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Genomic Technologies glossary & taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions? 
Mary Chitty MSLS
Last revised November 06, 2019

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 
Dolly at 20: the inside story Nature

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
Related terms: enucleated, directed evolution, molecular evolution, nuclear transfer, quiescence

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  See also CRISPR

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 vitroin 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 With rapid advancements in gene editing tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and single-cell analysis, genomics can prove to be a game-changer in driving decisions in drug discovery. Gene expression profiling, sequencing and editing can be used for identifying disease-associated genes and pathways, for functional screening and target identification, studying complex cell populations and for translating data for clinical applications

“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

Wikipedia   Related terms: Clustered Regularly Interspaced Short Palindromic Repeats:, CRISPR/Cas9, gene editing, genome editing, prime editing

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

CRISPR-Cas Systems: Adaptive antiviral defense mechanisms, in archaea and bacteria, based on DNA repeat arrays called CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS (CRISPR elements) that function in conjunction with CRISPR-ASSOCIATED PROTEINS (Cas proteins). Several types have been distinguished, including Type I, Type II, and Type III, based on signature motifs of CRISPR-ASSOCIATED PROTEINS. MeSH Year introduced: 2014 This comes under Gene Silencing, which comes under Gene Expression Regulation

DNA nanotechnology:  Ned Seeman, DNA Nanotechnology, New York Univ., US 

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 

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): 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  

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 cloningCompare 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,   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 vitroin vivo and ex vivo screening, for target and cellular pathway identification, and for therapeutic use. 

New Frontiers in Gene Editing and Repair Using CRISPR and Other Gene Editing Techniques to Drive Precision Medicine MARCH 28, 2019 Cambridge MA Gene editing, particularly using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, has very rapidly established its importance as a screening tool in drug discovery, and is now being used for therapeutic purposes as well.

Related terms: CRISPR, gene silencing, genome editing  Narrower term: pinpoint gene editing

gene knockout: Use of particular techniques to "knock out" the function of a gene in a model organism. Studying the effects of the gene knockout can help researchers understand the function of the gene that has been inhibited. Related terms: gene manipulation, knockdown, knockin, knockout

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

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

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    

Genome editing
, or genome editing with engineered nucleases (GEEN) is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of a living organism using engineered nucleases, or "molecular scissors." These nucleases create site-specific double-strand breaks (DSBs) at desired locations in the genome. The induced double-strand breaks are repaired through nonhomologous end-joining (NHEJ) or homologous recombination (HR), resulting in targeted mutations ('edits').  As of 2015 there were four families of engineered nucleases being used: meganucleaseszinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system.[1][2][3][4]  Accessed 2017 Oct 18

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,

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  See also chromatography & electrophoresis,   Gene Amplification & PCR,    Microarrays,   Sequencing 

genomic measurements: NIST will be leading a consortium to develop measurement solutions and standards that will support innovation and products in the genome editing technology space.  We help cancer biomarker discovery research laboratories establish confidence in sequencing measurements through interlaboratory studies funded by the Early Detection Research Network(link is external) (EDRN, National Cancer Institute) and with the erccdashboard(link is external) (link is external)software tool. Accurate genomic analysis is also critical for synthetic biology, where it is essential to understand and predict the regulatory nuances of gene position relative to other sequences. NIST DNA control sequences, known as ERCC control materials, can be used to evaluate gene expression analysis, and the Genome in a Bottle Consortium is providing a similar reference material and bioinformatics analysis for whole genome 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 

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

the process of change in the sequence composition of cellular molecules such as DNARNA, 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  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: 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   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,  
Narrower term RNAi; Broader term:  gene silencing process biology

prime editing: a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit. We performed more than 175 edits in human cells including targeted insertions, deletions, and all 12 types of point mutation without requiring double-strand breaks or donor DNA templates. We applied prime editing in human cells to correct efficiently and with few byproducts the primary genetic causes of sickle cell disease (requiring a transversion in HBB) and Tay-Sachs disease (requiring a deletion in HEXA), to install a protective transversion in PRNP, and to insert various tags and epitopes precisely into target loci. Anzalone, A.V., Randolph, P.B., Davis, J.R. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature (2019) doi:10.1038/s41586-019-1711-4  

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

Related terms: Clustered Regularly Interspaced Short Palindromic Repeats:, CRISPR, CRISPR/Cas9, gene editing, genome editing

recombinant DNA, rDNA: Biologically active DNA which has been formed by the in vitro joining of  segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected. MeSH, 1977 

recombinant DNA technology: A body of techniques for cutting apart and splicing together different pieces of DNA. When segments of foreign DNA are transferred into another cell or organism, the substance for which they code may be produced along with substances coded for by the native genetic material of the cell or organism. Thus, these cells become "factories" for the production of the protein coded for by the inserted DNA.  NIGMS  Related terms: biotechnology, genetic engineering; Cell biology clones, homologous recombination, vectors    

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  

reverse genetics: Going from a gene (or its DNA sequence), often discovered via high- throughput sequencing and bioinformatics technologies, to its biological function. Reverse genetic methods are much more amenable to whole genome, high- throughput analysis and to automation than is forward genetics. Contrast with forward genetics, in which one goes from a heritable phenotype to discovery of a gene and its function. Related term:  positional cloning, reverse genomics  

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.   Related term: reverse genetics

ribosome display:  Wikipedia 

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   
Nature Reviews Focus on RNAi  

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   Related term: RNAi RNA interference  

saturation mutagenesis:
A technique to mutate all bases of a gene. Glick

second- site mutations: Are not lethal themselves, but in combination with the primary defect cause lethality. Related term: synthetic lethal screening shuffling: Narrower terms: DNA shuffling, domain shuffling, exon shuffling, gene shuffling, protein shuffling

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, Electrochemical nucleic acid based biosensors includes aptamers. 
NHGRI (National Human Genome Research Institute), Talking Glossary of Genetic Terms, 250+ definitions. Includes extended audio definitions.
Schlindwein Birgid, Hypermedia Glossary of Genetic Terms, 2006. 670 definitions.

Genomics Conferences

How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

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