Mapping homologous recombination genes using multi-clade phylogenetic profiling of 600 species

Identifying the genetic cause of hereditary breast cancer remains a challenge as most patients do not harbor any known pathogenic mutations. Most key breast cancer susceptibility genes are part of the homologous recombination repair (HRR) pathway (e.g. BRCA1/2 and PALB2). To identify additional HRR factors that might explain part of this missing heredity, we developed a biologically relevant and significantly better phylogenetic profiling approach (CladePP). CladePP uses multi-scale co-evolution analysis in 578 eukaryote genomes to characterize the evolutionary patterns of the HRR at different evolutionary scales. After mapping all human genes we identified and validated nine novel genes that co-evolved with known HRR genes either globally across all eukaryotes or locally in different clades. Ourplatforms presents an optimized approach to map genes’ function.