Heritable Genetic Modification in Food Animals (2025)
Chapter: Front Matter
Consensus Study Report
NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by the National Academy of Sciences and the U.S. National Institutes of Health (Contract Number: HHSN263201800029I, Task Order Number: 75N98023F00004). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-71843-1
International Standard Book Number-10: 0-309-71843-0
Digital Object Identifier: https://doi.org/10.17226/27750
This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2025 by the National Academy of Sciences. National Academies of Sciences, Engineering, and Medicine and National Academies Press and the graphical logos for each are all trademarks of the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2025. Heritable Genetic Modification in Food Animals. Washington, DC: The National Academies Press. https://doi.org/10.17226/27750.
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.
The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.
The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.
The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.
Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.
Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.
Rapid Expert Consultations published by the National Academies of Sciences, Engineering, and Medicine are authored by subject-matter experts on narrowly focused topics that can be supported by a body of evidence. The discussions contained in rapid expert consultations are considered those of the authors and do not contain policy recommendations. Rapid expert consultations are reviewed by the institution before release.
For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.
COMMITTEE ON HERITABLE GENETIC MODIFICATION IN FOOD ANIMALS
ERIC M. HALLERMAN (Chair), Virginia Polytechnic Institute and State University, Blacksburg (emeritus)
BERNADETTE M. DUNHAM, George Washington University, Washington, D.C.
LYDA G. GARCIA, The Ohio State University, Columbus
FRED GOULD,1 North Carolina State University, Raleigh
DARRELL R. KAPCZYNSKI, U.S. Department of Agriculture, Agricultural Research Service, Athens, Georgia
ELIZABETH A. MAGA, University of California, Davis
FIONA M. MCCARTHY, University of Arizona, Tucson
MIKE J. MCGREW, University of Edinburgh, Scotland
WILLIAM M. MUIR, Purdue University, West Lafayette, Indiana (emeritus)
JAMES D. MURRAY, University of California, Davis (emeritus)
JON M. OATLEY, Washington State University, Pullman
PENNY K. RIGGS, Texas A&M University, College Station
THOMAS E. SPENCER,1 University of Missouri, Columbia
VIRGINIA STALLINGS,2 Children’s Hospital of Philadelphia, Pennsylvania
ASPEN M. WORKMAN, U.S. Department of Agriculture – Agricultural Research Service, Clay Center, Nebraska
Study Staff
ALBARAA SARSOUR, Staff Officer
ROBIN SCHOEN, Director, Board on Agriculture and Natural Resources
SAMANTHA SISANACHANDENG, Senior Program Assistant
MITCHELL HEBNER, Research Associate
ANNE FRANCES JOHNSON, Creative science writer
___________________
1Member of the National Academy of Sciences
2Member of the National Academy of Medicine
BOARD ON AGRICULTURAL AND NATURAL RESOURCES
JILL J. MCCLUSKEY (Chair), Washington State University, Pullman
AMY W. ANDO, University of Illinois, Urbana-Champaign
ARISTOS ARISTIDOU,1 Biomason, Inc., Durham, North Carolina
BRUNO BASSO, Michigan State University, East Lansing
BERNADETTE M. DUNHAM, George Washington University, Washington, D.C.
JESSICA E. HALOFSKY, U.S. Department of Agriculture – Pacific Northwest Research Station, Portland, Oregon
ERMIAS KEBREAB, University of California, Davis
MARTY D. MATLOCK, University of Arkansas, Fayetteville
JOHN P. MCNAMARA, Washington State University, Pullman
NAIMA MOUSTAID-MOUSSA, Texas Tech University, Lubbock
V. ALARIC SAMPLE, George Mason University, Fairfax, Virginia
ROGER E. WYSE, Spruce Capital Partners, San Francisco, California
Staff
ROBERTA SCHOEN, Director
CAMILLA YANDOC ABLES, Senior Program Officer
MALIA BROWN, Program Assistant
CYNTHIA GETNER, Senior Finance Business Partner
MITCHELL HEBNER, Research Associate
KARA N. LANEY, Senior Program Officer
ALBARAA SARSOUR, Program Officer
SAMANTHA SISANACHANDENG, Senior Program Assistant
___________________
1Member of the National Academy of Engineering
FOOD AND NUTRITION BOARD
SHARON DONOVAN (Chair),1 University of Illinois Urbana-Champaign
JAMY D. ARD,1 Wake Forest Baptist Medical Center, Winston-Salem
RODOLPHE BARRANGOU,2,3 North Carolina State University, Raleigh
LIA HASKIN FERNALD, University of California, Berkeley
BRUCE Y. LEE, City University of New York Graduate School of Public Health and Health Policy, New York
MARIAN L. NEUHOUSER, Fred Hutchinson Cancer Research Center, Seattle
JEFF NIEDERDEPPE, Cornell University, Ithaca
KATHLEEN M. RASMUSSEN, Cornell University, Ithaca
CHARLENE RUSSELL-TUCKER, Connecticut State Department of Education
DIANE W. SCHANZENBACK, Northwestern University, Evanston
REBECCA SEGUIN-FOWLER,1 Texas A&M University, College Station
ANNA MARIA SIEGA-RIZ, University of Massachusetts at Amherst
R. PAUL SINGH,3 University of California, Davis
Staff
ANN YAKTINE, Director
MELANIE ARTHUR, Research Assistant
HEATHER COOK, Senior Program Officer
CYPRESS LYNX, Associate Program Officer
AMANDA NGUYEN, Program Officer
MEREDITH PARR, Research Assistant
SARAH PONCET, Research Associate
JENNIFER STEPHENSON, Research Associate
ALICE VOROSMARTI, Associate Program Office
___________________
1Member of the National Academy of Medicine
2Member of the National Academy of Sciences
3Member of the National Academy of Engineering
This page intentionally left blank.
Reviewers
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by MICHAEL GALYEAN, Texas Tech University, and JIM RIVIERE (NAM), Kansas State University. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
This page intentionally left blank.
Acknowledgments
This study could not have been realized without the contributions of many colleagues who generously contributed their time and expertise. The Committee on Heritable Genetic Modification in Food Animals thanks those who participated in our workshops:
We express our appreciation to the National Academies of Sciences, Engineering, and Medicine Board on Agriculture and Natural Resources staff members Albaraa Sarsour, Robin Schoen, Samantha Sisanachandeng, and Mitchell Hebner.
Contents
2 HERITABLE GENETIC MODIFICATION IN FOOD ANIMALS
Group-Specific Methods, Applications, and Issues
Current State of Animal Biotechnology
3 POTENTIAL HAZARDS TO ANIMALS AND CONSUMERS
Hazards From Heritable Genetic Modifications
4 LIKELIHOOD OF HERITABLE GENETIC MODIFICATIONS PRESENTING HARMS TO FOOD ANIMALS OR HUMANS
Risk Analysis: Key Concepts and Application to HGM Animals and Derived Food Products
U.S. Policies for Assessment of Safety of Products of Animal Biotechnology
Application of Risk Assessment Principles to Products of Animals Derived from SCNT
Application of Risk Assessment Principles to Animal Products of Classical Gene Transfer
Application of Risk Assessment Principles to Genome-Edited Animal Products
Overview of Past Safety Assessments for HGM Food Products
Prospective Application of Risk Analysis
Toward Refinement of Risk Assessment Approaches
5 EXPERIMENTAL STRATEGIES FOR ADDRESSING RISK ISSUES
Approaches to Address Characterization of Inherited Sequence Changes
Approaches to Identify Phenotypic Changes in HGM Animals
Approaches to Address Assessment of Animal Welfare
Approaches for Identification and Analysis of Changes in Food-Animal Products
Host-Range Expansion into Livestock and Human Populations
6 SCIENTIFIC QUESTIONS TO BE ADDRESSED
Data Gaps That Require Further Research
Post-Editing Challenges and Pre-Commercial Development
Phenotypic Assessment of HGM Effects
Impacts of Heritable Genetic Modification on Food Composition
Allergenicity and Food Intolerance Aspects of HGM Animal Food Composition
Hazard of Disease Transmission from HGM Animals to Other Animals and Humans
International Harmonization of Assessment Methods and Policy
Communication, Public Outreach, and Education
Boxes, Figures, and Tables
BOXES
1-1 Terms Used in Discussions of Animal Biotechnology
3-1 Case Study: The Need for AIV-Resistant Animals
4-1 AquAdvantage Atlantic Salmon
4-4 Oversight and Commercialization of Genome-Edited Fishes
5-2 CD163 Knockout Pigs: A Case Study of the Difficulty of Determining the Source of a New Variant
5-3 Federal Protections for Animal Welfare
5-4 Animal Welfare Standards Certification
FIGURES
2-1 General overview of genome editing in food animals
2-2 Overview of genome editing in mammals
4-1 A multi-tiered approach for assessing potential exposures to HGM food animals
TABLES
S-1 New Lines of Food-Animal Species Generated Using Gene Transfer or Genome Editing
2-1 Methods for Producing Food Animals with Heritable Genetic Modifications
2-2 Common Methods for Making Site-Specific Modifications in the Genomes of Food-Animal Species
2-3 CRISPR-Cas and Derivative Gene-Editing Methods
2-4 Applications of Gene Transfer and Gene Editing in Mammals Used for Food
2-5 Applications of Gene Transfer and Genome Editing in Poultry
2-6 Applications of Gene Transfer and Genome Editing in Aquaculture Species
2-7 Regulatory Determinations for HGM Animals for Food Use by Country
Preface
“The foods developed by this [recombinant DNA] technology undergo far more testing than all the other foods that enter the grocery store, for food safety. There’s really a huge burden that’s placed on the developers to use this technology, and that is going to be an issue for developing countries and an issue for small companies. It is, in fact, scientifically difficult to justify a lot of the testing that is being done today for these foods in terms of the public health issues that they actually don’t raise. But most of this is now being done to provide confidence to the public that the foods are safe.”
Dr. James Maryanski (2006), past Biotechnology Coordinator, U.S. Food and Drug Administration
Humans have been breeding food animals for five millennia. The development of selectively bred livestock breeds with specified traits for production of meat, milk, eggs, wool, or other products traces back to the mid-1790s (Wykes, 2004). The development of quantitative genetic theory (Falconer and Mackay, 1996) and its systematic application to genetic improvement of livestock goes back to the early 20th century. After elucidation of the structure and function of DNA in the 1950s, the late 20th century saw the emergence of the field of molecular genetics. By the 1980s, this development supported the identification, functional characterization, and purposeful modification of genes with major effects upon the productivity of food animals (NRC, 2002).
The development of gene transfer and genome-editing methods offers the potential for enhancing the productivity and sustainability of animal agriculture. However, there are associated concerns regarding animal safety, food consumption risks, and other potential harms, as well as issues surrounding how best to conduct regulatory oversight of the application of agricultural animal biotechnology (Hallerman et al., 2022). Despite the commercialization of the first few lines of genetically modified and genome-edited animals, these issues remain current, with 16 percent of Americans caring “a great deal” about genetically modified foods (Funk and Kennedy, 2016). It was within this context that the Committee on Heritable Genetic Modification in Food Animals was formed by the National Academies of Sciences, Engineering, and Medicine.
The committee reviewed information from the scientific literature, presentations by experts at National Academies’-sponsored workshops, and previous National Academies’ reports. We discussed the issues, debated our findings, and drafted our consensus report. After peer review, we submitted our revised report to the sponsors, the scientific community, and the public.
This is an appropriate moment to consider the biological basis of risks relevant to heritable genetic modification of food animals. With a human population of over eight billion, there is rising demand for animal products. Limited arable land and water, as well as ongoing global climate change, affect the sustainability and resiliency of
animal production systems. There is increasing globalization of trade in animal products and increasing transmission of animal diseases across international borders. Consumers express increasing concern for animal welfare (Informa Markets, 2017) and food safety (Pearson et al., 2012). We hope that our findings transmitted in this report contribute to the sustainability of livestock production and to consumer confidence that products derived from animals with biotechnology-derived heritable genetic modifications are nutritious and safe to eat.
This study and its report would not have been realized without the dedication, skill, and hard work of Staff Officer Albaraa Sarsour, Director Robin Schoen, Senior Program Assistant Samantha Sisanachandeng, and Research Associate Mitchell Hebner of the NASEM Board on Agriculture and Natural Resources.
Eric M. Hallerman, Chair
Committee on Heritable Genetic Modification in Food Animals
REFERENCES
Falconer, D.S., and F.C. Mackay. 1996. Introduction to Quantitative Genetics, 4th ed. Prentice Hall, Harlow, Essex.
Funk, C., and B. Kennedy. 2016. Public opinion about genetically modified foods and trust in scientists connected with these foods. Chapter 3 in The New Food Fights: U.S. Public Divides Over Food Science. Pew Research Center, https://www.pewresearch.org/internet/2016/12/01/public-opinion-about-genetically-modified-foods-and-trust-in-scientists-connected-with-these-foods/. Accessed November 15, 2024.
Hallerman, E.M., J. Bredlau, L.S. Camargo, M.L.Z. Dagli, M. Karembu, G. Ngure, R. Romero-Aldemita, P. Rocha, M. Tizard, M. Walton, and D. Wray-Cahen. 2022. Towards progressive regulatory approaches for agricultural applications of animal biotechnology. Transgenic Research 31(2):167-199. https://doi.org/10.1007/s11248-021-00294-3.
Informa Markets. 2017. Survey: More consumers concerned about animal welfare. Beef Magazine, https://www.beefmagazine.com/cattle-welfare/survey-more-consumers-concerned-about-animal-welfare. Accessed November 15, 2024.
Maryanski, J. 2006. Oral history of the U.S. Food and Drug Administration. https://www.fda.gov/media/83918/download. Accessed September 22, 2023.
NRC (National Research Council). 2002. Animal Biotechnology: Science-Based Concerns. The National Academies Press, Washington, DC. https://doi.org/10.17226/10418.
Pearson, A.J., K. Mukherjee, V. Fattori, and M. Lipp. 2024. Opportunities and challenges for global food safety in advancing circular policies and practices in agrifood systems. NPJ Science of Food 8:60. https://doi.org/10.1038/s41538-024-00286-7.
Wykes, D.L. 2004. Robert Bakewell (1725-1795) of Dishley: Farmer and livestock improver. Agricultural History Review 52(1):38-55.
Acronyms and Abbreviations
| AIV | avian influenza virus |
| BLAST | basic local alignment search tool |
| bp | base pairs |
| BSE | bovine spongiform encephalopathy |
| contig | contiguous DNA sequence |
| CRISPR | clustered regularly interspersed short palindromic repeats |
| crRNA | CRISPR RNA |
| dsODNs | double-stranded oligo deoxynucleotides |
| ESC | embryonic stem cell |
| FAANG | Functional Annotation of Animal Genomes Consortium |
| FDA | U.S. Food and Drug Administration |
| FDA-CVM | FDA Center for Veterinary Medicine |
| FDA-CVM-VMAC | FDA CVM Veterinary Medicine Advisory Committee |
| FFDCA | Federal Food, Drug, and Cosmetic Act |
| GE | genetically engineered |
| GFI 187 | Guidance for Industry 187 |
| GH | growth hormone |
| gRNA | guide RNA |
| HACCP | Hazard Analysis and Critical Control Point |
| HDR | homology-directed repair |
| hLZ | human lysozyme |
| HGM | heritable genetic modification |
| HGT | horizontal gene transfer |
| HPAIV | high-pathogenicity avian influenza virus |
| IgE | immunoglobulin E |
| IVF | in vitro fertilization |
| IVP | in vitro production |
| KI | knock-in |
| KO | knockout |
| LALBA | human lactalbumin alpha |
| MALDI-ToF-MS | matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry |
| MDV | Marek’s disease virus |
| MHLW | Japanese Ministry of Health, Labor, and Welfare |
| NASEM | National Academies of Sciences, Engineering, and Medicine |
| NIH | National Institutes of Health |
| NRC | National Research Council |
| NHEJ | non-homologous end joining |
| PAM | protospacer-adjacent motif |
| PCR | polymerase chain reaction |
| PGC | primordial germ cell |
| PERVs | porcine endogenous retroviruses |
| PRLR | prolactin receptor |
| PRRSV | porcine respiratory and reproductive syndrome virus |
| rDNA | recombinant DNA |
| RVD | repeat variable diresidue |
| SCNT | somatic cell nuclear transfer |
| SDN | site-directed nuclease |
| sgRNA | single guide RNA |
| SNP | single nucleotide polymorphism |
| SNV | single nucleotide variant |
| SV | structural variant |
| T2T | telomere-to-telomere |
| TAL | transcription activator-like |
| TALEN | transcription activator-like effector nuclease |
| tracrRNA | trans-activating CRISPR RNA |
| tRNA | transfer RNA |
| TGEV | transmissible gastroenteritis virus |
| USDA | U.S. Department of Agriculture |
| USDA-FSIS | USDA Food Safety Inspection Service |
| UTR | untranslated region |
| ZFN | zinc finger nuclease |
Glossary
| Adeno-associated virus | A non-enveloped virus that can be engineered to deliver DNA to target cells, which has attracted attention for clinical-stage experimental therapeutic strategies |
| Allele | An alternative form of a gene, for example, leading to pale or red flowers in garden pea as described by Mendel |
| Allergenicity | The ability of an antigen to induce an abnormal immune response, an overreaction and different from a normal immune response in that it does not result in a protective or prophylactic effect, but rather causes physiological function disorder or tissue damage |
| Annotation | Definition, identification, or attribution of a function to genetic sequence (e.g., a gene, regulatory element, or repetitive element of the genome) |
| Base editing | A gene-editing technology that combines the DNA-scanning and sequence-identification capabilities of the CRISPR-Cas9 system with a deaminase enzyme, which introduces single nucleotide polymorphisms by chemically altering the target DNA sequence without the intentional generation of a DNA double-strand break. This chemical modification, known as deamination, removes an amino group from a nucleotide, which, after DNA repair or replication, results in the installation of a new base. The earliest base editors, called cytosine base editors, can substitute a cytosine base for a thymine (C→T), while newer base editors, called adenine base editors, introduce adenine-to-guanine (A→G) substitutions. More recently, base editors capable of cytosine-to-guanine or simultaneous adenine and cytosine substitutions have also been developed. |
| Basic local alignment and search tool | Software for querying a DNA sequence database to find DNA or protein sequences similar to sequences of interest |
| Bioactivity | The physiological effect of a substance upon a living organism or tissue |
| Biopharm animals | Transgenic animals modified to produce proteins for extraction, purification, and therapeutic use |
| Biopharming | The production of biopharmaceuticals in domestic animals |
| Bovine spongiform encephalopathy | An incurable and invariably fatal neurodegenerative disease of cattle. It is also described as a type of transmissible spongiform encephalopathy, and commonly referred to as “mad cow disease.” |
| Clone | A product of cloning; can refer to both molecular clones and whole-animal clones |
| 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. |
| Complementary DNA | A synthetic DNA molecule that is a copy of messenger RNA (mRNA) |
| Concatemer | A DNA molecule that contains multiple copies of the same DNA sequence in series |
| Conjugation | The process by which one bacterium transfers genetic material to another through direct contact |
| Conventional breeding | Propagation of animals without the use of biotechnological interventions. Selective breeding for purposes of genetic improvement is within the scope of conventional breeding. |
| Conventional counterpart | An animal line or breed with a known history of safe use as food from which an animal line was derived using biotechnology, as well as the breeding partners used in generating the animals ultimately used as food, or food derived from such animals. |
| CRISPR-Cas9 | A gene-editing technology involving a guide RNA matching a desired target gene and Cas9 (CRISPR-associated protein 9), an endonuclease that causes a double-stranded DNA break, allowing targeted modifications of the genome. |
| Critical control point | A key step in manufacturing processes for reducing error, hazard, and risk, and an element of the Total Quality Management process developed by W. Edwards Deming. Its application to food safety began with the National Aeronautics and Space Administration and the U.S. Space Program. See HACCP. |
| Disease resilience | The enhanced ability of an individual to recover from disease. In animal production, disease resilience can help maintain productive performance, leading to improved animal health, more sustainable production, and the potential for reduced antimicrobial use. |
| Disease resistance | The ability of an individual to prevent or reduce the occurrence of a disease. In animal production, disease resistance would render animals non-permissive to infection from a particular pathogen, leading to disease-free status and improved animal health. |
| Ectopic gene expression | Expression of a (trans)gene in a tissue where, or developmental stage when, such expression is not expected |
| Embryonic stem cell | A cell that comes from the inner cell mass of a blastocyst, an early-stage embryo that implants in the uterus. ESCs are pluripotent, that is, they can divide into more stem cells or differentiate into any type of cell in the body. |
| Enhancer | A DNA element that increases the rate of transcription of a gene or genes |
| Epigenetics | The study of how environmental factors and aging can cause changes to gene expression without altering the DNA sequence, meditated, for example, by methylation of cytosine bases on genomic DNA |
| Epigenome | Derived from the Greek word “epi,” which means “above,” the epigenome consists of chemical compounds that modify, or mark, the genome to affect the level, timing, and tissue distribution of gene expression. Different cells have different epigenetic marks. These epigenetic marks, which are not part of the DNA itself, can be transmitted from cell to cell as cells divide, and from one generation to the next. |
| Exon | Any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing |
| Expression vector | Often a plasmid or virus designed for promoting gene expression in cells. The vector is used to introduce a specific gene into a target cell and can commandeer the cell’s mechanism for protein synthesis to produce the protein encoded by the gene. |
| Fibroblast | A type of cell found in connective tissue throughout the body |
| Fitness | The ability of an individual to survive and reproduce, which may be defined as absolute probabilities or in comparison to individuals with specified genotypes or phenotypes |
| Food | In the context of this report, a food derived from an animal reflects a single ingredient. For example, muscle from a food animal is converted to meat. An HGM-derived food is a single ingredient item (e,g., meat, milk, or egg) derived from a food animal containing a heritable genetic modification. See also Food product. |
| Food intolerance | Food sensitivity wherein the digestive system has difficulty digesting a food. The affected individual may experience uncomfortable symptoms such as gas, diarrhea, and abdominal pain. |
| Food product | In the context of this report, a food product is composed of more than one food item, such as sausage or an omelet. |
| Food safety | The science and practice of mitigating the risk of biological, chemical, and physical hazards in foods typically consumed by humans in order to prevent the occurrence of foodborne illnesses. Food safety strategies are achieved through a series of risk mitigations through hazard analysis and critical control point (HACCP) planning to reduce the occurrence of any hazards. See also Safe food. |
| Founder HGM animal | An individual that has been subject to gene transfer or genome editing that is then used to propagate a new line and has transmitted the modification to descendants. A descendant that bears the desired modification may be the de facto founder of a line that will be multiplied and commercialized. |
| Functional annotation | The analytical process of attaching biological information to the sequences of genes or proteins. The basic level of annotation is performed using the sequence alignment tool BLAST for finding similarities to those of sequences of known function. |
| Galactose-α1,3-galactose | A carbohydrate found as a modification to cell surface glycoprotein on all mammals (and many other organisms) except for old-world primates (including humans), commonly referred to as alpha-gal. The presence of naturally occurring antibodies to this modification in humans is a major (but not the only) cause of rejection of xenotransplanted organs. |
| Gene conversion | The unidirectional transfer of genetic material from a “donor” sequence to a highly homologous “acceptor.” It is one of four pathways of homologous recombination, the other three being non-allelic homologous recombination, break-induced replication and single-strand annealing. |
| Gene- or genome-edited | Adjective referring to an animal that has been subjected to the group of technologies that give scientists the ability to add, remove, or alter particular locations in the genome. Genome editing refers to editing at any points within the genome, while gene editing specifically refers to the alteration of a single gene within the genome. |
| Gene or genome editing | A group of technologies that give scientists the ability to change an organism’s DNA, allowing genetic material to be added, removed, or altered at particular locations in the genome |
| Gene stacking | The approach of combining two or more transgenes or gene edits into a single line to improve a targeted trait. For example, genes might be stacked to improve disease or pest resistance so that the targeted pathogen or pest is much less likely to evolve resistance. |
| Gene transfer | The technique of introducing a gene under novel transcriptional control into a host. The gene may have originated from the same or another species. |
| Generation interval | The average age of parents when their offspring are born. |
| Genetic progress | The desired consequence of a genetic improvement program, measured as the increase in the average genetic value of offspring compared to that in the previous generation for a trait of interest. |
| Genetically engineered | Adjective referring to an organism that has been subject to gene transfer, gene editing, or any form of genome modification. |
| Genetically modified | Adjective referring to an organism whose genotype has been modified by application of modern biotechnology (e.g., gene transfer or genome editing). |
| Genetically modified organism | Narrowly defined, a term connoting an organism that has been subject to classical gene transfer or one of its descendants bearing the transgene |
| Genome viewer | A computer program that supports the observation and interpretation of genomic DNA sequence information |
| Genomic selection | An approach to selective breeding utilizing both genotypic and phenotypic data within a population to inform improved prediction equations of the genetic merit of individuals. The possibility of selecting animals at an early stage increases genetic progress while reducing costs. |
| Germline cells | The reproductive cells of sexually reproducing organisms that contain genetic information and are passed down from one generation to the next |
| Germline stem cells | Cells that provide a continuous supply of differentiated cells that sustain fertility. Division of a germline stem cell produces two daughter cells, a stem cell and a differentiating cell. Germline stem cells are long-lived, often surviving throughout the life of an organism. |
| Germline transmission | Mendelian inheritance of traits through the formation of egg and sperm by the gonads of the parents and their subsequent combination in a zygote. |
| H5N1 virus | A subtype of highly pathogenic avian influenza virus that infects birds and can spill over into mammals, including humans. The A/goose/Guangdong/1/1996-lineage of this subtype was the first observed to make the jump into humans in 1997 in Hong Kong. Global outbreaks of this lineage have recently been observed in marine mammals, peridomestic species, cattle, and humans. Avian influenza viruses are classified by a combination of two groups of proteins: hemagglutinin or “H” proteins, of which there are 16 (H1 to H16), and neuraminidase or “N” proteins, of which there are nine (N1 to N9). Many different combinations of “H” and “N” proteins are possible. Highly pathogenic avian influenza viruses in poultry are usually H5 or H7 subtypes of type A influenza, although low-pathogenicity forms of these H5 and H7 viruses also exist. |
| Haplotype | Haploid genotype, a group of DNA variations or genetic markers on a chromosome that are usually inherited together |
| Harm | Within the context of risk assessment, a negative outcome that is realized by exposure to a hazard. In the context of food safety assessment, harm would be some negative outcome upon the consumer, such as an allergic response. |
| Harvest | The slaughter of an animal |
| Hazard | A substance or agent that, upon exposure, might result in a defined harm |
| Hazard Analysis and Critical Control Point | A food safety system that helps ensure that food is safe from biological, chemical, and physical hazards. The system is based on scientific and technical principles and is applied at every step of food processing, from harvest to distribution. |
| HGM animal | An animal bearing a heritable genetic modification |
| Highly pathogenic avian influenza | Also known as bird flu, a highly contagious disease that can affect domestic poultry, wildlife, and sometimes humans and can be deadly to poultry, wiping out entire flocks within days. |
| Homologous recombination | Rearrangement of related DNA sequences on a different molecule by crossing over in a region of identical sequence |
| Homology-directed repair | The mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can be used by the cell only when there is a homologous piece of DNA present in the nucleus, mostly in the G2 and S phases of the cell cycle. |
| Horizontal gene transfer | The transfer of genetic material among organisms not through the hereditary, vertical mechanism, but (in the context of this report) from the target animal to other organisms in the gut, the environment, or the consumer |
| Hydatidiform mole | A slow-growing tumor that develops from trophoblastic cells (cells that help an embryo attach to the uterus and help form the placenta) after fertilization of an egg by a sperm. A hydatidiform mole contains many cysts (sacs of fluid). It is usually benign, but may spread to nearby tissues or become a malignant tumor called a choriocarcinoma. |
| Immunoglobulin E | A component of the human immune system implicated in the expression of allergies |
| Indel | An insertion or a deletion at a particular genomic site, which might arise from natural mutation or from the action of a genome-editing tool |
| Insertional mutation | The creation of mutations in DNA by the addition of one or more base pairs. Insertional mutations can occur naturally, can be artificially created for research purposes, or can occur as an unwanted consequence of a genetic manipulation procedure. |
| Introgression | Permanent transmission of genes from one population into the genome of another through a series of crossing and backcrossing events |
| Kilobase | A DNA sequence 1,000 base pairs long |
| Knock-down | Reduction or loss of expression of a targeted gene by RNA interference, that is, by expression of an RNA molecule complementary to the targeted gene’s mRNA and its binding to the host mRNA for that gene, effectively interfering with expression of that gene’s product |
| Knock-in | Replacement of a gene by a mutant version of the same gene using homologous recombination |
| Knockout | Inactivation of a gene by homologous recombination following transfection with a suitable DNA construct |
| Lentivirus | A genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods in humans and other mammalian species |
| Line | A group of animals descended from one or more common ancestors |
| Linkage drag | The phenomenon in which potentially undesirable alleles that are linked to a desired gene (i.e., occur close to it on a chromosome) are incorporated when that desired gene is introgressed into the genome of a recipient line |
| Lipid nanoparticle | A nonviral vector used to deliver nucleic acids and proteins for gene transfer, which may be applied in a therapeutic context |
| Locus | A specific location on a chromosome |
| Methylation | The process in which a methyl group (CH3) is added to a chemical entity. Methylation of DNA may affect gene expression as one mechanism of epigenetics; methylation of histone proteins also may affect gene expression. |
| Microinjection | The introduction of DNA into the nucleus of an oocyte, embryo, or other cell by injection through a very fine needle |
| MicroRNA | A type of non-coding RNA that can reduce gene expression and is found in plants, animals, and some viruses |
| Mobile genetic element | A genetic structure that can move within a genome, such as a transposon |
| Monozygotic twins | Twins developing from one zygote, that is, identical twins |
| Mosaicism | The condition in which some, but not all, of the cells in a genetically manipulated individual exhibit the effects of the genetic manipulation (e.g., some, but not all, cell lineages possess that modification). This may result from integration of a transgene into the host genome having occurred after the first cell division of a treated zygote. |
| N1 generation | First offspring bred from a genome-edited founder animal |
| Nickase | An enzyme that cuts one strand of double-stranded DNA at a specific recognition nucleotide sequence’s site. Such an enzyme hydrolyses only one strand of the DNA duplex, to produce DNA molecules that are “nicked,” rather than cleaved. |
| Non-homologous end joining | A pathway that repairs double-strand breaks in DNA, called “non-homologous” because the break ends are directly ligated without the need for a homologous template, in contrast to homology-directed repair, which requires a homologous sequence to guide repair |
| 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 |
| Nutrient | Any substance normally consumed as a constituent of food that provides energy, is needed for growth and development and maintenance of healthy life, or for which a deficit will cause characteristic biochemical or physiological changes to occur |
| Off-target effects | Nonspecific, unintended genetic modifications that can arise through the use of genome-editing technologies |
| Pangenome | The complete set of genes in a species, including both common and unique genomes |
| Plasmid | A small, circular DNA molecule capable of reproduction within bacteria. Plasmids are the usual means of propagation of desired DNA sequences for subsequent use in genetic modification experiments of for other purposes. |
| Pleiotropy | A phenomenon whereby a particular gene affects multiple traits |
| Pluripotent | Adjective referring to cells that are capable of giving rise to multiple cell types |
| Polymerase chain reaction | An analytical procedure that uses primers (short pieces of synthetic DNA annealing to specific sites in the genome), temperature cycling, and a polymerase enzyme to amplify a short, targeted segment of genomic DNA |
| Porcine respiratory and reproductive syndrome virus | The causal virus for porcine respiratory and reproductive syndrome, an economically important viral disease of pigs |
| Prime editing | A genome-editing tool that offers advantages over traditional genome-editing technologies. While CRISPR-Cas9 edits rely on non-homologous end joining (NHEJ) or HDR to fix DNA breaks, the prime editing system employs DNA mismatch repair. Prime editing requires one strand break, but does not require double-strand breaks, and therefore results in reduction of off-target effects. |
| Primordial germ cell | Specialized embryonic cells formed early in development that ultimately will produce gametes in the adult gonad |
| Promoter | A region of DNA just upstream of a gene where relevant proteins, such as RNA polymerase and transcription factors, bind to initiate transcription of that gene |
| Proteome | The complete set of proteins expressed by a cell, tissue, or organism |
| Protospacer adjacent motif | A 2-6-base-pair DNA sequence immediately following the DNA sequence targeted by the Cas9 nuclease in the CRISPR-Cas9 and most other genome-editing systems. Cas9 will not successfully bind to or cleave the target DNA sequence if it is not followed by the PAM sequence. |
| Proximate analysis | A chemical analysis that determines the main components of a food item, such as its moisture, protein, fat, fiber, and ash content |
| Ratites | Any of the mostly large, flightless birds with a flat breastbone, for example, ostrich, rhea, emu, cassowary, and kiwi |
| Realized heritability | An estimate of heritability that is measured as a response to selection, that is, the ratio of the single-generation response to selection to the selection differential of the parents relative to the population mean |
| Recombinant | A genotype with a new combination of variable types, in contrast to parental type |
| Recombinant DNA | DNA that has been formed artificially by combining sequences from different organisms |
| Recombinant DNA animal | An animal in which the genetic material has been changed through recombinant DNA techniques, including direct injection of nucleic acid into cells or organelles |
| Recombinant DNA techniques | Procedures used to join DNA segments in a cell-free system (an environment outside a cell or organism). Under appropriate conditions, a recombinant DNA molecule can enter a cell and replicate there, either autonomously or after it has become integrated into a cellular chromosome. |
| Recombinase | An enzyme that catalyzes recombination events within DNA |
| Recombination | The rearrangement of genetic material, especially by crossing over among homologous chromosomes during meiosis |
| Reference genome | A DNA sequence representative of a species genome, which may represent the DNA sequence of one individual or of a collection of individuals |
| Repeat variable diresidue | The 12th and 13th amino acids of the DNA-binding domain of the TAL polypeptide. The DNA-binding domain has a series of repeats, each with a conserved 33-34 amino acid sequence, with the 12th and 13th amino acids being variable. |
| Reservoir | A host organism that harbors an infectious agent, such as a bacterium or virus, that can cause disease in another species |
| Risk | The likelihood of a defined harm 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) x P(H/E)). |
| Risk analysis | The process of considering whether to take a proposed action, involving social and political contexts in addition to the narrower range of issues considered in classical risk assessment |
| Risk assessment | The process of identifying potential harms stemming from a proposed action, which involves identifying hazards, assessing the probability of exposure to the hazards, and assessing the probability of harm being realized given exposure. Risk assessment results in a qualitative or quantitative estimate of harm posed by taking the proposed action. |
| Risk management | The practice of implementing measures or operations management practices to minimize risk. Risk management should be regarded an integral part of the risk assessment process. |
| RNA interference | A mechanism that uses RNA complementary to a target RNA transcript to bind to it and thereby reduce translation of that transcript, effectively turning off expression of that gene |
| Safe food | Foods that are safe to eat. See also Food safety. |
| SDN-1 edit | A gene edit that produces a double-stranded break in the host genome without addition of foreign DNA; host-mediated repair of this break can lead to a mutation or deletion, causing gene silencing (shutdown of transcription of a gene), gene knockout, or a change in the activity of a gene |
| SDN-2 edit | A gene edit that produces a double-stranded break and for which a small nucleotide template is supplied that is complementary to the area of the break, which is used by the cell to repair the break. The template contains one to several small sequence changes in the genomic code that the DNA repair mechanism copies into the host genome, resulting in a mutation of the target gene. SDN-1 and SDN-2 mutations can be as specific as the editing of a single base. |
| SDN-3 edit | A gene edit that induces a double-stranded break in the DNA and is accompanied by a template containing a gene or other sequence of genetic material. The cell’s DNA repair system utilizes this template to repair the break, resulting in the introduction of new genetic material. |
| Sequencing depth | The number of times that a specific DNA sequence within the genome is read during the sequencing process. Higher sequencing depth provides more confidence in the accuracy of the base calls at that position and helps reduce sequencing errors. |
| Single guide RNA | RNA that directs intact or defective Cas9 activity for base edits or Castagged activators, repressors, methylases, acetylases, or fluorescent moieties to specific loci in a target DNA in the CRISPR-Cas genome-editing system |
| Soma | The collection of cells of a living organism other than the reproductive cells |
| Somatic cell nuclear transfer | A technique in which the nucleus of a somatic cell is transferred into an enucleated metaphase-II oocyte for the generation of a new individual, genetically identical to the somatic cell donor. The technique is useful for generating whole animals from transformed cultured cells. |
| Spillover | Cross-species transmission of a pathogen or parasite into a host population not previously infected |
| Starlink | A brand of transgenic maize approved for animal feed only, but which also has been found in the human food supply |
| Structural gene | A gene that encodes a protein or RNA product, except for regulatory factors |
| Structural variants | Mutations such as inversions, deletions, insertions, duplications, and translocations ranging from indels of fewer that 50 base pairs to tens or even millions of bases |
| Syngamy | Sexual reproduction by the union of gametes |
| T2T sequencing | Sequencing of a chromosome’s DNA from one telomere to the other |
| Telomere | A region of repetitive DNA sequences at the end of a chromosome. Telomeres protect the ends of chromosomes from becoming frayed or tangled. Telomeres become slightly shorter each time a cell divides, eventually becoming so short that the cell can no longer successfully divide and dies. |
| Toxicity | The quality of being toxic or poisonous |
| Transcription activator-like effector nuclease | A restriction enzyme that can be engineered to cut specific sequences of DNA useful for targeted gene editing |
| Transduction | The transfer of genetic material between bacteria using a virus (a bacteriophage) as a carrier |
| Transfer RNA | RNA consisting of folded RNA molecules that transport amino acids from the cytoplasm of a cell to a ribosome for translation of RNA to protein |
| Transformation | A natural process in which bacteria absorb foreign DNA from their environment and incorporate it into their chromosome(s) |
| Transgene | A gene construct bearing a gene from another species that was introduced into that organism by human intervention |
| Transgenic | Adjective describing the condition of an animal bearing a gene from another species through gene transfer |
| Transposable elements | DNA sequences that have the ability to change their position within a genome. These elements can create copies that then can integrate into new genomic sites. |
| Transposase | An enzyme capable of binding to the ends of a transposon and catalyzing its movement to another part of a genome |
| Trio sequencing | Whole-genome sequencing of the parents and a focal individual, applied to detect new mutations, transgene insertions, or off-target edits |
| Variant effect prediction | Determination of the effect of a variant (a SNP, insertion, deletion, copy number variant, or structural variant) on genes, transcripts, protein sequence, or regulatory regions |
| Whole-exome sequencing | Sequencing of the protein-encoding regions of the genome |
| Xenotransplantation | Transplantation of cells, tissues, or organs from one species to another |
| Zinc finger nuclease | An enzyme that can be designed to cleave DNA at a targeted site which is useful for gene editing |
