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Genomic Technologies glossary & taxonomy
Drug discovery & development term index Informatics term index Technologies term index Biology term index Chemistry term index Related glossaries include Drug & disease targets Informatics Drug discovery informatics Bioinformatics Cheminformatics Genomic informatics Clinical & Medical Informatics Technologies Cell & Tissue Technologies Microarrays PCR Sequencing Biology SNPs & genetic variations covers both technologies for detecting and informatics for interpreting genetic variants. Maps, genomic & genetic Functional genomics allosteric ribozymes (allozymes):
RNA and DNA molecules can be engineered to function as molecular switches
that trigger catalytic events when a specific target molecule becomes bound.
Recent studies on the underlying biochemical properties of these constructs
indicate that a significant untapped potential exists for the practical
application of allosteric nucleic acids. Engineered molecular switches can be
used to report the presence of specific analytes in complex mixtures, making
possible the creation of new types of biosensor devices and genetic control
elements.
Engineered
allosteric ribozymes as biosensor components.
Breaker RR. Curr Opin Biotechnol. 2002
Feb;13(1):31-9. Bacterial artificial chromosome BAC: A vector used to clone DNA fragments (100- to 300-kb insert size; average, 150 kb) in Escherichia coli cells. Based on naturally occurring F-factor plasmid found in the bacterium E. coli. Compare cloning vector. DOE DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes. MeSH, 2002 Related term: BAC maps. Maps, genetic & genomic base
editing:
a
new genome editing technology that enables the direct, irreversible
conversion of a specific DNA base into another at a targeted genomic
locus. Importantly, this can be achieved without requiring double-stranded
DNA breaks (DSB). Since many genetic diseases arise from point mutations,
this technology has important implications in the study of human health
and disease[1]. Alexis C. Komor, Guidelines for base editing in mammalian
cells 2016 chromatin immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing. MeSH 2005 clone: A population of genetically identical cells produced from a common ancestor. Sometimes also used to refer to a number of recombinant DNA molecules all carrying the same inserted sequence. IUPAC Medicinal Chemistry, IUPAC Compendium Clone was coined by Herbert J. Webber in 1903 for "a colony of organisms derived asexually from a single progenitor" and was quickly adopted by botanists and cell biologists. But the popular perception of cloning can be traced to Alvin Toffler's Future Shock (1970) and was quickly popularized (and extended to items such as computers). But Lee Silver, Professor of Molecular Biology and Public Affairs, Princeton Univ. concludes that "the scientific community has lost control over Webber's pleasant sounding little word. Cloning has a popular connotation that is impossible to dislodge. We must accept that democratic debate on cloning is bereft of any meaning. Science and Scientists would be better served by choosing other words to explain advances in developmental biotechnology to the public". L. Silver "What are clones? They're not what you think they are" Nature 412 (6842): 21, 5 July 2001 Narrower term: clone bank clone bank: Genomic library, a collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. Schlindwein Related term: genomic library cloning: Using specialized DNA technology (see cloning vector) to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. This process is used by researchers in the Human Genome Project, and is referred to as cloning DNA. The resulting cloned (copied) collections of DNA molecules are called clone libraries. A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. A third type of cloning produces complete, genetically identical animals such as the famous Scottish sheep, Dolly. DOE The process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism. NHGRI Human Cloning
FAQ , US President's Council on Bioethics http://bioethics.georgetown.edu/pcbe/topics/cloning_faq.html Of course many plants can be cloned (cuttings). And identical twins are (in a
technical sense) clones, who can be organ donors for each other without
immunosuppressants cloning vector: DNA molecule originating from a virus, a plasmid, or the cell of a higher organism into which another DNA fragment of appropriate size can be integrated without loss of the vectors capacity for self replication; vectors introduce foreign DNA into host cells, where it can be reproduced in large quantities. Examples are plasmids, cosmids, and yeast artificial chromosomes [YACs]; vectors are often recombinant molecules containing DNA sequences from several sources. DOE
Clustered Regularly
Interspaced Short Palindromic Repeats:
Repetitive nucleic acid sequences that are principal components of the
archaeal and bacterial CRISPR-CAS SYSTEMS,
which function as adaptive antiviral defense systems.
MeSH Year introduced: 2014 conditional knockout: A method by which a gene can be switched off and on. Cre-lox: A bacteriophage- derived, site- specific recombinase called Cre is used to selectively introduce a deletion into a particular cellular compartment. The method basically involves introducing loxP target sequences into the gene to be deleted, and engineering expression of the Cre recombinase enzyme under the control of a tissue- specific promoter. Thus, the enzyme is expressed only in the desired tissue, and it deletes the gene of interest via the loxP target sites. Tissue- specific gene deletion.
CRISPR for Precision Medicine
Developing Accuracy, Speed and Efficiency in
Gene Editing and Repair
MARCH 14-15, 2019 San
Francisco CA
Program
Gene editing,
particularly using the CRISPR (Clustered Regularly Interspaced Short
Palindromic Repeats)/Cas system, has very rapidly established itself as an
important tool in drug discovery and is now being exploited for
therapeutic purposes as well. … scientists
and clinicians to talk about the recent progress made in gene editing and
its potential going forward. At the same time, they will also discuss what
is being done to overcome some of the inherent challenges that exist in
terms of guide RNA design, delivery and off-target effects associated with
CRISPR/Cas9, and what are some of the alternatives being developed?
Experts from pharma/biotech, academic and government labs, and
technology/service companies will share their experiences leveraging the
utility of CRISPR-based gene editing for diverse applications such as
creating cell lines and disease models for functional in vitro, in vivo and ex vivo screening that will
ultimately pave the way for better and safer therapeutics.
CRISPR:
Next-Gen Genomics: Leveraging CRISPR & Single-Cells
June 20-21, 2018
Boston, MA
Program
“CRISPR” (pronounced
“crisper”) stands for Clustered Regularly Interspaced Short Palindromic
Repeats, which are the hallmark of a bacterial defense system that forms
the basis for CRISPR-Cas9 genome editing technology. In the field of
genome engineering, the term “CRISPR” or “CRISPR-Cas9” is often used
loosely to refer to the various CRISPR-Cas9 and -CPF1, (and other) systems
that can be programmed to target specific stretches of genetic code and to
edit DNA at precise locations, as well as for other purposes, such as for
new diagnostic tools. With these systems, researchers can permanently
modify genes in living cells and organisms and, in the future, may make it
possible to correct mutations at precise locations in the human genome in
order to treat genetic causes of disease. Other systems are now available,
such as CRISPR-Cas13’s, that target RNA provide alternate avenues for use,
and with unique characteristics that have been leveraged for sensitive
diagnostic tools, such as SHERLOCK. Questions & Answers about CRISPR: What
is CRISPR? , Broad Institute
https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr
Wikipedia
https://en.wikipedia.org/wiki/CRISPR
CRISPR/Cas9:
Several approaches to genome editing have been developed. A recent one is
known as CRISPR-Cas9, which is short for clustered regularly interspaced
short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9
system has generated a lot of excitement in the scientific community
because it is faster, cheaper, more accurate, and more efficient than
other existing genome editing methods.
What are genome editing and CRISPR-Cas9?
Genetics Home Reference, NIH NLM
https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting DNA nanotechnology: Ned Seeman, DNA Nanotechnology, New York Univ., US http://seemanlab4.chem.nyu.edu/ DNA shuffling: The use of DNA recombination ( RECOMBINATION, GENETIC) to prepare a large gene library of novel, chimeric genes from a population of randomly fragmented DNA from related gene sequences. MeSH 2003 DNA shuffling is the most powerful molecular evolution technique known to date, and it can be used to evolve proteins, plasmids and viruses in vitro. We are applying this method to improve efficacy or pharmacological properties of cytokines with therapeutic potential.... part of the project is done in collaboration with Maxygen (Santa Clara, CA), a biotechnology institute where the gene shuffling technology was developed by Dr. Willem Stemmer (Stemmer, Nature 370: 389- 391, 1994; Crameri et al. Nature 391: 288, 1998). A method for in vitro homologous recombination of pools of selected mutant genes by random fragmentation and polymerase chain reaction (PCR) reassembly. Computer simulations called genetic algorithms have demonstrated the importance of iterative homologous recombination for sequence evolution. WP Stemmer, Rapid evolution of a protein in vitro by DNA shuffling, Nature. 1994 Aug 4;370 (6488): 389- 391. Related/equivalent? term: gene shuffling. Related terms: domain shuffling, exon shuffling, protein shuffling Wikipedia http://en.wikipedia.org/wiki/DNA_shuffling embryonic lethal trait: In some cases, knockout of a gene believed to be important in a disease occurring in adult life (such as a cancer) will be lethal to the embryo, resulting in little or no information about the function of the gene in adult cells of interest. Related terms knockdown, synthetic lethal screening exon trapping (exon amplification): a molecular
biology technique
to identify potential exons in
a fragment of eukaryote DNA of
unknown intron-exon structure.[1] This
is done to determine if the fragment is part of an expressed gene.
…The technique has largely been supplanted by the approach of sequencing cDNA generated
from mRNA and
then using bioinformatics tools such as NCBI's BLAST server
to determine the source of the sequence, thereby identifying the appropriate
exon-intron splice sites. Wikipedia
accessed 2018 Sept 3 forward genetics: the approach of determining the genetic basis responsible for a phenotype. This was initially done by using naturally occurring mutations or inducing mutants with radiation, chemicals, or insertional mutagenesis (e.g. transposable elements). Subsequent breeding takes place, mutant individuals are isolated, and then the gene is mapped. Forward genetics can be thought of as a counter to reverse genetics, which determines the function of a gene by analyzing the phenotypic effects of altered DNA sequences.[1] Wikipedia https://en.wikipedia.org/wiki/Forward_genetics The traditional approach to genetics, which starts with a phenotype and then identifies genetic mutations or variations that control or cause that trait. Related term: positional cloning. Compare reverse genetics forward genomics: Given the advances in next-generation sequencing, a veritable zoo of genomic data from hundreds of animals have now been sequenced, allowing scientists unprecedented insights into how DNA changes may underlie the differences between species and the diversity of life on Earth. When viewed through the prism of evolution, these DNA changes either discard ancestral traits or gain entirely new ones, for example, in key senses like vision, speech and hearing. Now, in a new study, Prudent et al. (2016) have developed new computational approaches, called “Forward Genomics” which can hone in on key genomic locations amongst the millions of DNA changes that occurred between different species. Joseph Caspermeyer; New “Forward Genomics” Approach to Identify Keys to Loss of Vision in Blind Mammals, Molecular Biology and Evolution, Volume 33, Issue 8, 1 August 2016, Pages 2175, https://doi.org/10.1093/molbev/msw136 https://academic.oup.com/mbe/article/33/8/2175/2579436 Narrower terms: Post-Transcriptional Gene Silencing PTGS, RNA silencing; Related term: epigenetics functional genomics technologies include gene disruption, gene manipulation, gene shuffling, gene targeting, gene trapping, knockdowns, knockins, knockouts, mutagenesis, phage display, positional cloning, Post Translational Gene Silencing PTGS, RNA interference RNAi. Related terms chemical genetics, chemical genomics gene disruption: A key methodology in high- throughput gene functional analysis. Involves developing various methods for randomly disrupting genes throughout the genome of a model organism (resulting in knockouts, or null mutations of these genes) and then determining (1) which genes have been disrupted and (2) the phenotype (if any) of the mutant organism. Broader term: gene manipulation Narrower terms: knockdown, knockin, knockout, PTSG
gene
editing:
Gene editing, particularly using the CRISPR (Clustered Regularly
Interspaced Short Palindromic Repeats)/Cas system, has gained importance
both as a research tool in drug discovery and for drug therapy. Cambridge
Healthtech Institute’s fourth annual symposium on New Frontiers in
CRISPR-Based Gene Editing will bring together experts from research
and clinical laboratories to talk about the recent progress in gene
editing and its growing applications. However, the technology is not
without limitations. What is being done to overcome some of the inherent
challenges in guide RNA design, delivery and off-target effects associated
with CRISPR/Cas and what are some of the alternatives being developed?
Experts from pharma/biotech, academic and government labs, and technology
companies will share their experiences leveraging the utility of
CRISPR-based gene editing for creating cell lines and disease models, for
functional in vitro, in vivo and ex vivo screening,
for target and cellular pathway identification, and for therapeutic use.
gene library: A collection of cloned DNA fragments from a variety of species. IUPAC Biotech gene manipulation: The use of in vitro techniques to produce DNA molecules containing novel combinations of genes or altered sequences, and the insertion of these into vectors that can be used for their incorporation into host organisms or cells in which they are capable of continued propagation of the modified genes. IUPAC Biotech Narrower terms: knockdowns, knockins, knockouts, mutagenesis, biochemical genomics, exon trapping, gene disruption, gene targeting, gene trapping; Proteomics protein knockouts gene shuffling:
recombination
between dissimilar genes to create new recombinant genes (see, for example .
We here choose to call only this kind of recombination gene shuffling,
excluding, for example, duplication of domains within a gene. In such a gene
shuffling event, the parental genes may be either destroyed or preserved
. Gene shuffling is clearly the most potent of the three causes of functional
innovation because it can generate new genes with a structure drastically
different from that of either parental gene. Laboratory evolution studies show
that gene shuffling allows new gene functions to arise at rates of orders of
magnitudes higher than point mutations
The
rarity of gene shuffling in conserved genes
Gavin C Conant1* and Andreas
Wagner2
Genome Biology
2005, 6:R50 doi:10.1186/gb-2005-6-6-r50
http://genomebiology.com/2005/6/6/R50
Encompasses techniques to speed up genetic evolution to screen for high value proteins. Novel recombinant gene products are screened to identify candidate proteins with desired activities. Related terms: DNA shuffling, domain shuffling, exon shuffling, molecular evolution, protein shuffling, directed protein evolution gene manipulation, knockdown, knockin, knockout gene silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. MeSH, 2000 gene suppression: shRNA is useful where long-term gene suppression is required, or where the cells are resistant to other delivery methods. Its use, however, has been limited by lack of design and processing methods that provide reliable and reproducible gene silencing. BioIT World Weekly Update Sept 5, 2006 Broader term: gene disruption. Related term: Cancer tumor suppressor gene gene targeting: Drug & disease targets gene trapping: Traditional gene- trapping approaches, in which genes are randomly disrupted with DNA elements inserted throughout the genome, have been used to generate large numbers of mutant organisms for genetic analysis. Recent modifications of gene- trapping methods and their increased use in mammalian systems are likely to result in a wealth of new information on gene function. Durick K, et al. “Hunting with traps” Genome Research 9(11): 1019-1025. Nov. 1999 genetic engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. MeSH, 1989 Related term: recombinant DNA technology. IUPAC Compendium Genetic Perturbation Platform : The Genetic Perturbation Platform, formerly known as the RNA interference (RNAi) Platform, supports functional investigations of the mammalian genome that can reveal how genetic alterations lead to changes in phenotype. GPP develops technologies for perturbing genes and assists collaborators in experimental planning and execution by helping choose the best model system and experimental readout to assess the effects of genetic perturbation. Technologies include libraries of short hairpin RNAs (shRNAs), CRISPR/Cas9 constructs, and open reading frames (ORFs) to knock down or overexpress genes, in addition to other techniques such as TALEN and CRISPR/Cas9 for genome editing and "tough decoy" constructs to inhibit microRNAs. GPP Web Portal, Broad Institute https://portals.broadinstitute.org/gpp/public/ genetic recombination: Production of new arrangements of genes by various mechanisms such as assortment and segregation, crossing over, gene conversion, transformation, conjugation, transduction, F-duction, or mixed infection of viruses. MeSH, 1968 Happens during the cell division (meiosis) that occurs during the formation of sperm and egg cells. In this process, chromosomes pair up and may swap portions of genetic material in a phenomenon known as crossing over. The chromosomes then reassemble and separate, with each containing some material from the other. The chromosomes are then divvied out into individual sex cells. During crossing over, it is more likely that far- apart genes will be separated by a break than those that are close together. The genes that tend to stay together are said to be linked and therefore may serve as markers for one another — a pattern that is of particular interest when, for example, one of the genes is a disease gene. Related terms: recombinant, recombination genetic vector : Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from plasmids, bacteriophages or viruses. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition. MeSH, 1980
genome editing:
Genome editing (also called gene editing) is a group of technologies that
give scientists the ability to change an organism's DNA. These
technologies allow genetic material to be added, removed, or altered at
particular locations in the genome What
are genome editing and CRISPR-Cas9?
Genetics Home Reference, NIH NLM
https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting Genome Technology Program: Is refining current technologies to increase efficiency and decrease cost while maintaining or improving data quality and developing completely novel approaches to achieve orders-of-magnitude improvement. .NHGRI, https://www.genome.gov/Funded-Programs-Projects/Genome-Technology-Program genomewide knockdowns: RNAi is already making an impact. Genomewide knockdowns have been carried out in organisms including nematodes. Small interfering RNAs (siRNAs), which silence genes in mammalian cells, are now being designed against as many genes as possible. The RNA Revolution, BioIT World April 2003 genomic library: A collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. DOE A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). MeSH, 1990 One of the primary reasons for the success
of the Human Genome Project has been the development and use of high- throughput
strategies for data generation, and the placement of the data immediately in the
public domain. Most of the sequence data, the underlying maps and the sequence
assemblies were generated through the use of large- scale automated processes.
Now, methods such as sequence analysis of whole genomes, DNA microarray
technology and mass spectrometry have been or are being developed as high-
throughput approaches for additional types of genomic analyses, such as
determining the parameters of gene expression or the location of gene products
by the thousands at a time instead of individually. High- throughput methods to
determine the location of cis- regulatory elements and, to a lesser extent,
other sequence elements, are also beginning to be developed. However, at
present, there is no single approach or compilation of approaches that can
accurately and efficiently identify every sequence feature in genomic DNA.
DETERMINATION OF ALL FUNCTIONAL ELEMENTS IN HUMAN DNA RELEASE DATE, NHGRI,
February 21, 2003 RFA: HG-03-003 http://grants1.nih.gov/grants/guide/rfa-files/RFA-HG-03-003.html
See also chromatography
& electrophoresis, Gene
Amplification & PCR, Microarrays,
Sequencing insertional mutagenesis: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene. This process may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. MeSH, 1991 Enables researchers to both identify and sequence a gene, as well as get functional information about it. Is this related to gene trapping? Does not require knowing gene's identity or function. Related terms: embryonic lethal, knockdown knockdown: Altering the function of a gene so that it can be conditionally expressed. This is necessary when complete knockout of the gene would be lethal to the organism. Related terms: embryonic lethal trait, knockin, knockout; Pharmaceutical biology antisense; RNAI RNA Interference knockin: Gain of function through addition/ substitution of genetic material. One example of a knockin is deletion of a coding sequence of a gene in a mouse and then replacing it with human coding sequences. Related terms: knockdown, knockout knockout: Inactivation of specific genes. Knockouts are often created in laboratory organisms such as yeast or mice so that scientists can study the knockout organism as a model for a particular disease. NHGRI Narrower term: conditional knockout, random homozygous knockout Related terms gene knockout, knockdown, knockin, protein knockouts knockout mice: Model & other organisms Knockout-mouse technology is considered an essential and standard technique in functional genomics and target validation. knockout mouse phenotyping: Recognizing the value and utility of a readily accessible, genome-wide collection of knockouts as the lynchpin to determine how mammalian genes function, several international programs were launched in 2006 to build such a resource. Partners in this effort include the NIH funded Knockout Mouse Program (KOMP), the European Conditional Mouse Mutagenesis Program (EuCOMM) funded by the European Commission, and the North American Conditional Mouse Mutagenesis Project (NorCOMM) funded by Genome Canada. Collectively, these programs have created almost 8,000 prototype knockout mice, and they are on track to complete the resource by the end of 2011. This collection is complemented by the Texas A&M Institute for Genomic Medicine’s collection of mouse gene traps — mouse knockouts created using high-throughput approaches to introduce mutations across the mouse genome — resulting in a total of some 14,000 knockouts being available to the scientific community. The new Common Fund KOMP2 program will build upon this resource by expanding the efforts to characterize the mutant strains. Knockout Mouse Phenotyping, NIH Common Fund http://commonfund.nih.gov/KOMP2/overview.aspx molecular evolution: The aims and scope statement of the Journal of Molecular Evolution states that topics addressed cover "experimental and theoretical work aimed at deciphering features of molecular evolution and the processes bearing on these features, from the initial formation of macromolecular systems onward, includ[ing] the evolution of informational macromolecules and their relation to more complex levels of biological organization, up to populations and taxa. This coverage accommodates well such subfields as comparative structural and functional genomics, population genetics, the molecular evolution of development, the evolution of gene regulation and gene interaction networks, and in vitro evolution of DNA and RNA. Aims and Scope, Journal of Molecular Evolution, Springer http://link.springer.com/journal/239 the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes. Wikipedia accessed 2018 Nov 10 http://en.wikipedia.org/wiki/Molecular_evolution Narrower terms: molecular evolution directed, Proteomics directed protein evolution Related term: gene shuffling molecular evolution directed: Techniques used to produce molecules exhibiting properties that conform to the demands of the experimenter. MeSH, 1996 Related terms: directed protein evolution, molecular evolution morpholinos: http://www.macalester.edu/~montgomery/Morpholinos.html Broader term: antisense oligonucleotides mutagenesis: The introduction of permanent heritable changes (i.e., mutations) into the DNA of an organism. IUPAC Bioinorganic Narrower terms: chemical mutagenesis, insertional mutagenesis, saturation mutagenesis, site- directed mutagenesis. Broader terms: gene disruption, gene manipulation Related terms: knockouts, knockins, knockdowns pinpoint gene editing: More than 60,000 genetic aberrations have been linked to human diseases, and nearly 35,000 of them are caused by the tiniest of errors: a change in just one DNA base at a specific point in the genome. This year, researchers announced a major improvement of a nascent technique, called base editing, to correct such point mutations, not just in DNA, but in RNA as well. Science 2017 Breakthrough of the year runner-up http://vis.sciencemag.org/breakthrough2017/finalists/#crispr-offspring See related base editing. Post-Transcriptional Gene Silencing PTGS:
Was initially considered a bizarre phenomenon
limited to petunias and a few other plant species, is now one of the hottest
topics in molecular biology (1).
In the last few years, it has become clear that PTGS occurs in both plants and
animals and has roles in viral defense and transposon silencing mechanisms.
Perhaps most exciting, however, is the emerging use of PTGS and, in particular,
RNA interference (RNAi) — PTGS initiated by the introduction of
double-stranded RNA (dsRNA) — as a tool to knock out expression of specific
genes in a variety of organisms (reviewed in
1-3).
Ambion, RNA Interference and Gene Silencing,
http://web.mit.edu/beh.109/www/Module3/handouts/Handout%20Lect%201%20RNAi%20-%20www.ambion.com-techlib-hottopics-rnai.htm
A new form of the genome-editing tool CRISPR-Cas9 appears to significantly
expand the range of diseases that could be treated with the technology, by
enabling scientists to precisely change any of DNA’s four “letters” into
any other and insert or delete any stretch of DNA — all more efficiently
and precisely than previous versions of CRISPR. Crucially, scientists
reported on Monday, it accomplishes all that without making
genome-scrambling cuts in the double helix, as classic CRISPR and many of
its offshoots do. STAT
2019 Oct
https://www.statnews.com/2019/10/21/new-crispr-tool-has-potential-to-correct-most-disease-causing-dna-glitches/
restriction endonucleases: Stuart Linn and Werner Arber [52] and Matthew Meselson and Robert Yuan [53] found specific restriction endonucleases in bacteria, which act when the latter defend themselves against the attack of bacteriophages; thus these enzymes restrict the host range of the bacteriophages. Harry Smith and K. W. Wilcox [54] were able to purify these enzymes, and Thomas Kelly and Hamilton Smith [55], Kathleen Danna and Daniel Nathans [56] and Philip Sharp et al. [57], determined their mode of action. These enzymes cut DNA molecules each at a specific site. These observations made it possible to isolate genes, to clone them and analyze their biochemical structure in great detail. Following the action of restriction endonucleases, there often arise so- called cohesive ends in the DNA molecules [58], which tend to join together. By this means it is possible for example to join together DNA from any eukaryotic organism and that from the bacterial plasmids. Such recombinant DNA molecules were first constructed by David Jackson et al. [59], Peter Lobban and Armin Kaiser [60] and Stanley Cohen et al. [61]. Cloned DNA molecules can be physically mapped, using the cutting points of the restriction endonucleases as markers, [62] and sequenced by means of sophisticated biochemical methods [63, 64]. Petter Portin in "The Origin, Development and Present Status of the Concept of the Gene: A Short Historical Account of he Discoveries" Current Genomics, 2000 https://pdfs.semanticscholar.org/a61a/4e1a2c28e517d6e4ca9a43fd63bbb65379e4.pdf
reverse genomics: we present a computational "reverse genomics" approach that predicts the phenotypic functions of human CNEs. We identify thousands of human CNEs that were lost in at least two independent mammalian lineages (IL-CNEs), and match their evolutionary profiles against a diverse set of phenotypes recently annotated across multiple mammalian species. We identify 2,759 compelling associations between human CNEs and a diverse set of mammalian phenotypes. We discuss multiple CNEs, including a predicted ear element near BMP7, a pelvic CNE in FBN1, a brain morphology element in UBE4B, and an aquatic adaptation forelimb CNE near EGR2, and provide a full list of our predictions. As more genomes are sequenced and more traits are annotated across species, we expect our method to facilitate the interpretation of noncoding mutations in human disease and expedite the discovery of individual CNEs that play key roles in human evolution and development. "Reverse Genomics" Predicts Function of Human Conserved Noncoding Elements. Marcovitz A1, Jia R2, Bejerano G3. Mol Biol Evol. 2016 May;33(5):1358-69. doi: 10.1093/molbev/msw001. Epub 2016 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/26744417 Related term: reverse genetics
RNAi RNA interference:
A
gene silencing phenomenon whereby specific dsRNAs (
RNA, DOUBLE- STRANDED) trigger the degradation of homologous mRNA (
RNA, MESSENGER). The specific dsRNAs are processed into SMALL
INTERFERING RNA (siRNA) which serves as a guide for cleavage of the
homologous mRNA in the RNA- INDUCED SILENCING COMPLEX (RISC). DNA METHYLATION may
also be triggered during this process. MeSH 2003
See
also RNA Narrower terms: miRNA,
siRNA Broader terms: gene expression regulation, gene silencing
RNA silencing:
Although initially recognized as a handy tool to reduce gene expression, RNA
silencing, triggered by double- stranded RNA molecules, is now recognized as a
mechanism for cellular protection and cleansing: It defends the genome against
molecular parasites such as viruses and transposons, while removing abundant but
aberrant nonfunctional messenger RNAs. The underlying mechanisms in distinct
gene silencing phenomena in different genetic systems, such as cosuppression in
plants and RNAi in animals, are very similar. There are common RNA
intermediates, and similar genes are required in RNA silencing pathways in
protozoa, plants, fungi, and animals, thus indicating an ancient pathway.
Tijsterman M. et. al., The
genetics of RNA silencing, Annual Reviews Genetics; 36: 489- 519, 2002
second- site mutations:
Are not lethal themselves, but in combination
with the primary defect cause lethality. Related term:
synthetic lethal screening
SELEX Systematic Evolution of Ligands by Exponential Enrichment: Process for identifying aptamers by iterative enrichment of oligonucleotide mixtures with respect to their ability to bind a target. IUPAC COMBINATORIAL CHEMISTRY spiegelmer: The chiral inversions or mirror images of aptamers. Related term: photoaptamer; Broader term: aptamers
Genomic technologies resources IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry. |
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