Modifications (genetics)

The term modifications in genetics refers to both naturally occurring and engineered changes in DNA.
Incidental, or natural mutations 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 controversial.

Genetic modifications (incidental and intentional)

Modifications are changes in an individual's DNA due to
incidental mutation or intentional genetic modification using
various biotechnologies.[1][2] 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.[2] Both of these
subcategorizations result in a change affect an organism's obervable
characteristics, also known as their phenotype,caused due to
alterations in an organism's genotype, or their specific alleles,
resulting in altered gene expression.[3] Although heritability plays a
large role in an individual's expression, like in cases of epigenetic Visualization of genetic modification
modifications, not all instances of modification are heritable. No with a piece of DNA being removed
matter the origins of such variation at the genetic level, it clearly by tweezers.[1]
impacts the creation and interaction of proteins, changing cell
function, phenotype, and organism function.[4]

Types of modification

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.[1][2] This distinction between changes that occur naturally and
those that are intentional is key to understanding the difference between mutation and genetic
engineering.[2]

Mutation (incidental)

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.[2] Mutations can be attributed to many
factors and come in numerous different forms, however they can mostly be attributed to mistakes that occur
during DNA replication or exposure to external factors.[5] As cellular processes are highly efficient, they
are not perfect causing disparities between organisms of the same species.[5] These disparities can cause
many different phenotypic effects of all intensities, ranging from no observable impact at all to possible
inviability.[5] 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.[6][7]
The timing and duration 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.[8]

Methods:

There are several methods, or forms, of mutation that exist including spontaneous mutation, errors during
replication and repair, as well as mutation due to environmental effects.[9] These origins of mutations can
cause many different types of mutations which influence gene expression on both large and small scales.[9]

Genetic engineering (intentional)

Genetic engineering is a type of intentional genetic modification,

which uses biotechnology to alter an organism's genome.[1]
According to World Health Organization (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”.[10] This type of modification can involve
insertions or deletions of DNA bases into the existing genetic
This image depicts the general
code.[11] In biotechnological methodology, a series of four steps are
method of biotechnological genome
used in order to create a genetically modified organism (GMO).[12] editing using bacterial vectors.

1. 1. Identify
1. Researchers identify a trait of interest usually based on a desire to solve a
problem.[12]
2. Isolate
1. Researchers the sequence of the specific trait by comparing genomes of organisms
within the same species, with and without the trait.[12]
3. Insert
1. Next, they utilize the sequence(s) and various enzymes to insert the trait's genes into
a plasmid vector, which can then be inserted into bacteria to propagate the preferable
gene.[12]
4. Grow
1. 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.[12]

Methods:
CRISPR methods are a popularly used type of the aforementioned
process of genome editing.[13] Standing for 'Clustered Regularly
Interspaced Short Palindromic Repeats', CRISPR gene editing
allows scientists to manually alter gene expression, correcting errors
or creating new variations.[13] Since 2012, scientists 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.[14]

Examples

Mutation (incidental) Image depicts the CRISPR genome

editing proc
The dandelion: 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.[15] This
adaptation was possible due to a mutation occurring in a shorter-stemmed individual being selected by
environmental pressures.[16] Because the shorter-stemmed dandelions had higher fitness 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.[16]

Sickle cell disease: In a healthy individual, the HBB gene is responsible for encoding hemoglobin which
carries oxygen throughout the body.[17] 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.[17] This altered shape results in blockages of blood flow with serious health implications.[17] On
the other hand, those who inherit only one mutated copy of this gene have higher protection against
malaria.[18]

Genetic engineering (intentional)

Alzheimer's disease: In a synthetic example in a laboratory, scientists isolated the amyloid precursor protein
(APP) gene, known for using Alzheimer's in humans, and transmitted it into the nerve cells of worms.[11]
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.[11] 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.[11]

Insulin: The first use of genetically modified bacteria was for the medical insulin that diabetics need to
medically control their blood sugar.[19] Through the following steps, scientists are able to genetically
engineer a medical product that millions of people rely on worldwide:[11]

1. 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.
2. 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.
3. The genetically modified entity is reintroduced into a new bacterial or yeast cell.
4. This cell will then undergo mitosis and divide rapidly, producing insulin suitable for human
needs.
 5. 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.
6. When fermentation is complete, the mixture is filtered to produce the final the insulin.
7. The insulin is then purified and packaged into bottles and insulin pens for distribution to
patients with diabetes.

Ethics of genetic engineering

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.[20][21]
The scientific community recommends continued evaluation of
risks and benefits of utilizing genetically modified organisms in
everyday life.[22] 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.

Common products of genetic

Humans engineering

In April 2015, gene editing technology was used on human

embryos and debate about the ethics of such actions persisted since.[23] Nonetheless, scientists and
policymakers are in agreement that public deliberations should decide the legality of germ line genome
editing.[24] Modifying a person's non-heritable DNA with the goal of improving one's medical condition is
generally accepted and has a plethora of ethical protocols monitoring such procedures.[20] This includes
modifications like organ donation, bone marrow transplants, and types of gene therapies, all of which
consider cultural and religious values.[20] 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.[20]
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.[14] In order to
mitigate these concerns, studies using human embryos have used embryos from left over IVF
treatments.[14] Scientists have also suggested creating fertilized zygotes from donated sperm and eggs
strictly for research purposes.[14] 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.[14]

Foods

Debate also surrounds genetically engineered food in terms of the

controversial health and environmental effects that it may have in
various time scales.[25] Regulations have been implemented for
approval of genetically modified foods to reduce some uncertainty
that remains in this field.[26] The reasons in 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.[25] This image shows an example of
genetic modification utilized for
Additional benefits include improved herbicide tolerance, increased
agricultural benefits.
pest and bacterial/fungal/viral resistance, higher stress tolerance,
and increased nutrient content within the organism.[27] The biotechnology of genetic engineering provides
the opportunity to achieve global food security by addressing these problems and positively impacting the
food production economy.[25] 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.[28]
Environmental consequences are also considered due to disruptions within the food web when these
organisms are added to a previously balanced ecosystem.[25] 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.[27] Other impacts on the environment include unnatural gene flow,
modification of soil and water chemistry, and reduction of species diversity.[26]

Future implications of modification

Ethical considerations regarding gene editing are largely controversial within the scientific community due
to its open ended implications for the rest of society.[20] Although no consensus has been reached, there are
plans in place to utilize the available resources to continue education, scientific research as well as research
on ethical, legal, and social issues associated with genetic modification.[21]

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