Single Array CGH Method for Chromosomal Imbalance Detection
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Solution Overview
Problem
Current CGH array methods require multiple hybridizations when detecting chromosome imbalances in samples of unknown sex, such as embryos undergoing genetic screening, necessitating separate hybridizations with both male and female reference DNAs, which increases the number of tests and analysis time, and lacks effective internal quality control for reference DNA.
Innovation Solution
A single array CGH method where the test DNA is hybridized against a single reference DNA (male or female), with results combined from a separate reference hybridization array using DNAs from both sexes, reducing the number of arrays needed and introducing internal quality control to minimize biases and errors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple hybridizations with both male and female reference DNAs are performed for samples of unknown sex, then accurate detection of chromosomal imbalances is achieved, but the number of tests and analysis time increase
Solution Approach 1:
The patent applies preliminary action by performing a reference hybridization with both male and female reference DNAs before the actual sample analysis. This reference hybridization establishes baseline signal intensity ratios that can be used to interpret subsequent sample hybridizations, eliminating the need to perform separate male and female reference hybridizations for each sample.
Solution Approach 2:
The patent creates a universal reference hybridization array that serves multiple purposes: it establishes baseline ratios for both male and female chromosomes simultaneously, and these results can be applied to analyze any sample regardless of sex. This multi-functional reference array reduces the total number of hybridization tests required.
2Measurement precision
If multiple hybridizations with both male and female reference DNAs are performed for samples of unknown sex, then accurate detection of chromosomal imbalances is achieved, but the number of hybridization tests increases
Solution Approach 1:
The patent merges the male and female reference DNAs into a single reference hybridization array. Instead of performing separate hybridizations with male reference DNA and female reference DNA, both reference DNAs are hybridized together in one test, combining their functions into a single experimental step.
Solution Approach 2:
The universal reference hybridization array performs the function of both male and female reference controls simultaneously, reducing the total number of hybridization tests from multiple separate tests to a single combined test that provides all necessary baseline data.
3Ease of operation
If conventional CGH array methods are used without internal quality control, then the procedure is simpler, but biases and errors in reference DNA affect result reliability
Solution Approach 1:
The patent implements feedback by incorporating internal quality control measures where the reference hybridization results are used to validate and normalize the sample hybridization results. The signal intensity ratios from the reference hybridization provide feedback on the quality and reliability of the analysis, allowing identification and correction of potential biases or errors.
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 significantly reduces the number of hybridization tests and analysis time, providing accurate and reliable detection of chromosomal imbalances in both gonosomal and autosomal DNA with improved signal intensity processing and internal quality control, enhancing the efficiency and accuracy of CGH testing.
Implementation Method 1
Labeling with a first marker, said test-DNA, thus obtaining a labeled test-DNA; labeling with a second marker, different from the first, a male (or female) reference-DNA, thus obtaining a labeled male (or female) reference-DNA
Implementation Method 2
Hybridizing the DNAs obtained in steps a) and b) to a test hybridization array, thus obtaining a combined pattern of signal intensities from both markers
Data Source
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AI summary
New method to assess chromosomal imbalances in autosomal and gonosomal genomic DNA, via CGH technique, involving the use of a single array per DNA sample to be tested is described. The method, involving a strong reduction in the number of hybridization reactions, is most advantageously applicable to the determination of chromosomal imbalances in DNA samples whose sex is not known beforehand, such as happening in case of e.g. IVF protocols. The invention further includes data processing aimed at reducing the bias and to control the quality of the reference DNA used in the method. Supports and kits for performing the method are also provided.