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Genome-wide genetic screening with chemically-mutagenized haploid embryonic stem cells

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping defining synthetic-lethality, synthetic-viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, howeve...

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Detalles Bibliográficos
Autores principales: Forment, Josep V., Herzog, Mareike, Coates, Julia, Konopka, Tomasz, Gapp, Bianca V., Nijman, Sebastian M., Adams, David J., Keane, Thomas M., Jackson, Stephen P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5164930/
https://www.ncbi.nlm.nih.gov/pubmed/27820796
http://dx.doi.org/10.1038/nchembio.2226
Descripción
Sumario:In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping defining 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.