Lec 4

Question 1

Why do we not use repair and regeneration for genetic diseases

Answer 1

For genetic disease using repair and regeneration is not great because once the cells turnover you will be faced with the same problem.
Therefore we prefer the replace technique.

Question 2

basic gene and protein sizes

Answer 2

The average gene size is 27000 nucleotides
Average coding DNA is 1300 nucleotides
Average protein size is 430 amino acids (1amino is 3 nucleotides)

Question 3

Percentage of DNA in genes (introns and exons) ?

Percentage of DNA sequence in coding regions (exons) ?

Answer 3

27% and 1.5%

Question 4

where do the majority of mutations come from?

Answer 4

exons 90%

Question 5

What is a SNP

Answer 5

single nucleotide polymorphism (point mutation)

if it doesnt change the amino acid sequence it is synonymous

Question 6

what are the different type of non-synonymous SNPs?

Answer 6

Missense - when the Amino acid code changes

nonsense - when the sequence is stopped due to the SNP.

Question 7

What are INDELs

Answer 7

insertion or deletion mutations

If it isnt in multiples of 3 there is a frame shift.

Question 8

Example:

Epidermolysis Bullosa

Answer 8

From mutation in collagen 7 in the skin.
Collagen 7 gene encodes the alpha chain of Col7a1, the fibril is formed from 3 identical copies of the chain, they wind together from the C terminal.
Common Gly, x, y repeat.
There are many places in the sequence the mutation can occur, recessive forms are worse than dominant mutations.
The condition increases the risk of skin cancer (squamous cell carcinoma)
Fusion of fingers
DEBRA has been doing a lot of research into gene therapy (BM transplant)

Refer to lecture slide

Question 9

Sickle cell anaemia mutations?

Answer 9

There are 4 different mutations for SCA.
The 7th codon on exon 1 has a missense SNP glutamine changes to valine. A Polar to non-polar AA change.
Treatment includes:
Blood transfusion
BM transplant
Gene transfer/correction

Question 10

Beta-thalassaemia

Answer 10

There 250 different mutations
Majority is SNPs in introns which introduces a new splice site in the intron so the intron is inserted into the coding sequence.
Nonsense mediated decay of mRNA therefore no protein is made.
Pts get a build up of erythroid precursors, enlarged spleen, liver, heart and severe anaemia.
Tx: lifelong transfusions - but problem with iron build up
BM transplant (replace)
Gene transfer/correction