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Genomic Technologies glossary & taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions?
Revisions? Mary Chitty MSLS
mchitty@healthtech.com
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
https://benchling.com/pub/liu-base-editor
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
Dolly at 20: the inside story Nature
https://www.nature.com/news/dolly-at-20-the-inside-story-on-the-world-s-most-famous-sheep-1.20187
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 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
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
https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr
Wikipedia
https://en.wikipedia.org/wiki/CRISPR
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
https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting
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 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
http://en.wikipedia.org/wiki/Exon_trapping
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.
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.
http://www.optcongress.com/gene-editing
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
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 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: meganucleases, zinc 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]
https://en.wikipedia.org/wiki/Genome_editing
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,
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
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.
https://www.nist.gov/mml/bbd/core-capabilities/genomic-measurements
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
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
https://www.nature.com/articles/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
https://www.statnews.com/2019/10/21/new-crispr-tool-has-potential-to-correct-most-disease-causing-dna-glitches/
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
https://pdfs.semanticscholar.org/a61a/4e1a2c28e517d6e4ca9a43fd63bbb65379e4.pdf
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.
https://www.ncbi.nlm.nih.gov/pubmed/26744417
Related term:
reverse genetics
ribosome display: Wikipedia http://en.wikipedia.org/wiki/Ribosome_display
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 http://www.nature.com/focus/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 http://www.iupac.org/publications/pac/pdf/2010/pdf/8205x1161.pdf
includes aptamers.
NHGRI (National Human Genome Research Institute), Talking Glossary of Genetic
Terms, 250+ definitions.
Includes extended audio definitions.
https://www.genome.gov/genetics-glossary
Schlindwein Birgid, Hypermedia Glossary of Genetic Terms, 2006. 670 definitions.
http://www.weihenstephan.de/~schlind/index.html
Genomics Conferences http://www.healthtech.com/Conferences/Search.aspx?k=&r=&s=GENS
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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