19.2. Genetic technology applied to medicine

Question 1

Bioinformatics

Answer 1

the use of large and computer software to store and analyse information about living organisms
- for example, there are now databases listing the base sequences of DNA in several people

Question 2

Role of Bioinformatics

Answer 2

information stored in these databases is available to scientists all over the world

Uses:

• people have different combinations of alleles of genes in their cells, and this can effect their susceptibility to diseases and the way in which drugs work in their bodies
• knowing the detailed DNA sequences of different species or varieties of plasmodium can help scientists to develop drugs that will act against them
• matches can be made between DNA sequences and protein sequences, which can help to unravel how genes affect metabolism and therefore health
• when a genome has been sequenced, comparisons can be made with other known genomes.

Question 3

Advantages of producing human proteins by recombinant DNA techniques

Answer 3

• Production requires little space and can be undertaken
  almost anywhere
• Lots of protein product can be produced (continuously)
• Easy to cultivate under controlled conditions
• Supply doesn’t rely on harvesting from animals or donors (religions and cultures may be against the idea of harvesting insulin from a dead animal)

Question 4

Disadvantages of producing human proteins by recombinant DNA techniques

Answer 4

Proteins produced by bacteria are not identical to
human proteins as they do not modify them as humans
do
- It is much better, therefore, to use eukaryotic cells to produce human proteins.

Question 5

Examples of producing human proteins by recombinant DNA techniques

Answer 5

1) Factor VIII - haemophilia treatment, produced by GM hamster cells
2) Adenosine deaminase - severe combined immunodeficiency (SCI), produced by GM bacteria
3) Insulin - diabetes treatment, produced by e.coli

Question 6

Producing Factor VIII

Answer 6

• Genetically modifed hamster cells are used by several
  companies to produce factor VIII.
• This protein is essential for blood clotting, and people who cannot make it are said to have haemophilia.
• The human gene for making factor VIII has been inserted into hamster kidney and ovary cells
  which are then cultured in fermenters.
• The cells constantly produce factor VIII which is extracted and purifed before being used to treat people with haemophilia.
• These people need regular injections of factor VIII which, before the availability of recombinant factor VIII, came from donated blood.
• Using donated blood carried risks of infection – for
  example, from HIV
• Recombinant factor VIII avoids such problems.

Question 7

Producing Adenosine deaminase

Answer 7

• High yields of the enzyme adenosine deaminase
  (ADA), which is used to treat severe combined
  immunodefciency disease (SCID), are made by a
  genetically modifed insect larva, the cabbage looper moth caterpillar.
• This enzyme is administered to patients while they are waiting for gene therapy or when gene therapy is
  not possible

Question 8

Genetic Screening

Answer 8

analysis of a person’s DNA to check for the presence of a particular allele.

Question 9

Uses of Genetic Screening

Answer 9

1) Identify people who are carriers
2) in preimplantation genetic diagnosis
3) for prenatal testing (amniocentesis)
4) to identify people who will develop a genetic condition later in life
5) to identify people with alleles that put them in risk of developing other diseases

Question 10

Uses of Genetic Screening in identifying people who are carriers

Answer 10

• people may have a copy of a harmful recessive allele
• cystic fibrosis allele, sickle cell anaemia allele or haemophilia allele
• a couple with one of these genetic conditions in the family could therefore find out if they are both heterozygous and therefore might have a child with the condition

Question 11

Uses of Genetic Screening in preimplantation genetic diagnosis

Answer 11

• to check the genes of an embryo produced in vitro (fertilisation outside of the body) before it is placed in the mother’s uterus
• this can ensure that only embryos that do not have the genes for a genetic disease are implanted

Question 12

Uses of Genetic Screening for prenatal testing (amniocentesis)

Answer 12

• amniocentesis
• checking the genes of an embryo or fetus in the uterus
• this could enable the mother to decide to have her pregnancy terminated if the baby would have a genetic disease

Question 13

Uses of Genetic Screening to identify people who will develop a genetic condition later in life

Answer 13

• For example, Huntington’s disease is caused by a dominant allele, but does not manifest itself until middle age
• a person in the family could check if they have the gene before they decide to have children themselves

Question 14

Uses of Genetic Screening to identify people with alleles that put them in risk of developing other diseases

Answer 14

• For example, a woman who has relatives with breast cancer could find out if she has the BRCA1 or BRCA2 alleles
• These alleles are known to be associated with an increased rick of breast cancer, and could decide to have a mastectomy to prevent developing the illness

Question 15

Gene Therapy

Answer 15

Treatment of a genetic disease by changing the gene in a person’s cells.

It is only suitable for:

• diseases caused by a single gene
• diseases caused by a recessive allele of a gene
• serious diseases for which treatment is limited and no other cure is possible

Question 16

Vectors used for gene therapy

Answer 16

• Viruses (often retroviruses)
• Liposomes
• Naked DNA

Question 17

SCID (severe combined immunodefciency)

Answer 17

• immune system is crippled and sufferers die in infancy
  from common infections
• caused by a lack of the enzyme adenosine deaminase (ADA)
• the enzyme is vital for the functioning of the immune system.
• results from mutations in the gene for this enzyme

Question 18

Gene Therapy for SCID

Answer 18

• trials have been carried out using viruses as vectors
• T-lymphocytes were removed and normal alleles of the ADA gene were introduced into them
• This was not a permanent cure - regular transmissions were necessary to keep immune system functioning
• New method of gene therapy using stem cells harvested from bone marrow was successful
• Retroviruses insert their genes into the host’s genome, but they do so randomly.
• This means that they may insert their genes within another gene or, more dangerously, into the regulatory sequence of a gene, which may then activate a nearby gene causing cancer.
• The adeno-associated virus (AAV) is also now used as a vector. This virus does not insert its genes into the host genome and so they are not passed on to daughter cells when a cell divides - no cancer

Question 19

Cystic Fibrosis

Answer 19

a genetic disorder in which abnormally thick mucus is produced in the lungs and other parts of the body

• very prone to bacterial infections in the lungs because it is difficult for the mucus to be removed, allowing bacteria to breed in it
• The thick mucus adversely affects many other parts of the body.
• pancreatic duct may become blocked
• thick secretions block ducts in the reproductive system. so men become sterile

Question 20

Cystic Fibrosis Causes

Answer 20

• caused by a recessive allele of the gene that codes for a transporter protein called CFTR
• this protein sits in the cell surface membranes of cells in the alveoli (and also elsewhere in the body) and allows chloride ions to pass out of the cells.
• the recessive allele codes for a faulty version of this protein that does not act properly as a chloride ion transporter
• normally, the cells lining the airways and in the lungs
  pump out chloride ions (Cl−) through the channel in the
  cell surface membrane formed by CFTR.
• This results in a relatively high concentration of chloride ions outside the cells and reduces the water potential below that of the cytoplasm of the cells.
• So water moves out of the cells by osmosis, down the water potential gradient. It mixes with the mucus there, making it thin enough for easy removal by the sweeping movements of cilia
• However, in someone with cystic fibrosis, much less water moves out of the cells, so the mucus on their
  surfaces stays thick and sticky.
• The cilia, or even coughing, can’t remove it all.

Question 21

Gene Therapy for Cystic Fibrosis

Answer 21

• faulty CFTR alleles are recessive and caused by a single gene
• If the normal dominant allele could be inserted into
  cells in the lungs, the correct CFTR should be made.
• In theory, there is no reason why this should not happen.
• In practice, there have been major problems in getting
  the allele into the cells.
• The normal allele was inserted into liposomes (tiny balls of lipid molecules), which were then sprayed as an aerosol into noses
• This succeeded in introducing the allele into a few cells lining the nose, but the effect only lasted for a week, because these cells have a very short natural lifespan.
• Occasionally, DNA has been inserted directly into
  tissues without the use of any vector.
• This so-called naked DNA has been used in trials of gene therapy for skin, muscular and heart disorders.
• The advantage of using this method is that it removes the problems associated with using vectors.

Question 22

Choroiderernia

Answer 22

• genetic condition in which cells in the retina gradually die
• due to the faulty allele of the CHM gene on the X chromosome
• several patients have now had their eyesight restored after viruses carrying normal alleles of the CHM gene were injected beneath their retinas in one eye

Question 23

Somatic Therapy

Answer 23

• transfer of a section of DNA to any cell of the body that doesn’t produce sperm or eggs.
• effects of gene therapy will not be passed onto the patient’s children

Question 24

Germline Gene Therapy

Answer 24

• transfer of a section of DNA to cells that produce eggs or sperm
• effects of gene therapy will be passed onto the patient’s children and subsequent generations
• currently illegal in humans

Question 25

Social and Ethical concerns using gene testing and gene therapy

Answer 25

• how would the genetic screening affect a person’s life if they find out they have a genetic condition
• what would embryo do if it has cystic fibrosis
• is it allowed for IVF couples to choose gender of child