BRCA1 and BRCA2 play essential roles in maintaining the genome stability. Pathogenic germline mutations in these two genes disrupt their function, lead to genome instability and increase the risk of developing breast and ovarian cancers. BRCA mutations have been extensively screened in Caucasian populations, and the resulting information are used globally as the standard reference in clinical diagnosis, treatment and prevention of BRCA ‐related cancers. Recent studies suggest that BRCA mutations can be ethnic‐specific, raising the question whether a Caucasian‐based BRCA mutation information can be used as a universal standard worldwide, or whether an ethnicity‐based BRCA mutation information system need to be developed for the corresponding ethnic populations. In this study, we used Chinese population as a model to test ethnicity‐specific BRCA mutations considering that China has one of the latest numbers of breast cancer patients therefore BRCA mutation carriers. Through comprehensive data mining, standardization and annotation, we collected 1,088 distinct BRCA variants derived from over 30,000 Chinese individuals, one of the largest BRCA data set from a non‐Caucasian population covering nearly all known BRCA variants in the Chinese population ( https://dbBRCA-Chinese.fhs.umac.mo ). Using this data, we performed multi‐layered analyses to determine the similarities and differences of BRCA variation between Chinese and non‐Chinese ethnic populations. The results show the substantial differences of BRCA data between Chinese and non‐Chinese ethnicities. Our study indicates that the current Caucasian population‐based BRCA data is not adequate to represent the BRCA status in non‐Caucasian populations. Therefore, ethnic‐based BRCA standards need to be established to serve for the non‐Caucasian populations.

BackgroundGermline mutation in BRCA1 and BRCA2 (BRCA) is genetic predisposition for breast and ovarian cancer. Identification of mutation carriers is a critical step to prevent and treat the cancer in the mutation carriers. Human BRCA variation has been well determined as ethnic-specific by studies in Ashkenazi Jewish, Polish and Icelandic populations in the 1990s. However, sufficient evidence is lacking to determine if ethnic-specific BRCA variation is also present in Asia population, which is the largest and the most diversified in modern humans. Our current study aims to investigate ethnic-specific BRCA variation in Asian population.MethodsWe performed a comprehensive data mining to collect BRCA variation data in Indian, Chinese, Korean and Japanese populations derived from over 78 000 cancer and 40 000 non-cancer cases. We standardised all BRCA variation data following the international standard. We made a systematic comparison between the datasets including variant composition, variation spectrum, variant type, clinical class, founder mutation and high-frequent variants.ResultsOur analysis showed that over half of the Asian BRCA variants were Asian-specific, and significant differences were present between the four Asia populations in each category analysed.ConclusionData from our study reveal that ethnic-specific BRCA variation is commonly present in Asia population as existing in non-Asian populations. Our study indicates that ethnicity should be an important factor to consider in prevention and treatment of BRCA mutation-related cancer in the Asia population. We recommend that the current BRCA variation databases should include ethnic variation information in order to function as true global BRCA references.

Vibrio cholerae, the causative agent of cholera, could proliferate in aquatic environment and infect humans through contaminated food and water. Enormous microorganisms residing in human gastrointestinal tract establish a special microecological system, which immediately responds to the invasion of V. cholerae, through "colonization resistance" mechanisms, such as antimicrobial peptide production, nutrients competition, and intestinal barrier maintenances. Meanwhile, V. cholerae could quickly sense those signals and modulate the expression of relevant genes to circumvent those stresses during infection, leading to successful colonization on the surface of small intestinal epithelial cells. In this review, we summarized the crosstalks profiles between gut microbiota and V. cholerae in the terms of Type VI Secretion System (T6SS), Quorum Sensing (QS), Reactive Oxygen Species (ROS)/pH stress, and Bioactive metabolites. These mechanisms can also be applied to molecular bacterial pathogenesis of other pathogens in host.

DNA mismatch repair (MMR) genes play important roles in maintaining genome stability. Mutations in MMR genes disrupt their mismatch repair function, cause genome instability and lead to increased risk of cancer in the mutation carriers as represented by Lynch Syndrome. Studies have identified a large number of MMR variants, mostly in the Caucasian population, whereas data from non-Caucasian populations remain poorly illustrated. With the population size of 1.4 billion, knowledge of MMR variants in the Chinese population can be valuable in understanding the roles of ethnic MMR variation and cancer and to further guide clinical applications in MMR-related cancer prevention and treatment in the Chinese population. In this study, we systematically analysed the MMR variants from the Chinese population. Experimental design: We performed a comprehensive MMR data mining and collected all the MMR variation data reported from 33,998 Chinese individuals consisting of 23,938 cancer and 10,060 non-cancer cases between January 1997 to May 2019. For the collected data, we performed standardisation following Human Genome Variation Society nomenclature and reannotated the MMR variant data following American College of Medical Genetics and Genomics guidelines and comparing with non-Chinese MMR data on various aspects. Results: We identified a total of 540 MMR variants in the Chinese population, including 194 in MLH1, 181 in MSH2, 59 in MSH6, 53 in PMS2 single-base/indel changes and 53 large

Sensing and resisting oxidative stress is critical for Vibrio cholerae to survive in either the aquatic environment or the gastrointestinal tract. Previous studies mainly focused on the mechanisms of oxidative stress response regulation that rely on enzymatic antioxidant systems, while functions of non-enzymatic antioxidants are rarely discussed in V. cholerae. For the first time, we investigated the role of hydrogen sulfide (H2S), the simplest thiol compound, in protecting V. cholerae against oxidative stress. We found that degradation of L-cysteine by putative cystathionine β-synthase (CBS) is the major source of endogenous H2S in V. cholerae. Our results indicate that intracellular H2S level has a positive correlation with cbs expression, while the enhanced H2S production can render V. cholerae cells less susceptible to H2O2 in vitro. Using proteome analysis and real-time qPCR assay, we found that cbs expression could stimulate the expression of several enzymatic antioxidants, including reactive oxygen species (ROS) detoxifying enzymes SodB, KatG and AhpC, the DNA protective protein DPS and the protein redox regulator Trx1. Assays of ROS detoxification capacities revealed that CBS-derived H2S could promote catalase activity at the post-translational level, especially for KatB, which serves as an important way that endogenous H2S participates in H2O2 detoxification. The enhancement of catalase activity by H2S is achieved through facilitating the uptake of iron. Adult mice experiments showed that cbs mutant has colonization defect, while either complementation of cbs or exogenous supplement of N-Acetyl-L-Cysteine restores its fitness in the host environment. Herein, we proposed that V. cholerae regulates CBS-dependent H2S production for better survival and proliferation under ROS stress.