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

Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets.

Mengwasser KE, Adeyemi RO, Leng Y, Choi MY, Clairmont C, D'Andrea AD, Elledge SJ

BRCA1 or BRCA2 inactivation drives breast and ovarian cancer but also creates vulnerability to poly(ADP-ribose) polymerase (PARP) inhibitors. To search for additional targets whose inhibition is synthetically lethal in BRCA2-deficient backgrounds, we screened two pairs of BRCA2 isogenic cell lines with DNA-repair-focused small hairpin RNA (shRNA) and CRISPR (clustered regularly interspaced short palindromic repeats)-based libraries. We found that BRCA2-deficient cells ... [more]

Mol Cell Mar. 07, 2019; 73(5);885-899.e6 [Pubmed: 30686591]

Throughput

  • Low Throughput

Ontology Terms

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

Additional Notes

  • CRISPR GI screen
  • Cell Line: DLD-1 (BTO:0000391, CELLOSAURUS:CVCL_0248)
  • Cell Line: PEO1 (EFO:0005445, CELLOSAURUS:CVCL_2686)
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: DDR targeted library (Elledge, 2019)
  • Significance Threshold: EdgeR FDR<0.01

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
PARP1 BRCA2
Synthetic Lethality
Synthetic Lethality

A genetic interaction is inferred when mutations or deletions in separate genes, each of which alone causes a minimal phenotype, result in lethality when combined in the same cell under a given condition.

High-BioGRID
2342181
BRCA2 PARP1
Synthetic Lethality
Synthetic Lethality

A genetic interaction is inferred when mutations or deletions in separate genes, each of which alone causes a minimal phenotype, result in lethality when combined in the same cell under a given condition.

Low-BioGRID
2344243

Curated By

  • BioGRID