To acquire an understanding of the fundamental concepts of genomics and biotechnology, and their implications for human biology, evolution, medicine, social policy and individual life path choices in the 21st century.
Pharm Animals
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En provenance du cours de University of Maryland, College Park
Genes and the Human Condition (From Behavior to Biotechnology)
443 notes
University of Maryland, College Park
443 notes
À partir de la leçon
An Introduction to Genetic Engineering and Learning the Lingo
Module Five introduces the world of genetic engineering concepts and biotechnology.
Rencontrer les enseignants
Raymond J. St. LegerProfessor
Department of Entomology
Tammatha O'BrienLecturer
Department of Entomology
[MUSIC]
Hello and welcome back.
Today I'm going to continue talking about
biotechnology by talking about pharm animals.
That's pharm like pharmacy.
These are transgenic animals that have had
their genomes permanently altered through recombinant DNA technology.
These are animals, like transgenic sheep, that carry a gene to
synthesize a protein that can treat human diseases such as cystic fibrosis.
Creating transgenic animals is much more complicated
than creating transgenic bacteria or transgenic plants.
DNA must be inserted into the nucleus of an
egg or sperm, then carefully implanted into a surrogate mother.
If successful, these babies will be born with one copy
of the gene inserted into just one chromosome, so they're heterozygous.
To create an animal that has two copies of the gene, we need
to mate transgenic animals with each
other and identify which children are homozygous.
Once we create that animal line that's homozygous for the gene, we can mate
these animals with each other and the line will carry the gene that we inserted.
The most time consuming part of creating a transgenic animal, the
process of creating the initial line of animals that are homozygous.
Once this is done, it's a relatively inexpensive to continue the animal line.
A challenge faced when creating transgenic animals is inserting
the gene in the correct location.
The gene needs to be inserted next to or with a strong constitutive promoter.
You remember, that's a promoter that's always turned on, ensur-,
ensuring that the gene is transcribed and translated at high levels.
And, if you want the gene to be expressed in, say, the milk of sheep
or goat, you need to insert it next to a milk protein, such as casein.
So, the location of the gene insertion is critical for several reasons.
Remember, just like real estate, it's all about location, location, location.
The types of transgenic animals that can be
created are endless, but not without ethical implication.
Pigs, for instance, could be genetically modified for possible
human organ transplants, by inserting HLA, the human leukocyte angigen.
And when HLA is expressed in pigs, this will
allow their tissues to be compatible matches for humans.
But obviously there's a controversy over using animals, and specifically pigs.
As there could be cultural or religious issues, as well as ethical issues
at having to kill ascension animal to harvest tissue such as the heart.
But, by using animals to make human compatible organisms this would something
alleviate some, the sometimes fatal waiting game of long organ donor lists.
Another interesting aspect of DNA technology
is RNAi, also called RNA interference.
This is when a gene is inserted backwards
and makes a backwards copy of the transcript.
I'll explain how this affects gna-, gene transcription and translation.
The native RNA, that's the RNA that's normally
found in your body, that your body makes, will
bind with the backwards copy of the RNA that
we've created and produce a double stranded RNA complex.
This double stranded RNA complex will be cut off by your body.
That's because the cells of your body know that RNA should not be double stranded.
And it shouldn't be in your cells.
So, our cells have mechanisms to remove and destroy that double stranded RNA.
Scientists first observed the action of this RNAi,
when working with a flower called the petunia.
At the time they didn't fully understand what was happening.
They wanted to make a really purple flower, so they added
extra copies of the gene that coded for the purple pigment.
Well, in some plants, the extra purple pigment was inserted backwards.
And backwards copied the RNA transcript was made.
Instead of creating an
intensely super purple petunia, the researchers had flowers with
patches that were white, and lacked all purple pigment.
How could that be if they just inserted genes to make a lot of purple pigment?
The answer, as we now know, is RNAi.
When this double stranded RNA is encountered, not only do you destroy the
double stranded RNA, but our cells will go back and locate the original DNA
sequence that corresponded to the RNA and that sequence will be heavily methylated.
And do you remember what happens to DNA when it's heavily methylated?
The gene will no longer be expressed.
We can use what we know about RNAi to stop the expression of mutated
proteins that we see in certain cancers, or in the case of Huntington's disease.
That's due to a mutated Huntington protein that builds up in the brain.
You may have heard of gene therapy.
Gene therapy works to fix defective genes
by replacing them with properly functioning genes.
So, instead of removing gene function, like with
RNAI, we'll now discuss how to restore gene function.
One way to do that is by using transgenic viruses that contain a
properly functioning gene, along with a promotor
that'll be incorporated into a person's genome.
This introduced gene with its promotor will encounter,
enter the genome, replacing the function of a defective or missing gene.
Right now, gene therapy focuses on
treating diseases caused by single gene mutations.
Gene therapy's been approved for treating,
treatment of lipoprotein lipase deficiency, which affects
bod, the bodies ability to breakdown fatty acids and can cause severe pancreatitis.
With all of this DNA technology, ethical questions can be raised.
But most of us agree that using
this technology to treat diseases seems reasonable.
But, should genetically engineered human growth hormone be
used to stimulate growth in children who are deficient?
What would you consider deficient?
Should someone who's short, because both her
parents are short, be treated with growth hormone?
What about somebody who makes almost no growth hormone?
Where's that
threshold that warrants treatment?
So usually, short parents, we get short children.
But what if these parents just wanted a taller son?
And I say son, because parents are much less likely
to take a short daughter to get growth hormone therapy.
So should parents be allowed to use this medical
treatment to help a son develop a few inches taller?
The growth hormone shots can be painful, and
it teaches a child that they're not good enough
the way they are.
Is simply being short a condition that warrants medical intervention?
How do we decide what, when and who should be treated?
We can also use these technologies to diagnose disease.
In 2010, a young boy, Nicholas Volker, had a
serious intestinal issue that warranted many, many, many surgeries.
And the underlying cause of his intestinal condition wasn't known.
So, even though he underwent medical surgeries
to correct the symptoms, they didn't fix the
cause of his disease because doctors didn't
know what the cause of his disease was.
So they decided to do something extraordinary.
His doctors and researchers decide to sequence Nicholas' genome.
Researchers examined his genes, looking for the cause of this
rare disease to identify it, so they could hopefully treat it.
They found a mutation responsible for his intestinal
disease in a gene called X-linked inhibitor-of-apoptosis, XIAP.
He was deficient in it, so he had a point mutation.
Remember where we discussed point mutations in week one and,
with reference to the sickle cell trait?
In this case, it was just one substitution of
the 203rd amino acid of almost 500 amino acids.
And the amino acid, which was supposed to be
cytosine was pro-, was a completely different amino acid.
Tyrosine was present, which gave the protein a completely different shape.
And a different protein shape means the function of the protein was altered.
XIAP has two important jobs.
It blocks the process that makes cells die, which is called apoptosis
and it also helps prevent the immune system from attacking our intestines.
In the case of this young boy, the protein had an incorrect
sequence, so in his body the immune system was attacking his intestines.
This is called an autoimmune disease.
When the medical team diagnosed the correct gene defect, they gave
Nicholas a blood cord transplant using stem cells, that matched and
cured his gene defect.
The last interesting question for us to consider
in this talk has to deal with bio-technologies.
And should companies be allowed to own or patent genes?
Let's examine one gene, it's called delta 32 version CCR5.
It's inherited in a simple recessive fashion.
What that means is someone has to have two copies of delta 32
allele in order to have none of the CCR5 proteins present on their cells.
And people with two copies of this allele
are highly resistant to the common type of HIV.
They can be vulnerable to other strains.
But for the common HIV strain, it's very
difficult for the virus to enter the cells.
So, a patent of the gene, the CCR5 gene was given in 2000.
And obviously there was a lot of outrage in the scientific community.
Who should own the right to this gene sequence?
Should anyone own it?
Also back in 2000, a woman in England wanted
to become the first person to patent herself.
Donna McLean filed a patent for her
genomes stating that she was novel and useful.
In the United States there's been a lot of controversy over patenting genes.
BRCA, the breast cancer genes have been in
the news a lot, dealing with this patent law.
Patenting genes really limits the information available to researchers.
And because of this, the Supreme Court ruled in
2013, that naturally occurring genes may no longer be patented.
Not everyone was happy about this, as many private
industries kind of hoped to cash in on that patent.
[MUSIC]
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