FLAGS, frequently mutated genes in public exomes

Area of Science:

• Genomics
• Human Genetics
• Bioinformatics

Background:

• Whole exome sequencing (WES) has revolutionized rare disease gene discovery.
• Distinguishing pathogenic from benign genetic variants remains a significant challenge.
• Over 180 rare-disease-causing genes have been identified using WES.

Observation:

• A set of 100 genes (FLAGS) frequently exhibit rare variants in general populations.
• FLAGS possess longer coding sequences, more paralogs, and less evolutionary pressure.
• FLAGS are overrepresented in clinical literature and associated with disease phenotypes.

Findings:

• FLAGS overlap with recently discovered rare-disease genes.
• Mutation accumulation rates in genes provide valuable information for variant prioritization.
• A ranking system for prioritizing exome-captured genes based on mutation rates was developed.

Implications:

• This study introduces a method to prioritize candidate genes for rare disease research.
• Clinical reports linking FLAGS to diseases require careful evaluation.
• The findings enhance the interpretation of genetic variants in WES data.