SNP-Adapted Primers for Accurate DNA Profiling

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Solution Overview

Problem

Current DNA-based technologies face challenges in accurately matching DNA profiles due to allelic dropout, which occurs when unknown mutations or polymorphisms cause reduced amplification of target nucleic acids, making it difficult to compare DNA profiles within and between databases.

Innovation Solution

The method involves hybridizing primers to specific SNPs in STR loci, such as vWA, D13S317, TH01, D12S391, and D6S1043, using PCR and sequencing to amplify and detect SNPs, thereby improving the accuracy of DNA profiling by identifying predominant and variant SNPs, and using universal bases and fluorescent labels for enhanced primer binding and detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If new STR assays are developed to improve DNA profiling accuracy, then detection precision is improved, but allelic dropout occurs due to unknown mutations or polymorphisms causing reduced amplification

Engineering Contradiction:
Improvedetection precisionVSAvoidamplification reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies preliminary action by identifying and cataloging SNP variations in primer binding sites before developing new STR assays. By performing genotyping and sequencing analyses beforehand to discover SNPs, the invention enables designers to create primers that account for known genetic variations, preventing allelic dropout before it occurs in forensic applications

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by modifying primer sequences to accommodate detected SNP variations. When SNPs are identified in primer binding sites, the primer sequences are adjusted to maintain complementary binding, thereby preserving amplification efficiency and reliability across different genetic backgrounds while improving overall assay performance

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If DNA sequence alterations are detected to improve identification accuracy, then measurement precision is improved, but allelic dropout occurs making profile matching difficult

Engineering Contradiction:
Improveidentification accuracyVSAvoidDNA profile completeness
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent applies preliminary action by performing comprehensive SNP detection and genotyping before final DNA profiling. By identifying sequence variations in advance through sequencing analyses, the invention preserves complete DNA profile information by ensuring all alleles are properly amplified and detected, preventing information loss during profile matching

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies feedback by using detected SNP information to adjust and optimize primer design and assay parameters. The feedback loop involves analyzing sequencing data to identify SNPs, then using this information to refine primer sequences and assay conditions, thereby maintaining complete and accurate DNA profile information across diverse samples

Inventive Principle:
Principle #23Feedback

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 enhances the reliability of DNA profiling by reducing allelic dropout and improving the detection of SNPs, leading to more precise human identification and comparison of DNA profiles across databases.

Implementation Method 1

hybridizing a second primer to a second primer binding site in said locus wherein said second primer hybridizes to a single nucleotide polymorphism (SNP) nucleobase

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

amplifying the target nucleic acid sequence, wherein the amplifying yields at least a first amplified sequence comprising at least one SNP

Methodology Applied
Scientific EffectPCR amplification:

Implementation Method 3

the amplified sequence is detected by sequencing of the amplified sequence. In some embodiments, sequencing identifies at least one predominant or variant SNP in the target nucleic acid sequence

Methodology Applied
Scientific EffectSequencing:

Data Source

PatentEP2488668B1Novel human single nucleotide polymorphisms
Publication Date: 2023.07.26 LIFE TECHNOLOGIES CORP
  • EP2488668B1 patent drawingFigure 1

AI summary

Disclosed are methods for human identification utilizing newly discovered single nucleotide polymorphisms (SNPs) within CODIS loci which can cause allelic dropout. Also disclosed are kits useful in human identification.