genetic interaction

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draft genetic method expansion: ---genetic interference
This term refers to methods that aim at interfering with the activity of a specific gene by altering the gene regulatory or coding sequences. This goal can be achieved either by a classical genetic approach (random mutagenesis followed by phenotype characterization and genetic mapping) or by a reverse genetics approach where a gene of interest is modified by directed mutagenesis. ---------------random mutagenesis ---------------synthetic genetic analysis ---expression interference This term refers to methods designed to interfere with gene expression rather than with the gene itself. This class of methods are either designed to interfere with gene transcripts or directly with their protein products. ------------------RNA interference RNAi RNA interference (RNAi) is a post-translational gene silencing method reproducing a naturally occurring phenomena. RNAi is the process whereby double-stranded RNA (dsRNA) induces the sequence-specific degradation of homologous mRNA. RNAi or dsRNA-induced silencing phenomena are present in evolutionarily diverse organisms, e.g., nematodes, plants, fungi, and trypanosomes. The mechanisms by which RNAi works is initiated by a processive cleavage of dsRNA into 21 to 23 nucleotide (nt) short interfering RNAs (siRNAs). These native siRNA duplexes are then incorporated into a protein complex called RNA-induced silencing complex (RISC). ATP-dependent unwinding of the siRNA duplex generates an active RISC complex. Guided by the antisense strand of siRNA, the active RISC complex recognizes and cleaves the corresponding mRNA. 12408823 and 12110901 ------------------Antisense RNA This approach is based on the observation that expression of RNA that is complementary to a specific mRNA can decrease the synthesis of its gene product either by increasing the degradation of the targeted mRNA or by interfering with its translation. 1340158 ------------------inhibitor Antibodies Intracellular (or extracellular) expression of antibodies is used to target specific gene products in order to inactivate them. Most of the times the antibody scaffold need s to reengineered for efficient expression and solubility in the cytoplasm. 10189716 -------------------Perturbagens peptides This approach is based on the expression of peptides that bind to specific target proteins thereby interfering with their activity. In a standard approach the interfering peptide is expressed by genetic fusion to a stable protein scaffold. Interfering peptides can also be introduced into cells by fusing them to proteins or peptides (homeodomains, Tat protein…) having the property of penetrating the cell membrane. The peptide-carrier fusion protein is either synthesized chemically or produced in vivo, normally in bacteria. When the purified fusion protein is added to a cell culture, it penetrates the cell membrane thereby permitting the fused peptide to interfere with its target protein. 8606778 and 11731788 --------------------Inhibitor Small molecules Protein activity is inhibited by small inorganic molecules (drugs) that specifically bind to their targets. Recently this classical pharmacological approach is sometime referred to as “chemical genetics”. 10780927 and 10542155 ################################################ NOTE : such hierarchy is compatible with biopax evidence code. ################################################ Inferred from mutant phenotype. IMP inferred from mutant phenotype. The assertion was inferred from a mutant phenotype such as o Any gene mutation/knockout o Overexpression/ectopic expression of wild-type or mutant genes o Anti-sense experiments o RNA interference experiments o Specific protein inhibitors Comment: Inferences made from examining mutations or abnormal levels of only the product(s) of the gene of interest are covered by code EV-IMP (compare to code EV-IGI). Use this code for experiments that use antibodies or other specific inhibitors of RNA or protein activity, even though no gene may be mutated (the rationale is that EV-IMP is used where an abnormal situation prevvails in a cell or organism).

Inferred from genetic interaction. IGI inferred from genetic interaction. The assertion was inferred from a genetic interaction such as o "Traditional" genetic interactions such as suppressors, synthetic lethals, etc. o Functional complementation o Rescue experiments o Inference about one gene drawn from the phenotype of a mutation in a different gene This category includes any combination of alterations in the sequence (mutation) or expression of more than one gene/gene product. This category can therefore cover any of the IMP experiments that are done in a non-wild-type background, although we prefer to use it only when all mutations are documented. When redundant copies of a gene must all be mutated to see an informative phenotype, use the IGI code. (Yes, this implies some organisms, such as mouse, will have far, far more IGI than IMP annotations.) IMP also covers phenotypic similarity: a phenotype that is informative because it is similar to that of another independent phenotype (which may have been described earlier or documented more fully) is IMP (not IGI). We have also decided to use this category for situations where a mutation in one gene (gene A) provides information about the function, process, or component of another gene (gene B; i.e. annotate gene B using IGI).

Reported by: luisa_montecchi

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Any suggestion for genetic interaction TYPE is wellcome

Original comment by: luisa_montecchi

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Original comment by: luisa_montecchi

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proposal for genetic interaction type form MIPS: genetic (IGI) suppression suppression mutation suppression knockout suppression partial alteration suppression expression alteration suppression overexpression suppression underexpression suppression scalable synthetic phenotype synthetic lethal conditional synthetic lethal conditional synthetic lethal temperature-sensitivity conditional synthetic lethal nutrition-sensitivity synthetic growth effect1 synthetic growth defect synthetic growth increase see hierarchy at ftp://ftpmips.gsf.de/yeast/catalogues/evidencecat.scheme\

think about roles: suppressOR and suppressed

Original comment by: luisa_montecchi

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genetic interaction type definitions by Ulrich Gueldener <u.gueldener@gsf.de> :

references for these definitions : Better will be the MPact paper - published in the NAR database issue 2006: MPACT: The MIPS Protein Interaction Resource on Yeast Gueldener et al. (search pmid when paper out)

genetic (IGI) suppression -> The cause of a phenotype to be suppressed is either defined/known (suppressed by) or unknown/not defined. In the case of 'unknown/not defined' there is no gene/protein as 'suppressed', no pair of interactors.

suppression mutation suppression knockout -> Knocked out gene is the suppressor of a phenotype suppression partial alteration -> A mutation is the suppressor of a phenotype suppression expression alteration -> An altered expression is the suppressor of a phenotype suppression overexpression -> Overexpression is the suppressor of a p. suppression underexpression -> Underexpression is the suppressor of a p. suppression scalable -> Level of Over/Underexpression scales the 'extend' of a phenotype

synthetic phenotype -> A phenotype of an otherwise silent mutation is caused by ... synthetic lethal -> non-viable due to e.g. a mutation. conditional synthetic lethal conditional synthetic lethal temperature-sensitivity -> a silent mutation is lethal by altered temp. conditional synthetic lethal nutrition-sensitivity -> a silent mutation is lethal by altered nutrition

synthetic growth effect synthetic growth defect -> e.g. slow growth due to a second site mutation synthetic growth increase -> better growth compared to wt under a certain condition

Original comment by: luisa_montecchi

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approved at geneva psi meeting september 2005

Original comment by: luisa_montecchi

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Approved at PSI Geneva meeting see MI:0255 to MI:0260 for methods and MI:0261 to MI:0270 for interaction types

Original comment by: luisa_montecchi

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• status: open --> closed

Original comment by: luisa_montecchi