Pathogenic variants in non-protein-coding sequences

Area of Science:

• Genomics
• Human Genetics
• Molecular Biology

Background:

• Historically, focus has been on protein-coding genes for genetic disorders.
• Approximately 3000 human protein-coding genes are linked to monogenic disorders.
• The 'Medical Genome' encompasses all functional genomic elements contributing to phenotypes.

Purpose of the Study:

• To review pathogenic variants in non-protein-coding gene regions.
• To broaden the understanding of genetic variation in human disease.
• To emphasize the role of all functional genomic elements in phenotypes.

Main Methods:

• Literature review of pathogenic variants in non-protein-coding regions.
• Analysis of examples linking non-coding variants to Mendelian and complex phenotypes.
• Discussion of evolving sequencing and functional characterization methods.

Main Results:

• Identified examples of pathogenic variants within non-protein-coding gene regions.
• Demonstrated that non-coding variations can cause significant human disorders.
• Highlighted the expanding knowledge base beyond protein-coding genes.

Conclusions:

• Non-protein-coding genomic regions are significant reservoirs of pathogenic variation.
• Advancements in genomic technologies will reveal more disease-associated variants in these regions.
• A comprehensive view of the 'Medical Genome' is crucial for understanding both Mendelian and complex diseases.