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Human Genome Editing: Science, Ethics, and Governance (2017)

Chapter: Appendix E: Glossary

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Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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E

Glossary

Adult stem cell—An undifferentiated cell found in a differentiated tissue in an adult organism that can renew itself and can differentiate to yield specialized cell types of the tissue in which it is found (NRC, 2002, p. 259).

Allele—A variant form of a gene at a particular locus on a chromosome. Different alleles produce variations in inherited characteristics (NASEM, 2016a, p. 180).

Aneuploidy—The presence of an abnormal number of chromosomes in a cell.

Assisted reproductive technology (ART)—A fertility treatment or procedure that involves laboratory handling of gametes (eggs and sperm) or embryos. Examples of ART include in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) (NRC, 2002, p. 260).

Autologous transplant—Transplanted tissue derived from the intended recipient of the transplant. Such a transplant helps to avoid complications of immune rejection (IOM, 2005, p. 115).

Blastocyst—A preimplantation embryo in placental mammals (about 5 days after fertilization in humans) of 50-150 cells. The blastocyst consists of a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel or blastocyst cavity), and a cluster of cells in the in-

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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terior (the inner cell mass) (IOM, 2005, p. 115). Cells from the inner cell mass, if grown in culture, can give rise to embryonic stem cell lines.

Cas9 (CRISPR Associated Protein 9)—A specialized enzyme known as a nuclease that has the ability to cut DNA sequences. Cas9 makes up part of the “toolkit” for the CRISPR/Cas9 method of genome editing.

Chimera—An organism composed of cells derived from at least two genetically different individuals (NRC, 2002, p. 261).

Choriocarcinoma—A type of tumor that originates from the trophoblast, the precursor of the placenta, and invades the uterine wall.

Chromatin—The complex of DNA and proteins that forms chromosomes. Some of the proteins are structural, helping to organize and protect the DNA, while others are regulatory, acting to control whether genes are active or not, and to promote DNA replication or repair.

Chromosome—A thread-like structure that contains a single length of DNA, usually carrying many hundreds of genes. This is packaged with proteins to form chromatin. The DNA within the complete cellular set of chromosomes (23 pairs in humans) comprises two copies of the genome, one from each parent. The chromosomes usually reside in the nucleus of a cell, except during cell division when the nuclear membrane breaks down and the chromosomes become condensed and can be visualized as discrete entities.

Cleavage—The process of cell division in the very early embryo before it becomes a blastocyst (NRC, 2002, p. 261). Also used to describe breaking or cutting DNA.

Clinical application—The use of a biomedical reagent, procedure, or device to treat a clinical condition.

Clinical trial—A supervised and monitored experimental test in patients of a newly developed clinical application to ensure minimization of risk and optimization of efficacy. Clinical trials are required before a treatment is approved for general use.

CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)—A naturally occurring mechanism found in bacteria that involves the retention of fragments of foreign DNA, providing the bacteria with some immunity

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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to viruses. The system is sometimes referred to as CRISPR/Cas9 to denote the entire gene-editing platform in which RNA homologous with the targeted gene is combined with Cas9 (CRISPR Associated Protein 9), which is a DNA-cutting enzyme (nuclease) to form the “toolkit” for the CRISPR/Cas9 method of genome editing.

CRISPRa—CRISPR activation, using a guide RNA and nuclease-deficient or nuclease-dead Cas9 (dCas9) linked to one or more activation domains to increase transcription of a target gene.

CRISPRr/CRISPRi—CRISPR repression, or CRISPR interference, using a dCas9 or dCas9-repressor with a guide RNA to decrease transcription of a target gene.

Cultured cell—A cell maintained in a tissue culture allowing expansion of its numbers.

dCas9 (Nuclease-deficient Cas9 or nuclease-dead Cas9)—This can still bind DNA, together with a guide RNA, but not cut it. It is often linked to a transcription factor, chromatin-modifying enzyme, or fluorescent protein to mediate alterations to gene expression or to mark specific sites.

Deontology ethics—A normative theory regarding which choices are morally required, forbidden, or permitted.

Deoxyribonucleic acid (DNA)—A two-stranded molecule, arranged as a double helix, that contains the genetic instructions used in the development, functioning, and reproduction of all known living organisms.

Differentiation—The process whereby an unspecialized early embryonic cell acquires the features of a specialized cell, such as a heart, liver, or muscle cell (IOM, 2005, p. 116).

Diploid—Cells that contain a full set of DNA—half from each parent. In humans, diploid cells contain 46 chromosomes (in 23 pairs).

Divergence (evolutionary)—During evolution, variations occur in the sequences of genes; if these variations confer some advantage natural selection increases their prevalence. Different selective pressures select for different variations so that the prevalence of different gene variants diverges in different populations.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Dominant—A pattern of inheritance of a gene or trait in which a single copy of a particular allele (gene variant) confers a function independent of the nature of the second copy of the gene in a diploid cell of an organism.

Double-strand break (DSB)—A break in the DNA double helix in which both strands are cut, as distinct from a single-strand break or “nick.”

Ectoderm—The outermost of the three primitive germ layers of the embryo; it gives rise to skin, nerves, and brain (IOM, 2005, p. 116).

Ectopic—Found in an unusual location, such as an ectopic pregnancy outside the uterus.

Embryo—An animal in the early stages of growth and differentiation that are characterized by cleavage (cell division of the fertilized egg), differentiation of fundamental cell types and tissues, and the formation of primitive organs and organ systems; the developing human individual from the time of implantation to the end of the eighth week after conception, after which stage it becomes known as a fetus (adapted from IOM, 2005, p. 116).

Embryonic germ (EG) cell—A pluripotent stem cell that migrates during early development to the future gonads to form the progenitors of egg or sperm cells. The properties of EG cells are similar to those of embryonic stem cells, but may differ in the DNA methylation of some imprinted regions (NRC, 2002, p. 263).

Embryonic stem (ES) cell—A primitive (undifferentiated) cell from the embryo that has the potential to become a wide variety of specialized cell types (i.e., is pluripotent). It is derived from the inner cell mass of the blastocyst. An embryonic stem cell is not an embryo; by itself, it cannot produce the necessary cell types, such as trophectoderm cells, so as to give rise to a complete organism (NAS, 2002, p. 263). Embryonic stem cells can be maintained as pluripotent cells in culture and induced to differentiate into many different cell types.

Endoderm—Innermost of the three primitive germ layers of the embryo; it later gives rise to the lungs, liver, and digestive organs (IOM, 2005, p. 116).

Endogenous—Originating from within a cell or an organism.

Endometrium—The inner epithelial lining of the uterus into which embryos implant.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Endonuclease—An enzyme that breaks down a nucleotide chain into two or more shorter chains by cleaving at internal phosphodiester bonds.

Enhancement—Improving a condition or trait beyond a typical or normal level.

Enucleated cell—A cell whose nucleus has been removed (IOM, 2005, p. 116).

Enucleation—A process whereby the nuclear material of a cell is removed, leaving only the cytoplasm. When applied to an egg, can involve the removal of the maternal chromosomes, when they are not surrounded by a nuclear membrane (adapted from NRC, 2002, p. 263).

Enzyme—A protein that acts as a biological catalyst, speeding up chemical reactions.

Epiblast—A specific layer of cells in an early vertebrate embryo that gives rise to the entire embryo other than yolk sac and placenta. Epiblast cells are pluripotent and can give rise to embryonic stem cells.

Epigenetic effects—Changes in gene expression that occur without changing the DNA sequence of a gene; for example, in the epigenetic effect called genomic imprinting, chemical molecules called methyl groups attach to DNA and alter the gene’s expression (NRC, 2002, p. 263).

Epigenome—A set of chemical modifications to the DNA of the genome and to proteins that bind to DNA in the chromosomes to affect whether and how genes are expressed.

Ex vivo—Latin: “out of the living”; outside an organism.

Exogenous—Introduced or originating from outside a cell or an organism.

Fertilization—The process whereby male and female gametes (sperm and egg) unite (NRC, 2002, p. 264).

FokI—The nuclease from which the cleavage domain has been abstracted and joined to zinc finger (ZF) or transcription activator-like effector (TALE) DNA-binding domains. The FokI cleavage domain cuts only one strand of the DNA (a nick), so a pair of ZFNs or TALENs is required to create double-strand breaks. The FokI cleavage domain has also been linked to nuclease-deficient Cas9 (dCas9), and this fusion must also dimerize to cut DNA.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Gain of function—A type of mutation that results in an altered gene product that possesses a new molecular function or a new pattern of gene expression (NRC and IOM, 2015, p. 1).

Gamete—A reproductive cell (egg or sperm). Gametes are haploid (having only half the number of chromosomes found in somatic cells—23 in humans), so that when two gametes unite at fertilization, the resulting one-cell embryo (zygote) has the full number of chromosomes (46 in humans) (NRC, 2002, p. 264).

Gastrulation—The procedure by which an animal embryo at an early stage of development produces the three primary germ layers—ectoderm, mesoderm, and endoderm (IOM, 2005, p. 117).

Gene—A functional unit of heredity that is a segment of DNA in a specific site on a chromosome. A gene typically directs the formation of a protein or RNA molecule (NRC, 2002, p. 264).

Gene drive—A system of biased inheritance in which the ability of a particular genetic sequence to pass from a parent to its offspring through sexual reproduction is enhanced (NASEM, 2016a, p. 182). Gene drive technology actively copies a sequence on one chromosome to its partner chromosome, so that the organism carries two copies of the intentionally modified gene. This process ensures that all of an organism’s offspring and subsequent generations will inherit the edited genome and related trait(s). Thus, the result of a gene drive is the preferential increase of a specific genotype from one generation to the next, and potentially throughout a population (NASEM, 2016a, p. 182).

Gene editing—A technique that allows researchers to alter the DNA of cells or organisms to insert, delete, or modify a gene or gene sequences to silence, enhance, or otherwise change the gene’s characteristics (NASEM, 2016a, p. 182).

Gene expression—The process by which RNA and proteins are made from the instructions encoded in genes. Gene expression is controlled by proteins and RNA molecules that bind to the genome or to the RNA copy and regulate their levels of production and those of their products. Alterations in gene expression change the functions of cells, tissues, organs, or whole organisms and sometimes result in observable characteristics associated with a particular gene (adapted from NRC, 2002, p. 264).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Gene targeting—A procedure used to produce an alteration in a specific gene (IOM, 2005, p. 117).

Gene therapy—Introduction of exogenous genes into cells with the goal of ameliorating a disease condition.

Gene transfer—Any process often used to describe the transfer of genes into cells—as used in gene therapy.

Genetic element—A segment of the DNA in a genome that has some particular property conferred by its sequence, such as a gene encoding a protein or RNA—more often used to refer to sequences that are not such genes but may control gene expression or genome organization.

Genome—The complete set of DNA that makes up an organism (NASEM, 2016a, p. 182). In humans, the genome is organized into 23 pairs of homologous chromosomes.

Genome editing—The process by which the genome sequence is changed through the intervention of a DNA break or other DNA modification.

Genotype—Genetic constitution of an individual (IOM, 2005, p. 117).

Germ cell (or germline cell)—A cell at any point in the lineage of cells that will give rise to sperm or eggs. The germline is this lineage of cells. Eggs and sperm fuse during sexual reproduction to create an embryo. In so doing, the germline continues into the next generation.

Germ layer—In early development, the embryo differentiates into three distinct germ layers (ectoderm, endoderm, and mesoderm), each of which gives rise to different parts of the developing organism (IOM, 2005, p. 117).

Gestation—The period of development of an organism from fertilization of the egg until birth (NRC, 202, p. 265).

Governance—The process of exercising oversight through traditions (standards of practice) or regulations by which individuals and communities are held accountable. Governance often involves such policy tools as professional standards of practice and codes of conduct; formal guidelines, agreements, and treaties; and legislation or other governmental regulation (NASEM, 2016a, p. 183).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Guide molecule—A protein or short section of RNA used to guide the genome-editing machinery to the desired location in the DNA sequence.

Guide RNA (gRNA)—Short segments of RNA used to direct the DNA-cutting enzyme to the target location in the genome. gRNA segments contain the region of homology to the target sequence (usually 20 bases), and a sequence that interacts with the nuclease (e.g., Cas9). gRNAs used in genome editing are synthetic and do not occur in nature.

Haploid—Refers to a cell (usually a gamete or its immediate precursor) having only one set of chromosomes (23 in humans). In contrast, body cells (somatic cells) are diploid, having two sets of chromosomes (46 in humans) (adapted from NRC, 2002, p. 265).

Heritable genetic change—Modifications to genes that could be passed down through generations.

Heterozygous—Having two different variants (alleles) of a specific gene on the two homologous chromosomes of a cell or an organism.

Homologous recombination—Recombining of two like DNA molecules, including a process by which gene targeting produces an alteration in a specific gene (adapted from IOM, 2005, p. 118).

Homology-directed repair (HDR)—A natural repair process used to repair broken DNA, which relies on a DNA “template” with homology to the broken stretch of DNA. This usually occurs during or after DNA synthesis, which provides this template. In genome editing via HDR, the DNA template is synthesised or made by recombinant DNA techniques, and usually contains regions of exact homology to the target locus at each end, with the desired alteration contained within the middle.

Homozygous—Having the same variant (allele) of a specific gene on both homologous chromosomes of a cell or an organism.

Human Fertilisation and Embryology Authority (HFEA)—The United Kingdom’s independent regulator overseeing the use of germ cells and embryos in fertility treatment and research (HFEA, 2013). It also stands for the Human Fertilisation and Embryology Act, the law under which the Authority operates and which it upholds.

Implantation—The process by which an embryo becomes attached to the inside of the uterus (7-14 days in humans) (NRC, 2002, p. 265).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

In utero—Latin: “in the uterus.”

In vitro—Latin: “in glass”; in a laboratory dish or test tube; in an artificial environment (NRC, 2002, p. 265).

In vitro fertilization (IVF)—An assisted reproduction technique in which fertilization is accomplished outside the body (NRC, 2002, p. 265).

In vivo—Latin: “in the living”; in a natural environment, usually in the body of the subject. This term is often also used to refer to events in “living” cells in culture (adapted from NRC, 2002, p. 265).

Indel—An insertion or deletion of DNA sequence. Small indels (e.g., one to four base pairs) are often associated with nonhomologous end joining. These often result in the disruption of a gene by shifting the open reading frame and/or creating premature stop codons.

Induced pluripotent stem (iPS) cell—A cell induced by the introduction or activation of genes conferring pluripotency and stem celllike properties. Thus, cells already committed to a particular fate (e.g., skin) can be induced to become pluripotent. This is useful in regenerative medicine because the iPS cells can be introduced back into the donor of the original cells with much less risk of transplant rejection.

Insertional mutagenesis—The alteration of the sequence of a gene by the insertion of exogenous sequence such as by integration of viral sequences.

Institutional review board (IRB)—An administrative body in an institution (such as a hospital or a university) established to protect the rights and welfare of human research subjects recruited to participate in research activities conducted under the auspices of that institution. The IRB has the authority to approve, require modifications in, or disapprove research activities in its jurisdiction, as specified by both federal regulations and local institutional policy (NRC, 2002, p. 266).

Lentivirus—A subclass of retroviruses, viruses whose genome are made of RNA but during viral replication becomes copied into a DNA form that can integrate into the DNA genome of a cell. Often used as carriers of genes (vectors) to introduce genes into cells.

Ligase—An enzyme that catalyzes joining of two pieces of DNA.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Loss of function—A type of mutation in which the altered gene product lacks the molecular function of the wild-type gene (MGI, 2017).

Meganuclease—A special type of enzyme that binds to and cuts DNA at specific DNA sequences of a length that occurs at few sites in the genome. These are natural enzymes (and their synthetic derivatives) that catalyze DNA rearrangement events via DNA cleavage.. They can be used in genome editing for both nonhomologous end joining and homology directed repair–mediated alterations. It was the study of these that first revealed the basic mechanisms of DNA cleavage and the DNA repair processes on which genome editing depends.

Mesoderm—The middle layer of the embryo, which consists of a group of cells derived from the inner cell mass of the blastocyst; it is formed at gastrulation and is the precursor to blood, bone, muscle, and connective tissue.

Mitochondrial transfer (or mitochondrial replacement)—Novel procedures designed to prevent the maternal transmission of mitochondrial DNA (mtDNA) diseases (NASEM, 2016b, p. 1).

Mitochondrion (plural, Mitochondria)—A cellular structure in the cytoplasm that provides energy to the cell. Each cell contains many mitochondria. In humans, a single mitochondrion contains 37 genes on a circular mitochondrial DNA, compared with about 35,000 genes contained in the nuclear DNA (NRC, 2002, p. 267).

Mosaicism—Variation among cells, such that the cells are not all the same—for example, in an embryo when not all the cells are edited.

Multipotent stem cells—Stem cells from the embryo, fetus, or adult, whose progeny are of multiple differentiated cell types and usually, but not necessarily, all of a particular tissue, organ, or physiological system (NRC, 2002, p. 267).

Murine—Derived from mice.

Mutation—A change in a DNA sequence. Mutations can occur spontaneously during cell division or can be triggered by environmental stresses, such as sunlight, radiation, and chemicals (NRC, 2002, p. 267).

Nickase—A nuclease that cuts only one strand of the DNA double helix.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Nonhomologous end joining (NHEJ)—A natural repair process used to join the two ends of a broken DNA strand back together. This is prone to errors where short indels (usually of two to four base pairs of DNA) are introduced.

Normative theory—A theory of how people should make decisions, as opposed to how they actually do or will make decisions.

Nuclease—An enzyme that can cut through DNA or RNA strands.

Off-target effect—A direct or indirect, unintended, short- or long-term consequence of an intervention on an organism other than the intended effect on that organism (NASEM, 2016, p. 184).

Off-target event (or off-target cleavage)—when a genome-editing nuclease cuts DNA at a location other than the one for which it was targeted. This can occur because the off-target sequence is similar to but not identical with the intended target sequence.

Oocyte—Developing egg; usually a large and immobile cell.

Phenotype—Observable properties of an organism that are influenced by both its genotype and its environment.

Plasmid—A self-replicating circular DNA molecule. A plasmid can be engineered to carry and express genes of interest in target cells.

Pluripotent stem cell (PSC)—A stem cell that includes in its progeny all cell types that can be found in a postimplantation embryo, fetus, or developed organism (NRC, 2002, p. 268).

Population—All of the individuals of a given species within a defined ecological area (NASEM, 2016a, p. 184).

Preclinical research—Research conducted to investigate potential clinical applications but not involving humans. For example, research on molecules, cells, tissues, or animals.

Precursor cell or Progenitor cell—In fetal or adult tissues, it is a partially committed but not fully differentiated cell that divides and gives rise to differentiated cells (adapted from NRC, 2002, p. 269).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Preimplantation genetic diagnosis (PGD)—Before an in vitro–fertilized embryo is implanted in a woman’s uterus, it can be screened for specific genetic mutations that are known to cause particular genetic diseases or for chromosomal abnormalities. One or more cells are removed from the preimplantation embryo for testing (NRC, 2002, p. 269) and the surviving embryo that is implanted is one that is not carrying the genetic abnormality.

Prenatal diagnosis—Detection of abnormalities and disease conditions while a fetus is developing in the uterus. Many techniques for prenatal diagnosis, such as chorionic villus sampling and amniocentesis, require sampling placental tissue or fetal cells found in the amniotic fluid or fetomaternal circulation. Others, such as ultrasonography, can be performed without cell or tissue samples (NRC, 2002, p. 269).

Primitive streak—An elongated band of cells that forms along the axis of an embryo early in gastrulation by the movement of lateral cells toward the axis and that develops a groove along its midline through which cells move to the interior of the embryo to form the mesoderm (adapted from Grossinger, 2000, p. 815).

Pronucleus—The haploid nucleus of an oocyte or sperm, either prior to fertilization or immediately after fertilization, before the sperm and egg nuclei have fused into a single diploid nucleus.

Protein—A large complex molecule made up of one or more chains of amino acids. Proteins perform a wide variety of activities in the cell (NRC, 2002, p. 269).

Recessive—A recessive allele of a gene is one whose effects are masked by the second allele present in a diploid cell or organism, which is referred to as dominant.

Recombinant DNA—A recombinant DNA molecule is made up of DNA sequences that have been artificially modified or joined together so that the new genetic sequence differs from naturally occurring genetic material (IOM, 2014, p. 23).

Recombinant DNA Advisory Committee (RAC)—Oversees and reviews proposals for research funded by the National Institutes of Health (NIH) or similar projects conducted at institutions funded by NIH that involve recombinant or synthetic DNA, such as gene therapy (adapted from NASEM, 2016b, p. 62).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Recombination—The process, natural or engineered, in which two pieces of DNA undergo breakage and reunion to generate a new combination of DNA segments.

Regenerative medicine—Medical treatments that seek to replace defective, damaged, or missing tissue by engineered cells, tissues, or implants, often involving stem cells.

Restriction enzyme—An enzyme from bacteria that is used to cut DNA at defined sequences, used in DNA analysis and in joining DNA fragments through the cut ends.

Retrovirus—A virus whose genome is made of RNA but during viral replication becomes copied into a DNA form that can integrate into the DNA genome of a cell. Often used as carriers of genes (vectors) to introduce genes into cells. A subset of retroviruses is called lentiviruses.

Risk—The probability of an effect on a specific endpoint or a set of endpoints due to a specific set of a stressor or stressors. An effect can be beneficial or harmful (NASEM, 2016a, p. 185).

Risk assessment—The process by which all available evidence on the probability of effects is collected, evaluated, and interpreted to estimate the probability of the sum total of effects (NASEM, 2016a, p. 185).

RNA (ribonucleic acid)—A chemical that is similar in structure to DNA. One of its main functions is to translate the genetic code of DNA into structural proteins.

RNP (ribonuclear protein complex)—Many types exist within cells, and this is a general term encompassing all of these, but in the context of genome editing it is often used to refer to a guide RNA molecule combined with a DNA-cutting enzyme such as Cas9.

Selective advantage—Some variants of genes provide a trait that confers a survival or a reproductive advantage that can be selected by natural selection and therefore increases in prevalence in a population.

Single guide RNA (sgRNA)—A short piece of RNA that binds to a nuclease such as Cas9 and also to a specific DNA sequence to guide the nuclease to a specific location in the genome. This term is synonymous with guide RNA (vide infra) in most usages.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Somatic cell—Any cell of a plant or animal other than a reproductive cell or reproductive cell precursor. Latin: soma = body (NRC, 2002, p. 270).

Somatic cell nuclear transfer (SCNT)—The transfer of a cell nucleus from a somatic cell into an egg (oocyte) whose nucleus has been removed (IOM, 2005, p. 119).

Spermatogonial stem cells—The self-replicating precursors of sperm cells.

Stem cell—A nonspecialized cell that has the capacity to divide indefinitely in culture and to differentiate into more mature cells with specialized functions.

Stem cell therapy—The use of stem cells in regenerative medicine to replace defective, damaged, or missing tissue.

Syncytiotrophoblast cell—A cell derived from trophectodermal cells from the early mammalian embryo that fuse (into multinucleate syncitia) and contribute to the structure and function of the placentae.

Synthetic biology—The development of living cells from separate genetic components, using engineering principles to build desired functions into living organisms.

Synthetic DNA—DNA molecules that are chemically or by other means synthesized or amplified; they may be chemically or otherwise modified but can base pair, or be recombined with, naturally occurring DNA molecules.

T cells—Types of white blood cells that are of crucial importance in the immune system. They cooperate with other immune cells in killing infected or cancerous cells but can also participate in inflammation or in autoimmunity when they become activated against an organism’s own cells or tissues.

Target sequence—Specific sequence of DNA bases within the genome that is the target of genome-editing tools. For CRISPR/Cas9 methods this will be a 20 nucleotide sequence that the gRNAs are designed to recognize (i.e., they will contain a complementary sequence of the same length).

Therapy (or therapeutic intervention)—The treatment or prevention of disease or disability.

Tissue culture—The growth of cells or tissue segments in vitro in an artificial medium for experimental research (IOM, 2005, p. 120).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Totipotent cell—A stem cell that has unlimited developmental capability. The totipotent cells of the very early embryo (an embryo prior to the blastocyst stage) have the capacity to differentiate into extraembryonic tissues, membranes, the embryo, and all postembryonic tissues and organs (NRC, 2002, p. 271).

Transcription—Making an RNA copy from a gene or other DNA sequence. Transcription is the first step in gene expression (NRC, 2002, p. 271).

Transcription Activator-Like Effector Nuclease (TALEN)—A class of engineered restriction enzymes generated by the fusion of a transcription activator-like effector DNA-binding domain (that binds to a specific DNA sequence) to a DNA-cleavage domain (nuclease) to be used as a genome-editing tool (adapted from NASEM, 2016a, p. 186). TALENs followed zinc finger nucleases and preceded CRISPR/Cas9 as genome-editing tools.

Transcription factor—A protein that binds to control regions (enhancers and promoters) of genes to activate or repress their transcription (or expression).

Transfection—A method by which experimental DNA may be introduced into a cell (adapted from IOM, 2005, p. 120).

Transgene—A gene or genetic material that has been introduced into a cell or organism. Transgenes can be integrated at random, or targeted to a specific site by homologous recombination or by genome editing using methods of homology-directed repair.

Transgenic organism—An organism into which one or more genes from another species (transgenes) have been transferred or otherwise artificially introduced.

Transhumanism—A class of philosophies of life that seek the continuation and acceleration of the evolution of intelligent life beyond its currently human form and human limitations by means of science and technology, guided by life-promoting principles and values (More, 1990).

Translation—The process of forming a protein molecule from information contained in a messenger RNA (NRC, 2002, p. 271)—a step in gene expression following transcription (copying of RNA from DNA).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
×

Trophectoderm—The outer layer of the developing blastocyst that will ultimately form the embryonic side of the placenta (NRC, 2002, p. 271).

Undifferentiated—Not having developed into a specialized cell or tissue type (NRC, 2002, p. 271).

Unipotent stem cell—A stem cell that both divides and gives rise to a single mature cell type, such as a spermatogenic stem cell, which only gives rise to sperm (NRC, 2002, p. 271). Alternatively called a progenitor.

Utilitarianism—The morally right action as the action that produces the most “good.”

Variant—Genes have many variants in a population that can differ somewhat in function, some being advantageous and some being deleterious or nonfunctional.

Vector—A vehicle that transfers a gene into a new site (analogous to insect vectors that transfer a virus or parasite into a new animal host). Vectors used in molecular cell biology and genetic engineering include plasmids and modified viruses engineered to carry and express genes of interest in target cells. The most clinically relevant viral vectors for gene transfer include retroviral, lentiviral, adenoviral, and adeno-associated viral vectors.

Virtue ethics—A focus on moral character as opposed to duties (deontology) or consequences (consequentialism).

Wild type (noun); Wild-type (adjective)—The “normal” type of an organism or a gene.

X-inactivation—The process in which one X chromosome of the two present in a female mammalian cell is inactivated so that only the genes of one X chromosome are expressed.

Zinc finger—A small protein structure based on naturally occurring transcription factors that bind to defined DNA sequences to control the activity of nearby genes. Zinc fingers can be custom engineered to target a specific section of the DNA sequence for use in genome engineering.

Zinc finger nuclease (ZFN)—A class of engineered enzymes generated by the fusion of zinc finger DNA-binding domains to a DNA-cleavage enzyme (usually FokI) that can be used as a genome-editing tool (adapted from

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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NASEM, 2016a, p. 186). One of the first and a reliable method of genome editing.

Zygote—The one-cell embryo formed by the union of sperm and egg at fertilization (NRC, 2002, p. 272).

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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REFERENCES

Grossinger, R. 2000. Embryogenesis: Species, gender, and identity. Berkeley, CA: North Atlantic Books.

HFEA (Human Fertilisation and Embryology Authority). 2013. What we do. http://www.hfea.gov.uk/133.html (accessed May 10, 2017).

IOM (Institute of Medicine). 2005. Guidelines for human embryonic stem cell research, Vol. 23. Washington, DC: The National Academies Press.

IOM. 2014. Oversight and review of clinical gene transfer protocols: Assessing the role of the recombinant DNA advisory committee. Washington, DC: The National Academies Press.

MGI (Mouse Genome Informatics). 2017. MGI glossary, s.v. “loss of function.” http://www.informatics.jax.org/glossary/loss-of-function (accessed May 10, 2017).

More, M. 1990. “Religion, Eupraxophy, and Transhumanism” in Transhumanism: Towards a futurist philosophy. https://www.scribd.com/doc/257580713/Transhumanism-Toward-a-Futurist-Philosophy (accessed January 25, 2017).

NASEM (National Academies of Sciences, Engineering, and Medicine). 2016a. Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values. Washington, DC: The National Academies Press.

NASEM. 2016b. Mitochondrial replacement techniques: Ethical, social, and policy considerations. Washington, DC: The National Academies Press.

NRC (National Research Council). 2002. Scientific and medical aspects of human reproductive cloning. Washington, DC: National Academy Press.

NRC and IOM (Institute of Medicine). 2015. Potential risks and benefits of gain-of-function research: Summary of a workshop. Washington, DC: The National Academies Press.

Suggested Citation:"Appendix E: Glossary." National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
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Human Genome Editing: Science, Ethics, and Governance Get This Book
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Genome editing is a powerful new tool for making precise alterations to an organism’s genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions.

Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.

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