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Cards In This Set
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What is the structure of Fetal Hb?
What percentage of Hb is in the adult and fetal form following birth and where is HbF stored? |
Fetal Hb consists of two alpha-globin and two gamma-globin chains.
Following birth, 99% is adult Hb while 1 % remains HbF and is found in special RBCs called F cells |
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Thalassemias are hemoglobinopathies caused by mutations in what genes?
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The globin genes
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What is the genetic composition of a normal individual in terms of the globin genes?
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2 copies of alpha-globin on chromosome 16 and 1 copy of beta-globin on chromosome 11
Diploid Cell: 4 copies of alpha-globin and 2 copies beta-globin |
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Deficieny in the production of alpha-globin leads to what?
beta-globin? |
Alpha-globin: alpha-thalassemia
beta-globin: beta-thalassemia |
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What are the genetic defects in alpha and beta-thalassemia?
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Alpha-thalassemia = gene deletion
Beta-thalassemia = variety of mutations |
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What are the variety of mutations associated with Beta-thalassemia?
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Promoter region and cap site, exons and introns (nonsense and frame shift), splice-junctions occur at the exon-intro borders; polyadenylation site and 5' and 3' ends of the gene
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Why are there clinical differences between alpha and beta-thalassemia?
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The duplicity of the alpha chain
A singly mutated alpha gene will result in no symptoms even in homozygotes for the trait because they have another functioning copy. A missing or mutated beta-gene has no backup copy so severe anemia results in homozygotes. |
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Alpha-thalassemia
Hb hydrops fetalis (no alpha) |
Clinical outcome: severe anemia; death in utero
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Alpha-thalaseemia
HbH (one alpha) |
Clinical outcome: moderate anemia
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Alpha-thalassemia
Trait (two alphas) |
Clinical outcome: mild anemia
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Beta-thalassemia
Beta Major (no beta) |
Clinical outcome: severe anemia, transfusions required
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Beta-thalassemia
Beta Minor (one Beta) |
Clinical outcome: mild anemia
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Treatments for Beta-thalassemia
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RBC transfusions and iron chelation therapy
new: bone marrow transplantation and drug HbF Lentivirus vector delivery of antisense snRNA- corrects splicing errors in mutant gene; makes HbA |
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What is the single point mutation of sickle cell anemia?
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B-chain of Hb: Glu replaced by Val at 6th position
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Why does HbS offer a selective advantage for resistance to Malaria?
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Parasite is injected which decreases blood pH of invaded RBC thereby promoting deoxy-HbS and sickling
distorted HbS RBC membrane allows K+ and water to leak increased concentration of K+ in blood stream kills parasite low oxygen tension from vaso-occlusion induced by sickling impairs parasite growth |
