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Flashcards in Hemoglobinopathies Deck (60)
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1

Hemoglobin alpha cluster

We have four copies of alpha both of which are preceded by fetal zeta (5')

Chromosome 16

2

Hemoglobin beta cluster

epsilon
Ggamma
Agamma
delta
beta

3

How many copies of beta?

two total (one on each homolog 11)

4

Embryonic hemoglobin?

zeta2epsilon2
alpha2epsilon2
zeta2gamma2

5

fetal hemoglobin?

alpha2gamma2

6

adult hemoglobin?

95% alpha2beta2
3.5% alpha2delta2

7

Globin switching during development
alpha cluster?

5th week switch from zeta to alpha

8

Globin switching during development
beta cluster?

Switch from epsilon to gamma in-utero
Switch from gamma to beta at birth

9

Locus control region

10 kb upstream - Regulates globin transcription of beta cluster
Both timing and level

10

What happens if we delete LCR of beta cluster?

Hispanic epsilongammadeltabeta thalassemia --> have much lower expression of beta isoforms

11

Sickle Cell Disease

Single gene disease
Single point mutation at codon 6 in exon 1 of beta globin

12

Sickle cell disease
Amino acid substitution

Glutamine for valine

13

Hemaglobin C disease

Same codon affected as sickle cell disease but different mutation (effects first position of codon and sickle effects second)- results in glutamine to lysine transition

14

Sickle cell and hemoglobin C inheritance pattern?

Autosomal recessive

15

Clinical manifestiation of hemoglobin C?

decrease solubility of hemoglobin - tends to lyse red blood cells

16

Diagnosing sickle cell: DNA diagnosis

Mst II restriction enzyme normally cleaves 5'cctnagg-3' but the sickle cell mutation changes the a to t and thus it is not recognized by the restriction enzyme - leading to a single heavier band in sickle

17

How can we distinguish sickle cell from Hemoglobin C with DNA diagnosis?

Hemoglobin C mutation does not effect restriction site of MstII, so Mst II will still cleave the DNA and yield two bands

18

Weight of Hb bands?

1.15
0.20
1.35 if uncleaved

19

Can we diagnosis hemoglobin diseases with electrophoresis

Yes, because HbS (sickle) has been changed from a negative charge (glutamate) to valine - so we would expect that it would not travel as far to the anode

HbC the glutamate has beeen changed to lysine (a positive charge) so we would expect it to travel the least distance

In order of migration, from farthest to shortest distance traveled we would expect
HbA
HbS
HbC

20

Hemoglobin oxygenate form

The heme is planar when oxygen is bound - via Fe - which is also bound to His

21

Hemoglobin deoxygenated form

The heme is domed (nonplanar/tense) when O2 is not bound

22

Hemoglobin Kempsey

High oxygen affinity
Less O2 to tissues
Overproduction of blood cells leads to polycythemia

23

Hemoglobin Kansas

Low oxygen affinity
Lower O2 level in RBC
Cyanosis

24

Thalassemia are due to?

Globin level imbalance

25

Alpha thalassemias are usually caused by ____ where as beta thalassemias are usually caused by _____

Alpha are usually caused by deletions

Beta are usually caused by point mutations

26

Alpha thalassemia
alpha
beta
gamma

low or zero alpha
beta and gamma in excess and preicipitates

27

alpha thalassemia onset?

both fetal and postnatal

28

Alpha thalassemia usually caused by?

deletions in alpha globin genes

29

Beta thalassemia
alpha
beta

low or zero beta globin
alpha globin in excess and precipitates

30

Beta thalassemia onset?

Postnatal only