MCB Lecture 22 Gene Expression II Flashcards
Describe the function of haemoglobin
It carries four oxygen molecules per haemoglobin. It transports oxygen in the blood from lunch to tissue
Describe the structure of haemoglobin
Two alpha subunits, two beta subunits
It’s a tetramer
Describe the evolution of globin genes
There was a single gene
500 years ago: alpha and beta diverged
300 years ago: beta became epsilon, gamma, deta and beta
There are pseudogenes: chi globin
Describe the features of the beta globin gene cluster
It is highly conserved
Has pseudogenes
Has LINEs and SINEs
What are the chi genes an example of?
Pseudogenes
What is the epsilon gene?
It is the embryonic version of beta globin
What is the delta gene?
It is an adult beta globin, it has very low expression
What is the gamma gene?
It is the foetal globin instead of beta.
It has a high affinity for oxygen
What is the beta gene?
It is the adult version of the globin
How many copies of the alpha gene are there?
2
Describe the differential expression of the different globin genes during development. This is a classic example of …
Statiotemporalexpression
Embryo yolk sac: epsilon
Foetus, liver: gamma
Bone. Murrow in adult: beta
What controls the statiotemporalexpression of the globin genes?
Describe how this mechanism works
LCR
This is an enhancer that selectively activates either epsilon, gamma or beta globin
- Tissue specific signals bind to LCR
- Pre-initiation complex forms
- Appropriate gene is transcribed
What is an insulator?
It makes sure that the enhancer doesn’t activate inappropriately certain genes
The two insulators come together, forming a loop where all the globin genes are.
What are haemoglobinopathies?
Give examples
These are disorders of haemoglobin
Sickle cell anaemia
Alpha and beta thalassaemia
Describe the features of sickle cell anaemia
The cell is sickled and blocks arteries and can’t deliver enough oxygen
Describe how SCD arises. What is the mutation?
There is a mutation in the beta globin gene.
When the haemoglobin is synthesised, they all stick together in a rigid chain
Describe the mutation and how it arises in alpha thalassaemia
There is unequal crossing over of the alpha thalassaemia genes and then there is a reduced number of alpha globin genes
Describe the 5 categories of alpha thalassaemia
Four copies: Normal 3 copies: carrier 2 copies: minor 1 copy: major 0 copies: death
Describe the possible mutations leading to beta thalassaemia
SNP in promoter region, 5’ UTR, intron consensus sequences
What is important about beta thalassaemia and new born babies?
Newborn babies appear normal because they aren’t using beta globin yet, (still gamma)
The beta thalassaemia occurs later
Compare oxygen affinity in gamma and beta globin
Gamma has a higher affinity for oxygen
