Polymorphism Detection via Consensus Flanking Regions

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Solution Overview

Problem

Existing methods for identifying polymorphisms in nucleic acid sequences are hindered by secondary polymorphisms near primary polymorphisms, which can inhibit probe binding and result in false negatives.

Innovation Solution

Introducing known 5' and 3' flanking regions into amplicons based on consensus sequences to create a known probe binding site, ensuring the probe is an exact match and enhancing binding efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If probe binding is used to identify polymorphisms, then polymorphism detection is achieved, but secondary polymorphisms inhibit probe binding causing false negatives

Engineering Contradiction:
Improvepolymorphism detection accuracyVSAvoidfalse negative rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The method segments the target nucleic acid sequence into a known flanking region and a variable region containing the polymorphism. By designing probes to bind only to the known flanking region (which is identical across all variants), the method isolates the polymorphism detection from the interfering secondary polymorphisms in the variable region, thereby eliminating false negatives while maintaining detection accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The method extracts and removes the known flanking region from the target nucleic acid sequence to create a separate probe binding site. This extracted flanking region is used to design probes that are complementary only to this conserved sequence, effectively taking out the polymorphism-containing regions that cause inhibition and using only the clean, known sequence for probe binding, thus resolving the contradiction between detection accuracy and false negative rate

Inventive Principle:
Principle #2Taking out (Extraction)

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 reduces false negatives and improves the detection of primary polymorphisms by eliminating the inhibitory effect of secondary polymorphisms, allowing for more accurate identification of target nucleic acids.

Implementation Method 1

A probe may be designed having a probe sequence which is complementary to the exact sequence of a known probe binding site

Methodology Applied
Scientific EffectNucleic acid hybridization: Absorption (physical)

Data Source

PatentEP3052656B1Methods of determining polymorphisms
Publication Date: 2018.12.12 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • EP3052656B1 patent drawingFigure 1~2
  • EP3052656B1 patent drawingFigure 3
  • EP3052656B1 patent drawingFigure 3

AI summary

Methods and compositions for determining the presence of a polymorphism at a target nucleotide position in a plurality of target nucleic acid sequences is provided.