Treatment for genetic disorders using techniques that replace or

supplement the defective gene.

 But they are usually recessive, and therefore do
not cause problems.
 One dominant, normal allele can control the
production of a normal protein, so the person is
usually unaware that they have a defective gene.
 The allele frequency for the defective allele is
0.025 (in one person in 40)
 Therefore using Hardy-Weinberg, q2 = 0.025 x
0.025 = 0.000625
 In a population of 60 000 000 (roughly UK),
this means that 37,500 will suffer from this
condition.
 It is one of the commonest genetic disorders in
European/N. American populations
• Cf is caused by a deletion mutation of three bases
from the normal gene.
• The protein produced is still partly functional.
Why?
• The protein forms a trans-membrane channel for
chloride ions to move out of epithelial cells.
• Water follows the ions by osmosis. Thus the
epithelium is kept moist.
 The faulty gene produces a protein that does not
allow the chloride ions to move through.
 The epithelium is therefore too dry.
 Mucus produced from goblet cells is viscous and
sticky.
• Respiratory tract infections as cilia can’t move the cf
mucus which has trapped pathogenic organisms
entering the lungs.
• Digestive difficulties as cf mucus blocks ducts such
as pancreatic duct, through which enzymes pass to
mix with food. (These blockages form cysts, hence
the name of the condition.)
• Cf mucus blocks ducts in testes and oviducts, leading
to low fertility.
 Physiotherapy physically
moves the mucus out of
the respiratory tract.
 Enzymes are eaten with
food to help digestion.
 Antibiotics taken daily
keep infections under
control.
 There are two techniques that can help cystic
fibrosis and other genetic disorders:
 Gene replacement: the defective gene is replaced
with a healthy gene.
 Gene supplementation: one or more copies of the
healthy gene are added to the cell alongside the
defective gene. This works because the defective
gene is recessive, so the healthy gene is expressed.
 This replaces or supplements the gene in the zygote.
All cells that arise from the zygote, including the
gametes, therefore have a copy of the healthy gene
and the child should be born completely free of the
condition. Further, the next generation should also be
unaffected by the disease.
 Such a radical treatment has far-reaching ethical and
moral issues. This process is, at present, illegal.
 This targets the affected tissue, after birth.
 Only some of the affected cells are likely to take
up the healthy genes.
 All cells have a finite life. This means that the
treatment will need to be repeated when the
treated cells come to the end of their life and are
replaced by cells that carry the defective allele.
 The gametes will still carry the defective allele.
 A large number of the genes (i.e. pieces of
DNA) need to be produced/cloned. This will
be by in-vitro cloning (Polymerase Chain
Reaction).
 The gene will need to be carried into the
tissues by a vector. This could be a plasmid, a
modified virus or a liposome (sphere of lipid ).
 Viruses inject their DNA into host cells. Therefore
they should be ideal as vectors.
 The virus must be made harmless by blocking a gene
involved in its replication.
 The modified virus is then grown in cells along with a
plasmid containing the healthy gene.
 The virus takes up the plasmid plus the healthy gene.
 The cf sufferer is given the virus, often by inhalation
of a nasal spray.
 The virus infects the cells and in doing so injects the
gene.
 Lipids pass fairly readily through the phospholipid
bilayer of the cell membrane, so can introduce the
new gene into the cell.
 The gene is isolated from healthy human DNA and
inserted into a plasmid vector.
 The plasmids are put into bacterial cells. As the
bacteria multiply the plasmid plus gene is cloned (in-
vivo cloning).
 The plasmids are extracted from the bacteria and
enclosed in lipid molecules to form a liposome.
 The patient is given the liposomes as a nasal spray.
 People with this condition are unable to produce
antibodies and have no cell-mediated response.
 The defect is in a gene that codes for an enzyme, ADA.
 Copies of a normal ADA gene are isolated and cloned.
 The gene is inserted into a virus.
 The virus is multiplied in a laboratory by growing it
inside host cells.
 The viruses are mixed with the patients T-cells.
 The T-cells are then replaced back into the patient.
 Rarely, deaths have occurred as a result of the
virus.
 Immunity can develop to the virus, so it is
destroyed before it can introduce the gene.
 Liposomes are quite large, bigger than the
narrowest bronchioles, so some parts of the
lungs remain untreated.
 Even when the gene enters the cell, it is often
not expressed, for unknown reasons.
ADVANTAGES
 Can prolong life for affected
individuals
 Effective against some
cancers
 Improves quality of life for
affected individuals
 Could (germ line therapy)
reduce incidence of disease in
the population
DISADVANTAGES
 Effectiveness of treatment often
very short-lived
 Treatment needs to be frequently
repeated (somatic therapy)
 Some tissues are much less
accessible than lung or blood so
administration more difficult
 Allele in the wrong place could
cause cancer
 Gene could be over-expressed
producing too much protein
 Not likely to be useful if several
genes affected, e.g. in cancers
 Who decides what is “normal”? Clear in some examples
e.g. cystic fibrosis, but not in many other genetic
conditions.
 Must we cure genetic “faults” or accept them as part of
natural biological variation?
 Some apparently harmful conditions bring unusual
benefits: Down syndrome people hardly every suffer
from cancer because they have multiple copies of a gene
that produces an enzyme that helps eliminate mutations.
 Gene therapy and research are very expensive:
should money be spend on proven treatments
where success is more likely?
 The long-term effects of introducing genes
into a population cannot be predicted. Could it
be the forerunner of a system of eugenics?

 p105 of the revision guide has a worked

example of a data question.