L14 Hb a model system for human mutations

Question 1

Powerful model system for studying mutations in humans

Answer 1

some mutations in Hb cause disease and some do not

Question 2

Haemoglobinopathies

Answer 2

disease causing mutations in Hb and facilitate understanding of “genotype-phenotype” interactions

Question 3

Why study Hb system

Answer 3

in blood, easy to get in quantity

Hb diseases are a significant cause of disease in human populations

Question 4

System illustrates

Answer 4

see onenote

6 points

Question 5

Globin family tree

Answer 5

see onenote

evolution of globin proteins parallels evolution of vertebrates

major junctions - divergence of myoglobin from haemoglobin and later divergence of Hb into alpha and beta subunits

Question 6

Heme group

Answer 6

see onenote

contains Fe in the middle of Porphorin ring

Question 7

Levels of protein structure

Answer 7

see onenote

Hydrophobic aa buried on the inside
Hydrophilic aa on the outside

Mutation which results in change from polar to non-polar protein or vice versa usually results in a mutation that causes a disease, drastic change, causes refolding of the protein - contributes to the diseased phenotype

Question 8

Hb structure

Answer 8

see onenote slides

complex of two alpha and beta chains

• can bind four oxygen molecules
• heme groups buried insite

Question 9

Difference between Hb and myoglobin in terms of oxygen delivering capacity

Answer 9

see onenote

Myoglobin

• Michaelis-menten curve
• good for storing oxygen in muscle

Hb

• cooperative binding => exponential change
• sigmoidal curve

Question 10

Different Hb

Answer 10

see onenote slides

several globin genes whose encoded proteins can combine to form several different Hb e.g. foetal Hb, adult Hb

We’ve got 4 alpha globin genes - as we’re diploids
2 alpha globin genes in haploid
There was a gene duplication in the alpha gene

Selective pressure for alpha gene duplication

• As alpha is common to both foetus and adult, very necessary
• Insurance policy

Permutations and combinations of different alpha and beta globin variants can produce many different Hb in an individual

Question 11

alpha, beta, gamma

Answer 11

see onenote

Globin family

earlier divergence of alpha

Question 12

Sight of formation of Hb

Answer 12

see onenote

erythropoiesis

1. yolk sac
2. liver
3. spleen
4. bone arrow

Question 13

Formation of HbA,C,G,G/C

Answer 13

see onenote