Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells
2016; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês
10.1038/nchembio.2226
ISSN1552-4469
AutoresJosep V. Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V. Gapp, Sebastian Nijman, David J. Adams, Thomas Keane, Stephen P. Jackson,
Tópico(s)Gene Regulatory Network Analysis
ResumoA genetic screening approach using chemically mutagenized haploid mouse embryonic stem cells combined with next-generation sequencing identified recessive suppressor point mutations that elicit resistance to 6-thioguanine. In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.
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