Genetics

hi,

i have these questions that i,m finding quite difficult i would appreciate it if anyone could help.

1) explain why viruses are useful as vectors?
2) suggest a reason why gene theraphy for the treatment of cystic fibrosis has not yet been very successful?
3) in the UK, 1 in every 2,500 children have cystic fibrosis. what is the frequency of the cystic fibrosis allele in children in the UK?

hope someone is able to help.

thanks
if u have any questions about these questions please do mail me.

thanks
regards
kubra

Reply 1

Revenged

kubra

1) Viruses, like HIV, can become incorporated into a cells DNA... HIV isn't a virus vector for obvious reasons!

2) Because genes have multiple effects that are not well understood... gene therapy was done experimentally on some children with no immune system due to a genetic defect, half got completely better whereas the other half got leukaemia (cancer of the lymphatic system)

3) There's not much you can say with such limited info...

At least 1 in every 1250 children would have the allele... As there is a 50% two carriers as parents will give birth to a carrier whereas there is a 25% chance they will give birth to someone with a cystic fibrosis...

Should be more common than that though bearing in mind that only 1 carrier has a 50% to pass on the allele to the offspring...

Reply 2

laurcor

1) viruses work by inserting their DNA into the hosts DNA (our DNA) in order to make new viruses, its how they multiply, once the virus DNA is inserted into to the host, the host expresses the virus gene as if it were its own and makes virus protein which is put together to make another virus which then infects other cells. you can put in a gene into a virus genome which codes for a protein you need eg insulin, the new virus can still infect cells (eg insect, mamalian cells or bacteria) and put its DNA into the genome of the host.(including the gene you have put in the DNA). the host expresses your gene and the protein you need is made by the host.

2) cystic fibrosis affects the lungs so this is where you have to insert a gene that is defective in people with cystic fibrosis. mucus in the respiratory tract keeps foreign particles out of the lung. Gene vecors are also kept out.

3) the Hardy-Weinberg equation will give the answer,
that is p2 + 2pq + q2 =1 and p + q = 1

p = frequency of the dominant allele in the population
q = frequency of the recessive allele in the population (the cystic fibrosis allele in this case) this is what your looking for.
p2 = percentage of homozygous dominant individuals
q2 = percentage of homozygous recessive individuals (both alleles are the defective, a person who is homozygous recessive for cystic fibrosis would have the disease)
2pq = percentage of heterozygous individuals

cystic fibrosis is a recessive disease so each child with the disease will have to carry the defective gene on each allele

q2 is 1/2,500 or 0.0004. Therefore, q is the square root, or 0.02.
so the frequency of the cystic fibrosis (recessive) allele is 0.02 (or 2%), or 1in 50.

Reply 3

kubra

thanks great answers.

Reply 4

kubra

i dont know what i'd do without this forum and u people.

Reply 5

Helenia

Cystic fibrosis was actually initially thought to potentially be an ideal disease for gene therapy, because it was caused by a single mutation in a single protein, and the area where its expression causes most problems (the lungs) is very easily accessible. Theoretically, you could just inhale a nebulised viral solution and they would be taken up into the alveolar epithelium and express the CFTR - problem solved!

However, a number of barriers prevent this:
1) As has already been mentioned, cystic fibrosis sufferers have a lot of thick, sticky mucus in their lungs, which it would be hard to penetrate with the vector.
2) The alveolar epithelium is recycled frequently, so after a few months none of the cells which had been infected would be left, and the patient would need to take the treatment again.
3) Because it is a virus, the body will mount an immune response against it. Therefore if it is re-administered, it would not be able to infect cells as the immune system would fight it off.

They have attempted to use different vectors (e.g. adenoviruses which I think are less immunogenic; or liposomes containing the DNA) but so far these have been too unstable to establish long-term CFTR expression.

Reply 6

LordBishek

Hehe, First post. Nice to be here. Anyway, I thought that the CF mutation can be caused by many mutations in the gene code for the CFTR protein? Am I running around with half-baked knowledge, or am I right? Someone confirm me or put me right, because I'm confused :frown:

Reply 7

Helenia

LordBishek

There are different mutations which can cause CF, yes. By far the most common one though, is the ΔF508 mutation, which is found in ~70% of patients.

However, what I meant was (though it probably wasn't clear) - that one mutation in one gene is enough to cause disease. There are lots of diseases with genetic components, but they are a result of multiple mutations in multiple different genes, meaning that fiddling with DNA is not going to fix them easily. CF is an easy target because it only takes one mutation to produce an ineffective protein and cause disease. The nature of the mutation is probably beyond A-level :wink: