关键词：贫血细胞（生物学）；染色体；遗传性疾病
摘 要：Fanconi anemia (FA) is a rare disease characterized by developmental defects, progressive bone marrow failure (BMF) and pronounced cancer susceptibility. The FA proteins and the major breast cancer susceptibility gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have demonstrated that the FA-BRCA pathway plays an important role in the response of hematopoietic stem and progenitor cells to cellular stresses, and in particular oxidative stress caused by elevated levels of reactive oxygen species (ROS). In our research proposal, we have hypothesized that the FA-BRCA pathway may play an important role in the prevention of genome-wide de novo copy number variation. Chromosome copy number variation refers to gains or losses of large (>10 kb) genomic DNA segments. While copy number variation is a feature of normal genetic variation it is also strongly associated with genetic disease, including autism and psychiatric disorders. In addition, several recent studies have demonstrated that hematological malignancies show large numbers of de novo somatically acquired copy number variants (CNVs).