Genetic landscape of T cells identifies synthetic lethality for T-ALL

Introduction of random, deleterious mutations into the genome by ENU mutagenesis, aids determination of gene function in a phenotype-driven approach termed a forward genetic screen. In this study, we identified a collection of mutant zebrafish from a forward genetic screen that lack rag1 expression in the thymus at 5 days post-fertilization. We performed whole genome sequencing to identify missense mutation in genes underpinning the regulation T cell development.

通过N-乙基-N-亚硝基脲（ENU）诱变将随机、有害突变引入基因组，可借助一种名为正向遗传筛选（forward genetic screen）的表型驱动策略解析基因功能。本研究从正向遗传筛选中获得了一批突变斑马鱼，该类斑马鱼在受精后5天的胸腺中重组激活基因1（rag1）表达缺失。我们通过全基因组测序，鉴定出调控T细胞发育的相关基因所携带的错义突变。