Midterm 1 - Notes 4 (Part 4)

Question 1

Where does O2 bind in Hb?

Answer 1

To the heme on the Hb chain

- associated with iron

Question 2

What are Hb chains like in invertebrates and primitive fish? (2)

Answer 2

1. Single chains of globin

2. Has one binding site for O2 and one binding site for iron

Question 3

What events lead to a more complex vertebrate Hb?

Answer 3

Mutations

Question 4

What are Hb chains like in complex vertebrate Hb?

Answer 4

Tetramere of globins

Question 5

What makes up an adult Hb?

Answer 5

2 alpha subunits and 2 beta subunits

Question 6

How many O2 can bind in an adult Hb?

Answer 6

4

Question 7

What makes up fetal Hb?

Answer 7

a alpha subunits and 2 gamma subunits

Question 8

What does HbF have a higher affinity for compared to adults?

Answer 8

O2

Question 9

Why does HbF have a higher affinity for O2?

Answer 9

Because it allows higher levels of O2 from the mother to be transported to high levels of O2 in the fetus

Question 10

What are the 4 subsequent gene duplications and mutations?

Answer 10

1. Epsilon
2. Gamma
3. Beta
4. Delta

Question 11

What makes up early HbF development?

Answer 11

2 alpha and 2 epsilon

Question 12

What makes up late HbF development?

Answer 12

2 alpha and 2 gamma

Question 13

What makes up main adult Hb form?

Answer 13

2 alpha and 2 beta

Question 14

What makes up minor adult form of Hb only in primates?

Answer 14

2 alpha and 2 delta

Question 15

What % of HbF is in adults?

Answer 15

< 0.6%

Question 16

When does HbF decrease?

Answer 16

Relatively fast after birth

Question 17

People with HbF higher than 0.8% are considered what?

Answer 17

HPFH

Question 18

HPFH

Answer 18

High Percentage Fetal Hemoglobin

Question 19

What could happen if you could control/regulate HbF?

Answer 19

You might be able to help patients that are unable to produce adult Hb

Question 20

What is beta-thalassemia?

Answer 20

It is an autosomal recessive blood disease

- reduced beta, but excessive alpha

Question 21

Anemia

Answer 21

Reduced hemoglobin and number of RBC

Question 22

What can happen to people who lack adult Hb?

Answer 22

They may have less symptoms if they express high levels of HbF

Question 23

What are 3 types of beta-hemoglobin that are caused by mutations?

Answer 23

1. Beta-thalassemia minor
2. Beta-thalassemia intermedia
3. Beta-thalassemia major

Question 24

What kind of mutation is beta-thalassemia minor?

Answer 24

Heterozygous for HBB mutation

Question 25

HBB

Answer 25

Beta-hemoglobin

Question 26

What kinda of mutation is beta-thalassemia intermedia?

Answer 26

Homozygous for HBB mutation

Question 27

What kinda of mutation is beta-thalassemia major?

Answer 27

Homozygous for HBB mutation

Question 28

Beta-thalassemia minor (3)

Answer 28

1. Has one normal copy and one mutated copy 2. Mild anemia (if at all) 3. Can still produce beta-globin

Question 29

Beta-thalassemia intermedia (2)

Answer 29

1. Both have a mutated version | 2. Cant make any beta-globin

Question 30

Beta-thalassemia major (4)

Answer 30

1. Both have a mutated version 2. Lack of being able to produce adult Hb causes this phenotype 3. Severe anemia and multiple other problems - need regular blood transfusions 4. Cant produce beta-globin

Question 31

What varies greatly with beta-thalassemia?

Answer 31

Severity of its symptoms - many factors - -> eg) environment

Question 32

Beta-thalassemia patients feel better when expressing what?

Answer 32

HbF

Question 33

What did they figure out in the Hb study?

Answer 33

How to turn on HbF

Question 34

How did being able to turn on HbF help patients?

Answer 34

Developed help for patients lacking HBB expression

Question 35

Why do you need 7,000 samples?

Answer 35

To be able to detect genetic linkages

Question 36

Why is Sardinia a good place for the study? (5)

Answer 36

1. The disease is common in the Mediterranean - high incidence rate 2. Isolated population 3. Historically little migration 4. Typically founder population 5. Higher degree of relatedness 6. High frequency of beta-thalassemia - 5%, > 10% carrier 7. High variation of HbF - 0-23.6%

Question 37

Whats considered HPFH?

Answer 37

> 0.8%

Question 38

Why was it good to used grandparents from Sardinians? (2)

Answer 38

1. You increase you chances because back then there was little immigration 2. Had at least one fist degree relative in the study group

Question 39

What type of microarray did they use in the Hb study?

Answer 39

Affymetrix

Question 40

What did they do in the Hb study to minor alleles with frequency > 5%?

Answer 40

They kicked them out because if you are looking at association then you are running a big risk of having a high mutated phenotype that is not a genetic component