Genetics of blood

Question 1

What is blood type?

Answer 1

Classification of blood based on cell surface proteins such as antigens and the rhesus factor.

Question 2

What is the role of antigens and antibodies in blood typing?

Answer 2

Determining an individuals blood group. There are 4 blood groups, A, B, O and ABO. It corresponds to whether they have the A antigen, B antigen, both A and B antigen or neither.

Question 3

What are the blood antigens?

Answer 3

A and B antigens are carbohydrate structures which attach to glycolipids or glycoproteins on erythrocyte membranes which form interactions that determine blood type via glycosyltransferase enzyme catalysation.

Question 4

What are glycosyltransfersases?

Answer 4

Enzymes which determine blood type via catalysing the transfer of antigen carbohydrate structures to proteins on the erythrocyte membrane such as anion exchanger, GLUT1 and N-glycosylated glycoproteins. A antigen means group A, etc…

Question 5

How are glycosyltransferases synthesised?

Answer 5

It is an enzyme encoded by genes in the nucleus. There are only 2 forms because there are only 2 antigens. Galactosyltransferase and N-acetylgalactosaminyltransferase.

Question 6

What are the carriers of A and B antigens on erythrocytes?

Answer 6

Glycoproteins, band 3 anion exchangers and GLUT 1 glucose transporter

Question 7

What is the role of Band 3 anion exchangers in the blood?

Answer 7

Carrier for A or B antigens which is catalysed by glycosyltransferase enzyme. It is also responsible for the chloride shift between HCO3- and CL- for the delivery of O2 to metabolically active tissues.

Question 8

What is the role of GLUT transporters in the blood?

Answer 8

They uptake glucose in response to insulin levels. They are carriers for the A or B antigens which is catalysed by glucosyltransferase enzyme.

Question 9

What is the gene encoding for glycosyltransferase in Type A individuals?

Answer 9

N-acetylgalactosaminyltransferase

Question 10

What is the gene encoding for glycosyltransferase in Type B individuals?

Answer 10

Galactosyltransferase

Question 11

What is the gene encoding for glycosyltransferase in Type O individuals?

Answer 11

No transferase because no antigen is present

Question 12

What is the mechanism of action of glycosyltransferases?

Answer 12

The acceptor substrate for the antigen transferases is the H antigen. N-acetylaminogalactotransferase catalyses the transfer of the A antigen N-acetylgalactosamine from UDP N-acetylgalactosamine to the H antigen. Galactosyltransferase catalyses the transfer of the B antigen galactosyl from UDP-galactosyl to H antigen.

Question 13

How are blood groups inherited?

Answer 13

Non-Mendelian inheritance encoded by one gene on Chromosome 9. This has 3 allelic variants.

Question 14

What are isoagglutinogens?

Answer 14

Antibodies produced against foreign blood group antigens that causes agglutination of the RBC with the foreign antigen. A person with Type B group will produce antibodies against A.

Question 15

Which isoagglutinogens will be produced for a Type A individual?

Answer 15

Anti-B antibodies.

Question 16

Which isoagglutinogens will be produced for a Type B individual?

Answer 16

Anti-A antibodies

Question 17

Which isoagglutinogens will be produced for a Type O individual?

Answer 17

Anti-A and Anti-B

Question 18

Which isoagglutinogens will be produced for a Type O individual?

Answer 18

Both Anti-A antibodies and Anti-B.

Question 19

What is Rh?

Answer 19

Also known as Rhesus factor, it is a cell surface protein on blood cells which give blood types a positive or negative depending on if it is present. It is an importnant indicator of compatibility.

Question 20

What are the types of Rh?

Answer 20

5 antigens classifications of Rh:
RHC
RHc
RHD
RHE
RHe.
The most immunogenic is RhD.

Question 21

How is the Rh antigen produced?

Answer 21

Encoded by both RHD and RHCE genes

Question 22

How is Rhesus factor produced?

Answer 22

Rhesus factor is encoded by RHD gene which encodes for RHD and RHCE gene which encodes for RHC/c and RHE/e.

Question 23

How is RhD inherited?

Answer 23

Individuals who are RHD+ may be homozygous or hemizygous for RHD gene. As long as they have one copy of the RHD gene, they will express RHD on all erythrocytes.

Question 24

Why are some individuals RHD-?

Answer 24

The RHD gene has been deleted so there is no expression of the D antigen.

Question 25

What is Rhesus disease?

Answer 25

When a RH- mother carries a RH+ foetus. Antigens from foetus can enter the mother's blood during delivery and cause sensitisation which promotes the production of anti-RH antibodies. In response to this, subsequent pregnancy with a RH+ foetus will result in anti-RH maternal antibodies crossing placenta to damage the foetal RBC.

Question 26

What are the implications of Rhesus disease?

Answer 26

Can cause anaemia and jaundice which may develop into Kernicterus and lead to intrauterine death

Question 27

How is Rhesus disease treated?

Answer 27

Prophylaxis with Anti-RHD therapy that neutralises any RHD+ cells to prevent production of maternal antibodies.

Question 28

What is hydrops fetalis?

Answer 28

Foetus or baby with anaemia has severe fluid build up due to too much blood leaving bloodstream and entering tissues.

Question 29

What is Kernicterus?

Answer 29

Brain damage in babies caused by bilirubin build up as a result of untreated jaundice caused by haemolytic anaemia. A complication of Rhesus disease.

Question 30

Which group is a universal recipient?

Answer 30

Group AB+ which makes up 2% of donors.

Question 31

Which group is the universal donor?

Answer 31

Group O- which makes up only 12% of total donors.

Question 32

What is agglutination?

Answer 32

Immune response facillitated by antigen-antobody interactions that causes clumping. Agglutination indicates blood type for A and B antigens and RH factor.

Question 33

What is thalassaemia?

Answer 33

A type of haemoglobinopathy caused by reduction in quantity of alpha or beta globin chain.

Question 34

What is the cause of sickle cell anaemia?

Answer 34

Missense mutation of HBB gene replaces glutamic amino acid with valine amino acid and creates a HBS gene.

Question 35

How does sickle cell anaemia affect HB in hypoxic conditions?

Answer 35

It will complex and polymerise due to valine amino acid and this will distort the shape of RBC, disrupting its ability to travel through capillaries. Results in vaso-occlusion that causes episodic pain.

Question 36

Difference between sickle cell and thalassemia?

Answer 36

Thalassemia is when not enough globin chains are produced. Sickle cell is when the synthesis of the globin chains results in distorted shape.

Question 37

What is the world incidence of thalassemia?

Answer 37

Meditteranean, South and Southeast asian and Middleastern origin

Question 38

What is the world incidence of sickle cell anaemia?

Answer 38

African or carribean descent. Correlates with prevalence of plasmodium falciparum (mosquito) which has a selective survival advantage for individuals with AS genotype against malaria. Those with sickle cell anaemia have a worse outcome for malaria

Question 39

How are people with sickle cell trait impacted?

Answer 39

Mutated beta globin chain complexes less efficiently and have less symptoms. Genotype AS.

Question 40

What are the symptoms for sickle cell anaemia?

Answer 40

Vaso-occlusive episodes of pain in the bones, lung, spleen and brain. Severe haemolytic anaemia episodes. It may impact their daily life and reduces their lifespan.

Question 41

What is a venesection?

Answer 41

Drawing blood.

Question 42

How is polycythaemia treated?

Answer 42

Venesections, taking hydroxycarbamide medication and interferon.

Question 43

What are the symptoms of polycythaemia?

Answer 43

Flushed skin, itching, bleeding, tingling in hands or feet, feeling of fullness and swollen spleen.

Question 44

What is hydroxycarbamide?

Answer 44

A chemotherapy drug which inhibits DNA synthesis for RBC production to treat polycythaemia. Increases risk of infection and GI discomfort.

Question 45

Interferon alpha

Answer 45

Drug derived from the human cytokine interferon for immune defence, used to treat side effect of hydroxycarbamide.

Question 46

Megaloblastic anaemia

Answer 46

Large nucleated RBCs caused by B12 or folate deficiency

Question 47

Consequences of macrocytic anaemia

Answer 47

Damage to the nervous system and neurological complications due to low O2 levels