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Synthetic Viability
Synthetic rescue (or synthetic recovery or synthetic viability when a lethal phenotype is rescued) refers to a genetic interaction in which a cell that is nonviable, sensitive to a specific drug, or otherwise impaired due to the presence of a genetic mutation becomes viable when the original mutation is combined with a second mutation in a different gene. The second mutation can either be a loss-of-function mutation (equivalent to a knockout) or a gain-of-function mutation. The term synthetic rescue is derived from synthetic lethality, where the combination of two mutations leads to cell death (whereas neither alone is lethal). Synthetic rescue is the inverse process: instead of causing lethality, the second genetic change ''rescues'' the organism from the harmful effects of the first. This phenomenon occurs in the yeast Saccharomyces cerevisiae, wherein a deletion of the DNA helicase gene SRS2 compensates for the lethality and DNA repair defects caused by the loss of the RAD54 gen ...
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Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properties, and its behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code (its genotype) and the influence of environmental factors. Both factors may interact, further affecting the phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and again in his 1982 book '' The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as caddisfly larva cases and beaver dams ...
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Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis). Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics ( phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutati ...
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Loss-of-function Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis). Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutation is the ult ...
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Gain-of-function Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis). Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutation is the ul ...
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Synthetic Lethality
Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death or death of an organism. Although the foregoing explanation is wider than this, it is common when referring to synthetic lethality to mean the situation arising by virtue of a combination of deficiencies of two or more genes leading to cell death (whether by means of apoptosis or otherwise), whereas a deficiency of only one of these genes does not. In a synthetic lethal genetic screen, it is necessary to begin with a mutation that does not result in cell death, although the effect of that mutation could result in a differing phenotype (slow growth for example), and then systematically test other mutations at additional loci to determine which, in combination with the first mutation, causes cell death arising by way of deficiency or abolition of expression. Synthetic lethality has utility for purposes of molecular targeted cancer therapy. The first exampl ...
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Saccharomyces Cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of grapes. It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like '' Escherichia coli'' as the model bacterium. It is the microorganism which causes many common types of fermentation. ''S. cerevisiae'' cells are round to ovoid, 5–10  μm in diameter. It reproduces by budding. Many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. ''S. cerevisiae'' is currently the only yeast cell known to have Berkeley bodies present, which are involved in particular secretory pathways. Antibodies again ...
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Gene Therapy
Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in Phases of clinical research, phase I. In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as alipogene tiparvovec (2012), Strimvelis (2016), tisagenlecleucel (2017), voretigene neparvovec ...
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Auxotrophy
Auxotrophy ( "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this characteristic; ''auxotrophic'' is the corresponding adjective. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth. Prototrophic cells are self-sufficient producers of all required metabolites (e.g. amino acids, lipids, cofactors), while auxotrophs require to be on medium with the metabolite that they cannot produce. For example, a methionine auxotrophic cell could only grow on a medium that contained methionine; otherwise, it would starve. In this example, this is because it is unable to produce its own methionine. However, a methionine prototrophic cell would be able to function and replicate on a medium with or without methionine. Replica plating is a technique that transfer ...
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Suppressor Mutation
A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation in a process defined synthetic rescue. Genetic suppression therefore restores the phenotype seen prior to the original background mutation.Hartwell, L. H., Hood, L., Goldberg, M. L., Reynolds, A. E., Silver, L. M., & Veres, R. C. (2008). Genetics: From Genes to Genomes. New York: McGraw-Hill. Suppressor mutations are useful for identifying new genetic sites which affect a biological process of interest. They also provide evidence between functionally interacting molecules and intersecting biological pathways.Hodgkin J. Genetic suppression. 2005 Dec 27. In: WormBook: The Online Review of C. elegans Biology nternet Pasadena (CA): WormBook; 2005-. Intragenic vs. intergenic suppression Intragenic suppression Intragenic suppression results from suppressor mutations that occur in the same gene as the original mutation. In a classic study, Francis Crick (et al ...
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Telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of DNA, chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break. Discovery The existence of a special structure at the ends of chromosomes was independently proposed in 1938 by Hermann Joseph Muller, studying the fruit fly ''Drosophila melanogaster'', and in 1939 by Barbara McClintock, working with maize. Muller observed that the ends of irradiated fruit fly chromosomes did not present alterations such as deletions or inversions. He hypothesized the presence of a protective cap, which he coined "telomeres", from the Greek ' ...
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BRCA Mutation
A ''BRCA'' mutation is a mutation in either of the ''BRCA1'' and ''BRCA2'' genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Harmful mutations in these genes may produce a hereditary breast–ovarian cancer syndrome in affected persons. Only 5–10% of breast cancer cases in women are attributed to ''BRCA1'' and ''BRCA2'' mutations (with ''BRCA1'' mutations being slightly more common than ''BRCA2'' mutations), but the impact on women with the gene mutation is more profound. Women with harmful mutations in either ''BRCA1'' or ''BRCA2'' have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal. The risk of breast and ovarian cancer is higher for women with a high-risk ''BRCA1'' mutation than with a ''BRCA2'' mutation. Having a high-risk mutation ...
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KAIST
KAIST (originally the Korea Advanced Institute of Science and Technology) is a national university, national research university located in Daedeok Innopolis, Daejeon, South Korea. KAIST was established by the Korean government in 1971 as the nation's first public, research-oriented science and engineering institution. KAIST has been internationally accredited in business education, and hosts the Secretariat of the Association of Asia-Pacific Business Schools (AAPBS). KAIST has 10,504 full-time students and 1,342 faculty researchers (as of the Fall 2019 Semester) and had a total budget of US$765 million in 2013, of which US$459 million was from research contracts. In 2007, KAIST partnered with international institutions and adopted dual degree programs for its students. Its partner institutions include the Technical University of Denmark, Carnegie Mellon University, the Georgia Institute of Technology, Technische Universität Berlin, and the Technical University of Munich. Hi ...
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