Oligonucleotide Probes for High-Resolution Chromosomal Mapping
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Solution Overview
Problem
Current cytogenetics techniques, such as Giemsa banding and spectral karyotyping, have low spatial resolution, limiting the accurate determination of genomic structure boundaries to several megabases, making it difficult to map and characterize smaller genomic rearrangements like duplications, inversions, and translocations.
Innovation Solution
A physical genomic analysis composition comprising a solution of oligonucleotides, including at least two different oligonucleotides designed to hybridize to specific regions of a nucleic acid, allowing for high-resolution mapping of genomic structures by distinguishing portions of the genome as small as less than 1,000 bases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional cytogenetics techniques (G-banding, M-banding, SKY) are used, then chromosomal structures can be identified, but the spatial resolution is limited to several megabases
Solution Approach 1:
The patent divides the chromosome into many small segments by using multiple oligonucleotide probes that hybridize to specific regions. Each oligonucleotide acts as an independent marker, allowing the chromosome to be mapped in discrete segments rather than as a continuous structure, thereby achieving higher resolution mapping.
Solution Approach 2:
The patent introduces oligonucleotides as intermediary molecules that bridge the gap between traditional cytogenetic markers and the actual chromosomal DNA. These oligonucleotides hybridize to specific sequences and serve as detectable intermediaries, enabling precise localization of genomic structures without requiring direct visualization of the DNA itself.
2Ease of operation
If manual microdissection is used for M-banding, then specific chromosomes can be isolated, but the process is time-consuming and requires skilled operators
Solution Approach 1:
The patent employs oligonucleotide probes that automatically hybridize to their complementary sequences on chromosomes without requiring manual intervention. The probes self-assemble and bind to target regions based on sequence complementarity, eliminating the need for skilled operators to manually dissect and isolate chromosomes.
Solution Approach 2:
The patent replaces the mechanical process of manual microdissection with a molecular recognition process. Instead of physically cutting and isolating chromosomes under a microscope, the system uses biochemical hybridization between oligonucleotides and chromosomal DNA, substituting mechanical manipulation with molecular self-assembly.
3Manufacturing precision
If low resolution techniques are used, then chromosomal structures can be visualized, but accurate determination of genomic structure boundaries is limited
Solution Approach 1:
The patent applies different oligonucleotide probes to different local regions of the chromosome, with each probe designed to hybridize to a specific sequence. This local specificity allows precise determination of where genomic structures begin and end, as each probe provides information about a particular location rather than the entire chromosome.
Solution Approach 2:
The patent changes the parameters of the mapping system by using oligonucleotides of specific lengths (e.g., 20-100 nucleotides) with specific melting temperatures and hybridization conditions. By optimizing these parameters, the system achieves higher resolution and more accurate boundary determination while managing the complexity of the analysis composition.
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 high-resolution mapping of chromosomes and chromosomal rearrangements, improving the ability to identify and analyze genomic regions of interest with increased precision, facilitating the detection of smaller structural abnormalities.
Implementation Method 1
each of the first and second oligonucleotides comprises respective first and second sequences each selected to hybridize to a selected region of interest in the nucleic acid used in the assay
Data Source
AI summary
The present invention generally relates to spatial and structural genomic analysis compositions, which can be used for the mapping of chromosomes and structural analyses of chromosomal rearrangements, including the entire chromosome, as well as specific portions or regions of interest of the chromosomes. In some embodiments, multiple portions of the genome can be distinguished, for instance, using a first detection entity and a second detection entity different from the first detection entity. The detection entities may be immobilized relative to oligonucleotides, which may be selected to bind to different locations within the chromosome. For instance, the oligonucleotides may be at least substantially complementary to the chromosome, e.g., substantially complementary to a specific location of the chromosome.