Negative Genetic

Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. This term is reserved for high or low throughput studies with scores.

Publication

Combinatorial CRISPR screen identifies fitness effects of gene paralogues.

Thompson NA, Ranzani M, van der Weyden L, Iyer V, Offord V, Droop A, Behan F, Goncalves E, Speak A, Iorio F, Hewinson J, Harle V, Robertson H, Anderson E, Fu B, Yang F, Zagnoli-Vieira G, Chapman P, Del Castillo Velasco-Herrera M, Garnett MJ, Jackson SP, Adams DJ

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 ... [more]

Nat Commun Dec. 26, 2020; 12(1);1302 [Pubmed: 33637726]

Throughput

  • Low Throughput

Ontology Terms

  • phenotype: growth abnormality (HP:0001507) [viability (PATO:0000169)]
  • growth abnormality (HP:0001507) [viability (PATO:0000169)]

Additional Notes

  • CRISPR GI screen
  • Cell Line: A-375 cell BTO:0002806
  • Cell Line: MEWO cell BTO:0003301
  • Cell Line: RPE-1
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: Targeted CRISPR synthetic lethality library
  • Significance Threshold:FDR<0.1 and additional filtering of gene pairs with one gene with a large individual fitness defect

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
CLASP1 CLASP2
Affinity Capture-MS
Affinity Capture-MS

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner is identified by mass spectrometric methods.

High-BioGRID
3351425
CLASP1 CLASP2
Cross-Linking-MS (XL-MS)
Cross-Linking-MS (XL-MS)

An interaction is detected between two proteins using chemically reactive or photo-activatable cross-linking reagents that covalently link amino acids in close proximity, followed by mass spectrometry analysis to identify the linked peptides (reviewed in PMID 37406423, 37104977). Experiments may be carried with live cells or cell lysates in which all proteins are expressed at endogenous levels (e.g. PMID 34349018, 35235311) or with recombinant proteins (e.g., PMID 28537071).

High-BioGRID
3680452

Curated By

  • BioGRID