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

ABSTRACT: To capture the global gene network regulating the differentiation of immature T cells in an unbiased manner, large-scale forward genetic screens in zebrafish were conducted and combined with genetic interaction analysis. After ENU mutagenesis, genetic lesions associated with failure of T cell development were identified by meiotic recombination mapping, positional cloning, and whole genome sequencing. Recessive genetic variants in 33 genes were identified and confirmed as causative by additional experiments. The mutations affected T cell development but did not perturb the development of an unrelated cell type, growth hormone-expressing somatotrophs, providing an important measure of cell-type specificity of the genetic variants. The structure of the genetic network encompassing the identi

SUBMITTER: O'Meara CP 

PROVIDER: S-EPMC8528931 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature