Center for Biomedical Informatics, Brown University, Providence, RI, USA.
Rhode Island Quality Institute, Providence, RI, USA.
AMIA Annu Symp Proc. 2021 Jan 25;2020:677-686. eCollection 2020.
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) . 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.
鉴定 BRCA1 和 BRCA2 中的致病变异是进行乳腺癌预测的关键步骤。全基因组关联研究（GWAS）是推断致病变异最常用的方法。然而，使用 GWAS 鉴定致病变异可能具有一定难度。本研究的假设是，在许多物种中存在的人类 BRCA1/BRCA2 中的致病变异更有可能位于进化上保守的位点。本研究基于先前开发的特征属性组织系统（CAOS）来定义进化保守性。ClinVar 用于鉴定 BRCA1 和 BRCA2 中的人类致病变异。统计检验表明，与非致病变异相比，人类致病变异更有可能位于进化保守的位置。本研究提出的方法在鉴定人类致病变异方面显示出一定的前景，这表明该方法可能适用于其他与疾病相关的基因，以鉴定潜在的致病变异。
