Epigenetic Control Region Detection via CpG Density and Motif Analysis

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Solution Overview

Problem

Current methods fail to effectively identify and diagnose diseases caused by epigenetic modifications, which are not linked to genetic mutations and are heritable, as they do not account for epigenetic mechanisms in disease etiology and diagnostic tools.

Innovation Solution

Identification of epigenetic control regions (ECRs) in DNA using low CpG density and specific DNA sequence motifs (EDM1 and EDM2) to locate potential genomic locations and regulatory sites of epimutations, enabling diagnostic assays and therapeutic monitoring.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional genetic mutation-based diagnostic methods are used, then diseases with clear genetic abnormalities can be identified, but diseases caused by epigenetic modifications cannot be detected

Engineering Contradiction:

Improvedisease detection accuracyVSAvoidapplicability to epigenetic diseases

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention changes the detection parameter from DNA sequence composition to DNA sequence motif composition and CpG density. By analyzing the presence/absence of specific motifs (EDM1, EDM2) and CpG density patterns, the method detects epigenetic modifications rather than genetic mutations, enabling identification of diseases previously undetectable by conventional genetic methods.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If high CpG density regions (CpG islands) are targeted for disease detection, then conventional genetic markers can be identified, but epigenetic control regions associated with transgenerational inheritance cannot be located

Engineering Contradiction:

Improvelocation accuracy of genetic markersVSAvoidmissed epigenetic regulatory regions

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The invention inverts the conventional approach by targeting low CpG density regions instead of high CpG density regions. By identifying regions with CpG density below a threshold (e.g., <10%, <5%, or <1%) and containing specific motifs, the method locates epigenetic control regions that were previously overlooked, revealing their association with transgenerational inheritance of disease susceptibility.

Inventive Principle:

Principle #13The other way round (Inversion)

3Ease of manufacture

If diagnostic assays focus on DNA sequence mutations, then genetic diseases can be diagnosed, but epigenetically-modified regions associated with heritable diseases remain undetected

Engineering Contradiction:

Improvesimplicity of diagnostic assayVSAvoiddiagnostic coverage of heritable diseases

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The invention creates a copy or alternative representation of genetic disease detection by using motif presence/absence and CpG density patterns instead of sequence mutations. This parallel diagnostic approach maintains the simplicity of sequence-based assays while expanding detection capability to include epigenetically-modified regions, thereby increasing diagnostic coverage for heritable diseases.

Inventive Principle:

Principle #26Copying

Data Source

PatentUS9734283B2Genomic features associated with epigenetic control regions and transgenerational inheritance of epimutations

Publication Date: 2017.08.15 WASHINGTON STATE UNIVERSITY

AI summary

CpG densities and sequence motifs that are characteristic of regions of DNA associated with epimutations and control of epimutations are provided. Such regions include, within approximately 400 (or fewer) base pairs, at least one, usually two, and preferably all three of the following features: i) a CpG density of 15% or less; ii) the presence of the sequence motif ATTTGTTTTTTCTTTTnT (SEQ ID NO: 1) where n is A, T, C or G, and statistically relevant variants thereof; and iii) the presence of the sequence motif GGGGGnGGGG (SEQ ID NO: 2), where n is A, T, C or G, and statistically relevant variants thereof.