FLAGS, frequently mutated genes in public exomes

• DOI: 10.1186/s12920-014-0064-y
• Publication Date: 2014-12-02T19:30:18Z
• Authors: Casper Shyr; Maja Tarailo-Graovac; Michael Gottlieb; Jessica JY Lee; Clara van Karnebeek; Wyeth W Wasserman
• Keywords: Exome; Human genetics; Mendelian inheritance; dbSNP

Dramatic improvements in DNA-sequencing technologies and computational analyses have led to wide use of whole exome sequencing (WES) identify the genetic basis Mendelian disorders. More than 180 novel rare-disease-causing genes with inheritance patterns been discovered through exomes just a few unrelated individuals or family members. As rare/novel variants continue be uncovered, there is major challenge distinguishing true pathogenic from rare benign mutations. We used publicly available cohorts, together dbSNP database, derive list (n = 100) that most frequently exhibit (<1%) non-synonymous/splice-site general populations. termed these FLAGS for FrequentLy mutAted GeneS analyzed their properties. Analysis revealed significantly longer protein coding sequences, greater number paralogs display less evolutionarily selective pressure expected. are more reported PubMed clinical literature associated diseased phenotypes compared set human protein-coding genes. demonstrated an overlap between rare-disease causing recently WES studies 10) need replication rigorous statistical biological when associating disease. Finally, we showed how applied disease-causing variant prioritization approach on data affected by unknown disorder. some rare, likely functional population, observed analyzing diverse phenotypes. found rate at which accumulate mutations beneficial information prioritizing candidates. provided ranking system based mutation accumulation rates exome-captured genes, propose reports any disease/phenotype evaluated extra caution.