Genetics of blood Flashcards
What is blood type?
Classification of blood based on cell surface proteins such as antigens and the rhesus factor.
What is the role of antigens and antibodies in blood typing?
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.
What are the blood antigens?
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.
What are glycosyltransfersases?
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…
How are glycosyltransferases synthesised?
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.
What are the carriers of A and B antigens on erythrocytes?
Glycoproteins, band 3 anion exchangers and GLUT 1 glucose transporter
What is the role of Band 3 anion exchangers in the blood?
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.
What is the role of GLUT transporters in the blood?
They uptake glucose in response to insulin levels. They are carriers for the A or B antigens which is catalysed by glucosyltransferase enzyme.
What is the gene encoding for glycosyltransferase in Type A individuals?
N-acetylgalactosaminyltransferase
What is the gene encoding for glycosyltransferase in Type B individuals?
Galactosyltransferase
What is the gene encoding for glycosyltransferase in Type O individuals?
No transferase because no antigen is present
What is the mechanism of action of glycosyltransferases?
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.
How are blood groups inherited?
Non-Mendelian inheritance encoded by one gene on Chromosome 9. This has 3 allelic variants.
What are isoagglutinogens?
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.
Which isoagglutinogens will be produced for a Type A individual?
Anti-B antibodies.
Which isoagglutinogens will be produced for a Type B individual?
Anti-A antibodies
Which isoagglutinogens will be produced for a Type O individual?
Anti-A and Anti-B
Which isoagglutinogens will be produced for a Type O individual?
Both Anti-A antibodies and Anti-B.
What is Rh?
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.
What are the types of Rh?
5 antigens classifications of Rh:
RHC
RHc
RHD
RHE
RHe.
The most immunogenic is RhD.
How is the Rh antigen produced?
Encoded by both RHD and RHCE genes
How is Rhesus factor produced?
Rhesus factor is encoded by RHD gene which encodes for RHD and RHCE gene which encodes for RHC/c and RHE/e.
How is RhD inherited?
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.
Why are some individuals RHD-?
The RHD gene has been deleted so there is no expression of the D antigen.
What is Rhesus disease?
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.
What are the implications of Rhesus disease?
Can cause anaemia and jaundice which may develop into Kernicterus and lead to intrauterine death
How is Rhesus disease treated?
Prophylaxis with Anti-RHD therapy that neutralises any RHD+ cells to prevent production of maternal antibodies.
What is hydrops fetalis?
Foetus or baby with anaemia has severe fluid build up due to too much blood leaving bloodstream and entering tissues.
What is Kernicterus?
Brain damage in babies caused by bilirubin build up as a result of untreated jaundice caused by haemolytic anaemia. A complication of Rhesus disease.
Which group is a universal recipient?
Group AB+ which makes up 2% of donors.
Which group is the universal donor?
Group O- which makes up only 12% of total donors.
What is agglutination?
Immune response facillitated by antigen-antobody interactions that causes clumping. Agglutination indicates blood type for A and B antigens and RH factor.
What is thalassaemia?
A type of haemoglobinopathy caused by reduction in quantity of alpha or beta globin chain.
What is the cause of sickle cell anaemia?
Missense mutation of HBB gene replaces glutamic amino acid with valine amino acid and creates a HBS gene.
How does sickle cell anaemia affect HB in hypoxic conditions?
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.
Difference between sickle cell and thalassemia?
Thalassemia is when not enough globin chains are produced. Sickle cell is when the synthesis of the globin chains results in distorted shape.
What is the world incidence of thalassemia?
Meditteranean, South and Southeast asian and Middleastern origin
What is the world incidence of sickle cell anaemia?
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
How are people with sickle cell trait impacted?
Mutated beta globin chain complexes less efficiently and have less symptoms. Genotype AS.
What are the symptoms for sickle cell anaemia?
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.
What is a venesection?
Drawing blood.
How is polycythaemia treated?
Venesections, taking hydroxycarbamide medication and interferon.
What are the symptoms of polycythaemia?
Flushed skin, itching, bleeding, tingling in hands or feet, feeling of fullness and swollen spleen.
What is hydroxycarbamide?
A chemotherapy drug which inhibits DNA synthesis for RBC production to treat polycythaemia. Increases risk of infection and GI discomfort.
Interferon alpha
Drug derived from the human cytokine interferon for immune defence, used to treat side effect of hydroxycarbamide.
Megaloblastic anaemia
Large nucleated RBCs caused by B12 or folate deficiency
Consequences of macrocytic anaemia
Damage to the nervous system and neurological complications due to low O2 levels
