OBJECTIVE: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer. METHODS: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning. RESULTS: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein. CONCLUSION The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
Asian Continental Ancestry Group ; BRCA1 Protein ; genetics ; Breast Neoplasms ; genetics ; Exome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pedigree ; Phenotype

OBJECTIVE： To explore the component， target and pathway of Panax notoginseng for coronary heart disease （CHD） and its potential molecular mechanism. METHODS： Based on network pharmacology， active components of P. notoginseng were retrieved with TCMSP platform. The targets of P. notoginseng for CHD were screened by using DRAR-CPI server， GeneCards and DisGeNET databases. Cytoscape 3.6.0 software was used to form the effective components-CHD targets network of P. notoginseng. String database was used to draw target interaction network. Network Analyzer tool was used to calculate target connectivity， and potential core targets were screened. Molecular docking between the core targets and the effective components of P. notoginseng was performed by Systems Dock Web Site server. KEGG pathway enrichment analysis and gene ontology （GO） enrichment analysis were also carried out to explore the important signal pathway and molecular function of P. notoginseng for CHD. “Effective component-target-signal pathway”network of important signal pathway were constructed. RESULTS： Five effective components （stigmasterol， β-sitosterol， ginsenoside rh2， quercetin， notoginsenoside r1） were screened from P. notoginseng for CHD， which acted on 96 targets and had 134 functional relationships. Five core targets were protein kinase B （AKT）， interleukin 6 （IL-6）， vascular endothelial growth factor A （VEGFA）， c-JUN protein （c-JUN） and heparin binding epidermal growth factor （HB-EGF）， which played an important role in the treatment of CHD by altering protein binding and regulating signaling pathways as phosphatidylinositol-3 kinase-protein/kinase B （PI3K/AKT）， hypoxia-inducible factor-1 （HIF-1） and mitogen-activated protein kinase （MAPK）. CONCLUSIONS： P. notoginseng in the treatment of CHD is not only play a variety of effects through the role of multiple targets， but also produce complex network regulation effect through the interaction between targets.