Mutations and hemoglobinopathies flashcards

Question 1

Mutagens

Answer 1

Induce mutations in the genome

Question 2

Oxidative deamination

Answer 2

Converts C to U. During next replication U is matched with A and in the second replication A is matched with T.

Question 3

Apurination/Apyrimidation

Answer 3

Loss of purine/pyrimidine base

Question 4

O6-methyl guanosine

Answer 4

Highly mutagenic, causes different mutations

Question 5

Cyclobutane dimer

Answer 5

Forms between adjacent T-T dimers and blocks DNA polymerase

Question 6

Invariant amino acids

Answer 6

In the functionally active site of the molecule, may result in loss of function even if a conservative change

Question 7

Sickle cell disease mutation

Answer 7

6th amino acid of beta chain for Hb from Glu to Val

Question 8

HbC mutation

Answer 8

6th amino acid of beta chain for Hb from Glu to Lys

Question 9

Read-through mutation

Answer 9

Termination codon mutation which causes a larger than normal protein to be made

Question 10

Transition mutation

Answer 10

One purine-pyrimidine based substituted for another

Question 11

Transversion mutation

Answer 11

Purine-pyrimidine pair substituted for pyrimidine-purine pair and vice versa

Question 12

Nitrous acid

Answer 12

Can deaminate A to hypoxanthine and G to xanthine

Question 13

Peptide mapping (fingerprinting)

Answer 13

Sequences the protein and compares its primary structure to the normal protein. Enzymatic cleavage of protein and 2-D gel electrophoresis in 2 directions (one way for charge and one for size)

Question 14

What are the most common type of mutatons in hemoglobinopathies?

Answer 14

95% of the time in globin genes. Could be in alpha or beta gene but most often in beta.

Question 15

5 things Hb mutations can cause

Answer 15

1. Unstable structure 2. Increased or decreased oxygen affinity 3. Increase in oxidation from ferrous to ferric iron 4. Imbalance in synthesis of globin chains 5. Changes in properties of globin chains

Question 16

Unstable structure Hb mutations

Answer 16

Easily denature or precipitate and damage cell membrane seen as Heinz bodies. Substitution of Pro in alpha-helical region of globin fold will cause unstable Hb. Anemia, reticulocytosis (increase in reticulocytes), splenomegaly, urobilinuria (increased breakdown of Hb products in urine)

Question 17

Increased or decreased oxygen affinity Hb mutations

Answer 17

Hb cowton is example where His that dissociates 50% of Bohr protons is lost and destabilizes T conformation. Hemolytic anemia, Heinz body formation.

Question 18

Increase in oxidation from ferrous to ferric iron Hb mutations

Answer 18

HbM is an example. Cyanosis, weakness, possibly fatal.

Question 19

Imbalance in synthesis of globin chains Hb mutations

Answer 19

Thalassemias result. Most frequent single gene disorders. RBCs are microcytic and hypochromic.

Question 20

Beta thalassemia

Answer 20

Synthesis of beta-globin gene decreased or absent. Fetal hemoglobin synthesized but cannot be replaced by adult Hb. Alpha-globin chains form tetramers which precipitate and result in cell death. HbF and HbBart’s (4 gamma chains) accumulation typical.

Question 21

Beta thalassemia minor

Answer 21

Make some adult Hb and do not need treatment

Question 22

Cooley’s disease

Answer 22

Beta thalassemia major are homozygous. Severely anemic and require frequent blood transfusions resulting in iron overload (hemosiderosis). Bone marrow transplant helps.

Question 23

Alpha thalassemia

Answer 23

Synthesis of alpha-globin gene decreased or absent. Since 2 copies on each chromosome 16 many levels deficiency. Can make HbA, HbH, HbBart’s, beta-chain precipitate.

Question 24

Alpha thalassemia with 1 defective copy

Answer 24

Silent carrier with no symptoms

Question 25

Alpha thalassemia with 2 defective copies

Answer 25

Alpha-thalassemia trait with mild anemia

Question 26

Alpha thalassemia with 3 defective copies

Answer 26

Hemoglobin H with mild to severe hemolytic anemia (makes beta and gamma chains which form tetramers but are useless in carrying oxygen (no cooperativity and high oxygen affinity)

Question 27

Alpha thalassemia with 4 defective copies

Answer 27

Hydrops fetalis resulting in fetal death (can’t make HbF)