Hybridization Ligation Array for Copy Number Variation Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for detecting genetic abnormalities such as copy number variations (CNVs) are inefficient and lack reproducibility, particularly in identifying fetal aneuploidy and other genetic disorders.
Innovation Solution
The method involves interrogating loci from target genomic regions using fixed sequence oligonucleotides that hybridize and ligate, with the ligation products being captured on a solid support with complementary probes, allowing for the detection of copy number variations, insertions, deletions, translocations, polymorphisms, and mutations through hybridization and quantification of labeled oligonucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used for detecting genetic abnormalities, then detection can be performed, but the methods are inefficient and lack reproducibility
Solution Approach 1:
The method segments the detection process into distinct steps: hybridization of fixed sequence oligonucleotides to target loci, ligation of hybridized oligonucleotides, capture of ligation products on solid support, and quantification. This segmentation enables standardized protocols that improve reproducibility while maintaining efficiency.
Solution Approach 2:
The patent introduces fixed sequence oligonucleotides as intermediaries that hybridize to target genomic regions and serve as substrates for ligation. These intermediaries enable specific detection of genetic abnormalities through controlled hybridization and ligation reactions, improving both reliability and efficiency.
2Loss of information
If sequencing of ligation products is performed, then complete nucleotide sequence information is obtained, but it is not necessary for detecting copy number variations and other genetic characteristics
Solution Approach 1:
The method extracts only the necessary information for detecting genetic abnormalities (copy number variations, insertions, deletions, translocations, polymorphisms, and mutations) without requiring complete nucleotide sequencing. By using hybridization and ligation of fixed sequence oligonucleotides followed by capture and quantification, the method obtains sufficient diagnostic information while avoiding the complexity and cost of full sequencing.
Solution Approach 2:
Instead of sequencing the original ligation products, the method uses fixed sequence oligonucleotides that copy or hybridize to target regions, undergo ligation, and are then captured on solid support. The quantification of these copied/ hybridized products provides the necessary detection information without requiring direct sequencing of the target DNA.
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 provides a reliable and efficient method for detecting genetic characteristics, including fetal aneuploidy, by quantifying relative frequencies of target genomic regions, enabling accurate identification of genetic abnormalities without the need for sequencing the nucleotide sequence of the ligation products.
Implementation Method 1
introducing a first set of first and second fixed sequence oligonucleotides to a sample under conditions that allow the first and second fixed sequence oligonucleotides to hybridize specifically to complementary regions in loci from a first target genomic region
Implementation Method 2
ligating the hybridized fixed sequence oligonucleotides to create ligation products
Data Source
AI summary
The present invention provides detection systems and methods for detection of loci and genomic regions in a sample, including mixed samples, using hybridization to an array.