Appendixes



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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Appendixes

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects A Glossary Adventitious bacteria Bacteria that originate from a source other than the organism or environment in which they are found and are not inherent to that organism or environment. Agrobacterium A naturally occurring pathogenic bacterium of plants that can incorporate a portion of a plasmid deoxyribonucleic acid (DNA) into plant cells. Allele One of the variant forms of a gene at a particular locus, or location, on a chromosome. Different alleles produce variation in inherited characteristics, such as blood type. Antinutrient A compound (in food) that inhibits the normal uptake or utilization of nutrients or that is toxic in itself. Apoptosis The process of cell death, which occurs naturally as a part of normal development, maintenance, and renewal of tissue in an organism. Bacillus thuringiensis (Bt) A strain of bacteria that produces a protein toxic to certain insects that cause significant crop damage. The bacteria are often used for biological pest control. The gene that codes for the toxic protein has been engineered into other soil bacteria and also directly into some crop plants.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Bacteriophage (phage) A virus that infects bacteria. Bioinformatics The management and analysis of data (especially DNA sequence data) using advanced computing techniques. Biolistic device A device that bombards target cells with microscopic DNA-coated particles. Familiarly known as the Gene Gun, it was first developed in the early 1980s. Carcinogen A cancer producing agent or substance. A variety of chemical agents have been shown to induce malignancy in animals, but not all of them show the same capability in humans. Carotenoids A group of chemically similar red to yellow pigments responsible for the characteristic color of many plant organs or fruits, such as tomatoes and carrots. Carotenoids serve as light-harvesting molecules in photosynthetic assemblies and also play a role in protecting prokaryotes from the deleterious effects of light. Cell selection The process of selecting cells that exhibit specific traits within a group of genetically different cells. Selected cells are often subcultured onto fresh medium for continued selection. Chitinase gene A gene responsible for the activity of chitinase, an enzyme that breaks down chitin (a polysaccharide that gives structural strength to the exoskeleton of insects and the cell walls of fungi). Clone Defines both molecular, whole-animal, and plant clones; a collection of genetically identical copies of a gene, cell, or organism. Cloning The propagation of genetically exact duplicates of an organism by a means other than sexual reproduction, for example, the vegetative production of new plants or the propagation of DNA molecules by insertion into plasmids. Often, but inaccurately, used to refer to the propagation of animals by nuclear transfer. Cocultivation Growth of cultured cells together. Comparator A product that is compared to another product (e.g., a genetically engineered food and a non-genetically engineered food).

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Competent cells Cells (e.g., bacteria, plant, or yeast) that can take up DNA and become genetically transformed. Control elements DNA sequences in genes that interact with regulatory proteins (such as transcription factors) to determine the rate and timing of expression of the genes, as well as the beginning and end of the transcript. CpG methylation A heritable chemical modification of DNA (replacement of cytosine by 5-methyl cytosine) that, when present in a control region, usually suppresses expression of the corresponding gene. Cross-breeding Mating between members of different populations (lines, breeds, races, or species). Cytoplasmic inheritance Hereditary transmission dependent on cytoplasmic genes (genes located on DNA outside the nucleus). Ectopic gene expression Expression of a (trans) gene in a tissue or developmental stage when such expression is not expected. Electroporation Introduction of DNA into a cell mediated by a brief pulse of electricity. Endogenous Derived from within; from the same cell type or organism. Epithelial cell The tissue that forms the superficial layer of skin and some organs. It also forms the inner lining of blood vessels, ducts, body cavities, and the interior of the respiratory, digestive, urinary, and reproductive systems. Fitness The ability to survive to reproductive age and produce viable offspring. Fitness also describes the frequency distribution of reproductive success for a population of mature adults. Furanocoumarins Toxic compounds found primarily in species of the Apiaceae and Rutaceae plant families. They come in a variety of related chemical structures and have adverse effects on a wide variety of organisms, ranging from bacteria to mammals.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Galactosemia An inherited disorder characterized by an inability of the body to utilize galactose; literally, it means “galactose in the blood.” Gamete A mature reproductive cell capable of fusing with a cell of similar origin but of opposite sex to form a zygote from which a new organism can develop. Gametes normally have a haploid chromosome content. Gas chromatography (GC) An instrumental analytical technique in which the volatile components of a sample are injected into a stream of gas that flows through a long heated capillary column. The sample components separate according to their relative volatility and affinity for the interior surface of the column and are quantified as they exit the column using various types of detectors. Gas chromatography-mass spectrometry (GC-MS) An instrumental analytical technique in which the components of a sample enter a mass spectrometer directly following their separation by gas chromatography. Gene expression The conversion of the gene’s nucleotide sequence into an actual process or structure in the cell. Some genes are expressed only at certain times during an organism’s life and not at others. Gene introgression Introduction of new genes into a population by crossing between two populations, followed by repeated backcrossing to that population while retaining the new genes. Genetically modified Refers to an organism whose genotype has been altered and includes alteration by genetic engineering and nongenetic engineering methods. Genetic engineering Changes in the genetic constitution of cells resulting from the introduction or elimination of specific genes via molecular biology (i.e., recombinant DNA) techniques. Genotype The genetic identity of an individual. Genotype often is evident by outward characteristics. Germline cells Cells that contain inherited material that comes from the eggs and sperm and that might be passed on to offspring. Glycosylated Term used to describe a molecule that has under-done the post-translational addition of carbohydrate groups to it (e.g., glycosylated hemoglobin).

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Haplotype map An effort to find DNA landmarks that identify specific DNA sequences shared by many individuals. Hazard A substance or agent that, upon exposure, might result in a defined harm. Hemosiderosis A focal or general increase in tissue iron stores without associated tissue damage. Herpetiformis A chronic, extremely itchy rash associated with sensitivity of the intestine to gluten in the diet (celiac sprue). Heterozygous The condition in which an organism has inherited two different alleles of a specific gene pair from its parents. Hirudin A potent clotting inhibitor produced by leeches. The gene for this protein has been genetically engineered into canola plants. Homocystinuria An inherited disorder of the metabolism of the amino acid methionine; it is inherited as an autosomal recessive trait. Homologous recombination Rearrangement of DNA sequences on different molecules by crossing over in a region of identical sequence. Homologs In diploid organisms, a pair of matching chromosomes. Homozygous The condition in which an organism has inherited two identical alleles of a specific gene pair from its parents. Horizontal gene transfer Transmission of DNA involving close contact between the donor’s DNA and the recipient, uptake of DNA by the recipient, and stable incorporation of the DNA into the recipient’s genome. Hybrid Progeny of genetically different parents, usually of the same species, that has enhanced productivity over either parent. Generally, the more genetically diverse the parent lines, the more hybrid vigor, or heterosis, is observed in the hybrid progeny. Hybridoma A fast-growing culture of cloned cells made by fusing a cancer cell to some other cell, such as an antibody-producing cell.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Immunoglobulin E (IgE) A component of the human immune system implicated in the expression of allergies. Inbred line A population of plants that are self-pollinated over several generations and are largely genetically homogenous. Such inbreeding results in a population of plants with nearly identical genetic composition, and homozygosity, or genetic uniformity, at every gene locus. Integration The covalent joining of a piece of DNA into genomic DNA. Landrace A primitive cultivar (in contrast to a named modern cultivar). Landraces of a particular crop are a collection of plants that were developed and maintained by traditional farmers. While they are genetically improved over wild versions of the species, they are not as well developed as modern commercial cultivars. Lipofection A method of transfection in which DNA is incorporated into lipid vesicles (liposomes), which then are fused to the membrane of the target cells. Liquid chromatography (LC) An instrumental analytical technique in which the soluble components of a sample are injected into a stream of liquid solvent pumped through a tube (column) packed with small retentive particles. The sample components separate according to their relative affinity for the flowing solvent (mobile phase) and the surface of the solid particles with which the column is packed (stationary phase). The sample components are quantified as they exit the column using various types of detectors. In its contemporary format, analytical liquid chromatography is usually termed high-performance liquid chromatography (HPLC). Liquid chromatography-mass spectrometry (LC-MS) An instrumental analytical technique in which the components of a sample enter a mass spectrometer directly following their separation by gas chromatography. Locus The place on a chromosome which is occupied by a gene.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Locus-control regions Segments of DNA important for the correct and coordinated expression of large regions (such as those encoding hemoglobins). Lysine A basic amino acid that is produced chiefly from many proteins by hydrolysis. It is essential in the nutrition of humans and animals. Mass spectrometry (MS) An instrumental analytical technique in which a chemical compound is detected and identified according to the pattern of masses and abundances of charged particles obtained when that compound is subjected to ionization in an electron beam or other ionizing conditions. Meiosis The special cell division process by which the chromosome number of a reproductive cell becomes reduced to half (n) the diploid (2n) or somatic number. Mesenchymal cells Cells that form the supporting tissue of an organ or blood vessel. Metabolomics Systematic global analysis of nonpeptide small molecules, such as vitamins, sugars, hormones, fatty acids, and other metabolites. It is distinct from traditional analyses that target only individual metabolites or pathways. Methylation Addition of a methyl group (-CH3) to a macromolecule, such as a specific cytosine and, occasionally, adenine residues in DNA. Microinjection Introduction of DNA into a cell by injection through a very fine needle. Microprojectile bombardment Also known as particle acceleration, or biolistic bombardment (using the “Gene Gun”), this technique is used to transform cells using small gold or tungsten particles that are coated with DNA and literally shot into a cell. Microsatellite DNA A small segment of DNA with a repeated sequence. This segment is made up of short nucleotide sequences, which when tagged and amplified using polymerase chain reaction (PCR; see below), can be used as markers for research purposes. Mitochondria Small cytoplasmic organelles that carry out aerobic respiration; oxidative phosphorylation takes place to produce adenosine triphosphate.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Mitotic division A method of indirect division of a cell, consisting of a complex of various processes, by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes characteristic of the somatic cells of the species. Mobilization The transfer of genes from one place to another (in the same or a different cell or organism) mediated by a retrovirus or transposable element. Monoclonal antibody An antibody of a single type produced by a genetically identical group of cells (clone). Usually a fusion of an antibody-producing blood cell and a cancer cell. See hybridoma. Mutagenesis (or mutation breeding) A process whereby the genetic information of an organism is changed in a stable, heritable manner, either in nature or induced experimentally via the use of chemicals or radiation. In agriculture, these genetic changes are used to improve agronomically useful traits. Mycotoxins Toxic substances of fungal origin, such as aflatoxins. Neomycin phosphotransferase, type II A bacterial gene encoding resistance to several common antibiotics (kanamycin, neomycin, G418), widely used as a selectable marker in eukaryotic cells. Northern blot analysis A technique used to analyze ribonucleic acid (RNA). RNA is separated by size, blotted (transferred onto a membrane), and then is detected by a special probe that allows information (e.g., size and abundance) about a particular species of RNA to be revealed. Oligopeptide A molecule consisting of a small number of amino acid units. Oral gavage Feedings given through a tube passed through the mouth and into the stomach. Organoleptic Relating to the senses (taste, color, odor, feel). For example, traditional meat and poultry inspection techniques are considered organoleptic because inspectors perform a variety of such procedures, involving visually examining, feeling, and smelling animal parts to detect signs of disease or contamination.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Paracrine A form of signaling in which the target cell is close to the signal releasing cell. Neurotransmitters and neurohormones usually are considered to fall into this category. Phage See bacteriophage. Pharmacogenetics The study of how people’s genetic makeup affects their response to medicines. Phenotype/Phenotypic The visible and/or measurable characteristics of an organism (i.e., how it appears outwardly) as opposed to its genotype, or genetic characteristics. Phenotype Mapping A process used to identify landmarks on DNA through functional analysis of trait genes. Phenylketonuria A genetic disorder in which the body cannot break down the amino acid phenylalanine. Phytoalexins Plant-produced substances that are toxic or inhibit the growth of microorganisms, especially phytopathogenic fungi (and can be harmful for the host plant itself). Phytoalexins are many chemically distinct chemical compounds (e.g., isoflavonids, furanocoumarins). Plant population In a natural, or unmanaged, environment, a plant population typically is composed of many different species, some of which can be edible and desirable to humans, and others that might not. In the context of an agricultural, or managed, environment, a plant population could be a field of plants—typically of one variety—but invariably consisting of some plants of different varieties and some different species. Plasmid A circular DNA molecule capable of replication in host bacteria. Plasmids are the usual means of propagation of DNA for transfection or other purposes. Plasmids are also occasionally found in certain fungi and plants. Pleiotropy A phenomenon whereby a particular gene affects multiple traits. Polygenic Refers to a trait or phenotype whose expression is the result of the interaction of numerous genes. Polymerase chain reaction (PCR) A method for making multiple copies of fragments of DNA. It uses a heat-stable DNA polymerase enzyme and cycles of heating and cooling to successively split apart the strands of double-stranded DNA and use the single strands as templates for building new double-stranded DNA.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Polymorphism A natural variation in a gene, DNA sequence, or chromosome, which may not have adverse effects on the individual and occurs with fairly high frequency in the general population. Proctocolitis (eosinophilic proctocolitis) An inflammation of the colon and rectum, characterized by elevated levels of eosinophils (a type of white blood cell) in the tissues of these organs. Promoter A regulatory element that specifies the start site of transcription. Protease An enzyme that hydrolyzes proteins, cleaving the peptide bonds that link amino acids in protein molecules. Proteomics The analysis of complete complements of proteins. Proteomics includes not only the identification and quantification of proteins, but also the determination of their localization, modifications, interactions, activities, and, ultimately, their function. Protoplast fusion A technique in which protoplasts (plant cells from which the cell wall has been removed by mechanical or enzymatic means) are fused into a single cell. Provirus The integrated DNA form of a retrovirus. Proximate analysis The analytical determination of the major classes of food components, usually including total protein, fat, and carbohydrate, dietary fiber, water, and ash (minerals). Psoralens Mutagenic, carcinogenic agents that can act as phytoalexins. Psoralens are found in a variety of fruits and vegetables, such as celery and carrots, and they are known to make human skin sensitive to long-wave ultraviolet radiation. Radioallergosorbent (test) Allergen testing using blood samples to identify an allergen capable of causing an allergic response. Recombinant Refers to a genotype with a new combination of genes, in contrast to parental type. Recombinant DNA techniques Procedures used to join together DNA segments. Under appropriate conditions, a recombinant DNA molecule can enter a cell and replicate there.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Restriction endonuclease An enzyme that cuts a DNA molecule at a particular base sequence. Retroviral vectors Vector constructs in which the internal genes of a retrovirus are replaced by the gene of interest, flanked by the viral long terminal repeats and packaging signals. After transfection of helper cells, the vector is packaged into virus particles. Infection of target cells with these particles leads to integration of the gene into cellular DNA as part of a provirus. Retrovirus An enveloped virus that replicates by reverse transcription of its RNA genome into DNA, followed by integration of the DNA into the cell genome to form a provirus. Expression of the provirus (as though it were a cellular gene) leads to the production of progeny virus particles. Reverse transcription Risk The process of copying RNA into DNA. The likelihood of a defined hazard being realized, which is the product of two probabilities: the probability of exposure, P(E), and the probability of the hazard resulting given that exposure has occurred, P(H/E) (i.e., R = P(E) × P(H/E)). Selectable marker A gene, usually encoding resistance to an antibiotic, added to a vector construct to allow easy selection of cells that express the construct from the large majority of cells that do not. Selection Differential survival and reproduction phenotypes. Also, a system for either isolating or identifying specific organisms in a mixed culture; observing the characteristics of plants and choosing (selecting) to use only those organisms that have desired or superior characteristics. Serine phosphorylation The chemical attachment of phosphorus to a molecule of serine, an amino acid that serves as a storage source of glucose by the liver and muscles. Servomechanism An automatic feedback device in which the controlled variable is mechanical position or any of its time derivatives.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Sexual selection The type of selection in which there is competition among males for mates, and characteristics enhancing the reproductive success of the carrier are perpetuated irrespective of their survival value. Silencing Shutdown of transcription of a gene, usually by methylation of C residues. Solanaceous Pertaining to plants of the family Solanaceae which includes tomato, tobacco, potato, pepper, and many weeds. Somaclonal variation Epigenetic or genetic changes, sometimes expressed as a new trait, resulting from in vitro culture of higher plants. Somatic cells Cells of body tissues other than the germline. Southern blot analysis A technique used to obtain information about identity, size, and abundance of a specimen of DNA. DNA fragments are transferred to membrane filters so that specific base sequences can be detected. StarLink A commercial brand of transgenic maize approved for animal feed only, but which also had been found in the human food supply. Stromal cells Nonblood cells derived from blood organs, such as bone marrow or fetal liver, which are capable of supporting growth of blood cells in vitro. Stromal cells that make this matrix within the bone marrow are also derived from mesenchymal stem cells. Substantial equivalence A concept that has been proposed to measure whether a biotechnology-derived food or crop shares similar health and nutritional characteristics with its conventional counterpart. The Food and Agriculture Organization of the United Nations, and the World Health Organization have attempted to develop substantial equivalence as an internationally agreed upon principle. T-DNA DNA encoded on a plasmid of Agrobacterium that integrates into the genome of a plant cell. Telomerase The enzyme, absent from most somatic cells but present in germline cells, that restores telomeres to their normal length.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Telomeres The simple repeated sequences at the ends of chromosomes that protect them from loss of coding sequence during replication. In the absence of telomerase, telomeres become progressively shorter with each cell division, and this shortening is the major cause of senescence of cells in culture. Toxicant Any substance or material that can injure living organisms through physicochemical interactions. Toxin A poisonous substance (of animal, mineral, vegetable, or microbial origin) that can cause damage to any living tissues. Transfection Alteration of the genome of a cell by direct introduction of DNA, a small portion of which becomes covalently associated with the host cell DNA. Transgene A gene construct introduced into an organism by recombinant DNA methods. Transgenic organism An organism into which DNA has been introduced using recombinant DNA methods. Transposase The enzyme responsible for moving a transposon from one place to another. Transposon A DNA element capable of moving (transposing) from one location in a genome to another in the same cell through the action of transposase. Vector A type of DNA, such as a plasmid or phage, that is self-replicating and that can be used to transfer DNA segments among host cells. Also, an insect or other organism that provides a means of dispersal for a disease or parasite. Vertical transmission Inheritance of a gene from parent to offspring. Virion The extracellular form of a virus (i.e., a virus particle). Xanthophylls A yellow oxygen-containing carotenoid, present in chloroplasts.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects SUBREPORT ON ANIMAL CLONING Blastomere Any one of the cells formed from the first few cleavages in animal embryology. The embryo typically divides into two, then four, then eight blastomeres, and so forth. Casein The primary protein in milk. Chimeras Animals (or embryos) composed of cells of different genetic origin. Chromatin The genetic material that makes up chromosomes. Specifically, it is a tangled, fibrous mixture of DNA and protein found within a eukaryotic nucleus. Embryo rescue A sequence of tissue culture techniques used to enable a fertilized immature embryo resulting from an interspecific cross to continue growth and development, until it can be regenerated into an adult plant. Enucleated oocyte (cytoplast) An egg cell from which the nucleus has been removed mechanically. Epigenetics The study of mechanisms that produce phenotypic effects by altering gene activity without altering the nucleotide sequence or genotype of an organism. Hydrops fetalis Also known as fetal hydrops, this condition occurs when there is a presence of fetal subcutaneous tissue edema (the abnormal accumulation of serous fluid), including the escape of serous fluid into one or more body cavities, resulting in a newborn suffering from severe edema. Insulin-like growth factors Also known as IGF-I and IGF-II, they are polypeptides that have an amino acid sequence that shares some similarity with insulin. IGF-I is synthesized in the liver and other tissues. Synthesis of IGF-I is responsive to growth hormone, and IGF-II is known for having multiplication stimulating activity.

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Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects Knock-in Replacement of a gene by a mutant version of the same gene using homologous recombination. Knock-out Inactivation of a gene by homologous recombination following transfection with a suitable DNA construct. Major Histocompatibility Complex (MHC) A large genomic region or family of genes in most vertebrates, which contains several genes with important functions for the immune system. Monozygotic twin Identical twins that are the result of a single zygote (fertilized egg) splitting into two cell masses and becoming two individuals. The twins are genetically identical and are always of the same sex. Nuclear transfer The generation of a new animal nearly identical to another one by injection of the nucleus from a cell of the donor animal into an enucleated oocyte of the recipient. Oocyte The egg mother cell; it undergoes two meiotic divisions (oogenesis) to form the egg cell. The primary oocyte is before completion of the first meiotic division; the secondary oocyte is after completion of the first meiotic division. Parturition The process of giving birth. Pronuclear injection The use of a fine needle to inject DNA into the nucleus of an unfertilized egg. Senescent cells Animal cells that have nearly reached the limit of lifespan (usually around 50 doublings) in cell culture and are beginning to show signs of impending death. Xenotransplantation Transplantation of cells, tissues, or organs from one species to another. Zygote A fertilized oocyte

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