Genetics Human Genetic Disorders and Genetic Engineering

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Genetics Human Genetic Disorders and Genetic
Engineering
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Karyotypes

• Pictures of chromosomes, cut out and placed in
  order of size and location of centromere. Placed
  in homologous pairs.

Normal male karyotype
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Can show chromosomal problems

• Down Syndrome Trisomy 21 mental retardation,
  many physical differences

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Turner Syndrome female, small stature,
infertile
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Klinefelter Syndrome male, tall stature,
infertile
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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

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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

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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

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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

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Phenylketonuria - PKU

• Person cant 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

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Aneuploidy incorrect number of chromosomes

• Down Syndrome
• Turner Syndrome
• Klinefelter Syndrome

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Deletions

• Chromosome fragment breaks off and is lost
• Cri du chat syndrome mental retardation and
  many physical problems

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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

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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

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Ultrasound

• Only truly noninvasive test sound waves supply
  a view of the baby can see many physical
  deformities
• Totally risk free

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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?

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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

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Genetic Engineering

• We can manipulate DNA and genes to alter
  organisms or make them produce a product we need.

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Recombinant DNA DNA from two different sources
joined together.

• Cut the DNA and the plasmid using the same
  restriction enzyme (these enzymes recognize the
  same base sequences.
• Insert the foreign DNA into the plasmid.
• Replace the plasmid into the bacterium
• Allow the bacterium to reproduce all future
  generations have the new DNA
• Collect the product it might be insulin or
  growth hormone, or some other molecule.

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• III. Cloning and the Wider World of Biotechnology
  (Section 15.3)
• A. Definition of CloningTo make an exact genetic
  copy of can be a gene, a cell, or an entire
  organism.

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• 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.

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• 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.

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• 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.

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• C. Benefits of cloningWilmut 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.

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• IV. PCRPolymerase Chain Reaction (Section 15.4)
• A. Used to amplifymake 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.

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• 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)

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• 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.
• 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

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• 4. Animation DNA Tool kit from Chapter 15 Media
  Lab gel electrophoresis
• 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.

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• B. Sequencing DNA
• 1. Characterizing a stretch of DNA by the order
  of As, Gs, Cs, and Ts.
• 2. Regularly performed by machine.

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• C. SidebarDNA 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
  individuallike a bar code (Interactive Activity
  3)

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• 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)

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• VII. Uses of Biotechnology (Section 15.7)
• A. Biopharmaceuticals Table 15.1drugs produced
  from recombinant DNA technology
• B. Human Gene Transfergene 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. Problemsspecificity, triggering immune
  response, keeping cells producing the protein
  over generations.

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• 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

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• C. Biotechnology and food
• 3. Genetically altered cropsFirst 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)

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• D. Benefits of DNA sequence knowledge for
  understanding evolution.

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• 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?