Combinatorial CRISPR screen identifies fitness effects of gene paralogues
Authors
Thompson, N. A.Ranzani, M.
van der Weyden, L.
Iyer, V.
Offord, V.
Droop, A.
Behan, F.
Gonçalves, E.
Speak, A.
Iorio, F.
Hewinson, J.
Harle, V.
Robertson, H.
Anderson, E.
Fu, B.
Yang, F.
Zagnoli-Vieira, G.
Chapman, Phil
Del Castillo Velasco-Herrera, M.
Garnett, M. J.
Jackson, S. P.
Adams, D. J.
Affiliation
Wellcome Sanger Institute, Wellcome Trust Genome Campus, CambridgeIssue Date
2021
Metadata
Show full item recordAbstract
Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells.Citation
Thompson NA, Ranzani M, van der Weyden L, Iyer V, Offord V, Droop A, et al. Combinatorial CRISPR screen identifies fitness effects of gene paralogues. Nat Commun. 2021;12(1):1302.Journal
Nature CommunicationsDOI
10.1038/s41467-021-21478-9PubMed ID
33637726Additional Links
https://dx.doi.org/10.1038/s41467-021-21478-9Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41467-021-21478-9
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