Things to Remember II

Question 1

All of alpha and alpha like hemoglobin genes are in the ______ od chromosome ____.

Answer 1

alpha cluster on chromosome 16

Question 2

all of the beta and beta like genes are in the _____ cluster of chromosome _____

Answer 2

beta cluster on chromosome 11

Question 3

5’-3’ transcriptional orientation of alpha cluster

Answer 3

zeta-alpha2-alpha1

ζ-α2-α1

Question 4

5’-3’ transcriptional orientation of beta cluster

Answer 4

epsilon-gammaG-gamma-delta-beta

ε-γG-γA-δ-β

Question 5

The 5’-to-3’ spatial order of genes within each cluster coincides with the ______ order of their expression during development.

Answer 5

temporal

Question 6

Locus Control Region (LCR)

Answer 6

located 20 kB upstream of each hemoglobin cluster

controls expression of these genes

Question 7

Two Hb forms in adults

Answer 7

HbA- alpha2 beta2 (97%)
HbA2- alpha2 delta2 (2%)
*Note: gamma level much lower than beta because gamma has a weaker promoter

Question 8

Hb forms present during embryonic (3) and fetal (1) development

Answer 8

embryonic (made in yolk sac)
Hb Gower I (zeta 2 epsilon 2)
Hb Gower II (alpha 2 epsilon 2)
Hb Portland (zeta 2 gamma 2)

fetal (made in the liver)
HbF (alpha 2 gamma 2)

Question 9

Globin switching

Answer 9

a) turn-off of zeta and epsilon, turn on of alpha and gamma during early embryogenesis
b) turn-off of gamma, turn on of beta and delta around the time of birth

Question 10

Significance of globin switching

Answer 10

HbF has higher affinity for O2 at low pO2 than HbA

Question 11

Hereditary persistence of fetal hemoglobin (HPFH)

Answer 11

condition that impairs perinatal switch from gamma to beta globin, leading to continued high level production of HbF

Question 12

alpha-thal-1 allele (- -)

Answer 12

SE Asia
deletion of both copies of alpha globin genes
Homozygous-results in hydrops fetalis
Heterozygotes (αα/–) have mild anemia, a.k.a. α-thalassemia-1 trait

Question 13

alpha-thal-2 allele (α -)

Answer 13

Africa, mediterannean, and asia
Deletion of one of the two α-globin genes
Mild anemia in homozygotes (α-/α-), a.k.a. α-thalassemia-2 trait.

Question 14

alpha-thal-1/α-thal-2 (α -/- -)

Answer 14

Compound heterozygous individuals with only 25% of normal α-globin level. Severe anemia.

a.k.a. HbH disease. About 5-30% of their hemoglobin is β
4
(HbH), which precipitates.