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17 Cards in this Set
- Front
- Back
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Sickle cell Hb is an example of what type of genetic event?
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single point mutation. glutamic acid to valine at position 6.
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HbC Harlem is an example of what type of genetic event?
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double amino acid substitution, both position 6 and 73
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Hb gun Hill is an example of what type of genetic event?
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variant of hemoglobin with deletion. there is a deletion in the hydrophobic pocket near the heme.
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Hb Constant Spring is an example of what type of genetic event?
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chain termination mutants. the alpha chain mutates the stop codon and so there are extra amino acids. this genetic defect causes alpha thalassemia.
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Hb Wayne is an example of what type of genetic event?
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frame shift mutation. the frame shift causes an extended alpha chain.
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Hb Lepore is an example of what type of genetic event?
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fusion chain, unequal crossing over of the delta and beta genes produce a delta/beta gene. the rate of this gene is controlled by the delta promoter and is thus very low. this leads to beta thalassemia.
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Hb Grady is an example of what type of genetic event?
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insertion causes elongation of alpha gene. it carries a duplicated segment of alpha gene.
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The mutation in the sickle hemoglobin affects what aspect of the Hb?
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solubility.
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What is a possible cause for Hb with an abnormal oxygen affinity? are there more diseases with high affinity or low affinity
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Example the iron is in the three plus rather than the two plus state. This changes the oxygen affinity. there are more high affinity diseases than low.
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What is the defect in HbG
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no tight hydrophobic pocket
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What is the mechanism of disease for sickle cell hemoglobin?
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beta six mutation which causes sickling in deoxy form. erythrocytes assume abnormal shapes which causes cell lysis and hemolytic anemia. HbS has low O2 affinity, so it readily gives up the O2 to the tissue, but this makes it easier for sickling.
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How is HbC inherited and what does it cause? What is the mechanism?
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autosomal recessive, causes mild anemia. change of position six on beta chain from glu to lys. HbC precipitates in oxy form which causes shorter RBC life.
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What is the most common Hb variant in the world and what is the change? What is the heterozygous state like, homozygous? What is the clinical phenotype associated with?
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HbE common in SE Asians. change in 26 amino acid of the beta chain. heterozygous state is asymptomatic but RBC is microcytic. homozygous state has more microcytosis and hypochromia but still little anemia. HbE is not produced well compared to HbA so it is phenotypically similar to beta-thalassemia.
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What can changes in the hydrophobic pocket cause (in terms of RBC morphology)?
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changes in hydrophobic pocket alter heme stability. this leads to denaturation of affected globin chain and precipitation of globin chains (Heinz bodies). these inclusions are taken out by the spleen resulting in bite cells.
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What is methemoglobinemia? What is the mutation that can cause it? How is MetHb handled in the cell?
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MetHb has iron in the three plus state which cannot bind O2 well. Normally this is corrected by a reducatase in RBC. HbM is a mutation in the proximal or distal His which allows the heme to be oxidized more easily.
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What are some causes of Hb with increased O2 affinity? How is the O2 affinity curve shifted?
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Hb Ranier which has a mutated COOH salt bridge. Mutants with a substitution that affects DPG binding. The curve is left shifted.
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What are some causes of Hb with decreased O2 affinity? How is the O2 affinity curve shifted?
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destablized oxy form. Hb Kansas (with a far right P50). curve is right shifted. there are fewer known Hb with decreased O2 affinity than increased. it can also cause anemia due to decreased EPO response.
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