Allele-Specific Primers for GPR156 Variant Detection

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Solution Overview

Problem

Current understanding of G protein-coupled receptor 156 (GPR156) is limited, and its variants are not well-associated with mood disorders like unipolar depression and anxiety disorders, hindering the development of therapeutic agents that modulate its biological pathway.

Innovation Solution

The development of nucleic acid molecules specifically hybridized to allele-specific primers or probes encoding GPR156 proteins with aspartic acid mutations at specific positions, allowing for the identification and diagnosis of variants associated with unipolar depression and anxiety disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If allele-specific primers or probes are designed to identify GPR156 variants, then diagnostic precision for mood disorders is improved, but device complexity and manufacturing difficulty increase

Engineering Contradiction:
Improvediagnostic precisionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the GPR156 gene sequence into specific regions containing polymorphic sites, designing allele-specific primers and probes that target individual variant locations. This segmentation allows precise identification of specific GPR156 variants associated with mood disorders while managing complexity through focused, targeted approaches rather than comprehensive sequencing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by designing primers and probes with specific nucleotide sequences that match particular allele variants at specific positions in the GPR156 gene. Each primer/probe is locally optimized to bind only to its complementary allele, enabling precise discrimination between variants without requiring complex global analysis systems.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If allele-specific primers or probes are designed to identify GPR156 variants, then diagnostic precision for mood disorders is improved, but manufacturing difficulty increases

Engineering Contradiction:
Improvediagnostic precisionVSAvoidmanufacturing difficulty
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent performs preliminary action by pre-designing and synthesizing allele-specific primers and probes with exact nucleotide sequences matched to known GPR156 variants. These reagents are manufactured and validated in advance, allowing clinical laboratories to directly use them for diagnosis without needing to perform complex primer design or validation procedures themselves.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If GPR156 variants are identified to facilitate therapeutic agent development, then therapeutic effectiveness is improved, but time for identification and validation is increased

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidtime for identification
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary action by identifying and characterizing GPR156 variants associated with mood disorders before therapeutic development begins. The allele-specific detection methods are established in advance, creating a ready framework that allows rapid screening and validation of potential therapeutic agents against known variant markers, significantly reducing the time required for subsequent therapeutic development.

Inventive Principle:
Principle #10Preliminary action

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

These nucleic acid molecules enable the identification of GPR156 variants linked to unipolar depression and anxiety disorders, facilitating diagnosis and potential therapeutic interventions.

Implementation Method 1

a nucleic acid molecule specifically hybridized to an allele-specific primer or an allele-specific probe

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentEP3491014B1Allele-specific primer or probe hybridized to a nucleic acid molecule encoding a GPR156 variant
Publication Date: 2023.04.05 REGENERON PHARMACEUTICALS INC
  • EP3491014B1 patent drawingFigure 1
  • EP3491014B1 patent drawingFigure 2

AI summary

The disclosure provides nucleic acids, including cDNA, comprising alterations that encode aspartic acid at a position corresponding to position 533 of the hu man G protein- coupled receptor 156 protein (GPR156). The disclosure also provides isolated and recombinant human GPR156 protein variants that comprise an aspartic acid at a position corresponding to position 533. The change to aspartic acid, and the gene encoding this change, associate with unipolar depression. The disclosure also provides methods for determining whether a subject has or has a risk of developing unipolar depression, based on the identification of such alterations in the gene (DNA or RNA) encoding GPR156.