A Phylogenetic Approach to Analyze the Conservativeness of BRCA1 and BRCA2 Mutations.

Identifying pathogenic mutations in BRCA1 and BRCA2 is a critical step for breast cancer prediction. Genome-wide association studies (GWAS) are the most commonly used method for inferring pathogenic mutations. However, identifying pathogenic mutations using GWAS can be difficult. The hypothesis of this study is that the pathogenic mutations in human BRCA1/BRCA2, which are present in many species, are more likely to be located in the evolutionarily conserved sites. This study defines the evolutionary conservativeness based on the previously developed Characteristic Attribute Organization System (CAOS) software. ClinVar is used to identify human pathogenic mutations in BRCA1 and BRCA2. Statistical tests suggest that compared to the non-pathogenic mutations, human pathogenic mutations were more likely to locate at the evolutionary conserved positions. The approach presented in this study shows promise in identifying pathogenic mutations in humans, suggesting that the methodology may be applied to other disease-related genes to identify putative pathogenic mutations. ©2020 AMIA - All rights reserved.