Genomic DNA is under constant attack by environmental and internal metabolic factors. The damaged DNA must be repaired timely and spatially to maintain genome stability in order to prevent deleterious consequences. Living organism is equipped with a DNA damage repair (DDR) system to repair the damaged DNA. The DDR system consists of at least 9 different types of pathways, including Base Excision Repair (BER) pathway, Nucleotide Excision Repair (NER) pathway repair, and Direct Reversal repair (DR) pathway; Fanconi Anemia (FA) pathway; Mismatch Repair (MMR) pathway, and Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ) pathways. A group of genes in each pathway coordinately act to repair a given type of DNA damage. However, many DDR genes themselves are prone to genetic variation. These with deleterious impact can damage the function of the affected genes, cause genome instability, and lead to increased risk of disease development including cancer.
The medical importance of DDR gene mutation has caught extensive attention on DDR study. It is well determined that DDR gene mutation can be highly ethnic-specific in reflecting human evolution adaptation to different environments. Through comprehensive mining in different sources, we collected Pathogenic/Likely Pathogenic variants in DDR genes from global human populations, and developed the database dbDDR-GLOBAL v.1.0. The database provides 1,781 DDR Pathogenic/Likely Pathogenic (PLP) variations, their distribution in 81 DDR genes, and their origin of over 200,000 individuals in 17 global human populations. Users can explore the database to retrieve related information. We hope that the database should provide a useful resource to benefit DDR-related study in evolution, biology, and cancer.