1. Primary abnormalities occur when?
    • Primary--during the dogma
    • Secondary---modification of the production from primary
  2. The iron of the heme is covalently linked to what a.a?
    Histidine 92
  3. Which a.a holds the pocket of heme?
    Phe 42
  4. Alpha globin genes --what chromosome?
    • 16
    • 11
  5. the beta globin genes on ch 11 are identical except for what two a.a?
    • alanine
    • glycine
  6. At 6 weeks, the fetal liver takes over erythropoeises and what change in globin genes occurs?
    • epsilon---gamma
    • something else-----alpha
  7. What is the genetic make up of the globin genes?
    3 exons separated by 2 introns
  8. What is needed for high expression of globin genes
    temporal switching during development?
    Locus control region (LCR)
  9. The Locus control region contains cis acting elements of trans acting elements?
    cis acting elements
  10. the hispanic epsilon gamma delta beta globin gene product results from what?
    deletion of LCR
  11. Genetic Disorders of Hemoglobin can be classified into 3 broad categories, what are they?
    • Structrural variants----sickle cell
    • Thalassemias
    • Persistence of fetal hemoglobin(gamma) after birth
  12. What are two hemoglobins with novel properties?
    • Hb S
    • Hb C
  13. What are two unstable hemoglobins?
    • Hammersmith
    • Gunhill
  14. Hb Hammersmith is caused by what?
    missense mutation from Phe42 to serine
  15. What physical property results from the Hb S mutation?
    • loss of negative charge...decrease in solubility
    • microvascular occlusion
  16. In HbS when do RBC acquire the sickle shape?
    Under hypoxic condtions
  17. RFLP for HbS produces a larger or smaller fragment?
    Larger bc of the altered cleave site for the RE
  18. HbS and HbC are inherited how?
  19. Hb hammersmith and Hb Gunhill are inherited how?
    Autosomal dominant
  20. What happens in Hb Hammersmith?
    • Phe42Ser
    • Heme falls out of pocket
    • Hemolysis
    • cyanosis
  21. What produces chocolate cyanosis?
  22. Slipped mispairing is seen in what Hb?
    Hb Gun hill
  23. a 5 base pair deletion is seen in what Hb?
    Hb Gun Hill
  24. What is the mutation in Hb Hyde park?
    His92 to tyrosine
  25. Which Hb has a locked in mutation into a relaxed state?
  26. Which hemoglobin has a longer than usual b chain?
    Hb Tak
  27. Which Hb has an activated cryptic splice site?
    Hb E
  28. Hb Lapore results from what?
    fusion of delta and beta genes
  29. What is Hb Antilapore?
    both beta and delta globins expressed
  30. Which hemoglobins give a concomittant increase of Fetal Hb?
    Hb Lapore and antiLapore
  31. Defect in production of hemoglobin results in what type of anemia?
    microcytic, normochromic anemia
  32. Hb Bart and Hb H result from what thalassemia?
    • Hb Bart---gamma 4
    • Hb H-betta 4
  33. What results from alpha thalassemia in a fetus?
    Hydrops fetalis---systemic edema
  34. Whats the most common mechanism of creating alpha thalassemias?
    unequal crossing over
  35. In which thalassemia do you seen medullary hyperplasia and extramedullary erythropeoises?
    beta thalassemia
  36. chip munk facies and front bossing are characteristic of what?
    beta thalassemia
  37. most beta thalassemias are caused by what?
    single base deletion
  38. Splicing mutations tend to be the cause of what thalassemia?
    Beta thalasemia
  39. Hereditary persistence of fetal hemoglobin could be caused by what?
Card Set