Variant discovery using next-generation sequencing and its future role in pharmacogenetics

Area of Science:

• Genetics
• Pharmacology
• Bioinformatics

Background:

• Pharmacogenes influence drug response, with novel variants frequently discovered via next-generation sequencing (NGS).
• Current clinical guidelines primarily address common single nucleotide variants, overlooking rare variants and structural variations.
• Integrating rare variant data into clinical practice requires robust functional assessment.

Purpose of the Study:

• To highlight the role of NGS in identifying pharmacogene variants.
• To discuss the integration of rare variant functional data into clinical pharmacogenetics.
• To emphasize the potential of comprehensive genotype-guided pharmacotherapy.

Main Methods:

• Utilizing next-generation sequencing (NGS) for broad variant discovery in pharmacogenes.
• Employing in silico and large-scale functional assessments to evaluate rare variant effects.
• Reviewing current literature and guidelines on pharmacogenetic variant implementation.

Main Results:

• NGS facilitates the discovery of numerous rare and structural variants in pharmacogenes.
• Functional assessments are crucial for understanding the impact of these rare variants on protein function.
• A gap exists between variant discovery and clinical integration of rare variants.

Conclusions:

• NGS is a powerful tool for comprehensive pharmacogene variant discovery.
• Functional characterization of rare variants is essential for clinical utility.
• Genotype-guided pharmacotherapy, informed by NGS, promises enhanced patient care.