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Related glossaries include Applications Drug discovery & development, Expression;  Informatics Bioinformatics, Molecular modeling Technologies  Gene amplification & PCR, Microarrays, Biology Cell biology,  Gene Definitions, Genetic Variations, Model & other Organisms.  Nomenclature of genes is an increasing challenge, especially cross- species coordination,  as comparing completed genomes becomes increasingly possible.  Additional definitions appear in the In-depth glossary, after the Bibliography.

animal models: Model & other organisms glossary

antisense: Pharmaceutical biology glossary

biochemical genomics: We have recently developed a biochemical genomics approach to identify genes by the activities of their products, together with Stan Fields (Univ. Washington) and E. Grayhack. To this end, we first constructed a library of ca. 6000 strains, each of which expresses a unique yeast ORF as a GST- ORF fusion. To identify genes encoding different activities, the GST- ORFs are purified in pools, activity is assayed, and active pools are deconvoluted to determine the GST- ORF responsible for activity. Using this approach we have linked three previously unknown gene products with specific biochemical activities. We are exploring the potential of this biochemical genomics approach by developing new strategies to expand its versatility and by continuing to identify new genes encoding different activities. [MR Martzen et al  University of Rochester, US  “A biochemical genomics approach for identifying genes by the activity of their products. Science 286:1153-1155 1999]  http://www.urmc.rochester.edu/gebs/faculty/eric_phizicky.htm 

Related terms pathways In-depth deductive genomics; Drug discovery & development glossary  chemical genomics, chemogenomics

biochemical systems theory: Provides a potentially powerful tool for explaining why some genes respond to environmental stimuli by overexpression, underexpression, or no visible change at all; it even allows a semi quantitative assessment of the various strengths of changes in activity profiles  Eberhard Voit "Functional Integration of Genomic and Metabolic Data"  Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC    

biological function: One key problem in this discussion involves the definition of "biological function".  Geneticists, cellular biologists, structural biologists, bioinformaticians, and biophysical chemists use this term to mean different things.  Some speakers used the word "function" to refer to the general biochemical activity of the gene produce (e.g. kinase activity), others referred to the cellular process in which the gene product is involved, while to others "function" meant an understanding of the details of the atomic mechanism of catalysis or recognition.  Still others referred to function in the genetic sense of a generalized phenotype.  This lack of consensus in defining what aspect of function one might learn about from an examination of protein structure prevented the group from reaching a consensus on the role that large scale structural genomics will have in the related area of functional genomics.  [G. T. Montelione and S. Anderson, Report to the National Science Foundation:  Workshop on Structural Genomics - Understanding Proteins Universal to Life" Advanced Photon Light Source, Argonne Natl. Laboratories, Jan. 23 - 25, 1998] http://www-nmr.cabm.rutgers.edu/labdocuments/mtgsummaries/argonne/argonne.html

Related terms biological process, Gene Ontology (GO)

biological process: A biological objective to which the gene or gene product contributes. [Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000] 

A biological process is accomplished via one or more ordered assemblies of molecular functions. Usually there is some temporal aspect to it, although a process event may be essentially instantaneous. It often involves transformation, in the sense that something goes into a process and something different comes out of it. ... 

A biological process is not equivalent to a pathway. We are specifically not capturing or trying to represent any of the dynamics or dependencies that would be required to describe a pathway. [The semantic distinction between a biological process and a molecular function can, at times, be hard to draw, and GO takes a pragmatic, rather than dogmatic, approach: As a general rule a process must have >1 distinct steps.] [Gene Ontology Consortium General Documentation, 2001]  http://www.geneontology.org/GO.doc.html

Related terms biological function, gene function, Gene Ontology ^TM  

bioprocess: See pathways: BioPathways Consortium definition.

chemical genetics, chemical genomics, chemogenomics: Drug discovery & development glossary

comparative genomics: Comparative studies of whole genomes help researchers understand what parts of the genome in one organism are similar to those in another, how the overall structures of genes and genomes have evolved, and what these findings tell us about gene expression, gene regulation, and how to interfere with these events in model organisms or humans. Comparative genomics is also a critical enabling field for functional genomics, because it gives researchers an indication of which model organisms are most useful for which studies. [CHI Bioinformatics]

"We believe that the problem of the genome- phenotype connection, which, in a sense, is the central theme of biology, can be solved only through an experimental program strategically planned on the basis of comparative- genomic results. Much of the biological research of the next few decades is likely to develop along these lines. [E. Koonin et al "The Impact of Comparative Genomics on our Understanding of Evolution" Cell 101:573-576 June 9, 2000] 

Insights can be biochemical, genetic, metabolic and or physiological. The practice of uncovering the functions of human genes and other DNA regions by studying their parallels in nonhumans. 

Related terms biological process,  comparative proteomics, evolutionary genomics, molecular function; Gene definitions Gene Ontology Consortium Cell biology glossary cellular components; Maps genomic & genetic comparative genome mapping

comparative proteomics: Proteomics glossary

complex genomes: Genomics glossary

deductive genomics: Unlike conventional gene- to- function approaches, starts with medically important phenotypes that then lead to the target genes and the biochemical pathways responsible for the observed phenotypes. The advantage in reversing the flow of functional genomics lies in research productivity and cost savings that are increased by at least one order of magnitude when compared to conventional mammalian genomics approaches. [Ingenium Pharmaceuticals AG media release, Nov. 11, 2000] http://www.huginonline.ch/IND/SERV/PM/790304_5.html

discovery driven research: Research glossary

evolutionary genomics: Looking at how genes have been preserved through evolution, or how genes or their functions have diverged. [CHI Bioinformatics]

The field of  plant molecular systematics and phylogeny - using genes to inform taxonomic relationships and evolutionary history ... [aimed at improving our] understanding of how eukaryotic genomes evolve and interact. [BA Palevitz, "Evolutionary Genomics: A conversation with pioneer Jeffrey Palmer" The Scientist 14(16): 12, August 21, 2000] Related term  http://www.the-scientist.com/yr2000/aug/palevitz_p12_000821.htm

Related terms homology, phylogenomics

evolutionary homology: The methods currently available [1994] for interpreting DNA and protein sequences largely utilize evolutionary homology. The consensus sequence method looks for highly conserved amino acids or bases in specific locations. The weight matrix or profile methods perform the same task quantitatively. Sequence alignments even attempt to recapitulate evolution by specifically postulating substitution, insertion and deletion events that occurred during the evolutionary process. Using these evolutionary based methods, much hypothetical information can be gained from the study of a single gene and protein molecule.  However, these evolutionary methods do not give much insight into the flow of genetic information from genes to structure and to phenotype. [Douglas L. Brutlag "Understanding the human genome" in Leder, P., Clayton, D. A. and Rubenstein, E. (Ed.), Scientific American: Introduction to Molecular Medicine (pp. 153-168). New York NY: Scientific American Inc. 1994. http://cmgm.stanford.edu/~brutlag/Abstracts/brutlag94.html  

Broader term homology; Related term evolutionary genomics . 

exon shuffling: The exon shuffling theory, which contends that introns act as spacers where breaks for genetic recombination occur. Under this scenario, exons---which usually contain instructions for building a protein subunit---remain intact when shuffled during recombination. In this way, proteins with new functional repertoires can evolve…. [Peter Schmidt, "Shuffling, Recombination, and the Importance of ...Nonsense"  Swarthmore College]  www.swarthmore.edu/Humanities/pschmid1/array/Gnarl3/exon.html

Related terms domain shuffling, gene shuffling

exon trapping (exon amplification): A rapid and efficient means of finding expressed DNA sequences in a genome sequence and is based on selection for functional splice sites in genomic DNA. The advantages of exon trapping are that it does not require any prior knowledge about tissue- specific gene expression and can easily be performed on complex genomes. It can identify constitutive exons as well as alternative exons but cannot be used to identify intronless genes. [Clinical Molecular Genetics Society UK "Exon trapping" 2000] http://www.ich.ucl.ac.uk/cmgs/exontrap.htm

forward genetics: Involves studying genes one at a time. Only a small minority of genes are uniquely associated with an easily definable phenotype - -a characteristic that is critical for determining gene function by forward genetics. [CHI Functional Genomics] 

Related term positional cloning. Compare reverse genetics. 

function: The vagueness of the term 'function' when applied to genes or proteins emerged as a particular problem, as this term is colloquially used to describe biochemical activities, biological goals and cellular structure. [Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000] Narrower terms  biological function, gene function; Proteomics glossary protein function. Related terms Gene Ontology ^TM; Omes & omics glossary functome, transcriptome

functional genomics: Functional genomics aims to discover the biological function of particular genes and to uncover how sets of genes and their products work together in health and disease. In its broadest definition, functional genomics encompasses many traditional molecular genetic and other biological approaches.  [CHI Functional Genomics]  Gene Functional Analysis Feb. 28 - Mar. 1,  2002 Santa Clara CA

The development and application of global (genome- wide or system- wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics [in the original more limited sense of construction of high- resolution genetic, physical and transcript maps of an organism]. It is characterized by high throughput or large- scale experimental methodologies combined with statistical and computational analysis of the results. The fundamental strategy is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion. [Phil Hieter and Mark Boguski "Functional Genomics: It's All How You Read It" Science 278: 601-602, October 24, 1997]

Related terms: biological process, comparative genomics, genome function, homology, molecular function, networks, pathways, phylogenomics, physiological genomics

functional genomics data: A useful way to tackle noise and complexity of functional genomics information is to average the data from many different genes into broad 'omic categories (Jansen & Gerstein 2000. For instance, instead of looking at how the level of expression of an individual gene changes over a time- course, we can average all the genes in a functional category (e.g. glycolysis) together. This gives a more robust answer about the degree to which a functional system changes over the time- course. [Dov Greenbaum, Mark Gerstein et. al. "Interrelating Different Types of  Genomic Data" Dept. of Biochemistry and Molecular Biology, Yale Univ. 2001] http://bioinfo.mbb.yale.edu/e-print/omes-genomeres/text.pdf.

functional genomics technologies: Include gene disruption, gene manipulation, knockdowns, knockins, knockouts, mutagenesis, phage display, positional cloning, Post Translational Gene Silencing PTGS, RNA interference RNAi. 

Conditional or tissue- specific gene expression in animal models is a major area of interest. Other increasingly popular methods of downregulating gene expression, in order to study function, include antisense, ribozyme, and zinc finger protein (ZFP) approaches. In addition, a limited number of companies have developed chemical- genetics methods. [CHI Target Validation] Related terms chemical genetics, chemical genomics

functional glycomics: As doctors and drug companies struggle to interpret and exploit the recent explosion of data on genes and proteins, yet another field of biology is waiting to break out: glycomics. This emerging discipline seeks to do for sugars and carbohydrates what genomics and proteomics have done for genes and proteins - move them into the mainstream of biomedical research and drug discovery. ... For years, carbohydrates were one of the least glamorous subjects in biochemistry research. ... However, a very different portrait of sugars is gradually emerging. Biologists are finding that minor differences in sugar structures can have a huge impact on biological functions; in fact, sugars are involved in everything from embryonic development to regulation of  the immune system. [Erika Jonietz "Upstream: Glycomics" Technology Review Oct. 2001]http://www.techreview.com/magazine/oct01/upstream.asp

Consortium for Functional Glycomics, UCSD: Project brings together more than 40 researchers from all walks of scientific life - cell biology, chemistry, biophysics, genomics, bioinformatics and genetics.  ["NIGMS awards "Glue Grant" to study cell talk" Univ. California- San Diego, Oct. 9 2001]  http://ucsdnews.ucsd.edu/newsrel/health/gluegrant.htm

functional homology: Sequence homology does not necessarily indicate functional homology because, as is the case with sickle cell anemia, a single amino acid change can drastically alter the structure and therefore the function of a protein. [Glen Charydczak "Using genetic algorithms to predict protein secondary structure" Rutgers Univ.] http://morgan.rutgers.edu/glen/Abstract.html

functional maps: Maps: genomic & genetic glossary

functional metabolics: Related terms metabolic profiling; Expression glossary; Omes & omics glossary metabolome, metabolomics, metabonome, metabonomics

functional proteomics: Proteomics glossary

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. [CHI Functional Genomics] 

Broader term gene manipulation Narrower terms: knockdown, knockin, knockout, PTSG, RNAi

gene function: The genomics revolution has made possible a new era of predictive medicine and has the potential to change how we understand biology and medicine. The information from sequencing the human genome has revealed the lack of understanding about how biological networks function and how genetic regulation is controlled. It has also brought attention to the computing systems used to support this understanding which will need to be brought to bear on this task. Numerous databases have been created to catalog the genes, proteins, and metabolites involved in specific functions; however, a method for creating pathways that shed light on the interactive biology remains a challenge. Various approaches to modeling pathways will be addressed, along with the technical hurdles and accomplishments deployed towards that goal. Gene Functional Analysis Feb. 28 - Mar. 1  2002 Santa Clara CA

A chart from NCBI’s Cluster of Orthologous Groups (COGs) of proteins database lists as functional annotation descriptions: information storage and processing (translation, ribosomal structure and biogenesis, transcription, DNA replication, recombination and repair) Cellular processes (cell division and chromosome partitioning, post- translational modification, protein turnover, chaperones, cell envelope biogenesis, outer membrane, cell motility and secretion, inorganic ion transport and metabolism, signal transduction mechanisms) metabolism (energy production and conversion, carbohydrate transport and metabolism, amino acid transport and metabolism, nucleotide transport and metabolism, coenzyme metabolism, lipid metabolism) and poorly characterized.  [NCBI, COG website]    http://www.ncbi.nlm.nih.gov/COG/  Related terms biological function, function, genome function, molecular function; protein function Proteomics glossary

The lack of a common language for gene functions is … proving to be a serious problem. [E Pennisi "Seeking common language in a Tower of Babel" Science 286 (5439): 449 Oct. 15 1999]

The current view of gene function is focused on the molecular, cellular and organism levels. But it is crucially important to extend this view to include data at the population level, particularly in relation to human disease. ...  . In attempting to relate genotype to phenotype we need to take account of the possibility that different functions may arise in populations evolving in different environments. Population and evolutionary studies can, therefore, give a different view of gene function from studies on individuals considered in isolation. Thus, it is important to attach function not simply to genes but to alleles in a particular population. ... Although a variety of approaches have been used to integrate diverse data relating to gene function there have been few efforts to devise a systematic description of gene function itself. ["Meeting the challenge of building gene function databases" Report on a HUGO/EU Workshop held on 28^th and 29^th May 1999 at Hinxton, Cambridge, UK, Duncan Davidson and Rolf Apweiler]  http://www.hgu.mrc.ac.uk/Research/Reports/Genefunc/report.htm

gene interference: An effect similar to loss-of function mutations in organisms, as if the gene being studied were inactivated. Both sense and antisense RNA are already known to produce interference with the expression of the genes they correspond to by blocking protein synthesis. Antisense RNA is single- stranded RNA that is complementary to a particular mRNA sequence. Sense RNA, also single- stranded, is a shorter version of a particular mRNA strand. Another mechanism for gene interference using RNA has been developed in the past few years. This process, called RNA interference (RNAi) involves double- stranded RNA (dsRNA), and was first developed for use in invertebrates, later vertebrates, and now after much doubt, has been proved to work for mammals, specifically mice. [Dr. Bert Ely, Univ. of South Carolina, US]  http://www.biol.sc.edu/~elygen/caflisch.html  

Related terms gene disruption, knockout

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. [CHI Breaking Bottlenecks] 

Related terms gene manipulation, knockdown, knockin, knockout.

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 In-depth biochemical genomics, exon trapping, gene disruption, gene targeting, gene trapping,

Gene Ontology^TM (GO):  The goal of the Gene Ontology^TM Consortium is to produce a dynamic controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.  http://www.geneontology.org/
Participating Groups  (Page last updated: May 8, 2001 - last scanned May 15, 2001)
Arabidopsis (brassica or mustard family) - The Arabidopsis Information Resource (TAIR) http://www.arabidopsis.org/home.html
Caenorhabditis (nematode) - WormBase  http://www.wormbase.org/  http://wormbase.sanger.ac.uk/
Drosophila (fruitfly) - FlyBase http://flybase.nhri.org.tw/alt-views/mirrors/
Saccharomyces (budding yeast) - Saccharomyces Genome Database (SGD) http://genome-www.stanford.edu/Saccharomyces/  
Mus (mouse) - Mouse Genome Database (MGD) & Gene Expression Database (GXD) http://www.informatics.jax.org/
InterPro/ SWISS- PROT/ TrEMBL at EBI - InterPro
Schizosaccharomyces pombe (fission yeast) - Pombase http://www.sanger.ac.uk/Projects/S_pombe/ 
Compugen - Compugen's Internet Research Engine  http://www.labonweb.com/

Gene Ontology: tool for the unification of biology. The Gene Ontology Consortium (2000) Nature Genet. 25: 25-29 http://www.geneontology.org/GO_nature_genetics_2000.pdf

GO Term definitions, Gene Ontology Consortium ^TM http://www.geneontology.org/GO.defs.txt

Database integration will be an ongoing challenge for the foreseeable future. Related terms biological process, molecular function; cellular component Cell biology glossary.  Biological process, molecular function and cellular component are all attributes of genes, gene products or gene- product groups. [Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000]   The efforts of the Gene Ontology Consortium seems to represent an important (and promising) step in the right direction.

gene shuffling: Techniques to speed up genetic evolution and screening in search of high value  proteins ... the basic underlying premise is the ability to rapidly mutate genes and recombine these genes into novel sequence patterns. These novel recombinant products are then screened to identify candidate proteins that display desired activities. Multiple iterations of this evolutionary mutagenic process can then be used on candidates to create enzymes that exhibit superior characteristics to naturally occurring or previously created versions. ["Gene- shuffling companies do well on Wall Street",  NBIAP's Information Systems for Biotechnology, a joint project of USDA/CSREES and the Virginia Polytechnic Institute and State University, Mar 2000]  http://www.gene.ch/gentech/2000/Mar/msg00014.html  Related terms domain shuffling, exon shuffling, molecular evolution

genome function: Efficient interpretation of the functions of human genes and other DNA sequences requires that resources and strategies be developed to enable large-scale investigations across whole genomes. A technically challenging first priority is to generate complete sets of full- length cDNA clones and sequences for human and model-organism genes. Other functional genomics goals include studies into gene expression and control, creation of mutations that cause loss or alteration of function in nonhuman organisms, and development of experimental and computational methods for protein analyses. [Oak Ridge National Lab, Human Genome Management Information Services, US] http://www.ornl.gov/hgmis/resource/function.html

It is apparent that, despite its immense length, the linear sequence map of the human genome is an incomplete description of our genetic information. This is because information on genome function and gene regulation is also encoded in the way that the DNA sequence is folded up with proteins within chromosomes and within the nucleus. This information cannot be protrayed in the DNA sequence alone.  [Wendy Bickmore "Integrating Chromosome Structure and Function" MRC Human Genetics Unit, UK] http://www.hgu.mrc.ac.uk/Research/Cellgen/Chromstruc/wendy.htm

homolog, homologue, homologous: Used by geneticists in two different senses: (1) one member of a chromosome pair in diploid organisms, and (2) a gene from one species - -for example, the mouse - -that has a common origin and functions the same as a gene from another species -- for example, humans, Drosophila, or yeast. [NHLBI] Related terms lateral genomics, ortholog, orthologous, paralog, paralogous, synologous, xenolog, xenologous; Structural genomics glossary homology modeling

This is different from homologue as defined in the Pharmaceutical biology glossary

homology:  The relationship among sequences due to descent from a common ancestral sequence. An important organizing principle for genomic studies because structural and functional similarities tend to change together along the structure of homology relationships. When applied to nucleotide or protein sequences, means relationship due to descent from a common ancestral sequence. Two DNA molecules (or regions thereof) are homologous if they both "descended" through a series of replication from a single DNA strand … The terms "homology" and "similarity" are often, incorrectly, used interchangeably.

Homology has been used by various people with different meanings, even though similarity was a common denominator among these meanings. The two most important of these meanings related homology to similar structures and/ or to similar functions. By structures I mean both molecular sequences and morphology. Life would have been simple had phylogenetic homology necessarily implied structural homology or either of them necessarily implied functional homology. However, they map onto each other imperfectly and my definition of homology includes all forms of characters. We could reduce confusion by always indicating the kind of homology we are referring to when using the tern. [Walter Fitch "Homology a personal view on some of the problem" Trends in Genetics 16 (5): 227-231 May 2000].

Also termed comparative modeling or knowledge- based modeling, develops a three- dimensional model from a protein sequence based on the structures of homologous proteins.  [David R. Bevan, "Homology Modeling" Molecular Modeling of Proteins and Nucleic Acids, Virginia Tech, US, 2000]  http://www.biochem.vt.edu/courses/modeling/homology.html

Note that homology can be genic, structural, functional or behavioral.  I have collected many definitions and articles on homology, orthology and paralogy. More to come.  Related terms evolutionary homology, similarity; Proteomics glossary  regulatory homology; ; Sequencing sequence homology; Structural genomics glossary homology modeling, structural homology

horizontal gene transfer: See xenology; Omes & omics glossary microbiome

hypomorph: Loss of function.  Related term null mutation

hypothesis-driven research:  Research genomics glossary.

interactions- molecular: Try to link with cellular processes. Related terms: Omes & omics glossary interactome; Proteomics glossary protein- DNA interactions, protein- protein interactions, protein- RNA interactions

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. [CHI Functional genomics] Related terms embryonic lethal trait, knockin, knockout

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. [CHI Functional genomics] 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] 

Knockout-mouse technology is considered an essential and standard technique in functional genomics and target validation. [CHI Target Validation] 

Narrower term In-depth conditional knockout, random homozygous knockout Related terms gene knockout, knockdown, knockin; Proteomics glossary protein knockouts

lambda phage: See under In-depth bacteriophage

lateral genomics: It is possible that a single universal phylogenetic tree is not the best way to depict relationships between all living and extinct species. Instead a web- or not - like pattern, reflecting the importance of horizontal or lateral gene transfer between lineages of organisms, might provide a more appropriate visual metaphor.  [W. Ford Doolittle “Lateral genomics” Trends Millennial Issue (TCB 9(12) TIBS 24 (12) TIG 15 (12): M5-8 December 1999]

library, library - genomic: Cell biology glossary

metabolic flux profiling: High-throughput assessment of metabolic fluxes using NMR relies on cost- effective protocols for ¹³C-labeling and sensitive NMR detection schemes. Fractional ¹³C-labeling of proteinogenic amino acids combined with (i) two- dimensional ¹³C,¹H correlation NMR spectroscopy and (ii) software for rapid data analysis yields efficient metabolic flux ratio and bioreaction network topology analysis. The fractional ¹³C labeling approach has recently been extended to eukaryotic systems, and promises to become a potent complement to proteome and transcriptome analysis for metabolic profiling. Thomas Szyperski "Metabolic Flux Profiling by NMR" Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC    

metabolic phenotypes: Tumor cells assume their unique characteristics according to their diverse genetic aberrations. However, their invasive and proliferative characteristics are limited by the availability of substrates, nutrients, and metabolic pathway enzyme activities. Based on these factors, tumor cells exhibit distinct metabolic phenotypes determining the rate of proliferation, apoptosis, cell cycle arrest, and differentiation. Understanding of adaptive metabolic changes in glycolysis and anabolic reactions in response to tumor growth modulating agents is fundamental to the understanding of tumor patho- physiology. Laszlo Boros "Metabolic Profiling of Cell Growth and Death in Cancer" Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC  

metabolic profiling: The analysis of all cellular metabolites, provides a powerful new tool for gaining insight into functional biology. Snapshots of the level of numerous small molecules with a cell, and how those levels change under different conditions, is very complementary to gene expression and proteomic studies, and is actively being applied to studies of infectious diseases, production and model organisms, as well as human cells and plants. Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC  

Related terms functional metabolics; Expression glossary metabolite expression, metabolite systems biology, molecular profile Broader term profiling

metabolics: Metabolome projects are now generally accepted as parts of all integrated genome wide efforts in bacteria, yeast, Arabidopsis and man. ...  Data from metabolic profiling studies have been shown to be reliable indicators and predictors of a cell or organisms physiological state (e.g. actively growing, diseased, etc.). Current estimates point to over 500 human diseases with direct defects in metabolism. More complex diseases such as cancer, are also known to involve metabolic changes. Capturing this metabolic information by observing the broadest possible class of molecules and relating it to changes in the transcriptome and proteome remain a daunting challenge for the field of metabolomics. Related terms Omes & omics glossary John Hamer "Metabolics: Future Prospects and Challenges" Metabolic Profiling Dec. 3-4, 2001 Chapel Hill, NC  

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. [Journal of Molecular Evolution website] http://link.springer.de/link/service/journals/00239/about.html#aims.  Narrower term  applied molecular evolution.

molecular function: The biochemical activity including specific binding to ligands or structures) of a gene product. This definition also applied to the capability that a gene product (or gene product complex) carries as a potential. It describes only what is done without specifying where or when the event actually occurs.  [Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000] 

[There is a potential for semantic confusion between a gene product and its molecular function, because very often these are described in exactly the same words. For example, "alcohol dehydrogenase" can describe what you can put in an Eppendorf tube (gene product) or it can describe the function of this stuff. There is, however, a formal difference -- a "product" has a (potentially) many- to- many relationship with a "molecular function."  [Gene Ontology Consortium General Documentation, 2001]  http://www.geneontology.org/GO.doc.html  Related terms biological process; Cell biology glossary cellular component 

Related terms biological function: function, gene function, Gene Ontology TM; Gene definitions gene product 

molecular networks:  Molecular networks are composed of pathways. 

molecular systematics: See under evolutionary genomics 

mutagenesis: The introduction of permanent heritable changes (i.e., mutations) into the DNA of an organism. [IUPAC Bioinorganic] Narrower terms In-depth chemical mutagenesis, insertional mutagenesis, saturation mutagenesis, site- directed mutagenesis. Broader terms gene disruption, gene manipulation

network genomics: Genomics glossary

networks: The experimental task of mapping genetic regulatory networks using genetic footprinting and [yeast] two- hybrid techniques is well underway, and the kinetics of these networks is being generated at an astounding rate. Technology derivatives of genome data such as gene expression micro- arrays and in vivo fluorescent tagging of proteins through genetic fusion with the GFP [Green fluorescent] protein can be used as a probe for network interaction and dynamics. If the promise of the genome projects and the structural genomics effort is to be fully realized, then predictive simulation methods must be developed to make sense of this emerging experimental data. First is the problem of modeling the network structure, i.e. the nodes and connectivity defined by sets of reactions among proteins, small molecules and DNA. Second is the functional analysis of a network using simulation models built up from "functional units" describing the kinetics of the interactions. ... 

There are three bottlenecks in the numerical analysis of biochemical reaction networks. The first is the multiple time scales involved. Since the time between biochemical reactions decreases exponentially with the total probability of a reaction per unit time, the number of computational steps to simulate a unit of biological time increases roughly exponentially as reactions are added to the system or rate constants are increased. The second bottleneck derives from the necessity to collect sufficient statistics from many runs of the Monte- Carlo simulation to predict the phenomenon of interest. The third bottleneck is a practical one of model building and testing: hypothesis exploration, sensitivity analyses, and back calculations, will also be computationally intensive. [Lawrence Berkeley Lab "Advanced Computational Structural Genomics" Glossary] http://cbcg.lbl.gov/ssi-csb/Meso.html#anchor597905

Although there is no consensus definition of  "program" or "networks," these terms are most often encountered and understood in the context of the regulatory interactions that link groups of genes and gene products in developmental processes.  Many of these linkages have recently been elucidated in considerable detail for key events in a variety of species. [Sean Carroll "Communications breakdown?" (book review) Science 291: 1264-1265, Feb. 16, 2001]

Narrower terms biochemical networks, molecular networks. Related terms network models;  Molecular modeling glossary

null mutation: Genetic variations glossary In-depth

ortholog (orthologue): That relationship where sequence divergence follows speciation, that is, where the common ancestor of the two genes lines in the cenancestor of the taxa from which the two sequences were obtained … There is a tendency to wish that there could be only one ortholog in an organism. This is frequently not the case. [Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000].

orthologous: Homologous sequences in different species that arose from a common ancestral gene during speciation; may or may not be responsible for a similar function. [NCBI Bioinformatics]  

paralog (paralogue): That condition where sequence divergence follows gene duplication. Such genes might descend and diverge while existing side by side in the same lineage. [Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000].

paralogous: Homologous sequences within a single species that arose by gene duplication. [NCBI Bioinformatics]   Related term duplications Genetic variations glossary In-depth

pathways: A general term meant to include all forms of  molecular transactions and processes that are part of  biochemical systems. Some of these pathways may involve linear processing, but many involve complex branches, convergences, and even cycles. .... There are several different classes of biochemical pathways: metabolic pathways, signal transduction cascades, genetic networks, and drug metabolism pathways. In addition, protein interaction data  links protein data objects, and can therefore also be conceptualized as graphs. Although the relationship of  protein- interaction maps with biochemical pathways is undeniable, it is not obvious. ... the design of  adequate models for bio- process representation, manipulation and simulation is still a very open field of research. In conclusion, we will need to examine and discuss the relationships between all pathway information, protein interaction data, and biological process information in order to successfully produce informatics specifications for any of these kinds of  data.  [Biopathways Consortium "Definition"] http://www.biopathways.org/

The routes or processes by which genes and their products function in cells, tissues, and organisms. Pathways involving a particular gene or its product may be determined by two major types of methods. One involves identifying other proteins that specifically interact with the product of the gene of interest. The other involves carrying out specific genetic studies with model organisms. [CHI Functional Genomics report] 

Networks are composed of pathways. We are just beginning to untangle some basic understanding of pathways, and understanding of their interrelationships is even further in the future. 

Related terms networks; In-depth Biopathways Consortium,. 

peptide aptamers: Engineered protein molecules selected from combinatorial libraries, [used] to dissect the function of specific genes and alleles, and to trace genetic pathways. [Roger Brent "Peptide aptamers" Molecular Sciences Institute, 1999] Broader term: aptamers Pharmaceutical biology glossary

phage display: Use of genetically engineered phage to present peptides as segments of their native surface proteins. Peptide libraries may be produced by populations of phage with different gene sequences. [IUPAC Combinatorial Chemistry]

A fundamental tool in protein engineering. The directed evolution of proteins using display methods can be engineered for specific properties and selectivity. This year's meeting will delve into the new methods involved in protein detection, amplification and directed evolution. This is essential to the proteomics effort aimed at identifying, mapping and understanding all proteins in a comprehensive manner. A variety of display approaches are employed for the engineering of optimized antibodies, as well as protein ligands, for such diverse applications as protein arrays, separations, and drug development. The use of phage display in screening for novel high affinity ligands and their receptors has been crucial in functional genomics and proteomics. Display methods will make it possible to target essential components and pathways within many different diseases, including cancer, AIDS, cardiovascular, and autoimmune disorders.  Phage Display Technologies The Chemistry Set for Proteins April 22-23, 2002 Cambridge MA

An ideal functional genomics tool would provide the ability to monitor changes in the absolute amounts of specific proteins, as well as detect changes in the co- and post- translational modifications of those proteins. Conceptually, this can be accomplished by constructing microarrays of binding proteins specific for each of the intracellular proteins and their modified variants in the proteome, in a fashion analogous to the construction of gene chips. Such binding proteins with a high degree of specificity can be obtained through the use of phage display technology. Using this technology, antibodies can be made rapidly (and entirely in vitro) to any target. Moreover, selection methods allow for the identification of phage antibodies that recognize specific co- and or post- translational modifications of the same protein. There are obvious synergies between the use of microarray chip technology and phage display. ... Targets for phage display may originate from a number of sources, including differential display, microarrays, proteomic analysis by 2D gels - there are many ways in which phage display can interface with the elements of functional genomics. [CHI Summit Proteomics]

A fundamental tool in protein engineering. The directed evolution of proteins using display methods can be engineered for specific properties and selectivity. This year's meeting will delve into the new methods involved in protein detection, amplification and directed evolution. This is essential to the proteomics effort aimed at identifying, mapping and understanding all proteins in a comprehensive manner. A variety of display approaches are employed for the engineering of optimized antibodies, as well as protein ligands, for such diverse applications as protein arrays, separations, and drug development. The use of phage display in screening for novel high affinity ligands and their receptors has been crucial in functional genomics and proteomics. Display methods will make it possible to target essential components and pathways within many different diseases, including cancer, AIDS, cardiovascular, and autoimmune disorders.  Phage Display Technologies: Directed Protein Evolution April 22-24, 2002 • Cambridge, MA    Related terms In-depth bacteriophage, phage;  Assays, labels, signaling & detection glossary biopanning; Proteomics directed protein evolution

phenotypic profiling: The measurement of physical and chemical characteristics of an organism at one or more times during its life cycle.  Different measurements, when taken at specified times, produce a phenotype profile for a variant that we can compare to a phenotype profile for a normal organism to help understand the function of the modified gene. [Paradigm Genetics "Functional Genomics" 2001]  http://www.paragen.com/content/functional/p_profiling.html  Related terms Genomics glossary phenotype, phenotyping

phylogenomics: The study of the evolution of genes and gene families using DNA sequence information from organisms selected at major branch points along the phylogenetic continuum. [W.M. Keck Center for Comparative and Functional Genomics, University of Illinois Champaign Urbana, US] http://www.life.uiuc.edu/biotech/keck.html  

Related terms include cladistics, evolutionary genomics, lateral genomics, In-depth clades, phylogenetic profiles, phylogenetic tree

physiological genomics: The scope note for the journal Physiological Genomics indicates that it covers "a wide variety of studies from human and from informative model systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. The Journal encourages the submission of research that links genes to cell replication, development, metabolic function, cell signal transduction and intracellular signaling pathways, tissue and organ function, and whole organism function. Physiological Genomics encourages the utilization of approaches ranging from expression profiling, assays for molecular interactions, natural and directed gene alteration, selective breeding studies, gene identification, and the assessment of gene/environment interaction. ... new computational approaches, integrative models, and image analysis predictive of gene function." [Physiological Genomics website "journal scope"] http://physiolgenomics.physiology.org/misc/about.shtml

positional cloning: Involves using a genetic map to determine the location of a disease gene. Researchers use such maps to analyze genetic markers in extended families that include individuals affected by a heritable disease, and to pinpoint regions of the genome that are associated with the disease. They then use that information to isolate the DNA from the region, and to identify and sequence the disease gene and identify mutations. [CHI Breaking Bottlenecks]

A process which, through gene mapping techniques, is able to locate a gene responsible for a disease when little or no information is known about the biochemical basis of the disease. [NHGRI]

In the new genomic era, positional cloning is a key tool of  forward genetics. Like other forward genetics strategies, positional cloning starts with a phenotype, for example a Mendelianly inherited human disease trait. However, positional cloning requires a genetic map with a large number of markers (especially in the region of interest), and the use of physical mapping and DNA sequencing technologies to isolate and sequence the targeted gene. A disease gene is usually identified from among candidate genes in the region of interest by showing that affected individuals carry mutations within that gene. [CHI Functional Genomics]

Positional cloning was incorrectly called "reverse genetics" early on. Reverse genetics in its purest definition refers to the analysis of gene function by assaying proteins expressed from gene variants. "[Positional cloning] is not "reverse" at all, but rather genetics in its purest form, unadulterated by any influences of biochemistry, cell biology or physiology." ( Francis S Collins "Positional cloning: Let’s not call it reverse anymore" Nature Genetics. 1: 3-6, 1992) [David Chi, Washington Univ. Apr 2000] http://artsci.wustl.edu/~jstader/chi.html

Related terms functional cloning, positional candidate approach;  Genetic variations glossary candidate gene approach; Maps- genomic & genetic

Post-Transcriptional Gene Silencing PTGS: Silencing of an endogenous gene caused by the introduction of a homologous ds [double stranded] RNA, transgene or virus. In PTGS, the transcript of the silenced gene is synthesized but does not accumulate because it is rapidly degraded. This is a more general term than RNAi, since it can be triggered by several different methods.

Occurs in both plants and animals and has roles in viral defense and transposon silencing mechanisms. ... Although transgene- induced silencing in some plants appears to involve gene-specific methylation (transcriptional gene silencing, or TGS), in others silencing occurs at the post- transcriptional level [Ambion website " RNA Interference and Gene Silencing — An Update" June 2001]  http://www.ambion.com/hottopics/RNAi/rnai_jun2001.html  

Narrower term RNAi; Broader term Gene definitions gene silencing

program: See under pathways.

RNAi RNA interference: Can be used to suppress gene expression in a specific manner; in particular, this approach involves the injection of double- stranded RNA into organisms, thereby specifically inactivating genes containing homologous sequences. RNAi has arisen from the observation that sense and antisense RNA are equally effective in suppressing specific gene expression. This observation presented a paradox that was resolved by finding that small amounts of double- stranded RNA contaminating sense and antisense preparations suppress expression. RNAi has been observed in several model animals, including Drosophila and C. elegans. [CHI Breaking Bottlenecks]

Broader term Post-transcriptional gene silencing PTGS

regulatory homology: Proteomics glossary

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. [CHI Functional Genomics] 

Related term  positional cloning. 

second- site mutations: Are not lethal themselves, but in combination with the primary defect cause lethality. [CHI Target Validation] Related term synthetic lethal screening

sequence homology: Sequencing glossary

signal transduction: Any process that helps to produce biological responses to events in the environment or internal milieu (e.g., transduction of light into nerve impulses by the retina or transduction of hormone binding into cellular events by hormone receptors). [MeSH] 

The intercellular or intracellular transfer of activation or inhibition signals through a so- called signaling pathway. These signals can be initiated, for example, when a biologically active molecule binds to a receptor. Signal transduction is involved in many cellular processes, including cell proliferation and differentiation. [CHI Structural genomics] Related term physiological genomics

Signal Transduction Knowledge Environment, Science and Stanford Univ. http://stke.sciencemag.org/.  Updated weekly.

similarity: The extent to which nucleotide or protein sequences are related. The extent of similarity between two sequences can be based on percent sequence identity and/ or conservation. In BLAST similarity refers to a positive matrix score. [NCBI Bioinformatics] Related term homology.

siRNA: Small interfering RNA. Related terms RNAi, Post-Transcriptional Gene Silencing PTGS

structural homology: Structural genomics glossary

synology: See under xenology.

synthetic lethal screening: Second- site mutations that are not lethal themselves, but in combination with the primary defect cause lethality. Used in yeast genetics, but can be generalized to model organisms other than yeast. The rationale is that many mutations commonly found in tumors that result in instability of the genome are loss- of- function mutations, and it is difficult to replace the function of missing or altered proteins with a small- molecule drug. The idea of screening for second- site mutations is to identify targets that when inhibited by a specific novel drug may specifically result in the death of cells that have such a loss- of- function mutation, but that will be nontoxic to normal cells. [CHI Target Validation] 

Related terms embryonic lethal, knockdown

targeted mutation: A type of mutation in which a chromosomal gene is altered by the substitution of a DNA construct assembled in vitro. In mouse, the constructs are usually designed to eliminate gene function; such targeted mutations are often casually referred to as knock-outs. Some DNA constructs are designed to alter gene function; such targeted mutations are often casually referred to as knock-ins [Mouse Genome Informatics Glossary, Jackson Laboratories, US] http://www.informatics.jax.org/userdocs/glossary.shtml#synonym

transcriptome, transcriptomics: Omes & omics glossary

transgenic: See Model & other organisms glossary

translatome:Omes & omics glossary 

xenology (xenologous): That conditional (horizontal transfer) where the history of the gene involves an interspecies transfer of genetic material. It does not include transfer between organelles and the nucleus.  It is the only form of homology in which the history has an episode where the descent is not from parent to offspring but, rather, from one organism to another … Gogarten has proposed a special term, synology, for those xenologs that arise, not by the transfer of a gene between two species, but by a hybridization of two species.  [Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000].

Bibliography

[CHI Functional Genomics]  Functional Genomics Part 1: High-Throughput and System-Wide Approaches, Cambridge Healthtech Institute, Allan Haberman and Malorye Branca, May 2000  

GO Term definitions, Gene Ontology Consortium ^TM http://www.geneontology.org/GO.defs.txt

[Molecular systematics] and evolution, The Natural History Museum, London and Instituto Oswaldo Cruz, FIOCRUZ Rio de Janeiro, Brazil, 100 + terms. http://www.bioinf.org/molsys/glossary.html or  http://www.dbbm.fiocruz.br/james/glossary.html

[PhyloCode] Glossary, Ohio Univ.  2000. 40+ definitions http://www.ohiou.edu/phylocode/glossary.html

Science Magazine "Functional Genomics" website http://www.sciencemag.org/feature/plus/sfg/

Alpha glossary index

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

In-depth Functional genomics glossary

Alliance for Cellular Signaling AfCS: The overall goal of the Alliance for Cellular Signaling is to understand as completely as possible the relationships between sets of inputs and outputs in signaling cells that vary both temporally and spatially. The same goal, stated from a slightly different perspective, is to understand fully how cells interpret signals in a context- dependent manner. This will involve identification of all the proteins that comprise the various signaling systems, the assessment of time- dependent information flow through the systems in both normal and pathological states, and finally the reduction of the mass of detailed data into a set of interacting theoretical models that describe cellular signaling. [Alliance for Cellular Signaling website] http://www.cellularsignaling.org/

applied molecular evolution:  Includes phage display, SELEX and other molecular diversity techniques. Related terms combinatorial chemistry, molecular evolution.

bacteriophage: Many phage have proved useful in the study of molecular biology and as vectors for the transfer of genetic information between cells … lambda bacteriophage can also undergo a lytic cycle or can enter a lysogenic cycle, in which the page DNA is incorporated into that of the host, awaiting a signal that initiates events leading to replication of the virus and lysis of the host cell. [Glick]  

The workhorse of phage display is the M13 bacteriophage virus. [CHI Summit Proteomics]  Related terms phage, phage display.

biopanning: An in vitro selection process. In its simplest form, biopanning is carried out by incubating a library of phage- displayed peptides with a plate (or bead) coated with the target, washing away the unbound phage, and eluting the specifically- bound phage. (Alternatively the phage can be reacted with the target in solution, followed by affinity capture of the phage- target complexes onto a plate or bead that specifically binds the target.) The eluted phage is then amplified and taken through additional cycles of biopanning and amplification to successively enrich the pool of phage in favor of the tightest binding sequences. After 3- 4 rounds, individual clones are characterized by DNA sequencing and ELISA.  [TWC Biosearch International, Hong Kong, China]  http://www.asiaonline.net.hk/~twcbio/neb/phd.html Also referred to as panning. Related term phage display 

Biopathways Consortium: Researchers are poised to begin the next phase of  elucidating how living systems function. This involves the identification of  genes and their functions, followed by their organization according to their roles and interactions within  the more global context of cellular  mechanisms. Constructing representations of the latter will involve not only structural information, but more dynamic and causal forms relevant to  biochemical processes ... there is an urgent need to discuss and develop new informatics technologies  that will support such new forms of biological information. Data regarding  pathways and interactions is already being accumulated in dozens of different formats, but no standard way of representing or exchanging them exists to date. [Biopathways Consortium "Vision"]  http://www.biopathways.org/

candidate gene approach: Genetic variations glossary

cenancestor: The most recent common ancestor of the taxa under consideration.   [Walter Fitch “Homology a personal view on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000]. Related terms homology, phylogenomics

chemical mutagenesis:

clade: One of the two kinds of biological entities whose names are governed by this code; a group of species comprising a common ancestor and all of its descendants. [PhyloCode Glossary, Ohio Univ. US, 2000] http://www.ohiou.edu/phylocode/glossary.html  Compare species.

cladistics: (1) The Journal of the Willi Hennig Society. (2) The scientific discipline of classifying organisms according to the doctrine of Willi Hennig's 1966 book. (3) The belief that the organisation of taxa into groups can only be done by the identification of synapomorphies for that group.  [Molecular Systematics] 

conditional knockout: A method by which a gene can be switched off and on. [CHI Functional Genomics]

Cre-lox: Tissue- specific gene deletion. [CHI Functional Genomics]  

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.) [CHI Target Validation]

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. [CHI Functional Genomics] Related terms knockdown, synthetic lethal screening

functional cloning: Functional cloning presumes a disease is linked to some known biochemical function, usually involving a key protein or enzyme. The putative protein is followed by biochemical  fractionation and assayed for disease related function. N-terminal sequencing is performed and the responsible gene eventually cloned. Up to this point, this process is known as functional cloning. Subsequently, one can determine the location of this cloned gene by chromosome mapping (i.e. FISH) and other more refined sequencing techniques. [David Chi, "Positional cloning strategy" Washington Univ. St. Louis, April 2000] http://artsci.wustl.edu/~jstader/chi.html  Related term positional cloning

gene targeting: Genetic technique creating a recombinational event that produces exchange between DNA introduced into a cell and its homologous chromosomal target; involves two steps; pairing of DNA strands at the region of homology, and DNA strand exchanges. [MeSH/Metathesaurus]

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. November 1999;9(11):1019-1025.]

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] 

Enables researchers to both identify and sequence a gene, as well as get functional information about it. Is this related to gene trapping?

monophyletic: A group consisting of an ancestor and all of its descendants; usually used for groups the members of which are more closely related to each other than to any non- members in terms of common ancestry. [PhyloCode] http://www.ohiou.edu/phylocode/glossary.html  Related terms clade, species.

panning: See under biopanning

phage: A virus for which the natural host is a bacterial cell. [DOE]

Used as a vector for cloning segments of DNA. [Schlindwein] Related terms bacteriophage, phage display.

phylogenetic: Of or pertaining to the history of ancestry and descent. [PhyloCode Glossary, Ohio Univ. US, 2000] http://www.ohiou.edu/phylocode/glossary.html

phylogenetic definition: A statement explicitly linking a taxon name with a particular clade. [PhyloCode Glossary, Ohio Univ. US, 2000] http://www.ohiou.edu/phylocode/glossary.html

phylogenetic profiles: Proteins having the same pattern of presence or absence in surveyed genomes ... if there are n fully sequenced genes, there are up to 2ⁿ  phylogenetic profiles. Currently there are about 30 fully sequenced genomes in the public domain, meaning there are 2³⁰ (~10 ⁹ ) possible phylogenetic profiles. This number far exceeds the number of protein families, so that a protein’s phylogenetic profile is a nearly unique characterization of its pattern of distribution among genomes. Hence any two proteins having identical or similar phylogenetic profiles are likely to be engaged in a common pathway or complex. [David Eisenberg et al "Protein function in the post-genomic era" Nature 405: 823-826, 15 June 2000] 

Looks at the correlation of protein inheritance across different species. Each protein is given a phylogenetic profile denoting the presence or absence of that protein in various genomes. The result is that function can be assigned to uncharacterized proteins if they have a phylogenetic profile similar to the model profile. [S Spengler “Bioinformatics in the Information Age” Science 287 (5456: 1221-1223, 18 Feb. 2000, citing M. Pellegrini et al. “Assigning protein functions by comparative genome analysis: protein phylogenetic profiles” PNAS 1999 Apr 13, 96(8):4285-8.] 

Related terms phylogenetics, phylogenetic tree,  phylogenomics. 

phylogenetic tools: Phylogenetic methods have revolutionized modern systematics and become indispensable tools in evolution, ecology and comparative biology, playing an increasingly important role in analyses of biological data at levels of organization ranging from molecules to ecosystems. The construction of phylogenetic trees is becoming a methodology that is well- defined, with broad agreement on the central issues and questions. ... applications of phylogenetic methods to interesting problems outside of systematics is an area of special excitement, innovation, and controversy, and perspectives vary widely. [Workshop in Applied Phylogenetics" Bodega Marine Lab, April 22 -27, 2001] http://listproc.ucdavis.edu/archives/pbgg-stud/log0101/0054.html

phylogenetic tree: A diagram showing evolutionary lineages of organisms. [Edinburgh]

A graphical depiction of homology.

positional candidates: Putative disease related genes found by positional cloning …. not to be confused with the candidate gene strategy. [David Chi, "Positional cloning strategy" Washington Univ. St. Louis, April 2000] http://artsci.wustl.edu/~jstader/chi.html

The positional candidate approach relies on a three- step process that saves time and effort: (1) localizing a disease gene to a chromosomal subregion, generally by using traditional linkage analysis; (2) searching databases for an attractive candidate gene within that subregion; and (3) testing the candidate gene for disease- causing mutations. ... Since 1990, scientists have used this approach to find genes implicated in such conditions as Marfan syndrome, inherited nonpolyposis colon cancer, retinitis pigmentosa, long QT syndrome, Jackson-Weiss syndrome, Crouzon syndrome, Alzheimer's disease, and several others. ["Positional Cloning Approach Expedites Gene Hunts" Human Genome News, Mar.-Apr. 1995; 6(6): 1]  http://www.ornl.gov/hgmis/publicat/hgn/v6n6/1kuska.html

Related terms functional cloning, positional cloning.

random homozygous knockout: A genetic approach to identify genes whose inactivation leads to loss of a particular cell function, this provides a practical way to identify and map genes throughout the genome based on their biological actions and roles in human diseases. The single step of gene discovery and function validation allows rapid identification of genes and their genetic pathways relevant to human diseases and determination of their potentials as therapeutic targets. [Dr. Limin Li "Random homozygous knockout" CHI's Functional Genomics Oct. 9-10, 2001, Cambridge MA] http://www.functionalgenomics2001.com/fgen.htm

Does not require knowing gene's identity or function.

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

site-directed mutagenesis: The substitution or modification of a single amino acid at a defined location in a protein is performed by changing one or more base pairs in the DNA using recombinant DNA technology. [IUPAC Bioinorganic]

Mutagenesis where the mutation is caused by in vitro induction directed at a specific site in a DNA molecule. The most common method involves use of a chemically synthesized oligonucleotide mutant which can hybridize with the DNA target molecule. The resulting mismatch - carrying DNA duplex may then be transfected into a bacterial cell line and the mutant strands recovered. [MeSH]

species: One of the two kinds of biological entities whose names will eventually be governed by this code; a segment of a population- level lineage that is separate from other such lineage segments as indicated by one or more of various possible criteria (e.g., distinguishability, reproductive isolation, monophyly, etc.).  [PhyloCode Glossary, Ohio Univ. US, 2000] http://www.ohiou.edu/phylocode/glossary.html  Compare clade.

transposon: Gene definitions