fetal cells into the maternal circulation, providing an indirect but safe route to prenatal diagnosis.
2Ease of operation
If ccffDNA is used for fetal sex determination and Rhesus typing, then screening simplicity is improved, but diagnostic scope is limited
Solution Approach 1:
The invention develops a universal cfDNA analysis platform that can diagnose multiple types of genetic disorders, not just fetal sex or Rhesus status. By using PCR amplification and sequencing techniques that can target any genetic sequence, the method extends diagnostic capability to include recessive disorders, dominant disorders, and other monogenic conditions while maintaining the non-invasive simplicity of plasma sampling.
3Reliability
If both parents are carriers for the same recessive point mutation, then prenatal screening difficulty increases, but diagnostic need remains critical
Solution Approach 1:
The invention replaces complex manual analysis methods with automated PCR amplification and high-throughput sequencing technologies. By using molecular biology techniques that automatically amplify and detect specific mutations, the system overcomes the difficulty of analyzing mixed maternal-fetal DNA when both parents carry the same recessive mutation, providing reliable diagnosis through technological automation rather than manual interpretation.
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
This approach allows for accurate, non-invasive prenatal screening of recessive disorders by distinguishing between wild-type and mutant alleles, reducing the need for invasive procedures and improving diagnostic reliability.
Implementation Method 1
amplifying a region encompassing the site of a mutation responsible for the disorder, the amplification being performed on a DNA sample
Implementation Method 2
sequencing a plurality of products from the amplification and determining whether or not the mutant allele is represented at a different frequency
Data Source
AI summary
The present invention is concerned with prenatal screening and in particular non-invasive prenatal screening, as well as primers, primer sets and kits. In one instance, the invention provides a method of prenatal screening comprising: (a) amplifying a region encompassing the site of a mutation site responsible for the disorder, the amplification being performed on a DNA sample obtained from a pregnant female which comprises both maternal and fetal DNA; (b) sequencing a plurality of products from the amplification and determining whether or not the mutant allele is represented at a different frequency to that expected from the genotype of the pregnant female alone.