AbstractGenomic sequence mutations in both the germline and somatic cells can be pathogenic. Several authors have observed that often the same genes are involved in cancer when mutated in somatic cells and in genetic diseases when mutated in the germline. Recent advances in high-throughput sequencing techniques have provided us with large databases of both types of mutations, allowing us to investigate this issue in a systematic way. Here we show that high-throughput data about the frequency of somatic mutations in the most common cancers can be used to predict the genes involved in abnormal phenotypes and diseases. The predictive power of somatic mutation patterns is largely independent of that of methods based on germline mutation frequency, so that they can be fruitfully integrated into algorithms for the prioritization of causal variants. Our results confirm the deep relationship between pathogenic mutations in somatic and germline cells, provide new insight into the common origin of cancer and genetic diseases and can be used to improve the identification of new disease genes.
High-Throughput Sequencing and Rare Genetic Diseases
