L14 Hb a model system for human mutations Flashcards Preview

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Flashcards in L14 Hb a model system for human mutations Deck (13)
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1
Q

Powerful model system for studying mutations in humans

A

some mutations in Hb cause disease and some do not

2
Q

Haemoglobinopathies

A

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

3
Q

Why study Hb system

A

in blood, easy to get in quantity

Hb diseases are a significant cause of disease in human populations

4
Q

System illustrates

A

see onenote

6 points

5
Q

Globin family tree

A

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

6
Q

Heme group

A

see onenote

contains Fe in the middle of Porphorin ring

7
Q

Levels of protein structure

A

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

8
Q

Hb structure

A

see onenote slides

complex of two alpha and beta chains

  • can bind four oxygen molecules
  • heme groups buried insite
9
Q

Difference between Hb and myoglobin in terms of oxygen delivering capacity

A

see onenote

Myoglobin

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

Hb

  • cooperative binding => exponential change
  • sigmoidal curve
10
Q

Different Hb

A

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

11
Q

alpha, beta, gamma

A

see onenote

Globin family

earlier divergence of alpha

12
Q

Sight of formation of Hb

A

see onenote

erythropoiesis

  1. yolk sac
  2. liver
  3. spleen
  4. bone arrow
13
Q

Formation of HbA,C,G,G/C

A

see onenote