MCB Lecture 22 Gene Expression II

Question 0

Describe the function of haemoglobin

Answer 0

It carries four oxygen molecules per haemoglobin. It transports oxygen in the blood from lunch to tissue

Question 1

Describe the structure of haemoglobin

Answer 1

Two alpha subunits, two beta subunits

It’s a tetramer

Question 2

Describe the evolution of globin genes

Answer 2

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

Question 3

Describe the features of the beta globin gene cluster

Answer 3

It is highly conserved
Has pseudogenes
Has LINEs and SINEs

Question 4

What are the chi genes an example of?

Answer 4

Pseudogenes

Question 5

What is the epsilon gene?

Answer 5

It is the embryonic version of beta globin

Question 6

What is the delta gene?

Answer 6

It is an adult beta globin, it has very low expression

Question 7

What is the gamma gene?

Answer 7

It is the foetal globin instead of beta.

It has a high affinity for oxygen

Question 8

What is the beta gene?

Answer 8

It is the adult version of the globin

Question 9

How many copies of the alpha gene are there?

Answer 9

2

Question 10

Describe the differential expression of the different globin genes during development. This is a classic example of …

Answer 10

Statiotemporalexpression

Embryo yolk sac: epsilon
Foetus, liver: gamma
Bone. Murrow in adult: beta

Question 11

What controls the statiotemporalexpression of the globin genes?
Describe how this mechanism works

Answer 11

LCR
This is an enhancer that selectively activates either epsilon, gamma or beta globin

1. Tissue specific signals bind to LCR
2. Pre-initiation complex forms
3. Appropriate gene is transcribed

Question 12

What is an insulator?

Answer 12

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.

Question 13

What are haemoglobinopathies?

Give examples

Answer 13

These are disorders of haemoglobin

Sickle cell anaemia
Alpha and beta thalassaemia

Question 14

Describe the features of sickle cell anaemia

Answer 14

The cell is sickled and blocks arteries and can’t deliver enough oxygen

Question 15

Describe how SCD arises. What is the mutation?

Answer 15

There is a mutation in the beta globin gene.

When the haemoglobin is synthesised, they all stick together in a rigid chain

Question 16

Describe the mutation and how it arises in alpha thalassaemia

Answer 16

There is unequal crossing over of the alpha thalassaemia genes and then there is a reduced number of alpha globin genes

Question 17

Describe the 5 categories of alpha thalassaemia

Answer 17

Four copies: Normal 
3 copies: carrier
2 copies: minor
1 copy: major
0 copies: death

Question 18

Describe the possible mutations leading to beta thalassaemia

Answer 18

SNP in promoter region, 5’ UTR, intron consensus sequences

Question 19

What is important about beta thalassaemia and new born babies?

Answer 19

Newborn babies appear normal because they aren’t using beta globin yet, (still gamma)

The beta thalassaemia occurs later

Question 20

Compare oxygen affinity in gamma and beta globin

Answer 20

Gamma has a higher affinity for oxygen