Genomic Structural Variation Analysis for Heterosis Prediction

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Solution Overview

Problem

Current molecular biology techniques for predicting the degree of heterotic phenotypes in plants are inefficient due to high noise and low accuracy, particularly in polygenic traits and polyploid plants, where genomic DNA approaches struggle to detect subtle gene copy number changes and genetic markers lack predictive ability across different heterotic groups.

Innovation Solution

The use of structural variation analysis, specifically comparative genomic hybridization (CGH), to analyze copy number variation by contacting oligonucleotide probe molecules with plant genomic DNA, identifying probes with differing hybridization levels between parental lines to predict the degree of heterotic phenotypes in progeny plants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mRNA-based predictions are used to predict heterotic phenotypes, then molecular biology techniques are applied, but noise levels are high and prediction accuracy is low

Engineering Contradiction:
Improveprediction accuracyVSAvoidnoise levels
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and analyzes specific genomic regions showing copy number variations rather than analyzing the entire genome or mRNA transcripts. By focusing on structural variations in DNA copy number, the method eliminates the noise associated with mRNA expression analysis while maintaining predictive accuracy for heterotic phenotypes.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mRNA-based molecular biology approach with a genomic DNA-based structural variation analysis approach. This substitution moves from analyzing transient RNA molecules to analyzing stable DNA structural variations, fundamentally changing the measurement system to achieve lower noise and higher reliability.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If genomic DNA approaches using subtractive hybridization or fluorescent in situ hybridization are used, then copy number differences can be identified, but the results are not easily quantifiable and only gross differences can be detected

Engineering Contradiction:
Improvecopy number detection precisionVSAvoidquantification difficulty
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces traditional hybridization-based detection methods with quantitative PCR-based structural variation analysis. This substitution enables precise quantification of copy number differences through fluorescent signal intensity measurements, allowing detection of subtle variations (even single copy changes) while providing easily quantifiable results through digital signal processing.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If genetic markers are used to predict heterotic phenotypes, then predictions can be made for plants within the same heterotic group, but predictive ability greatly diminishes when plants from other heterotic groups are used

Engineering Contradiction:
Improvepredictive ability across heterotic groupsVSAvoidprediction accuracy
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops a universal genomic structural variation analysis method that can predict heterotic phenotypes across different heterotic groups. By analyzing conserved structural variations in DNA copy number that are relevant to polygenic traits, the method achieves broad applicability while maintaining prediction accuracy, unlike group-specific genetic marker approaches.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent changes the measurement parameter from genetic marker presence/absence to genomic structural variation magnitude. This parameter change allows the method to capture quantitative differences in DNA copy number that are relevant across diverse plant populations, enabling predictions for plants from different heterotic groups while maintaining reliability.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If traditional genetic marker techniques are used, then linkage to quantitative trait loci is required, but insufficient linkage and lack of gametic phase linkage disequilibrium limit predictive ability

Engineering Contradiction:
Improvepredictive abilityVSAvoidlinkage requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and directly measures structural variations in genomic DNA that are physically linked to quantitative trait loci through copy number differences. By focusing on the actual structural variations rather than using distant genetic markers, the method eliminates the need for strong linkage and linkage disequilibrium assumptions, directly measuring the causal or near-causal variants.

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 method provides a significant increase in predictive ability for heterotic phenotypes, overcoming the limitations of mRNA and genomic DNA approaches, and allows for the selection of parental lines without resource-consuming test crosses, offering a reliable assay for predicting yield and other traits in plant breeding.

Implementation Method 1

contacting oligonucleotide probe molecules with plant genomic DNA and the resultant mixture of hybridized probes and genomic DNA is analyzed

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS11053554B2Using structural variation to analyze genomic differences for the prediction of heterosis
Publication Date: 2021.07.06 CORTEVA AGRISCIENCE LLC
  • US11053554B2 patent drawing
  • US11053554B2 patent drawing
  • US11053554B2 patent drawing

AI summary

A novel method for prediction of the degree of heterotic phenotypes in plants is disclosed. Structural variation analyses of the genome are used to predict the degree of a heterotic phenotype in plants. In some examples, copy number variation is used to predict the degree of heterotic phenotype. In some methods copy number variation is detected using competitive genomic hybridization arrays. Further, methods for optimizing the arrays are disclosed, together with kits for producing such arrays, as well as hybrid plants selected for development based on the predicted results.