Donor SNP Allele Detection in Transplant Recipient Blood
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Solution Overview
Problem
Current methods for detecting transplant rejection are time-consuming and expensive, and often require DNA from the donor, which may not be available, especially in cases where the transplantation occurred years prior, necessitating a sensitive and rapid technique for early detection.
Innovation Solution
A method involving the monitoring of graft cell-free DNA (cfDNA) by assessing the level of donor-specific single-nucleotide polymorphisms (SNPs) in a recipient's blood sample, without the need for a separate donor sample, using pre-selected SNPs with a minor allele frequency of at least 0.4, and performing quantitative PCR to detect the presence of these SNPs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional methods are used to detect transplant rejection, then detection accuracy is maintained, but the method becomes extremely time-consuming and expensive
Solution Approach 1:
The invention extracts and utilizes only the necessary genetic information (SNP alleles) from the donor-recipient pair to create a simplified detection method. By focusing on specific SNP markers rather than comprehensive genomic analysis, the method achieves rapid detection without sacrificing accuracy in identifying transplant rejection
Solution Approach 2:
The invention changes the detection parameters by using SNP allele frequency thresholds (MAF ≥ 0.4) and specific genotyping approaches. This parameter optimization enables the method to achieve both high detection accuracy and rapid turnaround by efficiently identifying donor-specific alleles in recipient samples
2Reliability
If traditional methods are used to detect transplant rejection, then detection reliability is maintained, but the cost becomes prohibitively high
Solution Approach 1:
The invention employs cost-effective SNP genotyping assays that use inexpensive reagents and can be performed with standard laboratory equipment. The method relies on detecting specific SNP alleles rather than requiring expensive donor DNA samples or complex molecular biology procedures, making the test economically feasible for routine clinical use
3Measurement precision
If SNP-based methods are used to differentiate donor and recipient DNA, then detection sensitivity is improved, but the requirement for donor DNA samples increases complexity
Solution Approach 1:
The invention enables the recipient's own DNA samples to serve dual purposes: first to identify their SNP genotype, and then to detect donor-specific alleles that indicate transplant rejection. This self-referential approach eliminates the need for separate donor DNA samples, reducing sample collection complexity while maintaining high detection sensitivity through SNP allele comparison
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 allows for early and sensitive detection of transplant rejection, reducing the need for donor DNA and improving turn-around-time and cost-effectiveness, while enabling monitoring of transplant integrity and immunosuppressive therapy adjustments.
Implementation Method 1
performing a quantitative PCR reaction for the SNPs identified in (a) to detect the presence of the alternative allele for one or more of the SNPs
Data Source
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AI summary
This invention provides methods, compositions, and kits relating to detecting donor cell-free DNA in the circulation of an organ transplant recipient for the early identification of transplant rejection