Haemoglobin structure and function

Question 1

Describe the structure of haemoglobin

Answer 1

Made up of 2 alpha and 2 beta chains, each globin cahin is associated polyphyrin ring - haem group and iron in the centre

Question 2

Where does the polyphyrin ring bind to?

Answer 2

The histidine residues on E7 and F8

Oxygen lies between E7 histidine and iron atom

Question 3

HbA?

Answer 3

alpha 2 beta 2

Question 4

HbA2?

Answer 4

alpha 2 delta 2

Question 5

HbF?

Answer 5

alpha 2 gamma 2

Question 6

Hb Portland?

Answer 6

zeta 2 gamma 2

Question 7

Hb Gower 1?

Answer 7

zeta 2 epsilon 2

Question 8

Hb Gower 2?

Answer 8

alpha 2 epsilon 2

Question 9

Hb Barts?

Answer 9

gamma 4

Question 10

HbH?

Answer 10

Beta 4

Question 11

On which chromosomes can you find the alpha genes?

Answer 11

chromosome 16

Question 12

On which chromosome are the beta genes?

Answer 12

chromosome 11

Question 13

How does gene transcription occur?

Answer 13

It occurs in a temporal fashion in relation to the distance from 5’ end

Question 14

How are the genes for globin chains structured?

Answer 14

all 3 exons 2 introns

Question 15

What is the molecular pathology in thalassemias?

Answer 15

Nonsense mutations - coding of an aa changes to a stop codon
Frameshift - deletion of 2 adjacent bases leading to shift of transcription window
Promotor/polyA mutation - decreased mrna production
defective mRNA splicing - splice junction mutations - translation of introns
cryptic mutations - mutations in an intron which causes splicing at an different splice site

Question 16

What are the molecular pathologies associated with alpha thalassemia?

Answer 16

Deletions are more common

Question 17

What is the locus control region?

Answer 17

They move sequentially along to express different genes at different stages

Question 18

How do promotors and enhancers work?

Answer 18

They promote the gene in cis as they are 5’ to the gene they control
Enhancers works at a distance and can be either 5’ or 3’ to the gene

Question 19

How does the chromatin structure and histone modification work?

Answer 19

Histone acetyl transferase promote chromatin by opening and closing the gene
open - euchromatin is ready for transcription
methylation inhibits transcription
Acetylation of the histone promotes transcription

Question 20

Describe the alpha and beta globin gene clusters

Answer 20

(5’ to 3’)

• Alpha cluster: HS-40, zeta, alpha 2, and alpha 1 genes
• Beta cluster: LCR, epsilon, Ggamma, Agamma, delta and beta genes