Downstream Assays for Variant Resolution: Epigenetics, RNA Sequnncing, and Metabolomics

Area of Science:

• Genomics
• Molecular Biology
• Biochemistry

Background:

• Advanced molecular testing, including whole exome and genome sequencing, is becoming more accessible.
• Interpreting inconclusive results, such as variants of uncertain significance or negative findings in suspected genetic disorders, presents a significant challenge.

Purpose of the Study:

• To explore the utility of alternative and complementary genome-wide approaches to enhance diagnostic yield.
• To address the limitations of conventional genetic testing in diagnosing complex genetic disorders.

Main Methods:

• Utilizing advanced genome-wide techniques such as DNA epigenetic testing, RNA sequencing, and metabolomics.
• Integrating these novel methods with established genetic testing protocols.

Main Results:

• These complementary approaches provide additional data to support or refute specific genetic diagnoses.
• The combined use of conventional and novel genome-wide methods increases the overall diagnostic yield.

Conclusions:

• Genome-wide approaches beyond standard sequencing are crucial for resolving diagnostic challenges posed by inconclusive genetic test results.
• Integrating epigenetic, transcriptomic, and metabolomic data alongside genetic data offers a more comprehensive diagnostic strategy.