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favor of development of genetically modified foods include to meet the demands of the exponentially growing human population, to substitute for the decrease in farmable land, and to address the decrease in genetic diversity which limits possible improvement of species. Additional benefits include improved herbicide tolerance, increased pest and bacterial/fungal/viral resistance, higher stress tolerance, and increased nutrient content within the organism. The biotechnology of genetic engineering provides the opportunity to achieve global food security by addressing these problems and positively impacting the food production economy. Potential health risks are also being researched and there are requirements for the safety of genetically modified foods to be clarified before they are consumed by the public. Environmental consequences are also considered due to disruptions within the food web when these organisms are added to a previously balanced ecosystem. As genetic modification is so fast, the environment may not be able to adapt and integrate the new organism into the ecosystem or it could have unwanted effects on its surroundings. Other impacts on the environment include unnatural gene flow, modification of soil and water chemistry, and reduction of species diversity.
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DNA with the goal of improving one's medical condition is generally accepted and has a plethora of ethical protocols monitoring such procedures. This includes modifications like organ donation, bone marrow transplants, and types of gene therapies, all of which consider cultural and religious values. On the other hand, there is contention surrounding heritable gene modification exemplified by the fact that 19 countries have outlawed this type of genetic modification. For those who believe the vitility of a human embryo is equivalent to an adult, genome editing in early development occurring at or immediately following fertilization raises moral concerns. In order to mitigate these concerns, studies using human embryos have used embryos from left over
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236:(APP) gene, known for using Alzheimer's in humans, and transmitted it into the nerve cells of worms. In doing this, scientists aimed to study the progression of Alzheimer's disease in this simple organism by tagging the APP protein with green fluorescent protein which allowed them to better visualize the gene as the worm aged. Using what they learned from experimentation with the simple worm and the APP gene, scientists increased their understanding of this gene's role in causing Alzheimer's disease in humans.
119:(WHO), genetically modified organisms are defined as "Organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination”. This type of modification can involve insertions or deletions of DNA bases into the existing genetic code. In biotechnological methodology, a series of four steps are used in order to create a genetically modified organism (GMO).
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198:: Most dandelions have long stems, but an increase in potential threats in their environment have caused average dandelion stem length to decrease within certain species, allowing them to better avoid said threats. This adaptation was possible due to a mutation occurring in a shorter-stemmed individual being
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Fast-paced developments in the CRISPR-Cas9 gene editing technology has increased both the concerns and relevance of this ethical controversy as it has become more popularly used. The scientific community recommends continued evaluation of risks and benefits of utilizing genetically modified organisms
81:
Mutation can be more accurately defined as any non-combinatorial change in phenotype that is able to be consistently inherited from parent to offspring over generations. Mutations can be attributed to many factors and come in numerous different forms, however they can mostly be attributed to mistakes
26:
occur through errors during replication and repair, either spontaneously or due to environmental stressors. Intentional modifications are done in a laboratory for various purposes, developing hardier seeds and plants, and increasingly to treat human disease. The use of gene editing technology remains
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Debate also surrounds genetically engineered food in terms of the controversial health and environmental effects that it may have in various time scales. Regulations have been implemented for approval of genetically modified foods to reduce some uncertainty that remains in this field. The reasons in
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In April 2015, gene editing technology was used on human embryos and debate about the ethics of such actions persisted since. Nonetheless, scientists and policymakers are in agreement that public deliberations should decide the legality of germ line genome editing. Modifying a person's non-heritable
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of all intensities, ranging from no observable impact at all to possible inviability. Due to environmental conditions such as climate, diet, oxygen levels, light cycles, and mutagens or chemicals which are strongly related to disease susceptibility, genes expression can vary. The timing and duration
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gene is responsible for encoding hemoglobin which carries oxygen throughout the body. However, when a person has this disease due to inheriting two mutated copies of the HBB gene due to a base pair point mutation, their red blood cells are shaped differently. This altered shape results in blockages
180:
methods are a popularly used type of the aforementioned process of genome editing. Standing for 'Clustered
Regularly Interspaced Short Palindromic Repeats', CRISPR gene editing allows scientists to manually alter gene expression, correcting errors or creating new variations. Since 2012, scientists
318:
Ethical considerations regarding gene editing are largely controversial within the scientific community due to its open ended implications for the rest of society. Although no consensus has been reached, there are plans in place to utilize the available resources to continue education, scientific
54:
using various biotechnologies. Although confusion exists between the terms "modification" and "mutation" as they are often used interchangeably, modification differentiates itself from mutation because it acts as an umbrella term, encompassing both definitions of mutation and genetic engineering.
300:
treatments. Scientists have also suggested creating fertilized zygotes from donated sperm and eggs strictly for research purposes. However, this raises an additional ethical concern within the scientific community about the concept of a zygote being created only to be used for experimentation.
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Genetic modifications can occur naturally, through aforementioned mutations in an organism's genome, or through biotechnological methods of selecting a gene of interest to manipulate in order to make something new or improve upon what already exists. This distinction between changes that occur
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in everyday life. Genetic modifications are studied by researchers under controlled conditions after they are inserted into an organism, allowing for improved scientific understanding of the effects of certain gene modifications and certain organism responses.
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Howard, Heidi C.; van El, Carla G.; Forzano, Francesca; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; de Wert, Guido; Borry, Pascal; Cornel, Martina C.; Public and
Professional Policy Committee of the European Society of Human Genetics (January 2018).
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modifications, not all instances of modification are heritable. No matter the origins of such variation at the genetic level, it clearly impacts the creation and interaction of proteins, changing cell function, phenotype, and organism function.
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Tsatsakis, Aristidis M.; Nawaz, Muhammad Amjad; Tutelyan, Victor A.; Golokhvast, Kirill S.; Kalantzi, Olga-Ioanna; Chung, Duck Hwa; Kang, Sung Jo; Coleman, Michael D.; Tyshko, Nadia; Yang, Seung Hwan; Chung, Gyuhwa (2017-09-01).
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was for the medical insulin that diabetics need to medically control their blood sugar. Through the following steps, scientists are able to genetically engineer a medical product that millions of people rely on worldwide:
59:, caused due to alterations in an organism's genotype, or their specific alleles, resulting in altered gene expression. Although heritability plays a large role in an individual's expression, like in cases of
181:
have worked to develop this technology which has the opportunity to both cure genetic diseases and genetically modify traits to be most desirable, purposefully altering DNA with a high degree of precision.
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or exposure to external factors. As cellular processes are highly efficient, they are not perfect causing disparities between organisms of the same species. These disparities can cause many different
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Scientists grow the genetically modified bacteria or yeast in large fermentation vessels, which contain all of their necessary nutrients, and allow large amounts of insulin to be cultivated.
510:
Singer, Burton H.; Ryff, Carol D.; Health, National
Research Council (US) Committee on Future Directions for Behavioral and Social Sciences Research at the National Institutes of (2001).
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than long-stemmed dandelions and were able to survive more often, the genetic frequency of the population was altered, genetically modified through the original occurrence of a mutation.
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that exist including spontaneous mutation, errors during replication and repair, as well as mutation due to environmental effects. These origins of mutations can cause many different
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A small piece of DNA is extracted from a circular form of bacterial or yeast DNA called a plasmid. A scientist will extract this DNA through using specific restriction enzymes.
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of exposure to such elements is a critical factor as well as it can significantly impact the phenotypic response of an organism, generally increasing severity with time.
409:
Dalziel, Anne C.; Rogers, Sean M.; Schulte, Patricia M. (2009). "Linking genotypes to phenotypes and fitness: how mechanistic biology can inform molecular ecology".
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A sign of the creation of a successful GMO is growth and replication with the newly edited genome with no detriments to the organism due to the new modification.
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Then, a scientist will insert the human gene for insulin into the gap left by the extracted DNA. This plasmid is now considered a genetically modified entity.
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Liang, Puping; Xu, Yanwen; Zhang, Xiya; Ding, Chenhui; Huang, Rui; Zhang, Zhen; Lv, Jie; Xie, Xiaowei; Chen, Yuxi; Li, Yujing; Sun, Ying (2015-05-01).
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of blood flow with serious health implications. On the other hand, those who inherit only one mutated copy of this gene have higher protection against
1066:"One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans"
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Genetic engineering is a type of intentional genetic modification, which uses biotechnology to alter an organism's genome. According to
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Researchers the sequence of the specific trait by comparing genomes of organisms within the same species, with and without the trait.
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1123:. Frontier Technology Quarterly: Economic Analysis and Policy Division, Department of Economic and Social Affairs. May 2019.
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naturally and those that are intentional is key to understanding the difference between mutation and genetic engineering.
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Both of these subcategorizations result in a change affect an organism's obervable characteristics, also known as their
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The insulin is then purified and packaged into bottles and insulin pens for distribution to patients with diabetes.
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529:"Discovering how environmental exposures alter genes and could lead to new treatments for chronic illnesses"
347:"Crisis of the term "mutation" and its resolution in the context of the differential concept of variability"
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research as well as research on ethical, legal, and social issues associated with genetic modification.
1269:"Impact on environment, ecosystem, diversity and health from culturing and using GMOs as feed and food"
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in genetics refers to both naturally occurring and engineered changes in DNA. Incidental, or natural
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This cell will then undergo mitosis and divide rapidly, producing insulin suitable for human needs.
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Olden, Kenneth; Freudenberg, Nicholas; Dowd, Jennifer Beam; Shields, Alexandra E. (May 2011).
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Next, they utilize the sequence(s) and various enzymes to insert the trait's genes into a
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When fermentation is complete, the mixture is filtered to produce the final the insulin.
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Researchers identify a trait of interest usually based on a desire to solve a problem.
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Visualization of genetic modification with a piece of DNA being removed by tweezers.
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The genetically modified entity is reintroduced into a new bacterial or yeast cell.
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Johnson, Irving S. (1983-02-11). "Human
Insulin from Recombinant DNA Technology".
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by environmental pressures. Because the shorter-stemmed dandelions had higher
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1224:"Genetically modified foods: A critical review of their promise and problems"
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388:. United States of America: John Wiley & Sons, Inc. pp. 354–355.
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100:
87:
47:
23:
218:
145:
487:"Environmental Control of Gene Expression | Learn Science at Scitable"
1325:. TRANSGENIC PLANTS FOR FOOD SECURITY IN THE CONTEXT OF DEVELOPMENT.
177:
758:"Ethical issues in genetic modification and why application matters"
1136:"CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes"
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232:: In a synthetic example in a laboratory, scientists isolated the
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which influence gene expression on both large and small scales.
812:"Adaptation in Weeds - Dandelion | Integrated Crop Management"
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Mediterranean
Journal of Hematology and Infectious Diseases
1222:
Zhang, Chen; Wohlhueter, Robert; Zhang, Han (2016-09-01).
608:
What are genetically modified (GM) organisms and GM foods?
692:"CRISPR-Cas guides the future of genetic engineering"
46:
are changes in an individual's DNA due to incidental
1114:"Playing with genes: The good, the bad and the ugly"
1319:"Ethical arguments relevant to the use of GM crops"
690:Knott, Gavin J.; Doudna, Jennifer A. (2018-08-31).
466:"The causes of mutations - Understanding Evolution"
1192:"What are the Ethical Concerns of Genome Editing?"
756:Munsie, Megan; Gyngell, Christopher (2018-10-01).
31:Genetic modifications (incidental and intentional)
764:. Cell reprogramming, regeneration and repair.
580:"Genetic Mutation | Learn Science at Scitable"
762:Current Opinion in Genetics & Development
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173:Image depicts the CRISPR genome editing proc
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314:Future implications of modification
1070:European Journal of Human Genetics
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894:"Sickle Cell Anaemia and Malaria"
225:Genetic engineering (intentional)
111:Genetic engineering (intentional)
995:"Ethics of Human Genome Editing"
516:. National Academies Press (US).
423:10.1111/j.1365-294X.2009.04427.x
1228:Food Science and Human Wellness
993:Coller, Barry S. (2019-01-27).
345:Tikhodeyev, Oleg (March 2015).
212:: In a healthy individual, the
630:"What is genetic engineering?"
1:
386:Fundamental Molecular Biology
384:Allison, Lizabeth A. (2012).
274:Ethics of genetic engineering
244:genetically modified bacteria
1317:Weale, Albert (2010-11-30).
1273:Food and Chemical Toxicology
604:"Food, genetically modified"
869:"About Sickle Cell Disease"
816:crops.extension.iastate.edu
1389:
1241:10.1016/j.fshw.2016.04.002
1336:10.1016/j.nbt.2010.08.013
1285:10.1016/j.fct.2017.06.033
1152:10.1007/s13238-015-0153-5
1082:10.1038/s41431-017-0024-z
999:Annual Review of Medicine
774:10.1016/j.gde.2018.05.002
545:10.1377/hlthaff.2011.0078
363:10.1134/S2079086415020103
234:amyloid precursor protein
117:World Health Organization
892:Luzzatto, Lucio (2012).
351:Biology Bulletin Reviews
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716:10.1126/science.aat5011
910:10.4084/MJHID.2012.065
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68:Types of modification
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52:genetic modification
955:1983Sci...219..632J
708:2018Sci...361..866K
667:Science in the News
663:"How to Make a GMO"
242:: The first use of
230:Alzheimer's disease
210:Sickle cell disease
1140:Protein & Cell
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105:types of mutations
88:phenotypic effects
82:that occur during
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1323:New Biotechnology
1279:(Pt A): 108–121.
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19:modifications
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1199:. Retrieved
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1120:
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1073:
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1002:
998:
946:
942:
936:
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876:. Retrieved
872:
847:. Retrieved
843:
840:"GMOs, Yes!"
819:. Retrieved
815:
806:
765:
761:
699:
695:
671:. Retrieved
669:. 2015-08-09
666:
637:. Retrieved
633:
607:
598:
587:. Retrieved
583:
536:
532:
522:
512:
505:
494:. Retrieved
490:
481:
470:. Retrieved
468:. 2021-03-15
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410:
404:
385:
379:
354:
350:
317:
308:
294:
285:
238:
228:
208:
193:
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114:
98:
94:
93:
80:
71:
43:
42:
18:
17:
15:
1076:(1): 1–11.
1201:2019-11-14
1196:Genome.gov
878:2022-02-21
873:Genome.gov
849:2019-10-24
821:2022-02-17
673:2019-11-14
639:2019-09-19
589:2022-02-26
496:2022-02-17
472:2022-02-17
323:References
61:epigenetic
1345:1871-6784
1293:0278-6915
1250:2213-4530
1160:1674-8018
1021:0066-4219
782:0959-437X
431:1365-294X
196:dandelion
125:Identify
57:phenotype
24:mutations
16:The term
1373:Genetics
1367:Category
1353:20850572
1301:28645870
1178:25894090
1100:29192152
1047:59339196
1039:30691366
1030:11299715
928:23170194
798:44075935
790:29800628
768:: 7–12.
734:30166482
563:21555469
447:23160826
439:19912534
371:18758862
200:selected
185:Examples
165:Methods:
133:Isolate
101:mutation
95:Methods:
48:mutation
1169:4417674
1091:5839051
971:6337396
951:Bibcode
943:Science
919:3499995
725:6455913
704:Bibcode
696:Science
554:3877678
240:Insulin
219:malaria
204:fitness
141:Insert
1351:
1343:
1299:
1291:
1248:
1176:
1166:
1158:
1121:UN.org
1098:
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732:
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561:
551:
445:
437:
429:
392:
369:
291:Humans
178:CRISPR
1117:(PDF)
1043:S2CID
794:S2CID
443:S2CID
367:S2CID
305:Foods
153:Grow
1349:PMID
1341:ISSN
1297:PMID
1289:ISSN
1246:ISSN
1174:PMID
1156:ISSN
1096:PMID
1035:PMID
1017:ISSN
967:PMID
924:PMID
786:PMID
778:ISSN
730:PMID
559:PMID
435:PMID
427:ISSN
390:ISBN
194:The
1331:doi
1281:doi
1277:107
1236:doi
1164:PMC
1148:doi
1086:PMC
1078:doi
1025:PMC
1007:doi
959:doi
947:219
914:PMC
906:doi
770:doi
720:PMC
712:doi
700:361
549:PMC
541:doi
419:doi
359:doi
298:IVF
214:HBB
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