Probe Array Genotyping for Copy Number in Pseudogenes

Solution Overview

Problem

Existing nucleic acid analysis methods struggle to accurately assign signals to individual genes due to the presence of pseudogenes with high sequence similarity, complicating genotype and copy number determination.

Innovation Solution

A method involving an array with distinct sets of probes that hybridize to regions with differing and identical sequences in target polynucleotides, allowing for signal detection and analysis to determine genotype and copy number variations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional array-based analysis methods are used to detect nucleic acid sequences, then the analysis can be performed with standard techniques, but the signals detected correspond to multiple genes including pseudogenes, making it difficult to accurately assign signals to individual genes and determine genotype and copy number

Engineering Contradiction:

Improvesignal assignment accuracyVSAvoidprobe design complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The probe set is divided into multiple subsets, where each subset targets a specific gene or pseudogene. This segmentation allows signals to be accurately assigned to individual genes by using the unique combination of probe hybridization patterns for each target sequence

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different probe subsets are designed with specific local sequence characteristics that match unique regions of different genes. Each probe subset has tailored hybridization properties that enable discrimination between highly similar sequences by exploiting local sequence variations

Inventive Principle:

Principle #3Local quality

2Measurement precision

If probes hybridize to identical regions in both target gene and pseudogene, then the analysis is simpler, but the signals cannot be distinguished between the two sequences, leading to inaccurate genotype determination

Engineering Contradiction:

Improvegenotype determination accuracyVSAvoidsignal analysis complexity

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The probe set is divided into multiple subsets, where each subset targets a specific gene or pseudogene. This segmentation allows signals to be accurately assigned to individual genes by using the unique combination of probe hybridization patterns for each target sequence

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Instead of trying to distinguish genes by their unique sequences directly, the method uses probe subsets that hybridize to both gene and pseudogene but in different proportions or patterns. The genotype is determined by analyzing the relative hybridization signals rather than absolute sequence differences

Inventive Principle:

Principle #13The other way round (Inversion)

3Measurement precision

If multiple probe subsets are used to target different genes and pseudogenes, then accurate signal assignment becomes possible, but the array design and signal analysis become more complex

Engineering Contradiction:

Improvecopy number estimation accuracyVSAvoidarray design complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The probe set is divided into multiple subsets, where each subset targets a specific gene or pseudogene. This segmentation allows signals to be accurately assigned to individual genes by using the unique combination of probe hybridization patterns for each target sequence

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The same array platform and hybridization methodology can be used for analyzing different gene families and pseudogene sets. The universal approach reduces overall system complexity by reusing established protocols across different applications

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

Enhances the accuracy of genotyping and copy number estimation by distinguishing between similar sequences, facilitating precise genetic information retrieval.

Implementation Method 1

a first set of probes and a second set of probes that hybridize to a first target polynucleotide and a second target polynucleotide

Methodology Applied

Scientific EffectHybridization:

Data Source

PatentUS20260011404A1Array based method and kit for determining copy number and genotype in pseudogenes

Publication Date: 2026.01.08 AFFYMETRIX INC

AI summary

Provided herein are methods and associated compositions, kits, systems, devices and instruments useful for genetic analysis where there is/are a sequence(s) similar to the gene of interest in a sample. In the methods, a combined copy number for related genes (e.g., a gene of interest and its pseudogene) can be determined via an assay. In addition, relative amounts of the related genes, i.e., a ratio of the related genes can be determined via the assay. Using the data of the combined copy number and the ratio of the related genes, the genotype of the gene of interest (as well as its pseudogene(s), if desired) can be determined with high accuracy.