Download Genetics – Human Genetic Disorders and Genetic Engineering

Genetics – Human Genetic
Disorders and Genetic
Engineering
Karyotypes
• Pictures of chromosomes, cut out and
placed in order of size and location of
centromere. Placed in homologous pairs.
Normal male karyotype
Can show chromosomal
problems:
• Down Syndrome: Trisomy 21; mental
retardation, many physical differences
Turner Syndrome – female, small
stature, infertile
Klinefelter Syndrome – male, tall
stature, infertile
These disorders result from
NONDISJUNCTION
• Failure of chromosomes to separate
normally during meiosis –
– Eggs or sperm get one too many chromosomes
or one too few.
– Ex – Down syndrome has one extra #21
–
Klinefelter has one extra X chromosome
–
Turner has one too few – only one X
Other Human Disorders
• Sickle Cell Anemia –
– autosomal recessive
– Found most often among people of African
ancestry
– Blood cells sickle (change shape) when
oxygen-deprived (exertion, increase in altitude)
– Causes sickle cell event – pain and immobility
and death of tissue ( dangerous if in organ)
– Treatment – hospitalization and oxygen
– Carriers are resistant to malaria
Tay Sachs Disease
• Autosomal recessive
• Found most often among Jews of
Mediterranean ancestry
• Child born appearing normal, but fat builds
up in brain and child dies by age 5
• No treatment, no cure
Huntington Disease
• Autosomal dominant
– Symptoms do not appear until age 30-40.
– Death takes about 5-10 years
– No treatment, no cure – but there is a test to see
if you have it before symptoms begin
– Results in mental impairment and
uncontrollable spastic movements
Phenylketonuria - PKU
• Person can’t breakdown phenylalanine (one
of the 20 amino acids)
• OK when born, but if phenylalanine not
restricted by diet, mental retardation will
result, getting worse the longer
phenylalanine is in the diet.
• Diet prevents PKU
Aneuploidy – incorrect number
of chromosomes
• Down Syndrome
• Turner Syndrome
• Klinefelter Syndrome
Deletions
• Chromosome fragment breaks off and is lost
• Cri du chat syndrome – mental retardation
and many physical problems
Prenatal Tests to detect
chromosomal problems:
• Amniocentesis – removes a little amniotic
fluid from around baby – fluid is then tested
for abnormal proteins and the cell in it can
be karyotyped.
• Risk of miscarriage
Chorionic Villus Sampling
• Take a piece of the chorionic villus from the
placenta – it is made of baby cells – and test
as in amniocentesis
– Can be done earlier than amniocentesis
– Risk of miscarriage
– Has been linked to deformed fingers
Ultrasound
• Only truly noninvasive test – sound waves
supply a view of the baby – can see many
physical deformities
• Totally risk free
Bioethical Dilemma
• Once a prenatal diagnosis of a genetic
disorder is made, what are the parents to
do?
– Do nothing and give birth to child with disorder
– Abort embryo/fetus
• Who should make the decision?
•What should enter into making the decision?
Genetic Counseling
• Genetic counselor:
– educates the parents about the disorder,
– tells them of their options without influencing
their decision,
– and tells them of the consequences of each
option
Genetic Engineering
• We can manipulate DNA and genes to alter
organisms or make them produce a product
we need.
Recombinant DNA – DNA from two
different sources joined together.
1. Cut the DNA and the plasmid using the
same restriction enzyme (these enzymes
recognize the same base sequences.
2. Insert the foreign DNA into the plasmid.
3. Replace the plasmid into the bacterium
4. Allow the bacterium to reproduce – all
future generations have the new DNA
5. Collect the product – it might be insulin or
growth hormone, or some other molecule.
III. Cloning and the Wider World
of Biotechnology (Section 15.3)
A. Definition of Cloning—To make an
exact genetic copy of; can be a gene, a
cell, or an entire organism.
B. How Dolly was cloned
1. In 1997 by researcher Ian Wilmut and colleagues
at PPL Therapeutics.
2. Figure 15.6 is Animated in the Chapter 15 Media
Lab.
a) A cell was taken from udder of adult sheep
and grown in culture in a laboratory to create
many daughter cells.
b) An egg was taken from another sheep, and its
nucleus was removed.
c) The udder cell and the
denucleated egg were fused by
electricity, stimulating the egg
to develop as if it had been
fertilized using the diploid
udder cell nucleus instead of
the sperm and egg nuclei.
d) The embryo that developed
was implanted into a surrogate
mother sheep, and was born as
Dolly, with the exact DNA from
the original udder cell.
C. Benefits of cloning—Wilmut and colleagues were not
just interested in cloning on its own; instead, they
wanted to combine cloning with recombinant DNA
technology for a variety of benefits:
1. Creating livestock that contain human genes needed
to treat genetic disorders like hemophilia (Factor
VIII).
2. Creating livestock to serve as organ donors, or blood
donors.
IV. PCR—Polymerase Chain Reaction
(Section 15.4)
A. Used to “amplify”—make large amounts of a specific
piece of DNA from a very small sample.
B. Technique: Figure 15.7
1. Heat a starting quantity of DNA to separate the
double helix.
2. Add a collection of all four nucleotides, and DNA
polymerase to copy the DNA, and some primers,
and cool the sample.
3. Primers are short sections of DNA that are
complementary to the region on both ends of the
DNA that you wish to copy. Primers act as signals
to tell DNA polymerase where to copy. As the
solution cools, they stick to the DNA you wish to
copy and allow polymerase to do its job.
4. Heating the sample again unwinds the new
duplicated strands; cooling again allows more
primers to bind. If you repeat this as a cycle, you
can make millions of copies of the original DNA.
(Interactive Activity 2)
V. Visualizing DNA Sequences (Section 15.5)
A.
So many bases, it is best to visualize them all in some organized
fashion.
1. Restriction enzymes can be used to cut the chromosomes
from many cells into manageable pieces.
2. There will be a collection of copies of fragment 1, which is a
different size than fragment 2, and so on.
3. The pieces can be ordered according to size using gel
electrophoresis (moving the fragments in an electric field
through a gel matrix). Larger pieces are more easily
retarded by holes in the gel, so they travel less than smaller
pieces: Figure 15.8
4. Animation: DNA Tool kit from Chapter 15 Media Lab:
gel electrophoresis
5. Dyes that bind DNA can then be used to visualize the
fragments as bands that can be compared to
reference DNA fragments of known size.
B. Sequencing DNA
1. Characterizing a stretch of DNA by the order of
As, Gs, Cs, and Ts.
2. Regularly performed by machine.
C. Sidebar—“DNA in the Courtroom”
1. Use of VNTRs (variable number of tandem
repeats; different individuals have different
numbers of repetitive stretches of DNA, for
example, GGAGG). One individual might have 6,
another 12.
2. VNTRs can be analyzed by gel electrophoresis,
creating a banding pattern specific to each
individual—like a bar code (Interactive Activity 3)
VI. The Human Genome Project
(Section 15.6)
A. Massive undertaking to locate and
catalogue every bit of genetic information in
the human genome.
B. Budget of $300 million in 1998
C. Limitations:
1. Knowing all the sequence is not the same
as knowing what all the genes do,
2. Just a good reference point to start.
(Interactive Activity 4)
VII. Uses of Biotechnology (Section 15.7)
A. Biopharmaceuticals: Table 15.1—drugs produced
from recombinant DNA technology
B. Human Gene Transfer—gene therapy, replacing
defective gene with a working one to treat genetic
conditions
1. Insert gene into vectors which will allow it to be
added to human cells.
2. Best cells to infect are stem cells.
3. Problems—specificity, triggering immune
response, keeping cells producing the protein over
generations.
C. Biotechnology and food:
1. Boost milk production 25 percent in cows with
bovine growth hormone made in bacteria.
2. Fast-growing salmon: Figure 15.10
C. Biotechnology and food:
3. Genetically altered crops—First came to market in
1994, by 1998 there were 45 million acres in
production. Two categories of genetic alterations:
a) Added genes for herbicide resistance
b) Added genes for killing pests: Figure 15.11
(Bacillus thuringensis Bt toxin). Concerns
about insects building resistance, plants
passing genes to wild relatives, or inadvertently
killing off beneficial insects like butterflies.
(Interactive Activity 5)
D. Benefits of DNA sequence knowledge for
understanding evolution.
VIII. Ethical Questions in Biotechnology
(Section 15.8)
A. Five percent of the Human Genome Project is
devoted to ethical ramifications
1. Ethical to modify humans, how far should we go?
Chickens without legs or eyes?
2. Will biotech produce new harmful organisms?
3. Are biotech diagnoses running far ahead of
treatments?
4. Genetic discrimination? Who can have access to
this information?