HUMAN GENETICS

GENETIC ENGINEERING
History:
• Genetic engineering previously referred to various techniques used for the
manipulation and modification of organisms through process of heredity and reproduction
(artificial selection, artificial insemination, in vitro fertilisation, cloning,...) until the later
part of the 20th century
• In 1960s after discovery of DNA, scientists bombarded plants with radiation in order
to cause mutation & obtain useful variation by pure chance (science in 60s was wild)
• In 1970s scientists inserted DNA snippets into bacteria, plants, and animals to
modify and study them
• In 1974 a first genetically modified animal was born (it was a mouse)
• In 1980s a patent was given for a microbe engineered to absorb oil
• In 1990s we took a first step into human engineering, for example, to treat infertility
in mothers, babies were made in a way that they carried genetic information from 3 humans

• The more recent genetic engineering used methods of GENE CLONING, in which
DNA from two or more sources is combined (within cells or in vitro) and are inserted into
host organisms in which they are able to propagate
o this became possible thanks to the discovery of RESTRICTION ENZYMES in 1968
by a Swiss microbiologist Werner Arber
1969- Hamilton O. Smith purified type II. Restriction enzymes= important for genetic
engineering thanks to their ability to cleave (adhere firmly and closely) a specific site within
the DNA (type I. Restriction enzymes cleave DNA at random sites)

Process and techniques:

• Most recombinant DNA technology involves the insertion of foreign genes into the
plasmids of common lab stains of bacteria (E. coli is commonly used thanks to its fast
reproduction rate and simple maintenance) – this allows the researchers to obtain almost
limitless number of copies of the inserted gene
o if the gene is operative (directs protein synthesis), the modified bacteria will produce
the specified protein, for example insulin- thanks to insulin producing bacteria we don´t
need to extract it from animal organs (which is more efficient and effective)

GENE THERAPY
• a medical approach that treats or prevents disease by correcting the underlying
genetic problem
• Its techniques allow doctors to treat a disorder by altering a person’s genetic makeup
instead of using drugs or surgery

The earliest method of gene therapy, often called GENE TRANSFER or GENE ADDITION,
was developed to:
o Introduce a new gene into cells to help fight a disease
o Introduce a non-faulty copy of a gene to stand in for the altered copy causing disease

GENOME EDITING (an example of which is CRISPR-Cas9)

CRISPR-Cas9
• clustered regularly interspaced short palindromic repeats and CRISPR-associated
protein 9
• In 21st century a new revolutionary technology in genetic engineering has been
discovered= CRISPR
• It allowed the cost of genetic engineering to drop by astonishing 99% and instead of
years it now takes weeks to conduct an experiment + it is much simpler and more accurate
than before

Where does CRISPR come from?

o adapted from a naturally occurring genome editing system that bacteria use
as an immune defence
o when infected with viruses, bacteria
capture small pieces of the viruses' DNA and
insert them into their own DNA in a particular
 pattern to create segments known as CRISPR
arrays
o The CRISPR arrays allow the bacteria to
"remember" the viruses (or closely related ones)

How does it work?

• If a virus attacks again, the bacterium makes an RNA copy from the archive and
activates a protein CAS-9 or a similar enzyme = scans the bacterium's insides for signs of the
virus genes by comparing every bit of DNA to the sample from CRISPR
• When it finds a perfect match, it activates, cuts out the viral DNA and disables the
virus

How do we use it?

• CRISPR is modifiable, we can give it a copy of DNA we want to modify and put the
system into a living cell
• It is very precise, cheap and easy to use

• it is being studied to:

o Fix a genetic alteration underlying a disorder, so the gene can function properly
o Turn on a gene to help fight a disease
o Turn off a gene that is functioning improperly
o Remove a piece of DNA that is impairing gene function and causing disease (prevents
genetic mutation from developing)

● It allows us to modify living cells and target and study particular DNA sequences

• so far, gene therapies treat a small number of diseases, including:

o an eye disorder- Leber congenital amaurosis
o a muscle disorder- Spinal muscular atrophy

● With the improvement of this technology we will be able to treat more and more
diseases, for example: mice in labs that are infected by HIV virus have been treated
almost completely with CRISPR, which gives us hope to find a cure for this disease

• CRISPR is only the beginning, new and better tools are being made and used all the
time, but without CRISPR it wouldn't have been possible
APPLICATION
• Agriculture- genetically modified organisms (GMOs)
o Majority of food we eat has been genetically modified
• Medicine- insulin, human growth hormone
• Products- golden rice (contains vitamin A), bacteria producing milk (with same
nutrition values as normal milk), yeast injected with carrot genes + a blueprint for DNA
printing
• Fun little things :P- glowing fish, bioluminescent plants

AGEING AND GENES

• In a new study led by Thomas Stoeger published on 9th of December, researchers
used artificial intelligence to analyse data from a wide variety of tissues, collected from
humans, mice, rats and killifish. They discovered that the length of genes can explain most
molecular-level changes that occur during ageing.
o They found that longer genes are linked to longer lifespans, and shorter genes are
linked to shorter lifespans
o They also found that ageing genes change their activity according to length. More
specifically, ageing is accompanied by a shift in activity toward short genes. This causes the
gene activity in cells to become unbalanced.

● Ageing is also related to shortening of telomeres and subsequent damage to the

genetic information contained inside of a chromosome
● That causes the cell to "forget" it's role and eventually die
● As we age, our bodies are less efficient at replacing the damaged tissues
● What to do to slow down ageing?
○ Eat less and limit protein intake
○ Exercise more HIIT trainings
○ Avoid DNA damage (radiation (wear sunscreen for example))
○ Be uncomfortably cold or hot

GENE REGULATION
• is the process used to control the timing, location and amount in which genes are
expressed
• the process can be complicated and is carried out by a variety of mechanisms,
including through regulatory proteins and chemical modification of DNA
• it is key to the ability of an organism to respond to environmental change
• thanks to gene regulation, each cell type in our body has a different set of active
genes – despite the fact that almost all the cells of our body contain the exact same DNA,
these different patterns of gene expression cause various cell types to have different sets of
proteins, making each cell type uniquely specialised to do its job
For example, one of the jobs of the liver is to remove toxic substances like alcohol from the
bloodstream. To do this, liver cells express genes encoding subunits (pieces) of an enzyme
called alcohol dehydrogenase. This enzyme breaks alcohol down into a non-toxic molecule.
The neurons in a person's brain don’t remove toxins from the body, so they keep these genes
unexpressed, or “turned off.” Similarly, the cells of the liver don’t send signals using
neurotransmitters, so they keep neurotransmitter genes turned off.

How do cells "decide" which genes to turn on?

Broadly speaking, we can say that a cell's gene expression pattern is determined by
information from both inside and outside the cell.
• Examples of information from inside the cell: the proteins it inherited from its
mother cell, whether its DNA is damaged, and how much ATP it has.
• Examples of information from outside the cell: chemical signals from other cells,
mechanical signals from the extracellular matrix, and nutrient levels.

Cells have molecular pathways that convert information – such as the binding of a chemical
signal to its receptor – into a change in gene expression.

GENETIC
ABSTRACTION