Parental Genotype Analysis for Low-DNA Aneuploidy Detection
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Solution Overview
Problem
Current methods for detecting chromosomal anomalies in low amounts of genetic material are prone to bias and noise due to amplification, and require phased genotype data from family members, making them cumbersome and unreliable.
Innovation Solution
A method using unphased genotype information from both parents and allele frequency analysis to detect chromosomal anomalies, allowing discrimination between meiotic and mitotic anomalies without the need for phased data or additional family samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple separate reactions are performed in different tubes followed by separate analysis, then each reaction can be optimized independently, but the analysis time increases and labor costs increase
Solution Approach 1:
The patent combines multiple separate reactions (hybridization, washing, and detection reactions) that were previously performed in different tubes into a single microarray system. This merging allows all reactions to occur simultaneously in one integrated platform, eliminating the need for sequential processing across multiple tubes, thereby reducing analysis time while maintaining reaction optimization through controlled conditions.
Solution Approach 2:
The microarray system serves multiple functions within a single device: it performs hybridization of genetic material to probes, washing of unbound material, and detection of bound complexes. This multi-functionality consolidates what were previously separate specialized reactions into one universal platform, reducing both time and labor requirements.
2Reliability
If multiple separate reactions are performed in different tubes, then each reaction can be controlled independently, but labor costs increase
Solution Approach 1:
The patent merges multiple labor-intensive separate reactions into a single automated microarray process. By combining hybridization, washing, and detection into one integrated system, the number of manual operations is dramatically reduced, lowering labor costs while maintaining independent reaction control through spatial separation of probe elements on the array.
Solution Approach 2:
The microarray system is designed to perform washing and detection functions automatically without requiring separate manual intervention for each reaction step. The system self-manages the multiple reactions through programmed sequences, reducing dependence on manual labor while preserving reaction control.
3Reliability
If genetic material is analyzed by traditional methods, then the process is well-established, but the process is time-consuming and costly
Solution Approach 1:
The patent segments the genetic material analysis into numerous individual probe elements arranged on a microarray surface. Each probe targets a specific sequence, allowing parallel analysis of multiple genetic regions simultaneously. This segmentation enables high-throughput analysis while maintaining the reliability of established hybridization and detection methods for each individual probe.
Solution Approach 2:
The patent transitions from linear sequential analysis in tubes to a two-dimensional microarray surface. By arranging probes spatially across the surface of a slide, the system enables simultaneous multi-point analysis, dramatically increasing throughput while preserving the reliability of individual reaction processes through maintained chemical conditions.
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
Improves the accuracy of aneuploidy detection and chromosomal mosaicism analysis in samples with low DNA amounts, reducing bias and simplifying the process by eliminating the need for phased data and additional family samples.
Implementation Method 1
manipulation of the magnetic particles with magnetic means
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 1E~1H
AI summary
The present invention is directed to a method for the analysis of genetic material in a subject. More in particular, the present invention relates to a method for the analysis of genetic material using unphased genotype information of polymorphic variants of a first and second parent of a subject in combination with the allele frequency of the polymorphic variants in the genetic material of the subject. In a further aspect, the method of the present invention is particularly useful for the analysis of genetic material isolated from a sample comprising a low amount of genetic material and/or detection of low level chromosomal mosaicism.