Combined CGH and SNP Array for Genetic Abnormality Detection

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current array-based comparative genomic hybridization (CGH) methods are unable to detect balanced structural chromosome aberrations and copy number neutral loss of heterozygosity due to uniparental disomy, as they primarily focus on copy number variations and lack the capability to analyze single-nucleotide polymorphisms (SNPs).

Innovation Solution

A method combining standard array CGH techniques with SNP array analysis, where SNP probes are designed to function under CGH conditions, allowing for simultaneous detection of copy number variations and SNPs on the same nucleic acid array, enabling the differentiation between loss of heterozygosity caused by chromosomal deletion or isodisomy by filtering for allele frequencies and homology scores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard array CGH methods are used to detect copy number variations, then copy number analysis is improved, but the ability to detect SNPs and balanced structural chromosome aberrations deteriorates

Engineering Contradiction:

Improvecopy number detection accuracyVSAvoiddetection capability for SNPs and balanced aberrations

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent combines array CGH and SNP array analysis into a single hybridisation assay. The nucleic acid array contains both CGH probes (for copy number detection) and SNP probes (for allele-specific detection), allowing simultaneous detection of copy number variations, SNPs, and balanced structural chromosome aberrations in one experiment, thus resolving the contradiction between copy number detection accuracy and detection versatility

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The nucleic acid array is designed to perform multiple functions: it detects copy number variations through CGH probes, identifies SNPs through allele-specific probes, and detects balanced structural chromosome aberrations and uniparental disomy. This multi-functional array resolves the limitation of standard array CGH by making the system versatile enough to handle multiple types of genetic abnormalities simultaneously

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If separate arrays are used for array CGH and SNP analysis, then detection accuracy for each function is maintained, but experimental complexity and time consumption increase

Engineering Contradiction:

Improvedetection accuracyVSAvoidnumber of arrays required

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the functionality of separate array CGH and SNP arrays into a single nucleic acid array. The array contains both CGH probes and SNP probes that can be hybridised with the same labelled test and reference DNA samples simultaneously, eliminating the need for separate experiments and reducing overall system complexity while maintaining detection accuracy for both copy number variations and SNPs

Inventive Principle:

Principle #5Merging (Combining)

3Adaptability or versatility

If SNP probes are designed to function under CGH conditions, then simultaneous detection is enabled, but probe design complexity increases

Engineering Contradiction:

Improvesimultaneous detection capabilityVSAvoidprobe design complexity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent applies local quality by designing different types of probes with specific properties for different detection purposes on the same array. CGH probes are designed for copy number detection with appropriate length and hybridisation characteristics, while SNP probes are designed with allele-specific sequences and modified 3' ends to prevent extension. This localized optimization of probe properties enables simultaneous detection while managing design complexity through systematic design rules

Inventive Principle:

Principle #3Local quality

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 combined approach enables the simultaneous analysis of copy number variations and SNPs, allowing for the accurate determination of whether loss of heterozygosity is due to uniparental isodisomy or chromosomal deletion, thereby improving the detection of genetic abnormalities associated with diseases.

Implementation Method 1

The technique relies on the comparison of two labelled samples by allowing them to hybridise and subsequently looking for regions of differential hybridisation

Methodology Applied

Scientific EffectNucleic acid hybridisation: Absorption (physical)

Data Source

PatentUS10198553B2Combined CGH and allele specific hybridisation method

Publication Date: 2019.02.05 OXFORD GENE TECH OPERATIONS

AI summary

The invention combines the fields of comparative genomic hybridization (CGH) analysis and SNP array analysis. It relates to methods for detecting and mapping genetic abnormalities associated with various diseases. In particular the invention provides a method for simultaneously performing array CGH and SNP array analysis on a genomic DNA sample comprising contacting a nucleic acid array which comprises a first probe set and a second probe set with a genomic DNA sample, comprising a test and reference sample, under hybridization conditions, comparing the amount of test sample and reference sample hybridized to the hybridization probes of the first probe set, comparing the amount of test sample and reference sample hybridized to the hybridization probes of the second probe set; and using the data obtained to determine the copy number of at least one locus; and at least one SNP in the genomic DNA sample.