STR Repeat Unit Counting via Ternary Complex Detection
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Solution Overview
Problem
Current methods for analyzing short tandem repeats (STRs) in human genomes are inefficient and require extensive examination steps, often biased by flanking regions, which complicates the direct determination of STR alleles and repeat units.
Innovation Solution
A method involving the incorporation of a subset of nucleic acid base types into a primed nucleic acid, followed by detection of a ternary complex with a preselected nucleic acid base type, allows for the direct determination of STR repeat units without examining each nucleotide base, using techniques such as sequencing-by-synthesis and ternary complex stabilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional sequencing methods are used to determine STR alleles, then complete sequence information is obtained, but the analysis process becomes extensive and inefficient
Solution Approach 1:
The patent extracts only the essential information needed for STR allele determination - specifically the repeat unit count - rather than sequencing the entire region. By using targeted approaches that focus solely on counting repeat units rather than determining complete sequences, the method eliminates unnecessary sequencing steps while maintaining accuracy for the specific application of STR analysis.
Solution Approach 2:
The patent segments the STR region analysis into discrete repeat unit counting rather than continuous sequencing. By dividing the STR region into individual repeat units and counting them directly, the method simplifies the analysis process from examining each nucleotide base to simply determining the number of repeats, thereby reducing analysis time while maintaining precision.
2Loss of information
If complete sequencing of STR regions is performed, then all sequence information is obtained, but bias from flanking regions complicates the determination
Solution Approach 1:
The patent extracts only the STR repeat region information while excluding flanking regions from the analysis. By designing methods that specifically target and amplify only the STR repeat units without incorporating extensive flanking sequences, the approach eliminates the bias and complications that flanking regions introduce while retaining the essential repeat unit count information needed for accurate allele determination.
3Measurement precision
If extensive sequencing steps are used to examine each nucleotide base, then complete sequence data is obtained, but the process becomes complex and time-consuming
Solution Approach 1:
The patent segments the complex sequencing process into a simpler repeat unit counting approach. Instead of examining each nucleotide base individually through multiple sequencing steps, the method divides the STR region into discrete repeat units and counts them directly, thereby reducing process complexity while maintaining the precision needed for accurate allele determination.
Solution Approach 2:
The patent inverts the traditional approach by not sequencing the entire region and then analyzing the data, but rather by directly determining repeat unit count through targeted methods. This inversion simplifies the process from complex multi-step sequencing and analysis to a more direct counting approach that achieves the same analytical goal with reduced complexity.
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 enables rapid and accurate counting of STR repeat units, reducing the need for extensive sequencing and minimizing bias from flanking regions, thus enhancing the efficiency and accuracy of STR analysis.
Implementation Method 1
incorporating a subset of nucleic acid base types into a primed nucleic acid to form an extended nucleic acid
Implementation Method 2
detecting a ternary complex comprising the extended nucleic acid, a polymerase and a preselected nucleic acid base type
Data Source
AI summary
Provided herein are methods for analyzing a signature sequence in a nucleic acid sample by rapid sequencing of a target nucleic acid region. The method examines the target nucleic acid directly and minimizes the number of examination steps needed to determine a signature that is characteristic of a genetic feature of the nucleic acid sample.