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M2M Unit II > Hemoglobinopathies > Flashcards

Flashcards in Hemoglobinopathies Deck (60):
1

defective globin switching

persistence of fetal hemoglobin

2

microcytosis

small cells

3

hydrops fetalis

fetal death due to complete lack of alpha hemoglobin genes

4

What is the embryonic hemoglobin?

HbG

4

The tense hemoglobin state is the ______ state, while the relaxed state is _______ and planar.

deoxygenated; oxygen-bound

5

Where are most structural hemoglobin variants found?

in the Beta-globin chain

5

hemoglobin H disease

severe anemia because only 1/4 alpha globin gene is functional

6

What is non-covalently linked in between the globins?

iron and a heme group

6

How many genetic variants of hemoglobin are known?

600

7

What is the fetal hemoglobin?

HbF (alpha 2 gamma 2)

8

How do you test for sickle cell?

1) DNA sequencing with PCR or electrophoresis 2) southern blot

8

Thalassemia minor

mild phenotype; doesn't req transfusions

9

In beta-thalassemia, defects are seen _____.

postnatally only

10

How are hemoglobin C and hemoglobin S different?

Same codon, different mutations, different phenotypes

11

HbKemsey has _____ O2 binding while hemoglobin Kansas has ______ O2 binding.

too tight; too weak

12

Which form of hemoglobin is the best oxygen carrier?

alpha-beta

13

Where is hemoglobin synthesized?

in the bone marrow

14

How many copies of the beta globin gene are there?

1

14

What is the major adult hemoglobin?

HbA

14

In HbKempsey, the O2 binding affinity is _____, so _____ O2 is delivered to the tissues, and to compensate, red blood cells are ________. This condition is called _______.

higher; less; overproduced; polycythemia

16

The 5'-3' ____ order of genes within each cluster coincides with the _____ order of their expression during development.

spatial; temporal

17

structural variants/qualitative hemoglobinopathies

mutations that alter the globin's properties without affecting its synthesis

18

Phenotypically, having 2 out of the 4 alpha globin genes results in _____.

mild anemia

19

How many oxygens does each globin bind?

one each; 4 per molecule

19

hypochromia

pale blood cells

20

What is hereditary persistence of fetal hemoglobin?

benign conditions that impair the perinatal switch from gamma to beta globin synthesis (high GbF in adults)

21

Beta-thalassemia is most often caused by _______.

point mutations in the beta-globin gene

22

Alpha-thalassemia is a ______ of alpha-globin and an excess of _____.

low or no amount; beta and gamma

23

thalassemia major

beta-zero; no beta proteins being produced

24

How many identical copies of the alpha globin gene are there on each chromosome?

2

25

What does the alpha cluster encode?

zeta- alpha2- alpha1

26

Where is embryonic hemoglobin made?

in the yolk sac

27

What do structural variants of hemoglobin do?

alter O2 binding

29

What does the beta cluster encode?

epsilon- gamma G-gamma A- delta- beta

31

Why is delta hemoglobin transcribed less?

it has a weaker promoter

32

thalassemias

low to no synthesis of one globin chain

33

What is globin switching?

transitioning between hemoglobins as development progresses

34

What kind of globin is expressed in fetal development?

gamma

36

What are the 3 genetic disorders of hemoglobin?

1) structural variants 2) thalassemias 3) defective globin switching

37

What is a pseudogene?

a gene that doesn't make a protein

39

Why does globin switching occur?

HbF in fetal blood is better suited to bind O2 at the placenta than HbA (lower pO2), which binds O2 better in the lung (higher pO2)

40

hemolysis

destruction of blood cells

41

Where is fetal hemoglobin made?

in the liver

42

Why is beta globin often affected by mutations?

there are only 2 copies of it, not 4 like alpha

43

Complex beta-thalassemia is caused by ____.

large deletions

44

In sickle cell anemia, a glutamate at position 6 is changed to ______, which changes the position that Mst II cleaves at, making a ______ protein than the wildtype.

valine; larger

45

What is the minor form of adult hemoglobin?

HbA2 (alpha 2 delta 2)

46

What is the solubility of hemoglobin S?

normal when oxygen is bound, but only 20% of normal when unbound

47

What happens when the LCR is knocked out of the beta cluster?

beta thalassemias result and alpha-globin chains precipitate

48

Alpha-thalassemia is occasionally caused by _______.

deletions in the LCR or the beta-gene cluster

49

In HbKansas, the O2 binding affinity is _____, so _____ O2 is delivered to the tissues, and ______ occurs.

decreased; less; cyanosis

50

Alpha-thalassemia is caused by _______.

a deletion of the alpha-globin gene(s)

52

Where is the alpha globin gene cluster located?

chromosome 16

54

Which is the first globin expressed?

epsilon

55

What does LCR stand for?

locus control region

56

Beta-thalassemia is a ______ of beta-globin and an excess of ________.

low or no amount; alpha-globin

57

Hemoglobin is a tetramer of 2 _____ polypeptides and 2 _____ polypeptides.

alpha; beta

58

What is the LCR of hemoglobin?

the promoter region about 20kb away from the first hemoglobin gene that regulates sequential transcription of all the genes

59

In alpha-thalassemia, defects are seen _____.

fetally and postnatally

60

Where is the beta globin gene cluster located?

chromosome 11